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| 1 | Clinical characteristics and outcome of a cohort of 101 patients with hepatocellular carcinoma显示文摘AIM To conduct a cohort study of 101 patients with hepatocellular carcinoma (HCC) presenting to a tertiary care medical referral center in Germany between 1997 and 1999.METHODS AND RESULTS Data were retrospectively analyzed by chart review. In 95cases (72 males and 23 females) sufficient data were available for analysis. Twenty-five (29%)of 8.5 patients were HBsAg or anti-HBc positive,21/85 (25%) were anti-HCV positive, and 6/85(7%) were positive for both HBV and HCV-markers. Age was significantly lower in HBV-positive patients than in the other two groups.Thirty-one (34%) of 90 patients had histories of alcohol abuse, In 79/ 94 (84%) patients,cirrhosis was diagnosed. Of these cirrhotic patients, 29/79 (37%) belonged to Child-Pugh's group (CHILD) A, 32/79 (40%) to CHILD B, and 18/79 (23%) to CHILD C. AFP was elevated in 61/91 (67%) patients. A single tumor nodule was found in 38/94 (40%), more than one nodule in 31/94 (34%), and 25/94 (26%) had a diffusely infiltrating tumor, i.e. the tumor margins could not be seen on imaging procedures. Portal vein thrombosis was present in 19/ 94 (20%).Imaging data consistent with lymph node metastases were found in 10/92 (11%), while distant metastases were found in 8/93 (9%).According to Okuda 28/94 (30%) were grouped to stage Ⅰ, 53/94 (56%) were grouped to stage Ⅱ, and 13/94 (14%) were grouped to stage Ⅲ.Survival data were available for 83 patients. The Kaplan-Meier estimate for median survival was 8.4 months. Factors influencing survival were the Okuda score, the presence of portal vein thrombosis, and the presence of ascites. The presence of non-complicated liver cirrhosis by itself, distant metastases, or infection with hepatitis viruses did not influence survival. AFP positivity by itself did not influence survival,though patients with an AFP value greater than 100μg/L did experience shortened survival.Treatment besides tamoxifen or supportive care was associated with prolonged survival. The influence of therapy on survival was most pronounced in Okuda stage Ⅱ patients. There was longer survival in those Okuda stage Ⅱpatients who were treated with percutaneous ethanol injection.CONCLUSION Even in a Iow incidence area such as Germany, the majority of HCC is caused by viral hepatitis and therefore potentially preventable. Reflecting the high proportion of advanced stage tumors in our patients, the median survival was poor. Patients who received active therapy had a longer survival. | Christian Rabe Tillmann Pilz Christoph Klostermann Marc Berna Hans H.Schild Tilman Sauerbruch Wolfgang H.Caselmann | 2001 | World Journal of Gastroenterology2001，7，2： | 60 |
| 2 | HCV-specific cytokine induction in monocytes of patients with different outcomes of hepatitis C显示文摘AIM:Cytokine release by macrophages critically determines the type of immune response to an antigen Therefore.we studied hepatitis C virus (HCV0-Specific induction of interleukins-1β,-10,-12(IL-1β,il-10,IL-12),and tumor necrosis factor-α(TNF-α) in monocytes.METHODS:Intracellular cytokine expression was studied by flow cytometry in 23 patients with chronic hepatitis C,14 anti-HCV seropositives without viremia and 11 controls after stimulation of peripheral blood mononuclear cells with recombinant core,NS3,NS4 NS5a and NS5b proteins .RESULTS:Patients with HCV viremia revealed greater spontaneous exprssion of IL-1β,TNF-α,and IL-10,Furthermore,greater than twofold higher IL-10 epression was induced by the HCV antigens in chronic hepatitis C than in the other two groups (P<0.05) In contrast,neither IL-12 noir TNF-α was induced preferentially.CONCLUSION:In chonic hepatitis C antigen-specific cytokine induction in monocytes is apparently shifted towards predominant IL-10 induction-not counterbalanced by antiviral type 1 cytokines,This may contribute to persistent viral replication. | Rainer P.Woitas Uwe Petersen Dirk Moshage Hans H.Brackmann Bertfried Matz Tilman Sauerbruch Ulrich Spengler | 2002 | World Journal of Gastroenterology2002，8，3： | 15 |
| 3 | Yangtze Three Gorges Reservoir, China: A holistic assessment of organic pollution, mutagenic effects of sediments and genotoxic impacts on fish显示文摘Besides obvious benefits,the Three Gorges Dam's construction resulted in new pollution scenarios with the potentials to threaten the Three Gorges Reservoir(TGR) ecosystem.In order to record organic contamination,to find links to ecotoxicological impacts and to serve as reference for ensuing monitoring,several sites in the TGR area were screened applying the triad approach with additional lines-of-evidence as a holistic assessment method.Sediments and the benthic fish species Pelteobagrus vachellii were sampled in 2011 and 2012 to determine organic pollution levels,mutagenic potentials and genotoxic impacts.Two regional hot-spots near the cities of Chongqing and Kaixian were identified and further investigated in 2013.Only polycyclic aromatic hydrocarbons(PAHs) could be detected in sediments in 2011(165–1653 ng/g),emphasizing their roles as key pollutants of the area.Their ubiquity was confirmed at Chongqing(150–433 ng/g) and Kaixian(127–590 ng/g) in2013.Concentrations were comparable to other major Chinese and German rivers.However,the immense sediment influx suggested a deposition of 216–636 kg PAH/day(0.2–0.6 mg PAH/(m2·day)),indicating an ecotoxicological risk.PAH source analysis highlighted primary impacts of combustion sources on the more industrialized upper TGR section,whereas petrogenic sources dominated the mid-low section.Furthermore,sediment extracts from several sites exhibited significant activities of frameshift promutagens in the Ames fluctuation assay.Additionally,significant genotoxic impairments in erythrocytes of P.vachellii were detected(Chongqing/Kaixian),demonstrating the relevance of genotoxicity as animportant mode of action in the TGR's fish.PAHs,their derivatives and non-target compounds are considered as main causative agents. | Tilman Floehr Bj?rn Scholz-Starke Hongxia Xiao Josef Koch Lingling Wu Junli Hou Anja Wolf Axel Bergmann Kerstin Bluhm Xingzhong Yuan Martina Ro?-Nickoll Andreas Sch?ffer Henner Hollert | 2015 | Journal of Environmental Sciences2015，27，12： | 9 |
| 4 | Transjugular portosystemic stent shunt in treatment of liver diseases显示文摘INTRODUCTIONMore than 10 years ago ,an interventional technique for the creation of an intrahepatic decompressive shunt between a branch of the portal vein and a main hepatic vein using expandable metallic stents has been intriduced for the treatmint of portal hypertension[1,2],This transjugular portosystemic intrahepatic stent shunt (TIPS) functions as a side to side shunt ,similarly to surgical shunts . | Michael Schepke Tilman Sauerbruch | 2001 | World Journal of Gastroenterology2001，7，2： | 6 |
| 5 | Transjugular intrahepatic portosystemic shunt in refractory chylothorax due to liver cirrhosis显示文摘A pleural effusion containing chylomicrons is termed chylothorax and results from leakage of lymph fluid into the pleural cavity.We report on the case of a 59-year-old woman with severe dyspnea due to a large chylothorax.She was known to have liver cirrhosis but no ascites.There was no history of trauma,cardiac function was normal and thorough diagnostic work-up did not reveal any signs of malignancy.In summary,no other etiology of the chylothorax than portal hypertension could be found.Therapy with diuretics as well as parenteral feeding failed to relieve symptoms.After a transjugular intrahepatic portosystemic shunt(TIPS) had successfully been placed,pleural effusion decreased considerably.Eight months later,TIPS revision had to be performed because of stenosis,resulting in remission from chylothorax.This case shows that even in the absence of ascites,chylothorax might be caused by portal hypertension and that TIPS can be an effective treatment option. | Philipp Lutz Holger Strunk Hans Heinz Schild Tilman Sauerbruch | 2013 | World Journal of Gastroenterology2013，19，7： | 6 |
| 6 | C-reactive protein is a prognostic indicator in patients with perihilar cholangiocarcinoma显示文摘AIM: To evaluate prognostic indicators for the outcome of patients with perihilar extrahepatic cholangiocarcinoma in an unselected cohort. METHODS: We retrospectively analyzed 98 patients with perihilar cholangiocarcinoma. Twenty-three patients (23.5%) underwent tumor resection. Patients with non- resectable tumors underwent either transpapillary or percutaneous transhepatic biliary drainage. Additionally, 32 patients (32.7%) received photodynamic therapy (PDT) and 18 patients (18.4%) systemic chemotherapy. Predefined variables at the time of diagnosis and characteristics considering the mode of treatment were entered into a Cox’s proportional hazards model. Included in the analysis were age, tumor stage following the modified Bismuth-Corlette classification, bilirubin, prothrombin time (PT), C-reactive protein (CRP), carbohydrate antigen 19-9 (CA19-9), history of weight loss, surgical resection, chemotherapy and PDT. RESULTS: The Kaplan-Meier estimate of overall median survival was 10.5 (95%CI: 8.4-12.6) mo. In the univariate analysis, low Bismuth stage, low CRP and surgical resection correlated significantly with better survival. In the multivariate analysis, only CRP (P = 0.005) and surgical resection (P = 0.029) were found to be independently predictive of survival in the cohort. Receiver operating characteristic (ROC) analysis identified a CRP level of 11.75 mg/L as the value associated with the highest sensitivity and specificity predicting a survival > 5 mo. Applying Kaplan-Meier analysis, patients with a CRP < 12 mg/L at the time of diagnosis had a signifi cantly longer median survival than patients with higher values (16.2 vs 7.6 mo; P = 0.009).CONCLUSION: This retrospective analysis identif ied CRP level at the time of diagnosis as a novel indicator for the prognosis of patients with perihilar cholangiocarcinoma. It should be evaluated in future prospective trials on this entity. | Thomas Gerhardt Sabine Milz Michael Schepke Georg Feldmann Martin Wolff Tilman Sauerbruch Franz Ludwig Dumoulin | 2006 | World Journal of Gastroenterology2006，12，34： | 5 |
| 7 | Treatment of metastatic colorectal carcinomas by systemic inhibition of vascular endothelial growth factor signaling in mice显示文摘AIM: Tumor angiogenesis has been shown to be promoted by vascular endothelial growth factor (VEGF) via stimulating endothelial cell proliferation, migration, and survival. Blockade of VEGF signaling by different means has been demonstrated to result in reduced tumor growth and suppression of tumor angiogenesis in distinct tumor entities. Here, we tested a recombinant adenovirus, AdsFIt1-3, that encodes an antagonistically acting fragment of the VEGF receptor 1 (Flt-1), for systemic antitumor effects in pre-established subcutaneous CRC tumors in mice. METHODS: Murine colorectal carcinoma cells (CT26) were inoculated subcutaneously into Balb/c mice for in vivo studies. Tumor size and survival were determined. 293 cell line was used for propagation of the adenoviral vectors. Human lung cancer line A549 and human umbilical vein endothelial cells were transfected for in vitro experiments. RESULTS: Infection of tumor cells with AdsFlt1-3 resulted in protein secretion into cell supernatant, demonstrating correct vector function. As expected, the secreted sFlt1-3 protein had no direct effect on CT26 tumor cell proliferation in vitro, but endothelial cell function was inhibited by about 46% as compared to the AdLacZ control in a tube formation assay. When AdsFlt1-3 (5×109 PFU/animal) was applied to tumor bearing mice, we found a tumor inhibition by 72% at d 12 after treatment initiation. In spite of these antitumoral effects, the survival time was not improved. According to reduced intratumoral microvessel density in AdsFIt1-3-treated mice, the antitumor mechanism can be attributed to angiostatic vector effects. We did not detect increased systemic VEGF levels after AdsFlt1-3 treatment and liver toxicity was low as judged by serum alanine aminotransferase determination. CONCLUSION: In this study we confirmed the value of a systemic administration of AdsFIt1-3 to block VEGF signaling as antitumor therapy in an experimental metastatic colorectal carcinoma model in mice. | Volker Schmitz Miroslaw Kornek Tobias Hilbert Christian Dzienisowicz Esbher Raskopf Christian Rabe Tilman Sauerbruch Cheng Qian Wolfgang H Caselmann | 2005 | World Journal of Gastroenterology2005，11，28： | 4 |
| 8 | Distribution and effects of polymorphic RANTES gene alleles in HIV/HCV coinfection - A prospective cross-sectional study显示文摘AIM: Chemokines and their receptors are crucial for immune responses in HCV and HIV infection. RANTES gene polymorphisms lead to altered gene expression and influence the natural course of HIV infection. Therefore,these mutations may also affect the course of HIV/HCV coinfection.METHODS: We determined allele frequencies of RANTES-403 (G→A), RANTES-28 (C→G) and RANTESIN1.1 (T→C) polymorphisms using real-time PCR and hybridization probes in patients with HIV (n = 85), HCV (n= 112), HIV/HCV coinfection (n = 121), and 109 healthy controls. Furthermore, HIV and HCV loads as well as CD4+ and CD8+ cell counts were compared between different RANTES genotypes.RESULTS: Frequencies of RANTES-403 A, RANTES-28 G and RANTES-IN1.1 C alleles were higher in HIV infected patients than in healthy controls (-403: 28.2% vs 15.1%,P = 0.002; -28: 5.4% vs 2.8%, not significant; IN1.1:19.0% vs 11.0%, P = 0.038). In HIV/HCV coinfected patients, these RANTES alleles were less frequent than in patients with HIV infection alone (15.4% P = 0.002;1.7%; P = 0.048; 12.0%; not significant). Frequencies of these alleles were not significantly different between HIV/HCV positive patients, HCV positive patients and healthy controls.CONCLUSION: All three RANTES polymorphisms showed increased frequencies of the variant allele exclusively in patients with HIV monoinfection. The finding that the frequencies of these alleles remained unaltered in HIV/HCV coinfected patients suggests that HCV coinfection interferes with selection processes associated with these alleles in HIV infection. | Golo Ahlenstiel Agathe Iwan Jacob Nattermann Karin Bueren Jürgen K Rockstroh Hans H Brackmann Bernd Kupfer Olfert Landt Amnon Peled Tilman Sauerbruch Ulrich Spengler Rainer P Woitas | 2005 | World Journal of Gastroenterology2005，11，48： | 3 |
| 9 | Hepatic and serum levels of miR-122 after chronic HCV-induced fibrosis显示文摘 | Jonel Trebicka Evrim Anadol Natalia Elfimova Ingo Strack Michael Roggendorf Sergei Viazov Inga Wedemeyer Uta Drebber Jürgen Rockstroh Tilman Sauerbruch Hans-Peter Dienes Margarete Odenthal | 2012 | Journal of Hepatology2012，，： | 2 |
| 10 | Effect of Adiponectin and Ghrelin on Apoptosis of Barrett Adenocarcinoma Cell Line显示文摘 | Peter C. Konturek Grzegorz Burnat Tilman Rau Eckhart G. Hahn Stanislaw Konturek | 2008 | Digestive Diseases and Sciences2008，，3： | 2 |
| 11 | Eutrophication: impacts of excess nutrient inputs on freshwater, marine, and terrestrial ecosystems显示文摘 | V.H. Smith G.D. Tilman J.C. Nekola | 1999 | Environmental Pollution1999，，1： | 2 |
| 12 | Differential diagnosis in patients with suspected bile acid synthesis defects显示文摘AIM: To investigate the clinical presentations associated with bile acid synthesis defects and to describe identification of individual disorders and diagnostic pitfalls. METHODS: We describe semiquantitative determination of 16 urinary bile acid metabolites by electrospray ionization-tandem mass spectrometry. Sample preparation was performed by solid-phase extraction. The total analysis time was 2 min per sample. We determined bile acid metabolites in 363 patients with suspected defects in bile acid metabolism. RESULTS: Abnormal bile acid metabolites were found in 36 patients. Two patients had bile acid synthesis defects but presented with atypical presentations. In 2 other patients who were later shown to be affected by biliary atresia and cystic fibrosis the profile of bile acid metabolites was initially suggestive of a bile acid synthesis defect. Three adult patients suffered from cerebrotendinous xanthomatosis. Nineteen patients had peroxisomal disorders, and 10 patients had cholestatic hepatopathy of other cause. CONCLUSION: Screening for urinary cholanoids should be done in every infant with cholestatic hepatopathy as well as in children with progressive neurological disease to provide specific therapy. | Dorothea Haas Hongying Gan-Schreier Claus-Dieter Langhans Tilman Rohrer Guido Engelmann Maura Heverin David W Russell Peter T Clayton Georg F Hoffmann Jürgen G Okun | 2012 | World Journal of Gastroenterology2012，18，10： | 2 |
| 13 | Drought and biodiversity in grasslands显示文摘 | Tilman D El Haddi A | 1992 | Oecologia1992，89，： | 1 |
| 14 | The resources-ratio hypothesis of plant succession显示文摘 | TILMAN D | 1985 | American Naturalist1985，125，： | 1 |
| 15 | The relationships among root and leaf traits of 76 grassland species and relative abundance along fertility and disturbance gradients 显示文摘 | Craine J M Froehle J Tilman D G | 2001 | Oikos2001，93，2： | 1 |
| 16 | Forecasting agriculturally driven global environmental change 显示文摘 | Tilman D Fargione J Wolff B | 2001 | Science2001，，13： | 1 |
| 17 | The influence of functional diversity and composition on ecosystem processes显示文摘 | Tilman D Knops J Wedin D | 1997 | Science1997，277，： | 1 |
| 18 | Agricultural sustainability and intensive production practices显示文摘 | Tilman D Cassman K Matason P A | 2002 | Nature2002，418，6898： | 1 |
| 19 | Plant diversity and ecosystem productivity:Theoretical considerations显示文摘 | Tilman D Lehman C L Bristow C E | 1997 | Proceedings of the National Academy of Sciences1997，94，： | 1 |
| 20 | Plant strategies and the structure and dynamics of plant communities显示文摘 | Tilman D | 1985 | The American Naturalist1985，125，6： | 1 |
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