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  1. AU="Karel J van Erpecum"
  2. AU=Oltean Mihai
  3. AU="Relph, Katharine A"
  4. AU=Li Jifen AU=Li Jifen
  5. AU="Diamant, Eran"
  6. AU="Kyoung, Henry" AU="Kyoung, Henry"
  7. AU=al-Gazali L I
  8. AU="Maillet, Jean-Michel"
  9. AU="Enlong Liu"
  10. AU="Afria, Dikshant"
  11. AU="Duggal, M. S."
  12. AU="Narcisa G. Pricope"
  13. AU="Kunisada, Toshiyuki"
  14. AU="Barvkar, Vitthal"

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  1. Artikel ; Online: Surveillance for hepatocellular carcinoma in chronic liver disease

    Suzanne van Meer / Robert A de Man / Peter D Siersema / Karel J van Erpecum

    World Journal of Gastroenterology, Vol 19, Iss 40, Pp 6744-

    Evidence and controversies

    2013  Band 6756

    Abstract: Primary liver cancer is the sixth most common cancer in the world and the third cause of cancer-related death. Hepatocellular carcinoma (HCC) represents more than 90% of primary liver cancers and generally occurs in patients with underlying chronic liver ...

    Abstract Primary liver cancer is the sixth most common cancer in the world and the third cause of cancer-related death. Hepatocellular carcinoma (HCC) represents more than 90% of primary liver cancers and generally occurs in patients with underlying chronic liver disease such as viral hepatitis, hemochromatosis, primary biliary cirrhosis and non-alcoholic steatohepatitis. Especially cirrhotic patients are at risk of HCC and regular surveillance could enable early detection and therapy, with potentially improved outcome. We here summarize existing evidence for surveillance including ultrasound, other radiological modalities and various serum biomarkers, and current international guideline recommendations for surveillance. Ultrasound and α-fetoprotein (alone or in combination) are most frequently used for surveillance, but their sensitivities and specificities are still far from perfect, and evidence for surveillance remains weak and controversial. Various other potential surveillance tools have been tested, including serum markers as des-carboxyprothrombin, lectin-bound α-fetoprotein, and (most recently) circulating TIE2-expressing monocytes, and radiological investigations such as computed tomography-scan or magnetic resonance imaging-scan. Although early results appear promising, these tools have generally been tested in diagnostic rather than surveillance setting, and in most cases, no detailed information is available on their cost-effectiveness. For the near future, it remains important to define those patients with highest risk of HCC and most benefit from surveillance, and to restrict surveillance to these categories.
    Schlagwörter Hepatocellular carcinoma ; Surveillance ; Chronic liver disease ; Diseases of the digestive system. Gastroenterology ; RC799-869 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Gastroenterology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2013-01-01T00:00:00Z
    Verlag Baishideng Publishing Group Co., Limited
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: Patient adherence to antiviral treatment for chronic hepatitis B and C

    Faydra I. Lieveld / Lotte G. van Vlerken / Peter D. Siersema / Karel J van Erpecum

    Annals of Hepatology, Vol 12, Iss 3, Pp 380-

    a systematic review

    2013  Band 391

    Abstract: Introduction. Poor adherence to treatment for various chronic diseases is a frequent phenomenon. Current guidelines for the treatment of chronic hepatitis B (HBV) and hepatitis C (HCV) recommend optimal adherence, since it has been suggested that poor ... ...

    Abstract Introduction. Poor adherence to treatment for various chronic diseases is a frequent phenomenon. Current guidelines for the treatment of chronic hepatitis B (HBV) and hepatitis C (HCV) recommend optimal adherence, since it has been suggested that poor adherence is associated with an increased risk of virological failure. We aimed to give an overview of studies exploring adherence to combination treatment (PEG-interferon plus ribavirin) for HCV and nucleos(t)ide analogues for HBV.Material and methods. A systematic review was conducted using the databases PubMed, Embase, Cochrane Library and Web of Knowledge. Search terms included “adherence” or “compliance” combined with “hepatitis B”, “hepatitis C” or “viral hepatitis”.Results. The final selection included 19 studies (13 HCV, 6 HBV). Large differences in patient numbers and adherence assessment methods were found between the various studies. For HCV mean adherence varied from 27 to 97%, whereas the proportion of patients with ≥ 80% adherence varied from 27 to 96%. Mean adherence reported in HBV studies ranged from 81 to 99%, with 66 to 92% of patients being 100% adherent. For both HCV and HBV studies, the highest adherence rates were reported in studies using self-report whereas lower adherence rates were reported in studies using pharmacy claims. Poor adherence to treatment was associated with an increased risk of virological failure.Conclusion. Non-adherence to treatment in chronic viral hepatitis is not a frequent phenomenon. However, given the increased risk of virological failure in poorly adherent patients, clinicians should routinely address adherence issues in all patients treated for chronic viral hepatitis.
    Schlagwörter Compliance ; Nucleos(t)ide analogues ; Peg-interferon ; Ribavirin ; Viral hepatitis ; Specialties of internal medicine ; RC581-951
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2013-05-01T00:00:00Z
    Verlag Elsevier
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    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  3. Artikel ; Online: Clinical and basal aspects of anemia during antiviral therapy for hepatitis C

    Hanneke van Soest / Willem Renooij / Karel J. van Erpecum

    Annals of Hepatology, Vol 8, Iss 4, Pp 316-

    2009  Band 324

    Abstract: Background and Rationale. Anemia is a major side effect of combination therapy for chronic hepatitis C. In this study, severity, potential risk factors for and potential underlying mechanisms of anemia were evaluated.Patients and methods. 44 chronic ... ...

    Abstract Background and Rationale. Anemia is a major side effect of combination therapy for chronic hepatitis C. In this study, severity, potential risk factors for and potential underlying mechanisms of anemia were evaluated.Patients and methods. 44 chronic hepatitis C patients on interferon-ribavirin treatment were included. Anemia-related parameters were measured before and during treatment. Potential changes in membrane phospholipids composition of erythrocytes of patients on anti-viral treatment and potentially increased erythrocyte susceptibility to osmotic or bile salt induced stress were explored.Results. Anemia was almost universal during treatment, with evidence of hemolysis. Decrease of Hb after six months of therapy was 2.1 ± O.I mmol/L (range -0.6-4.1). Higher pre-treatment Hb, highest ribavirin dose (1S-17.S mg/kg) and lower pre-treatment platelet level were independent risk factors for decrease of Hb. Serum erythropoietin levels increased during treatment with negative correlation to Hb levels at week 12 (r = -0.70, p = 0.002) and 24 (r = -0.72, p = 0.002). Erythrocyte membrane phospholipid composition did not differ between anemic patients and healthy controls. Also, resistance to osmotic or bile salt induced stress was normal in anemic patients. Phosphatidylserine exposure at the outer membrane leaflet did not change upon 24 hrs ex vivo incubation with pharmacological ribavirin concentration.Conclusions. Anemia is almost universal during anti-HCV treatment. The extent of anemia correlates with pre-treatment levels of thrombocytes and Hb and with high ribavirin dosing. Although we found hemolysis as contributing factor, our data do not indicate that altered membrane phospholipids composition is an important factor in pathogenesis of anemia.
    Schlagwörter Erythropoietin ; Interferon ; Ribavirin ; Hemolysis ; Phospholipid ; Specialties of internal medicine ; RC581-951
    Sprache Englisch
    Erscheinungsdatum 2009-10-01T00:00:00Z
    Verlag Elsevier
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  4. Artikel ; Online: Hepatitis B viral load and risk of HBV-related liver disease

    Soeradj Harkisoen, M.D. / Joop E. Arends / Karel J. van Erpecum / Anneke van den Hoek / Andy I.M. Hoepelman

    Annals of Hepatology, Vol 11, Iss 2, Pp 164-

    from East to West?

    2012  Band 171

    Abstract: Chronic hepatitis B has a variable course in disease activity with a risk of clinical complications like liver cirrhosis and hepatocellular carcinoma. As clinical symptoms present in a late stage of the disease, identification of risk factors is ... ...

    Abstract Chronic hepatitis B has a variable course in disease activity with a risk of clinical complications like liver cirrhosis and hepatocellular carcinoma. As clinical symptoms present in a late stage of the disease, identification of risk factors is important for early detection and therefore improvement of prognosis. Recently, two REVEAL-HBV studies from Taiwan have shown a positive correlation between viral load at any point in time and the development of cirrhosis and hepatocellular carcinoma. Due to differences in viral and host factors between Asians and other populations, it is unclear whether these results can be extrapolated to different populations. This manuscript will discuss viral predictors of hepatitis B related liver disease in relation to ethnic origin.
    Schlagwörter Cirrhosis ; Hepatitis B virus ; Hepatocellular carcinoma ; Viral load ; Specialties of internal medicine ; RC581-951
    Sprache Englisch
    Erscheinungsdatum 2012-03-01T00:00:00Z
    Verlag Elsevier
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  5. Artikel ; Online: Complementary role of HCV and HIV in T-cell activation and exhaustion in HIV/HCV coinfection.

    Thijs Feuth / Joop E Arends / Justin H Fransen / Nening M Nanlohy / Karel J van Erpecum / Peter D Siersema / Andy I M Hoepelman / Debbie van Baarle

    PLoS ONE, Vol 8, Iss 3, p e

    2013  Band 59302

    Abstract: OBJECTIVES: To investigate whether T-cell activation and exhaustion is linked to HCV- and HIV disease parameters in HIV/HCV infected individuals, we studied T-cell characteristics in HIV/HCV coinfected patients and controls. METHODS: 14 HIV/HCV ... ...

    Abstract OBJECTIVES: To investigate whether T-cell activation and exhaustion is linked to HCV- and HIV disease parameters in HIV/HCV infected individuals, we studied T-cell characteristics in HIV/HCV coinfected patients and controls. METHODS: 14 HIV/HCV coinfected, 19 HCV monoinfected, 10 HIV monoinfected patients and 15 healthy controls were included in this cross-sectional study. Differences in expression of activation and exhaustion markers (HLA-DR, CD38, PD-1, Tim-3 and Fas) and phenotypic markers on CD4(+) and CD8(+) T-cells were analysed by flow cytometry and were related to HCV disease parameters (HCV-viremia, ALT and liver fibrosis). RESULTS: Frequencies of activated CD4(+) and CD8(+) T-cells were higher in HIV/HCV-coinfected compared to healthy controls and HCV or HIV mono-infected individuals. Coinfected patients also showed high expression of the exhaustion marker PD-1 and death receptor Fas. In contrast, the exhaustion marker Tim-3 was only elevated in HIV-monoinfected patients. T-cell activation and exhaustion were correlated with HCV-RNA, suggesting that viral antigen influences T-cell activation and exhaustion. Interestingly, increased percentages of effector CD8(+) T-cells were found in patients with severe (F3-F4) liver fibrosis compared to those with no to minimal fibrosis (F0-F2). CONCLUSIONS: HIV/HCV coinfected patients display a high level of T-cell activation and exhaustion in the peripheral blood. Our data suggest that T-cell activation and exhaustion are influenced by the level of HCV viremia. Furthermore, high percentages of cytotoxic/effector CD8(+) T-cells are associated with liver fibrosis in both HCV monoinfected and HIV/HCV coinfected patients.
    Schlagwörter Medicine ; R ; Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2013-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
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  6. Artikel ; Online: Pharmacological activation of the bile acid nuclear farnesoid X receptor is feasible in patients with quiescent Crohn's colitis.

    Fiona D M van Schaik / Raffaella M Gadaleta / Frank G Schaap / Saskia W C van Mil / Peter D Siersema / Bas Oldenburg / Karel J van Erpecum

    PLoS ONE, Vol 7, Iss 11, p e

    2012  Band 49706

    Abstract: BACKGROUND: The bile acid-activated nuclear receptor Farnesoid X Receptor (FXR) is critical in maintaining intestinal barrier integrity and preventing bacterial overgrowth. Patients with Crohn's colitis (CC) exhibit reduced ileal FXR target gene ... ...

    Abstract BACKGROUND: The bile acid-activated nuclear receptor Farnesoid X Receptor (FXR) is critical in maintaining intestinal barrier integrity and preventing bacterial overgrowth. Patients with Crohn's colitis (CC) exhibit reduced ileal FXR target gene expression. FXR agonists have been shown to ameliorate inflammation in murine colitis models. We here explore the feasibility of pharmacological FXR activation in CC. METHODS: Nine patients with quiescent CC and 12 disease controls were treated with the FXR ligand chenodeoxycholic acid (CDCA; 15 mg/kg/day) for 8 days. Ileal FXR activation was assessed in the fasting state during 6 hrs after the first CDCA dose and on day 8, by quantification of serum levels of fibroblast growth factor (FGF) 19. Since FGF19 induces gallbladder (GB) refilling in murine models, we also determined concurrent GB volumes by ultrasound. On day 8 ileal and cecal biopsies were obtained and FXR target gene expression was determined. RESULTS: At baseline, FGF19 levels were not different between CC and disease controls. After the first CDCA dose, there were progressive increases of FGF19 levels and GB volumes during the next 6 hours in CC patients and disease controls (FGF19: 576 resp. 537% of basal; GB volumes: 190 resp. 178% of basal) without differences between both groups, and a further increase at day 8. In comparison with a separate untreated control group, CDCA affected FXR target gene expression in both CC and disease controls, without differences between both groups. CONCLUSIONS: Pharmacological activation of FXR is feasible in patients with CC. These data provide a rationale to explore the anti-inflammatory properties of pharmacological activation of FXR in these patients. TRIAL REGISTRATION: TrialRegister.nl NTR2009.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2012-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
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    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  7. Artikel ; Online: Impact of global Fxr deficiency on experimental acute pancreatitis and genetic variation in the FXR locus in human acute pancreatitis.

    Rian M Nijmeijer / Frank G Schaap / Alexander J J Smits / Andreas E Kremer / Louis M A Akkermans / Alfons B A Kroese / Ger T Rijkers / Marguerite E I Schipper / André Verheem / Cisca Wijmenga / Hein G Gooszen / Karel J van Erpecum

    PLoS ONE, Vol 9, Iss 12, p e

    2014  Band 114393

    Abstract: Background Infectious complications often occur in acute pancreatitis, related to impaired intestinal barrier function, with prolonged disease course and even mortality as a result. The bile salt nuclear receptor farnesoid X receptor (FXR), which is ... ...

    Abstract Background Infectious complications often occur in acute pancreatitis, related to impaired intestinal barrier function, with prolonged disease course and even mortality as a result. The bile salt nuclear receptor farnesoid X receptor (FXR), which is expressed in the ileum, liver and other organs including the pancreas, exhibits anti-inflammatory effects by inhibiting NF-κB activation and is implicated in maintaining intestinal barrier integrity and preventing bacterial overgrowth and translocation. Here we explore, with the aid of complementary animal and human experiments, the potential role of FXR in acute pancreatitis. Methods Experimental acute pancreatitis was induced using the CCK-analogue cerulein in wild-type and Fxr-/- mice. Severity of acute pancreatitis was assessed using histology and a semi-quantitative scoring system. Ileal permeability was analyzed in vitro by Ussing chambers and an in vivo permeability assay. Gene expression of Fxr and Fxr target genes was studied by quantitative RT-PCR. Serum FGF19 levels were determined by ELISA in acute pancreatitis patients and healthy volunteers. A genetic association study in 387 acute pancreatitis patients and 853 controls was performed using 9 tagging single nucleotide polymorphisms (SNPs) covering the complete FXR gene and two additional functional SNPs. Results In wild-type mice with acute pancreatitis, ileal transepithelial resistance was reduced and ileal mRNA expression of Fxr target genes Fgf15, SHP, and IBABP was decreased. Nevertheless, Fxr-/- mice did not exhibit a more severe acute pancreatitis than wild-type mice. In patients with acute pancreatitis, FGF19 levels were lower than in controls. However, there were no associations of FXR SNPs or haplotypes with susceptibility to acute pancreatitis, or its course, outcome or etiology. Conclusion We found no evidence for a major role of FXR in acute human or murine pancreatitis. The observed altered Fxr activity during the course of disease may be a secondary phenomenon.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2014-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  8. Artikel ; Online: Resistance-associated polymorphisms in Dutch hepatitis C genotype 1a patients with and without HIV infection

    Faydra I. Lieveld / Niels Swaans / Astrid M. Newsum / Cynthia K.Y. Ho / Janke Schinkel / Richard Molenkamp / Jan T.M. van der Meer / Joop E. Arends / Andy I.M. Hoepelman / Anne M.J. Wensing / Peter D. Siersema / Karel J. van Erpecum / Greet J. Boland

    Annals of Hepatology, Vol 15, Iss 5, Pp 696-

    2016  Band 704

    Abstract: Background and aim. Resistance-associated variants (RAVs) on the NS3 region of the hepatitis C virus (HCV) may be relevant for antiviral therapy, but data in human immunodeficiency virus (HIV) coinfected patients are scarce. We assessed frequencies of ... ...

    Abstract Background and aim. Resistance-associated variants (RAVs) on the NS3 region of the hepatitis C virus (HCV) may be relevant for antiviral therapy, but data in human immunodeficiency virus (HIV) coinfected patients are scarce. We assessed frequencies of NS3 RAVs in patients infected with HCV genotype 1a with or without HIV coinfection.Material and methods. HCV NS3 amino acids 1-181 were sequenced by the Sanger method and analyzed for RAVs. RAVs and their distribution between HCV genotype 1a clade I and II viruses were compared between HIV-infected versus HIV-uninfected patients.Results. 148 samples were available (n = 68 HIV and n = 80 non-HIV). Relative frequency of clade I and clade II was significantly different between HIV (85% and 15%) and non-HIV groups (49% and 51%). Overall, HIV infected patients exhibited significantly lower prevalence of RAVs than HIV-uninfected patients (62% vs. 79%, p = 0.03). However, Q80K prevalence was significantly higher in HIV-infected subjects (50% vs. 24%, p = 0.001), whereas prevalence of S122D/G/N/S (2% vs. 16%, p = 0.002) and N174G/N/S (10% vs. 55%, p < 0.0001) polymorphisms were significantly lower. Q80K was found exclusively in clade I viruses. S122 (3% vs. 22%, p=0.001) and N174 (13% vs. 75%, p<0.0001) polymorphisms had significantly lower prevalence in clade I than clade II viruses.Conclusions. In the Netherlands, prevalence of clade I viruses and Q80K was significantly higher in HCV genotype 1a infected patients with HIV coinfection than in those without HIV coinfection. Prevalence of N174 and S122 polymorphisms was significantly higher in clade II than clade I viruses.
    Schlagwörter Hepatitis C virus ; HIV ; Genotype 1a ; Q80K ; Drug resistance ; Specialties of internal medicine ; RC581-951
    Sprache Englisch
    Erscheinungsdatum 2016-09-01T00:00:00Z
    Verlag Elsevier
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  9. Artikel ; Online: Evaluation of gallbladder motility

    Susanne Stads / / Niels G. Venneman / Robert C.H. Scheffer / Melvin Samsom / Karel J. van Erpecum

    Annals of Hepatology, Vol 6, Iss 3, Pp 164-

    comparison of two-dimensional and three-dimensional ultrasonography

    2007  Band 169

    Abstract: Since impaired gallbladder emptying contributes to gallstone formation, the evaluation of gallbladder motility requires accurate methodology. Recently developed 3-dimensional ultrasonography may take into account various gallbladder shapes more ... ...

    Abstract Since impaired gallbladder emptying contributes to gallstone formation, the evaluation of gallbladder motility requires accurate methodology. Recently developed 3-dimensional ultrasonography may take into account various gallbladder shapes more accurately than conventional 2-dimensional ultrasonography. Therefore, volumes of water-filled balloons of various sizes were determined in vitro by 2-dimensional ultrasonography with the sum of cylinders method and by 3-dimensional ultrasonography. Also, in 15 gallstone patients and 6 healthy volunteers, fasting gallbladder volumes and postprandial motility were determined by both methods. Volumes of water-filled balloons as measured by both methods correlated strongly with true volumes (R= 0.93 for 2-dimensional and R = 0.98 for 3-dimensional ultrasonography). Gallbladder volumes measured by both methods were also correlated (R = 0.66, P < 0.001). In gallstone patients, 3-dimensional ultrasonography yielded smaller gallbladder volumes than 2-dimensional ultrasonography (P = 0.007), but not in healthy subjects. With both methods, gallstone patients exhibited decreased postprandial gallbladder motility compared to healthy subjects. In conclusion, gallbladder volume measurements by 3-dimensional and 2-dimensional ultrasonography are strongly correlated. Nevertheless, in gallstone patients, gallbladder volumes by 3-dimensional ultrasonography tend to be smaller than by 2-dimensional ultrasonography, possibly due to interference of gallstones with the volume measurement.
    Schlagwörter Gallstone ; ultrasonography ; Specialties of internal medicine ; RC581-951
    Sprache Englisch
    Erscheinungsdatum 2007-07-01T00:00:00Z
    Verlag Elsevier
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  10. Artikel ; Online: Trans-arterial 90yttrium radioembolization for patients with unresectable tumors originating from the biliary tree

    Joost W. Wijlemans / Karel J. Van Erpecum / Marnix G.E.H. Lam / Beatrijs A. Seinstra / Maarten L.J. Smits / Bernard A. Zonnenberg / Maurice A.A.J. Van Den Bosch, MD, PhD

    Annals of Hepatology, Vol 10, Iss 3, Pp 349-

    2011  Band 354

    Abstract: Patients with malignant tumors originating from the biliary tree have a poor prognosis, since only a minority of tumors can be resected and most palliative regimens have shown only limited success. We present two patients with unresectable tumors, who ... ...

    Abstract Patients with malignant tumors originating from the biliary tree have a poor prognosis, since only a minority of tumors can be resected and most palliative regimens have shown only limited success. We present two patients with unresectable tumors, who were treated with trans-arterial 90yttrium radioembolization: a patient with an infiltrating gallbladder carcinoma and a patient with an extensive intrahepatic cholangio-carcinoma. In both cases the treatment was technically feasible, effective in controlling tumor growth, and without significant side effects. In conclusion, the presented cases demonstrate the potential of 90yt-trium radioembolization as a palliative treatment option for malignant tumors of the biliary tree.
    Schlagwörter Intrahepatic cholangiocarcinoma ; Gallbladder carcinoma ; 90yttrium radioembolization ; Specialties of internal medicine ; RC581-951
    Sprache Englisch
    Erscheinungsdatum 2011-07-01T00:00:00Z
    Verlag Elsevier
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