[Diagnostic quality of transluminal biopsy in undetermined biliary duct stenosis by primary PTCD with "cross and push" technique - a prospective monocentric pilot study]. / Diagnostische Güte der transluminalen Biopsie bei unklaren Gallenwegstenosen im Rahmen der primären PTCD-Anlage mit der "Cross and Push"-Technik ­ eine prospektive monozentrische Pilotstudie.

BACKGROUND: Histological characterisation of a biliary duct stenosis can be essential for further therapeutic steps. Access to the stenosis is not given in every patient by endoscopic retrograde cholangiography. In these cases, a percutaneous transhepatic cholangiodrainage (PTCD) may be helpful. The optimal preparation and diagnostic precision of taking a biopsy by PTCD is not sufficiently evaluated. METHODS: After a training phase of 10 patients, PTCDs in 30 patients with a biliary duct stenosis and lack of adequate drainage by ERC were done in a time range of 24 months. The stenosis was passed with a wire and then a directed forceps-biopsy was performed in a "cross and push" technique (Transluminal Biliary Biopsy Forceps Set, Cook Medical™), using a wire-guided introducer (7 Fr. inner diameter). The result of the histological survey was then correlated with the definite diagnosis. The follow-up time was 18 months. RESULT: Out of 30 patients, there were 22 (73 %) with a malignant stenosis (10 biliary duct neoplasms, 12 non-biliary carcinoma/metastases/lymphomas). Eight (27 %) out of 30 patients had a benign stenosis. In case of all 30 patients, there was enough tissue gained by biopsy for histologic survey. Sub-group analysis was performed for biliary duct cancer and non-biliary cancer. Thereby, 8 out of 10 patients with biliary duct neoplasms were also classified as malignant by histology (sensitivity 80 %); whereas, only 8 out of 12 non-biliary cancers could be histologically classified as malignant (sensitivity 66.6 %, difference not significant, p = 0.0577). In all patients with benign stenosis, histological evaluation of biopsies revealed benign histology (specificity 100 %). There were no intervention-related complications. CONCLUSION: This prospective cohort-study shows a high diagnostic precision for the percutaneous transductal biopsy-set to evaluate an undetermined biliary duct stenosis-particularly in biliary processes. Because it can be difficult to gain histology in malignant biliary duct processes using different methods, the "cross and push" biopsy completes the spectrum of diagnostic procedures.

Reviving pegylated interferon as a therapeutic agent for hepatitis D: no more room for nucleos(t)ides?

BACKGROUND: Chronic infection with hepatitis B virus and hepatitis delta virus (HDV) results in the most severe form of viral hepatitis. There is no currently approved treatment. We investigated the safety and efficacy of 48 weeks of treatment with peginterferon alfa-2a plus adefovir dipivoxil, peginterferon alfa-2a alone,and adefovir dipivoxil alone. METHODS: We conducted a randomized trial in which 31 patients with HDV infection received treatment with 180 lg of peginterferon alfa-2a weekly plus 10 mgof adefovir daily, 29 received 180 lg of peginterferon alfa-2a weekly plus placebo, and 30 received 10 mg of adefovir alone weekly for 48 weeks. Follow-up was conducted for an additional 24 weeks. Efficacy end points included clearance of HDV RNA,normalization of alanine aminotransferase levels, and a decline in levels of hepatitis B surface antigen (HBsAg). RESULTS: The primary endpoint­normalization of alanine aminotransferase levels and clearance of HDV RNA at week 48--was achieved in two patients in the group receiving peginterferon alfa-2a plus adefovir and two patients in the group receiving peginterferon alfa-2a plus placebo but in none of the patients in the group receiving adefovir alone. At week 48, the test for HDV RNA was negative in 23% of patients in the first group, 24% of patients in the second, and none of those in the third (P» 0.006 for the comparison of the first and third groups; P» 0.004 for the comparison of the second and third). The efficacy of peginterferon alfa-2a was sustained for 24 weeks after treatment, with 28% of the patients receiving peginterferon alfa-2a plus adefovir or peginterferon alfa-2a alone having negative results on HDV-RNA tests; none of the patients receiving adefovir alone had negative results. A decline in HBsAg levels of more than 1 log10 IU per milliliter from baseline to week 48 was observed in 10 patients in the first group, 2 in the second, and none in the third (P<0.001 for the comparison of the first and third groups and P»0.01 for the comparison of the first and second). CONCLUSIONS: Treatment with peginterferon alfa-2a for 48 weeks, with or without adefovir, resulted in sustained HDV RNA clearance in about one quarter of patients with HDV infection.

Computer-based classification of small colorectal polyps by using narrow-band imaging with optical magnification.

BACKGROUND: Recent studies have shown that narrow-band imaging (NBI) is a powerful diagnostic tool for the differentiation between neoplastic and non-neoplastic colorectal polyps. OBJECTIVE: To develop a computer-based method for classification of colorectal polyps. DESIGN: A prospective study. SETTING: University hospital. PATIENTS: A total of 214 patients with colorectal polyps who underwent a zoom NBI colonoscopy. INTERVENTIONS: A total of 434 detected polyps 10 mm or smaller were imaged and subsequently removed for histological analysis. MAIN OUTCOME MEASUREMENTS: Diagnostic performance in polyp classification by 2 experts, 2 nonexperts, and a computer-based algorithm. RESULTS: The expert group and the computer-based algorithm achieved a comparable diagnostic performance (expert group: 93.4% sensitivity, 91.8% specificity, and 92.7% accuracy; computer-based algorithm: 95.0% sensitivity, 90.3% specificity, and 93.1% accuracy) and were both significantly superior to the nonexpert group (86.0% sensitivity, 87.8% specificity, and 86.8% accuracy) in terms of sensitivity, negative predictive value, and accuracy. Subgroup analysis of 255 polyps 5 mm or smaller revealed comparable results without significant differences in the overall analysis of all polyps. LIMITATIONS: No fully automatic classification system. CONCLUSIONS: The study demonstrates that computer-based classification of colon polyps can be achieved with high diagnostic performance.

Gp130 signaling promotes development of acute experimental colitis by facilitating early neutrophil/macrophage recruitment and activation.

IL-6 is known to play a crucial role in the pathogenesis of chronic intestinal inflammation by modulating T cell functions. In this study, we investigated the role of gp130, the common signal transducer for all IL-6 cytokines, in a murine model of acute T cell independent colitis to better characterize the impact of gp130 on innate immune cells and the early stages of inflammation. Experimental colitis was induced by dextran sulfate sodium treatment of mice with inducible systemic deletion of gp130 (MxCre/gp130(-/-)), macrophage/neutrophil-specific gp130-deficiency (LysCre/gp130(-/-)), or bone marrow chimeric mice and compared with wild-type controls (gp130(f/f)). Systemic deletion of gp130 (MxCre/gp130(-/-)) protected mice from severe colitis and wasting and attenuated the mucosal inflammatory infiltrate as well as local cytokine, chemokine, and adhesion molecule expression. Experiments in newly generated macrophage/neutrophil-specific gp130-deleted animals (LysCre/gp130(-/-)) and gp130 bone marrow chimeric mice, revealed a dual mechanism of proinflammatory effects mediated by gp130. Leukocyte recruitment was impaired in gp130-deleted animals and gp130-deleted recipients of wild-type bone marrow, demonstrating a central role of gp130-dependent signals in nonmyeloid cells for directing leukocytes to sites of inflammation, which was further confirmed in a model of sterile peritonitis. In contrast, macrophage/neutrophil-specific gp130 deficiency delayed and attenuated the disease but only marginally affected the inflammatory infiltrate, indicating a defective activation of mucosal leukocytes. We provide evidence that IL-6 cytokines acting via gp130 are required in the acute stages of intestinal inflammation by modulating the dynamics of innate immune cell recruitment and activation.

Henoch-Schönlein purpura complicated by cardiac involvement: case report and review of the literature.

Involvement of the kidneys in Henoch-Schönlein purpura (HSP) occurs in approximately 50% of patients with HSP, with varying severity. In general, disease outcome is favorable for adolescents. However, severe courses with vasculitis impairing multiple organ systems in addition to the kidney, including brain, heart, and intestine, may occur. This involvement, often manifesting more subtly, requires alertness for diagnosis and escalation of immunosuppressive therapy for treatment. We report a case of severe HSP nephritis with cardiac involvement in a young man. Cardiac involvement was noted initially on an electrocardiogram and visualized by using cardiac magnetic resonance imaging. HSP remission was induced with aggressive cytotoxic therapy, consisting of cyclophosphamide (750 mg/m(2) every 4 weeks) in addition to high-dose prednisolone. The case presentation is followed by a review of the literature for manifestations, treatments, and outcomes in patients with HSP complicated by cardiac involvement.

Management of primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease with major morbidity and mortality. Therapeutic management is difficult, due to lack of conclusive data and individual disease progression. High-dose UDCA was used for years as a pharmacotherapeutic agent to prevent disease progression, based on a positive trend in pilot studies, but has recently been proven to have a negative effect in advanced disease. Immunosuppressants might be useful in patients with overlap syndromes. Dominant bile duct stenoses should be treated endoscopically, and cholangiocellular carcinoma (CCC) still remains a therapeutic challenge in PSC patients. Early diagnosis of CCC must be improved and new strategies such as neoadjuvant radiochemotherapy with subsequent liver transplantation in selected patients are further options to be considered.

Molecular dissection of gp130-dependent pathways in hepatocytes during liver regeneration.

Interleukin-6 (IL-6) via its signal transducer gp130 is an important mediator of liver regeneration involved in protecting from lipopolysaccharide (LPS)-induced liver injury after partial hepatectomy (PH). Here we generated mice either defective (Delta) in hepatocyte-specific gp130-dependent Ras or STAT activation to define their role during liver regeneration. Deletion of gp130-dependent signaling had major impact on acute phase gene (APG) regulation after PH. APG expression was blocked in gp130-DeltaSTAT animals, whereas gp130-DeltaRas mice showed an enhanced APG response and stronger SOCS3 regulation correlating with delayed hepatocyte proliferation. To define the role of SOCS3 during hepatocyte proliferation, primary hepatocytes were co-stimulated with IL-6 and hepatocyte growth factor. Higher SOCS3 expression in gp130-DeltaRas hepatocytes correlated with delayed hepatocyte proliferation. Next, we tested the impact of LPS, mimicking bacterial infection, on liver regeneration. LPS and PH induced SOCS3 and APG in all animal strains and delayed cell cycle progression. Additionally, IL-6/gp130-dependent STAT3 activation in hepatocytes was essential in mediating protection and thus required for maximal proliferation. Unexpectedly, oncostatin M was most strongly induced in gp130-DeltaSTAT animals after PH/LPS-induced stress and was associated with hepatocyte proliferation in this strain. In summary, gp130-dependent STAT3 activation and concomitant SOCS3 during liver regeneration is involved in timing of DNA synthesis and protects hepatocyte proliferation during stress conditions.