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Bellecave P.,University of Lausanne | Sarasin-Filipowicz M.,University of Basel | Sarasin-Filipowicz O.D.,Apotech Corporation | Kennel A.,University of Lausanne | And 10 more authors.
Hepatology | Year: 2010

HepatitisCvirus (HCV) infection induces the endogenous interferon (IFN) system in the liver in some but not all patients with chronic hepatitis C (CHC). Patients with a pre-activated IFN system are less likely to respond to the current standard therapy with pegylated IFN-α Mitochondrial antiviral signaling protein (MAVS) is an important adaptor molecule in a signal transduction pathway that senses viral infections and transcriptionally activates IFN-. The HCVNS3-4A protease can cleave and thereby inactivate MAVS in vitro, and, therefore, might be crucial in determining the activation status of the IFN system in the liver of infected patients. We analyzed liver biopsies from 129 patients with CHC to investigate whether MAVS is cleaved in vivo and whether cleavage prevents the induction of the endogenous IFN system. Cleavage of MAVS was detected in 62 of the 129 samples (48%) and was more extensive in patients with a high HCV viral load. MAVS was cleaved by all HCV genotypes (GTs), but more efficiently by GTs 2 and 3 than by GTs 1 and 4. The IFN-induced Janus kinase (Jak)-signal transducer and activator of transcription protein (STAT) pathway was less frequently activated in patients with cleaved MAVS, and there was a significant inverse correlation between cleavage ofMAVSand the expression level of the IFN-stimulated genes IFI44L, Viperin, IFI27, USP18, and STAT1. We conclude that the pre-activation status of the endogenous IFN system in the liver of patients with CHC is in part regulated by cleavage of MAVS. Copyright © 2010 by the American Association for the Study of Liver Diseases.

Ruf J.,Otto Von Guericke University of Magdeburg | Heuck F.,Medizinische Klinik M. S. Hepatologie und Gastroenterologie | Schiefer J.,Otto Von Guericke University of Magdeburg | Denecke T.,Klinik Strahlenheilkunde | And 7 more authors.
Neuroendocrinology | Year: 2010

Aim: Retrospective evaluation of the impact of integrated positron emission tomography/computed tomography (PET/CT) using 68Ga-DOTA(0)-Phe(1)- Tyr(3)-octreotide (68Ga-DOTATOC) on the therapeutic management of patients with neuroendocrine tumors (NET). Methods: The 68Ga-DOTATOC- PET/CT data of 66 patients (31 male, 35 female; age: 29-79, mean age: 56 years) with known or suspected NET were included. Imaging data (PET and triple-phase contrast-enhanced CT) were evaluated in consensus by two readers for the visualization of NET manifestations. Combined PET/CT, clinical and imaging follow-up as well as histopathology (if available) served as the reference standard. In order to assess the impact of the respective submodalities on the therapeutic strategy chosen, the results were compared to the treatment decision made by the interdisciplinary NET tumor board of our institution. Results: Two of the initial 66 patients included did not suffer from NET according to further immunohistopathological examination. In 50 of the remaining 64 (78%) NET patients, a total of 181 NET manifestations were detected by PET/CT. 59/181 (32.6%) were detected by one submodality only (CT 17.1%, PET 15.5%, p for comparison of both = 0.459). Combined PET/CT reading had an impact on the therapeutic management in 24 of 64 (38%) NET patients: primary resection (n = 5), curative lymph node resection (n = 1), initiation/switch of chemotherapy (CTx) due to progressive disease (n = 10), no surgery due to systemic disease (n = 2), radiopeptide receptor therapy instead of CTx (n = 1), additional bisphosphonate therapy (n = 4), and hepatic brachytherapy (n = 1). In 12 of 24 (50%) of these patients, relevant findings were detected by a single submodality only: CT (n = 5), PET (n = 7); p for comparison = 0.774). Conclusion: 68Ga-DOTATOC-PET/CT influences therapeutic management in about one third of patients examined. CT and PET are comparably sensitive, deliver complementary information and equally contribute to therapeutic decision-making. Thus, despite the merits of the PET modality, the CT component must not be neglected and an optimized multiphase CT protocol is recommended. © 2009 S. Karger AG, Basel.

Ruf J.,Universitatsklinikum Magdeburg Aor | Schiefer J.,Universitatsklinikum Magdeburg Aor | Kropf S.,Otto Von Guericke University of Magdeburg | Furth C.,Universitatsklinikum Magdeburg Aor | And 7 more authors.
Neuroendocrinology | Year: 2013

Aim: In combined positron emission tomography/computed tomography (PET/CT) of neuroendocrine neoplasms using 68Ga-DOTA(0)-Phe(1)-Tyr(3)- octreotide (68Ga-DOTATOC), partial volume effects (PVEs) may occur in smaller lesions. This study determined the lesional cutoff size for the occurrence of PVEs in a clinical setting. Methods: Retrospective assessment of 51 PET/CT examinations (16-slice PET/CT device) for malignant PET foci was carried out. In all foci, the maximal standardized uptake value (SUVmax) and maximal lesion diameter on axial CT was documented. Determined SUVmax and lesional sizes were correlated via LOESS regression. In the resulting curve, the cutoff point for SUVmax size dependency was determined visually and mathematically using 2 approximating straight lines. Results: In 45 patients, 313 of 413 PET foci found were malignant, measurable on CT and had a roughly spherical geometry (SUVmax: 2.5-103.3, mean ± SD 20.5 ± 15.18; CT diameter: 5-103 mm, mean ± SD 21.8 ± 13.1 mm). The cutoff lesional size for the occurrence of PVEs was 20.4 mm by the mathematical approach and 25 mm by visual assessment. Conclusion: In 68Ga-DOTATOC imaging, the clinical lesional size threshold is far larger than expected from systemic resolution only. Thus, tracer uptake quantification is only acceptable in sufficiently large lesions. Copyright © 2013 S. Karger AG, Basel.

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