Integrated PET/CT fusion imaging and endoscopic ultrasound in the pre-operative staging and evaluation of esophageal cancer.

PURPOSE: Accurate staging of esophageal cancer (ECA) is critical in determining appropriate therapy. Endoscopic ultrasound (EUS), computed tomography (CT) and positron emission tomography (PET) scanning can be used, but limited data exists regarding the use of combined PET/CT fusion imaging and EUS in ECA staging. The objective of this study is to evaluate the role of integrated PET/CT imaging and EUS in the staging of ECA. PROCEDURES: Identification of patients diagnosed with ECA from 2004 to 2007 that underwent staging PET/CT and EUS. Data regarding tumor detection, lymph node identification, presence of metastatic disease, and affect on patient management were collected and compared between PET/CT and EUS. RESULTS: Eighty-one patients (65 male, 16 female) were identified with mean age of 63.5 years who underwent EUS and PET/CT to stage known ECA. PET/CT identified the primary tumor in 74/81 (91.4%) of cases, compared to 81/81 (100%) with EUS. Locoregional adenopathy was seen by PET/CT in 29/81 (35.8%) of cases, compared to 49/81 (60.5%) by EUS (p = 0.0001). PET/CT identified celiac axis adenopathy in 8/81 (9.9%) of cases, compared to 11/81 (13.6%) with EUS (p = 0.5050). PET/CT identified 17/81 (21.0%) of patients with distant metastases who subsequently did not undergo attempt at curative surgical resection. CONCLUSIONS: In ECA, EUS is superior to PET/CT for T staging and in identifying locoregional nodes, while PET/CT provides M staging. EUS and integrated PET/CT appear to independently affect treatment decisions, indicating complimentary and necessary roles in the staging of ECA.

Effect of antimetabolite immunosuppressants on Flaviviridae, including hepatitis C virus.

BACKGROUND: Recurrence of hepatitis C virus (HCV) after liver transplantation is almost universal and decreases both graft and patient survival. Medications that alter nucleic acid metabolism, including some common immunosuppressants used in HCV-infected patients, may affect viral replication. METHODS: Bovine viral diarrhea virus (BVDV) is in the Flaviviridae family and is closely related to HCV. We measured the effect of two immunosuppressants, azathioprine (AZA) and mycophenolate acid (MPA), on both BVDV replication by plaque assay and host-cell replication by flow cytometry. We also compared the effect of ribavirin and AZA on the level of HCV replicon RNA by real-time reverse-transcriptase polymerase chain reaction. RESULTS: At doses that achieved similar cytotoxicity, AZA decreased BVDV replication 10 times more than MPA. The inhibition of BVDV by AZA occurred at lower doses than the cellular cytotoxicity and did not depend on cytotoxicity. A two-log reduction in viral titers occurred despite blocking the cytotoxicity of AZA by inhibiting ribonucleotide reductase with high concentrations of thymidine. A metabolite of AZA, 6-mercaptopurine, still possessed this antiviral effect, but a metabolite further downstream, 6-thioguanine, did not, even though 6-thioguanine is the metabolite responsible for cellular toxicity. The effect of AZA on a HCV replicon was at least as large as that of ribavirin. CONCLUSIONS: This report suggests that AZA is a more potent antiviral than MPA for Flaviviridae and may exert a specific antiviral effect on HCV. Additional clinical studies to investigate this previously unanticipated antiviral effect of AZA on HCV in the posttransplant setting are indicated.