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The aim of this phase I clinical trial was to assess the feasibility and safety of intratumoral administration of a first-generation adenoviral vector encoding herpes simplex virus thymidine kinase (HSV-TK) gene (Ad.TK) followed by systemic ganciclovir to patients with advanced hepatocellular carcinoma (HCC). Secondarily, we have analyzed its antitumor effect. Ten patients were enrolled in five dose-level cohorts that received from 10 10 to 2 Â 10 12 viral particles (vp). Ad.TK was injected intratumorally and patients received up to three doses at 30-day intervals. Positron emission tomography was used to monitor TK gene expression. Ad.TK injection was feasible in 100% of cases. Treatment was well tolerated and dose-limiting toxicity was not achieved. Cumulative toxicity was not observed. Hepatic toxicity was absent even in cirrhotic patients. Fever, flu-like syndrome, pain at the injection site and pancytopenia were the most common side effects. No partial responses were observed and 60% of patients showed tumor stabilization of the injected lesion. Importantly, two patients who received the highest dose showed signs of intratumoral necrosis by imaging procedures. One of them achieved a sustained stabilization and survived for 26 months. In conclusion, Ad.TK can be safely administered by intratumoral injection to patients with HCC up to 2 Â 10 12 vp per patient.

The aim of this article is to present our experience with positron emission tomography (PET) and localized fibrous mesothelioma and to review the literature on this issue. During the past five years we found three patients with a complete clinical history who underwent a CT scan of the thorax and (18)F-fluorodeoxyglucose positron emission tomography ([(18)F]-FDG-PET) and were diagnosed with localized fibrous mesothelioma. Two of the patients were asymptomatic men and the third was a woman with chest pain. The standardized uptake value was 2.1 in one case, and in the other two an absence of FDG uptake was seen. All three had complete resection of the tumor, and in one case the presurgery diagnosis was adenocarcinoma. In one patient the tumor relapsed twice, and the other two patients are alive without any evidence of disease. The value of FDG-PET in the differential diagnosis of pulmonary and pleural abnormalities has gained ground during the last few years. As in most benign tumors, the FDG uptake is usually low (< 2.5) in the localized fibrous mesothelioma. However, more studies are necessary to define the role of FDG-PET in assessing this tumor.

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