Prognostic factors of locally invasive well-differentiated thyroid carcinoma involving the trachea.

To report our experience with tracheal invasive thyroid carcinoma with emphasis on clinical characteristics and treatment modalities, and to identify the prognostic factors for tracheal invasive thyroid carcinoma. Totally 1919 patients underwent surgical extirpation of thyroid cancer from 1990 to 2010. Among them, 65 patients had well-differentiated thyroid cancer with tracheal invasion. The incidence was higher in male and older patients. Patients were treated with tracheal shave excision (n = 18), tracheal resection (n = 37) and total laryngectomy (n = 10). Locoregional recurrence occurred in 39 patients, and metastasis occurred in 25 patients. Simultaneous involvement of the trachea and the esophagus was associated with locoregional recurrence (p = 0.039) in univariate analysis, but not confirmed by multivariate analysis. There was significant difference in the disease-specific survival (DSS) according to laryngeal involvement (p = 0.002). All the patient in the shave excision group survived until the end of the study period. Although it is categorized in same classification of T4a, simultaneous involvement of the trachea and the esophagus showed higher locoregional recurrence and laryngeal involvement showed lower DSS. Despite the invasion of thyroid cancer into the adjacent aerodigestive tract, many patients showed long survival when they underwent appropriate surgery.

Conditionally replicating adenovirus improves gene replication efficiency and anticancer effect of E1-deleted adenovirus carrying TRAIL in head and neck squamous cell carcinoma.

To overcome the low efficiency of gene therapy, we combined a conditionally replicating adenovirus (CRAd) and an adenoviral vector with a therapeutic gene. CRAd has an oncolytic activity in cancer cells with abnormal Rb activity and helps the replication of therapeutic genes incorporated in the E1-deleted adenovirus. We investigated the anticancer effect of a combination of CRAd and adenovirus carrying tumor necrosis factor-related apoptosis inducing ligand (ad-TRAIL). We expected to see increased gene expression in cancer cells as well as an antitumor effect. With the combined application of CRAd and ad-luciferase in head and neck cancer cell lines, we observed considerably increased luciferase activity that was 10- to 50-fold greater than with ad-luciferase alone. The combination of CRAd and ad-TRAIL showed significant suppression of growth in cell lines and increased the sub-G(1) portion of cells 30-fold compared to any single treatment. The expression of TRAIL was highly amplified by the combined treatment and was accompanied by expression of molecules related to apoptosis. In a xenograft animal model, mice treated with CRAd and ad-TRAIL showed complete regression of established tumors, whereas mice treated with CRAd or ad-TRAIL alone did not. In conclusion, this combined strategy using CRAd and adenovirus carrying a therapeutic gene increased the gene transfer rate and enhanced antitumor effects. We expect that this combination strategy could be extended to a multitarget cancer gene therapy by combining multiple adenoviruses and CRAd.