Pelvic exenteration and sacral resection for locally advanced primary and recurrent rectal cancer.

PURPOSE: The only possibility of a surgical cure in patients with locally advanced primary or recurrent rectal cancer would be an extended resection such as pelvic exenteration and sacral resection. The aim of this study was to evaluate the safety, tolerability, and survival benefits of these procedures. METHODS: Between 1988 and 1999, 64 patients with locally advanced primary or recurrent rectal cancer underwent abdominoperineal resection, with sacral resection in 9 patients, anterior pelvic exenteration in 8 patients, total pelvic exenteration in 27 patients, and total pelvic exenteration with sacral resection in 20 patients. RESULTS: Rates of morbidity, reoperation, and mortality were 50, 4.5, and 0 percent in 22 patients with primary cancer, and 60, 2.4, and 2.4 percent in 42 patients with recurrent disease, respectively. Major complications, such as sepsis, intra-abdominal abscess, and enteric fistula caused one hospital death and reoperation in two patients. In 21 patients who underwent curative resection for primary cancer, the overall five-year survival rates were 74.1 percent for Dukes B and 47.4 percent for Dukes C, although the difference was not statistically significant. Thirty patients with recurrent cancer who underwent curative resection had significantly improved survival, with a five-year survival rate of 22.9 percent, compared with 12 patients who underwent palliative resection, resulting in a survival rate of 0 percent (P = 0.0065). CONCLUSIONS: Pelvic exenteration and sacral resection for primary or recurrent rectal cancer are tolerable procedures with a low mortality rate. Although they provide a survival benefit if curative resection is possible, the associated morbidity remains high and should be followed up closely.

Adenovirus HSV-TK construct with thyroid-specific promoter: enhancement of activity and specificity with histone deacetylase inhibitors and agents modulating the camp pathway.

The successful use of tissue- or tumor-selective promoters in targeted gene therapy for cancer depends on high and selective activity. Tg is a thyroid-specific protein that is expressed in the normal thyroid and a majority of thyroid tumors. In the present study, we show, using a luciferase reporter assay, that a construct containing the putative Tg promoter and enhancer is active in 4 thyroid carcinoma cell lines (including 2 anaplastic thyroid carcinoma cell lines) and not in 5 cancer cell lines arising from nonthyroid tissues. Furthermore, both the activity and the specificity of this construct were increased by pretreatment with 8-Br-cAMP and the histone deacetylase inhibitor depsipeptide (FR901228). Expression of thymidine kinase in thyroid cancer cells infected with a recombinant adenovirus (Ad) carrying a Tg enhancer/promoter-thymidine kinase expression cassette (AdTg enhancer/promoter-TK) correlated with the level of Tg enhancer/promoter activity in these cells. Under similar conditions, TK expression was not observed in cancer cell lines arising from nonthyroid tissues. Cells infected with AdTg enhancer/promoter-TK demonstrated preferential GCV sensitivity, with up to a 100,000-fold increase in GCV sensitivity in thyroid cancer cell lines compared to cancer cell lines of nonthyroid origin. The construct described herein can be used to selectively target thyroid cancer cells, and its expression can be modulated to further increase its specificity and selectivity, especially in anaplastic thyroid carcinoma cells, using 8-Br-cAMP and depsipeptide.