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Early presentation of endometrial cancer permits effective management with excellent clinical outcome. The addition of hysteroscopy to dilatation and curettage (D&C) in the evaluation of postmenopausal bleeding adds little to the detection of malignancy. Imaging studies such as computed tomography, magnetic resonance imaging, and positron-emission tomography may be of use in determining the presence of extrauterine disease in patients medically unfit for surgical staging. However, these studies are not sufficiently sensitive to replace surgical staging and have little role in routine preoperative evaluation. Clinical staging alone is clearly inadequate, as 23% of preoperative clinical stage I/II patients are upstaged with comprehensive surgical staging. Preoperative tumor grade from D&C or office biopsy may be inaccurate and lead to an underestimate of tumor progression if used to determine which patients should be surgically staged. Clinical estimation of depth of invasion, with or without frozen section, is inaccurate and may lead to underestimation of disease status when surgical staging is not performed. The practice of resecting only clinically suspicious" nodes should be discouraged as it is no substitute for comprehensive surgical staging. Comprehensive surgical staging provides proper guidance for postoperative adjuvant therapy, avoiding needless radiation in 85% of clinical stage I/II patients. Finally, resection of occult metastasis with surgical staging may improve survival. [ABSTRACT FROM AUTHOR]

Purpose: Current animal tumor models are inadequate for the evaluation of toxicity and efficacy of conditionally replicative adenoviruses. A novel model system is needed that will provide insight into the anticipated therapeutic index of conditionally replicative adenoviruses preclinically. We endeavored to show a novel model system, which involves ex vivo evaluation of conditionally replicative adenovirus toxicity and therapeutic efficacy in thin, precision-cut slices of human primary tumor and liver., Experimental Design: The Krumdieck thin-slice tissue culture system was used to obtain and culture slices of tumor xenografts of ovarian cancer cell lines, human primary ovarian tumors, and human liver. We determined the viability of slices in culture over a period of 36 to 48 hours by ([3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxphenyl-2-(4-sulfophenyl)-2H-tetrazolium, inner salt)]) (MTS) assay. In vitro Hey cells, slices of Hey xenografts, and human ovarian tumor or human liver slices were infected with 500vp/cell of either replication competent wild-type adenovirus (Ad5/3wt), conditionally replicative adenovirus (Ad5/3cox-2), or the replication deficient adenovirus (Ad5/3luc1). At 12-, 24-, and 36-hour intervals, the replication of adenoviruses in these slices was determined by quantitative reverse transcription-PCR of adenoviral E4 copy number., Results: Primary tumor slices were able to maintain viability for up to 48 hours after infection with nonreplicative virus (Ad5luc1). Infection of Hey xenografts with Ad5/3cox-2 showed replication consistent with that seen in Hey cells infected in an in vitro setting. Primary tumor slices showed replication of both Ad5/3wt and Ad5/3cox over a 36-hour time period. Human liver slices showed replication of Ad5/3wt but a relative reduction in replication of Ad5/3cox-2 indicative of conditional replication "liver off" phenotype, thus predicting lower toxicity., Conclusions: The thin-slice model system represents a stringent method of ex vivo evaluation of novel replicative adenoviral vectors and allows assessment of human liver replication relative to human tumor replication. This is the first study to incorporate this system for evaluation of therapeutic efficacy and replicative specificity of conditionally replicative adenoviruses. Also, the study is the first to provide a valid means for preclinical assay of potential conditionally replicative adenovirus-based hepatotoxicities, thus providing a powerful tool to determine therapeutic index for clinical translation of conditionally replicative adenoviruses.