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CME Learning Objectives Describe the range of palliative procedures utilized in gynecologic cancers. Evaluate the indications for palliative bowel surgery in ovarian cancer. Assess the clinical scenario for which palliative pelvic exenteration would be considered. Compare the morbidities associated with palliative gynecologic surgeries to the potential benefits gained. The decision to undergo major palliative surgery in end-stage gynecologic cancer is made when severe disease symptoms significantly hinder quality of life. Malignant bowel obstruction, unremitting pelvic pain, fistula formation, tumor necrosis, pelvic sepsis, and chronic hemorrhage are among the reasons patients undergo palliative surgeries. This review discusses and summarizes the literature on surgical management of malignant bowel obstruction and palliative pelvic exenteration in gynecologic oncology.

We have previously shown that lysophosphatidic acid (LPA) promotes the ovarian cancer metastatic cascade. In this study, we evaluated the role of LPA on endometrial cancer invasion.Transient mRNA knockdown was accomplished using pre-designed siRNA duplexes against LPA receptor 2 (LPA2) and human matrix metalloproteinase-7 (MMP-7). RT-PCR was used to characterize LPA receptor and MMP-7 expression. Analysis of in vitro invasion was performed with rat-tail collagen type I coated Boyden chambers. Gelatin zymography was used to evaluate the MMP activity in cell culture conditioned media. Cell-cell and cell-matrix attachment was also assessed upon LPA2 knockdown to further illuminate the LPA2 cascade.LPA increases HEC1A cellular invasion at physiologic concentrations (0.1-1 muM). Of the four principle LPA receptors, LPA2 is predominantly expressed by HEC1A cells. Transient transfection of LPA2 siRNA reduced LPA2 mRNA expression in HEC1A cells by 93% (P0.01). Silencing LPA2 eliminated the LPA-stimulated increase in invasion (P0.05) and reduced LPA-induced MMP-7 secretion/activation, without significantly affecting cell-cell or cell-matrix adhesion. Silencing MMP-7 reduced overall invasion but did not eliminate LPA's pro-invasive effect on HEC1A cells, as compared to negative control (P0.05). Gelatin zymography confirmed that LPA2 and MMP-7 knockdown reduced MMP-7 activation in HEC1A conditioned media.LPA2 mediates LPA-stimulated HEC1A invasion and the subsequent activation of MMP-7.

Objectives. To evaluate the role of LPA in regulating E-cadherin cell surface expression, adhesion, and invasion in epithelial ovarian carcinoma (EOC) cells. Methods. E-cadherin mRNA expression in OVCA429 and IOSE-29 cells was evaluated by real-time RT-PCR. Immunofluorescence and Western blot analysis were performed to determine cell surface expression and shedding of E-cadherin 80-kDa soluble fragment by LPA. Kinetics of LPA-induced uPA activity was followed with a colorimetric enzymatic assay. Invasion assays were performed in a modified Boyden chamber where cells were allowed to migrate to the bottom compartment through a porous filter coated with collagen. Additionally we measured the 80-kDa form from the ascites of women with stage III/IV EOC. Results. LPA induces E-cadherin shedding of a soluble 80-kDa fragment. We found that this process is mediated by the uPA proteolytic cascade. High levels of soluble E-cadherin were found in the ascites from women with advanced stage EOC. LPA and a soluble recombinant E-cadherin-Fc chimera promotes invasion of OVCA429 cells. Conclusions. LPA induces shedding of an 80-kDa E-cadherin-soluble fragment in an uPA-dependent manner and promotes in vitro invasion. High levels of soluble E-cadherin in malignant ascites may also affect ovarian metastasis.

Even after countered with and responding to maximal surgical and chemotherapy efforts, advanced ovarian cancer usually ultimately recurs. One strategy employed to forestall recurrence is maintenance chemotherapy, an extension of treatment following a complete response to conventional measures. Many agents have been studied and many more are currently under investigation in maintenance regimens. While phase III data suggest that taxane maintenance prolongs progression-free survival, no overall survival benefit has been established. This article reviews the current status of maintenance therapy for advanced ovarian cancer, including phase III evidence and new and upcoming trials.