Assessment of outcomes and morbidity following diaphragmatic peritonectomy for women with ovarian carcinoma

Objective: To describe the technique of diaphragmatic peritonectomy (DP) for ovarian cancer cytoreduction and to assess associated morbidity. Methods: Retrospective review yielded 56 patients who underwent DP as part of a cytoreductive procedure for primary or recurrent ovarian cancer between 1988 and 2004. Patients who underwent diaphragmatic resection, removal of diaphragmatic implants with CUSA, cautery, curette, or finger fracture, and patients with pseudomyxoma were excluded from analysis. Results: DP was performed as a component of primary or secondary cytoreduction in 37 (66%) and 19 (34%) patients, respectively. Extended procedures including bowel resection, hepatic resection, splenectomy, or radical hysterectomy were performed with DP in 47 patients (82%). Resection of all disease > 1\ua0cm was achieved in 95% (microscopic residuum in 43%). For those undergoing primary cytoreduction, median survival was 59\ua0months and 5-year survival was 49% with median follow-up of 34\ua0months. When performed for recurrent ovarian carcinoma, 5-year survival was 16% and median survival was 23\ua0months. No intra-operative complications could be specifically attributed to DP. Post-operative complications included a 30% rate of pleural effusion which was associated with entry into the pleural space during DP (p < 0.0001); thoracentesis was required in 12.5%. Conclusions: Diaphragmatic metastases are a common obstacle to optimal cytoreduction for patients with ovarian cancer. When necessary, utilizing DP in concert with other extended procedures to obtain maximal cytoreduction is associated with excellent survival. It should be recognized that DP is associated with an increased incidence of post-operative pleural effusion, particularly when the pleural space is entered

Gene expression profiling of monkeypox virus-infected cells reveals novel interfaces for host-virus interactions

Monkeypox virus (MPV) is a zoonotic Orthopoxvirus and a potential biothreat agent that causes human disease with varying morbidity and mortality. Members of the Orthopoxvirus genus have been shown to suppress antiviral cell defenses, exploit host cell machinery, and delay infection-induced cell death. However, a comprehensive study of all host genes and virus-targeted host networks during infection is lacking. To better understand viral strategies adopted in manipulating routine host biology on global scale, we investigated the effect of MPV infection on Macaca mulatta kidney epithelial cells (MK2) using GeneChip rhesus macaque genome microarrays. Functional analysis of genes differentially expressed at 3 and 7 hours post infection showed distinctive regulation of canonical pathways and networks. While the majority of modulated histone-encoding genes exhibited sharp copy number increases, many of its transcription regulators were substantially suppressed; suggesting involvement of unknown viral factors in host histone expression. In agreement with known viral dependence on actin in motility, egress, and infection of adjacent cells, our results showed extensive regulation of genes usually involved in controlling actin expression dynamics. Similarly, a substantial ratio of genes contributing to cell cycle checkpoints exhibited concerted regulation that favors cell cycle progression in G1, S, G2 phases, but arrest cells in G2 phase and inhibits entry into mitosis. Moreover, the data showed that large number of infection-regulated genes is involved in molecular mechanisms characteristic of cancer canonical pathways. Interestingly, ten ion channels and transporters showed progressive suppression during the course of infection. Although the outcome of this unusual channel expression on cell osmotic homeostasis remains unknown, instability of cell osmotic balance and membrane potential has been implicated in intracellular pathogens egress. Our results highlight the role of histones, actin, cell cycle regulators, and ion channels in MPV infection, and propose these host functions as attractive research focal points in identifying novel drug intervention sites

Ovarian cancer

Ovarian cancer is not a single disease and can be subdivided into at least five different histological subtypes that have different identifiable risk factors, cells of origin, molecular compositions, clinical features and treatments. Ovarian cancer is a global problem, is typically diagnosed at a late stage and has no effective screening strategy. Standard treatments for newly diagnosed cancer consist of cytoreductive surgery and platinum-based chemotherapy. In recurrent cancer, chemotherapy, anti-angiogenic agents and poly(ADP-ribose) polymerase inhibitors are used, and immunological therapies are currently being tested. High-grade serous carcinoma (HGSC) is the most commonly diagnosed form of ovarian cancer and at diagnosis is typically very responsive to platinum-based chemotherapy. However, in addition to the other histologies, HGSCs frequently relapse and become increasingly resistant to chemotherapy. Consequently, understanding the mechanisms underlying platinum resistance and finding ways to overcome them are active areas of study in ovarian cancer. Substantial progress has been made in identifying genes that are associated with a high risk of ovarian cancer (such as BRCA1 and BRCA2), as well as a precursor lesion of HGSC called serous tubal intraepithelial carcinoma, which holds promise for identifying individuals at high risk of developing the disease and for developing prevention strategies

EPV122/#421 Isolated lymphatic recurrence in endometrial cancer: a retrospective study

Objectives We investigated factors associated with cause-specific survival (CSS) after isolated lymphatic recurrence (ILR) in endometrial cancer (EC). Methods We identified patients who developed ILR among 4,216 EC patients surgically treated at the Mayo Clinic between 1984 and 2017. ILR was defined as the first and unique evidence of recurrence in lymph node-bearing areas (with or without (\ub1) vaginal recurrence). Univariate and mul- tivariable Cox regression analysis was used to evaluate factors associated with CSS after ILR. Results We observed 70 cases of ILR: 12 pelvic, 15 paraaortic, 14 pelvic and paraaortic, and 29 distant (\ub1 pelvic and/or par- aaortic). Most women (90.0%) underwent pelvic and/or para- aortic lymphadenectomy during primary surgery, and 68.3% had positive nodes. Among 70 patients, 50 died of disease with median survival after ILR of 1.4 years. Patients who did not die of EC had a median follow-up after ILR of 6.6 (IQR 4.8\u201310.0) years. By univariate analysis, histologic grade, lym- phovascular space invasion, ILR site, concomitant vaginal recurrence, and ILR treatment were significantly associated with CSS after ILR. CSS after ILR was not associated with primary lymphadenectomy, stage, or adjuvant therapy. Results of the multivariable analysis are reported in the Table. Conclusions Histologic grade 2 or 3 of the primary tumor and concomitant recurrence in the pelvic and paraaortic lymph node basins or at the vaginal cuff were independent predictors of poor CSS after ILR. The choice to surgically treat ILR in some patients was associated with improved CSS