Pathologic distribution at the time of interval tumor reductive surgery informs personalized surgery for high-grade ovarian cancer.

INTRODUCTION: The surgical approach for interval debulking surgery after neoadjuvant chemotherapy has been extrapolated from primary tumor reductive surgery for high-grade ovarian cancer. The study objective was to compare pathologic distribution of malignancy at interval debulking surgery versus primary tumor reductive surgery. METHODS: Patients with a diagnosis of high-grade serous or mixed, non-mucinous, epithelial ovarian, fallopian tube or primary peritoneal cancer who underwent neoadjuvant chemotherapy or primary tumor reductive surgery and had at least 6 months of follow-up were identified through tumor registry at a single institution from January 1995 to April 2016. Pathologic involvement of organs was categorized as macroscopic, microscopic, or no tumor. Statistical analyses included Mann-Whitney and Fisher's exact tests. RESULTS: Of 918 patients identified, 366 (39.9%) patients underwent interval debulking surgery and 552 (60.1%) patients underwent primary tumor reductive surgery. Median age was 62.3 years (range 25.3-92.5). The majority of patients in the interval debulking surgery group were unstaged (261, 71.5%). In the patients who had a primary tumor reductive surgery, 406 (74.6%) had stage III disease. In both groups, the majority of patients had serous histology: 325 (90%) and 435 (78.8%) in the interval debulking and primary tumor reductive surgery groups, respectively. There was a statistically significant difference between disease distribution on the uterus between the groups; 31.4% of the patients undergoing interval debulking surgery had no evidence of uterine disease compared with 22.1% of primary tumor reductive surgery specimens (p<0.001). In the adnexa, there was macroscopic disease present in 253 (69.2%) and 482 (87.4%) of cases in the interval vs primary surgery groups, respectively (p<0.001). Within the omentum, no tumor was present in the omentum in 52 (14.2%) in the interval surgery group versus 91 (16.5%) in the primary surgery group (p<0.001). In the interval surgery group, there was no tumor involving the small and large bowel in 49 (13.4%) and 28 (7.7%) pathologic specimens, respectively. This was statistically significantly different from the small and large bowel in the primary surgery group, of which there was no tumor in 20 (3.6%, p<0.001) and 16 (2.9%, p<0.001) of cases, respectively. CONCLUSION: In patients undergoing interval debulking surgery, there was less macroscopic involvement of tumor in the uterus, adnexa and bowel compared with patients undergoing primary cytoreductive surgery.

Use of social media to conduct a cross-sectional epidemiologic and quality of life survey of patients with neuroendocrine carcinoma of the cervix: a feasibility study.

OBJECTIVE: To determine the feasibility of using social media to perform cross-sectional epidemiologic and quality-of-life research on patients with rare gynecologic tumors, we performed a survey of patients with neuroendocrine tumors of the cervix using Facebook. METHODS: After approval from our Institutional Review Board, a support group of patients with neuroendocrine tumors of the cervix was identified on Facebook. Group members were asked to complete a survey comprising 84 questions evaluating clinical presentation; treatment; recurrence; quality of life; and sexual function. RESULTS: The survey was posted for 30 days, during which 57 women responded from 8 countries across 4 continents treated at 51 centers. All respondents provided a detailed clinical and tumor history. The mean age was 38.5 years. The stage distribution was stage I, 36 patients (63%); II, 13 (23%); III, 2 (4%); and IV, 6 (11%). Forty-nine patients (86%) had small cell and 8 (14%) had large cell tumors. Forty-five of the respondents (79%) had completed primary therapy and were without evidence of disease. Five (9%) had recurrence, 3 (5%) had persistent disease after therapy, and 4 (7%) were still under treatment. Forty-one patients (72%) reported symptoms at time of presentation. Thirty-seven patients (65%) received multimodality primary therapy. Quality of life instruments demonstrated high scores for anxiety and a negative impact of anxiety and cancer on functional and emotional well-being. Sexual function scores did not differ significantly between respondents and the PROMIS reference population. CONCLUSIONS: Use of a social media network to perform epidemiologic and quality of life research on patients with rare gynecologic tumors is feasible and permits such research to be conducted efficiently and rapidly.

TGF-ß modulates ovarian cancer invasion by upregulating CAF-derived versican in the tumor microenvironment.

TGF-ß has limited effects on ovarian cancer cells, but its contributions to ovarian tumor growth might be mediated through elements of the tumor microenvironment. In the present study, we tested the hypothesis that TGF modulates ovarian cancer progression by modulating the contribution of cancer-associated fibroblasts (CAF) that are present in the microenvironment. Transcriptome profiling of microdissected stromal and epithelial components of high-grade serous ovarian tumors and TGF-ß-treated normal ovarian fibroblasts identified versican (VCAN) as a key upregulated target gene in CAFs. Functional evaluations in coculture experiments showed that TGF-ß enhanced the aggressiveness of ovarian cancer cells by upregulating VCAN in CAFs. VCAN expression was regulated in CAFs through TGF-ß receptor type II and SMAD signaling. Upregulated VCAN promoted the motility and invasion of ovarian cancer cells by activating the NF-κB signaling pathway and by upregulating expression of CD44, matrix metalloproteinase-9, and the hyaluronan-mediated motility receptor. Our work identified a TGF-ß-inducible gene signature specific to CAFs in advanced high-grade serous ovarian tumors, and showed how TGF-ß stimulates ovarian cancer cell motility and invasion by upregulating the CAF-specific gene VCAN. These findings suggest insights to develop or refine strategies for TGF-ß-targeted therapy of ovarian cancer.

Identification of FGFR4 as a potential therapeutic target for advanced-stage, high-grade serous ovarian cancer.

PURPOSE: To evaluate the prognostic value of fibroblast growth factor receptor 4 (FGFR4) protein expression in patients with advanced-stage, high-grade serous ovarian cancer, delineate the functional role of FGFR4 in ovarian cancer progression, and evaluate the feasibility of targeting FGFR4 in serous ovarian cancer treatment. EXPERIMENTAL DESIGN: Immunolocalization of FGFR4 was conducted on 183 ovarian tumor samples. The collected FGFR4 expression data were correlated with overall survival using Kaplan-Meier and Cox regression analyses. The effects of FGFR4 silencing on ovarian cancer cell growth, survival, invasiveness, apoptosis, and FGF1-mediated signaling pathway activation were evaluated by transfecting cells with FGFR4-specific siRNAs. An orthotopic mouse model was used to evaluate the effect of injection of FGFR4-specific siRNAs and FGFR4 trap protein encapsulated in nanoliposomes on ovarian tumor growth in vivo. RESULTS: Overexpression of FGFR4 protein was significantly associated with decreased overall survival durations. FGFR4 silencing significantly decreased the proliferation, survival, and invasiveness and increased apoptosis of ovarian cancer cells. Also, downregulation of FGFR4 significantly abrogated the mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB), and WNT signaling pathways, which are activated by FGF1. Targeting FGFR4 with the FGFR4-specific siRNAs and FGFR4 trap protein significantly decreased ovarian tumor growth in vivo. CONCLUSIONS: FGFR4 is a prognostic marker for advanced-stage, high-grade serous ovarian carcinoma. Silencing FGFR4 and inhibiting ligand-receptor binding significantly decrease ovarian tumor growth both in vitro and in vivo, suggesting that targeting ovarian cancer cells with high levels of FGFR4 protein expression is a new therapeutic modality for this disease and will improve survival of it.

A randomized trial of secondary closure of superficial wound dehiscence by surgical tape or suture.

OBJECTIVE: : Evaluate secondary closure of superficial wound dehiscence with suture versus tape. METHODS: : Postoperative obstetrics and gynecologic patients with superficial wound dehiscence were eligible. Wounds were opened for their entire length, debrided, and irrigated. They were packed with moistened gauze until the granulation tissue covered the wound. Randomization occurred when the patient selected a sealed envelope containing a closure technique. Demographic data and wound characteristics were recorded. Pain was determined by using a 100-mm visual analogue scale, which the patient marked immediately after the procedure. Wound closure was measured in minutes. Healing time was measured in days from wound closure to complete wound epithelialization and no need for further wound care. Reopening a closed wound defined treatment failure. Time for complete healing was the primary outcome. RESULTS: : Fifteen patients were randomized to each arm over a 20-month period. Demographics and wound characteristics were similar between groups. Pain scores were significantly less in the tape group (21.4 ± 17.0 vs 60.7 ± 23.0 mm, P < 0.001) as was time for closure (12.3 ± 3.6 vs 31.0 ± 6.8 minutes, P < 0.001). Time for complete healing was significantly less in the suture group (23.0 ± 7.9 vs 16.1 ± 3.36 days, P < 0.001). One wound (7%) in each group was reopened. CONCLUSIONS: : Suture closure seems to be the superior technique for secondary closure of wound dehiscence based on the primary outcome of time to complete healing for this study. Therefore, suture closure seems to be the best option for secondary closure of superficial wound dehiscence.However, both suture and surgical tape are effective treatments when historically compared with second intention.

Growth of Escherichia coli in iron-enriched medium increases HPI catalase activity.

Escherichia coli has two catalases, HPI and HPII. HPI is induced during logarithmic growth in response to low concentrations of hydrogen peroxide. This induction is OxyR-dependent. On the other hand, HPII is not peroxide-inducible but is induced in entry to the stationary phase. We demonstrate here that E. coli displayed higher HPI catalase activity when compared to the cultures that were grown in a normal medium, if grown in a medium supplemented with iron-citrate. Iron supplementation had no effect on HPII catalase. This increase of HPI activity was OxyR-independent and not observed in a Deltafur mutant. The physiological significance of the increase of HPI activity is unclear, but it appears that the katG gene that codes for HPI catalase is among the genes that are regulated by Fur.