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Yolk-sac tumors account for about 20% of ovarian germ cell tumors and occur predominantly in women below 35 years of age. Modern evidence-based treatment strategies have ensured long term post-treatment survival, but with increased survival, attention has been turned to an urgent need for developing fertility sparing treatment strategies. In this report we describe the successful treatment of a young woman who was able to conceive and deliver two children, in spite of the loss of one ovary two years prior to being diagnosed with an ovarian yolk-sac tumor on the remaining ovary.

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OBJECTIVE: Although locally advanced cervical cancer can be cured, patients with stage IVB disease have poor prognosis with limited treatment options. Our aim was to describe the pattern of care and analyze health disparity variables that may account for differences in treatment modalities and survival in this population. METHODS: The National Cancer Database was queried for patients diagnosed between 2004 and 2013 with metastatic squamous cell carcinoma or adenocarcinoma of the cervix. Codes representing parenchymal and lymphatic metastasis (beyond the para-aortic radiation fields) were used to identify the cohort. Variables included age, race, insurance status, comorbidity, treatment modality, and outcomes. We used Kaplan-Meier methods to compare survival curves and Cox proportional hazards to estimate the association between variables and overall survival (OS). Log-rank method was used to compare Kaplan-Meier curves. RESULTS: There were 4576 patients identified. The majority was white (59.7%); 19.5% were Hispanic, and 9.6% were black. Fifty-one percent had Medicare/Medicaid; 33.7% had private, and 12.5% had no insurance. The majority (56.3%) received chemotherapy (CMT) alone or in combination with radiation therapy (RT) and/or surgery. Median follow-up was 7.3 months (0-124.8 months). Median OS was 11.5 months (10.5-12.5 months). Higher probability of receiving CMT and RT was associated with having private insurance (P < 0.001). Significant prognostic values positively affecting survival on multivariate analysis included black and Asian race, private insurance, comorbidity index of 0, metastatic site at initial presentation (lung), and treatment modality. Patients treated with CMT + RT with or without surgery had significantly better median OS (12 months) compared with those treated with CMT alone (8.3 months), RT alone (4.8 months), or those untreated (2.3 months) (P < 0.001). CONCLUSIONS: Insurance status influences treatment options in patients with distant metastatic cervical cancer. Race, comorbidity index, metastatic site, and suboptimal treatment appear to affect survival outcomes. Regardless of treatment, survival was extremely limited.

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PURPOSE: While overall survival from gynecologic malignancies has greatly improved over the last three decades, required treatments can lead to multiple health issues for survivors. Our objective was to identify health concerns that gynecologic cancer survivors face. METHODS: A systematic, stratified sample of women with gynecologic malignancies was surveyed for 18 health issues occurring before, during, or after treatment. The impact of clinical features and treatment modality on health issues was assessed through multivariate logistic regression models. RESULTS: Of 2,546 surveys mailed, 622 were not received by eligible subjects secondary to invalid address, incorrect diagnosis, or death. Thus, 1924 survivors potentially received surveys. Of the 1,029 surveys (53.5%) completed, median age was 59 years; diagnoses included 29% cervical, 26% endometrial, 26% ovarian/primary peritoneal/fallopian tube, 12.1% vulvar, and 5.4% vaginal cancers. The most frequently reported health issues included fatigue (60.6%), sleep disturbance (54.9%), urinary difficulties (50.9%), sexual dysfunction (48.4%), neurologic issues (45.4%), bowel complaints (42.0%), depression (41.3%), and memory problems (41.2%). These rankings were consistent with patients' self-reported rankings of "highest impact" personal issues. After controlling for demographic and clinical variables, multivariate analyses revealed that treatment modality impacted the odds of experiencing a given health issue. CONCLUSIONS: Our study demonstrates that gynecologic cancer survivors experience a high frequency of health conditions and highlights the association between treatment modality and specific health concerns. IMPLICATIONS FOR CANCER SURVIVORS: The study findings highlight the multiple health concerns experienced by gynecologic cancer survivors and suggest the potential for developing interventions to mitigate these concerns in survivorship.

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PAX2 is one of nine PAX genes that regulate tissue development and cellular differentiation in embryos. However, the functional role of PAX2 in ovarian cancer is not known. Twenty-six ovarian cancer cell lines with different histology origins were screened for PAX2 expression. Two ovarian cancer cell lines: RMUGL (mucinous) and TOV21G (clear cell), with high PAX2 expression were chosen for further study. Knockdown PAX2 expression in these cell lines was achieved by lentiviral shRNAs targeting the PAX2 gene. PAX2 stable knockdown cells were characterized for cell proliferation, migration, apoptosis, protein profiles, and gene expression profiles. The result indicated that these stable PAX2 knockdown cells had reduced cell proliferation and migration. Microarray analysis indicated that several genes involved in growth inhibition and motility, such as G0S2, GREM1, and WFDC1, were up-regulated in PAX2 knockdown cells. On the other hand, over-expressing PAX2 in PAX2-negative ovarian cell lines suppressed their cell proliferation. In summary, PAX2 could have both oncogenic and tumor suppression functions, which might depend on the genetic content of the ovarian cancer cells. Further investigation of PAX2 in tumor suppression and mortality is warranty.

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Low-grade (LG) serous ovarian carcinoma is believed to arise from serous borderline ovarian tumors; yet the progression from serous borderline tumors to LG serous ovarian carcinoma remains poorly understood. The purpose of this study was to identify differentially expressed genes between the 2 groups. Expression profiles were generated from 6 human ovarian surface epithelia, 8 serous borderline ovarian tumors (SBOTs), 13 LG serous ovarian carcinomas, and 24 high-grade (HG) serous ovarian carcinomas. The anterior gradient homolog 3 (AGR3) gene was found to be highly upregulated in serous borderline ovarian tumors. This finding was validated by real-time quantitative reverse-transcription polymerase chain reaction, Western blotting, and immunohistochemistry. Anti-AGR3 immunohistochemistry was performed on an additional 56 LG and 103 HG tissues, and the results were correlated with clinical data. Expression profiling determined that 1254 genes were differentially expressed (P<0.005) among SBOT, LG, and HG tumors. SBOTs exhibited robust positive staining for AGR3, with a lower percentage of tumor cells stained in LG and HG. Immunofluorescence staining indicated that AGR3 expression was limited to ciliated cells. Tumor samples with a high percentage (>10%) of AGR3 positively stained tumor cells were associated with improved longer median survival in both the LG (P=0.013) and HG (P=0.008) serous ovarian carcinoma groups. The progression of SBOT to LG serous ovarian carcinoma may involve the dedifferentiation of ciliated cells. AGR3 could serve as a prognostic marker for survival in patients with LG and HG serous ovarian carcinomas.

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► Robotic surgery offers several advantages in the management of endometrial cancer. ► No long-term data exist regarding recurrence in patients undergoing robotic surgery. ► Metastasis or recurrence may result in bowel obstruction post surgery.

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OBJECTIVE: Intestinal perforation is associated with high morbidity and mortality in gynecologic oncology patients. We investigated potential factors associated with survival after perforation which may influence treatment recommendations. METHODS: A retrospective review of all gynecologic oncology patients experiencing intestinal perforation between 1993 and 2007 was performed. Demographics, cancer history, presenting symptoms, vital signs, laboratory values, and management of perforation were collected, and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were calculated for each patient. Factors affecting survival from the time of perforation were analyzed using Kaplan-Meier method and univariate and multivariate Cox proportional hazard models. Student's t-test and chi(2) analysis were also utilized to evaluate potential associations. RESULTS: Fifty-three patients met the inclusion criteria. No difference in survival was found based on disease site, history of radiation therapy, presenting symptoms, smoking history, or presence of bowel procedures performed during the most recent abdominal surgery prior to perforation. APACHE II score, disease status, body mass index, and treatment method of perforation were found to be significant prognostic factors for survival. After multivariate Cox regression analysis, only APACHE II scores remained significantly associated with an increased risk of death. Median survival of patients with APACHE II scores <15 was 28.13 months compared to 2.90 months in patients with scores> or =15 (P<0.0001). CONCLUSION: Many factors must be examined when determining the management of intestinal perforation in gynecologic oncology patients. Clinicians should consider the APACHE II score in their assessment to assist risk stratification and treatment planning of these patients.

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Ovarian tumors of low malignant potential and low-grade ovarian serous carcinomas are thought to represent different stages on a tumorigenic continuum and to develop along pathways distinct from high-grade ovarian serous carcinoma. We performed gene expression profiling on three normal human ovarian surface epithelia samples, and 10 low-grade and 10 high-grade ovarian serous carcinomas. Analysis of gene expression profiles of these samples has identified 80 genes upregulated and 232 genes downregulated in low-grade ovarian serous carcinomas. PAX2 was found to be one of the most upregulated genes in low-grade ovarian serous carcinoma. The upregulation of PAX2 was validated by real-time quantitative RT-PCR, western blot and immunohistochemical analyses. Real-time RT-PCR showed a statistically significant difference in PAX2 mRNA expression (expressed as fold change in comparison to normal human ovarian surface epithelia) among ovarian tumors of low malignant potential (1837.38, N=8), low-grade (183.12, N=17), and high-grade (3.72, N=23) carcinoma samples (P=0.015). Western blot analysis revealed strong PAX2 expression in ovarian tumors of low malignant potential (67%, N=3) and low-grade carcinoma samples (50%, N=10) but no PAX2 protein expression in high-grade carcinomas (0%, N=10). Using immunohistochemistry, tumors of low malignant potential (59%, N=17) and low-grade carcinoma (63%, N=16) samples expressed significantly stronger nuclear staining than high-grade ovarian carcinoma samples (9.1%, N=263). Furthermore, consistent with earlier immunohistochemical findings, PAX2 expression was expressed in the epithelial cells of fallopian tubes but not in normal ovarian surface epithelial cells. Our findings further support the two-tiered hypothesis that tumors of low malignant potential and low-grade ovarian serous carcinoma are on a continuum and are distinct from high-grade ovarian carcinomas. In addition, the absence of PAX2 expression in normal ovarian epithelia but expression in fallopian tube fimbria and ciliated epithelial inclusions would suggest the potential development of tumors of low malignant potential and of low-grade ovarian serous carcinomas from secondary Müllerian structures.

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Ovarian cancer is a leading cause of gynecologic cancer death among women. Tumors diagnosed early (in stage I) have a cure rate approaching 90%. However, because specific symptoms and screening tools are lacking, most ovarian cancers are very advanced when finally diagnosed. CA125 expression and pelvic ultrasonography are of limited efficacy in screening, and the search for new, complementary ovarian cancer biomarkers continues. New technology and research techniques have allowed the identification of over 100 possible tumor markers, many of which are still being evaluated for clinical relevance and several of which have entered clinical trials. Here, we review the methods of biomarker discovery, address the significance and functions of newly identified ovarian cancer tumor markers, and provide further insight into the future of ovarian cancer biomarkers.

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BACKGROUND: Acute colonic pseudoobstruction, or Ogilvie's syndrome, is a rare but serious medical and obstetric complication. When diagnosed early, treatment with expectant management or more invasive decompression is often successful. However, if not recognized promptly or managed appropriately, this condition can be fatal. CASE: We present an unusual case of acute colonic pseudoobstruction occurring after management of preterm labor in a monochorionic-diamniotic twin pregnancy at 29 weeks' gestation complicated with twin-twin transfusion syndrome. CONCLUSION: Acute colonic pseudoobstruction should be considered in the differential diagnosis in pregnant women who present with abdominal distention and vomiting.

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BACKGROUND: Phlegmasia cerulea dolens is an extremely rare condition caused by complete venous occlusion and often results in tissue necrosis, limb amputation, or death. Treatment options include systemic anticoagulation, systemic thrombolytic therapy, fasciotomy, or surgical thrombectomy. Rare case reports have described the use of catheter-directed thrombolysis in the treatment of this condition. Prompt diagnosis and treatment initiation are important to prevent gangrene, amputation, and ultimately death. CASE: We report two unusual cases of phlegmasia cerulea dolens that presented in patients with aggressive gynecologic malignancies and who were successfully treated with catheter-directed thrombolytic therapy. CONCLUSION: To maximize the opportunity for limb salvage, catheter-directed venous thrombolytic therapy should be considered in the treatment of phlegmasia cerulea dolens that presents in the gynecologic oncology patient.

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BACKGROUND: Polypropylene mesh for abdominal wall reconstruction increases the risk of postoperative complications in previously irradiated patients or patients with contaminated operative fields. A novel alternative, acellular dermal matrix, easily incorporates into native tissue when used for fascial reconstruction, forming a strong repair with minimal adhesions and lower infection rates. CASE: We describe a patient previously treated with radiation for cervical cancer who presented with a contaminated operative field due to enteral spillage and pelvic infection. Acellular dermal matrix was used as part of a stepwise secondary closure of a large fascial defect in the anterior abdominal wall that was the result of repeated surgical procedures. CONCLUSION: Use of acellular dermal matrix rather than traditional polypropylene mesh should be considered for patients with contaminated or irradiated operative fields.

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PURPOSE: To examine the effect of different school-level factors on the percent return of consent or refusal forms, the percent student participation/enrollment rate, and the percent completion rate of all 3 immunizations in the vaccination series in a school-based hepatitis B immunization initiative. METHODS: The Houston Hepatitis B Immunization Initiative (HBII) was conducted from 1998 through 2001 to provide free hepatitis B immunizations to elementary school students in low socioeconomic areas. At the end of each academic school year, the nurse from each school participating in the initiative was asked to complete a survey evaluating the different strategies utilized in each school to aid in the program's success. The effect of different organizational methods on rate of return of consent/refusal forms, participation rates, and immunization completion rates from the program year 1999-2000 was determined using frequencies, Mann-Whitney analyses, Kruskal-Wallis analyses, and Spearman's correlations. RESULTS: An increase in percent return of signed consent/refusal forms was more likely when teachers helped in publicity/promotion (p = .012) and educational packet distribution (p = .041). Additionally, when teachers assumed responsibility for collecting the forms, the percent return of signed consent/refusal forms (p = .018) and the percent of students receiving all 3 vaccines in the series through HBII (p = .030) were more likely to increase. An increase in signed consent/refusal forms returned was also associated with increased rates of student participation in the program for each school. In schools where students helped specifically with educational packet distribution (p = .039), the percent of students receiving at least 1 vaccine dose from the program was more likely to be higher. CONCLUSIONS: The involvement of teachers in vaccination programs is very important for program success, especially in the enrollment and return of consent/refusal form phases of immunization initiatives. Student involvement may empower the students and encourage other students to participate in the program. Future school-based immunization initiatives can utilize these data to incorporate the most effective school-level factors into their programs to maximize the number of students immunized.

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