A novel proteomic-based screening method for ovarian cancer using cervicovaginal fluids: A window into the abdomen.

OBJECTIVE: Our objective is to develop a site-specific proteomic-based screening test for ovarian cancer(OC) using the mucus of the cervix and vagina and evaluate a potential means for home testing. METHODS: Cervicovaginal fluid samples were obtained from ovarian cancer and normal control patients for LC-mass spectrometry(MS) proteomic evaluation. Statistical modeling determined the protein panel with the highest penetrance across ovarian cancer samples. A subcohort of patients consented to provide self-collected vaginal samples at home with questionnaire on feasibility. Cohen's kappa methodology was utilized to determine agreement between physician-collected and patient-collected samples. RESULTS: A total of 83 consecutive patient samples were collected prospectively (33 ovarian cancer & 50 controls). Thirty patients consented for self-collection. Using LC-MS, 30 peptides demonstrated independent statistical significance for detecting ovarian cancer. Using statistical modeling, the protein panel that determined the best predictor for detecting OC formed a "fingerprint" consisting of 5 proteins: serine proteinase inhibitor A1; periplakin; profilin1; apolipoprotein A1; and thymosin beta4-like protein. These peptides demonstrated a significant increase probability of detecting ovarian cancer with the ROC curve having an AUC of 0.86 (p = 0.00001). Physician-collected and patient-collected specimens demonstrated moderate agreement with kappa average of 0.6 with upper bound of 0.75. CONCLUSIONS: Using novel site-specific collection methods, we identified an OC "fingerprint" with adequate sensitivity and specificity to warrant further evaluation in a larger cohort. Agreement of physician-collected and patient-collected samples were encouraging and could improve access to screening with a home self-collection if this screening test is validated in future studies.

Intraperitoneal (IP) port cytology after completion of primary therapy for advanced stage ovarian cancer: A novel approach to a "second look".

OBJECTIVE: To determine whether IP port cytology predicts early recurrence and/or poor prognosis in patients with ovarian cancer who have completed primary therapy. METHODS: A prospective study of patients with advanced stage ovarian cancer undergoing IP port removal after debulking followed by IV/IP chemotherapy was performed. Ports were flushed with 10 cc of normal saline into ThinPrep fixative to be analyzed for cytology. Results were correlated with clinical factors and cancer outcomes. Survivals were calculated using Kaplan-Meier curves and compared using log-rank analysis. RESULTS: Effluent from 53 IP ports was analyzed, and patients were followed for a median of 62 months. Mean age was 58.5, with the majority of patients being white (90%), with stage 3 (62%), serous histology (87%). Seven (13.2%) patients had positive IP cytology. POS and NEG groups were similar with regard to age, BMI, stage, grade, and GOG status. Patients with POS results had increased risk of recurrence HR 3.2 (95%CI 0.4, 28.9), and death HR 6.5 (95%CI 0.7, 58.8), and were more likely to recur before 12 months, 71% vs. 22% (p = 0.007). Compared to NEG, POS conferred a shorter median survival with PFS of 32 vs. 7 months (p = 0.02) and OS of 84 vs. 42 months (p = 0.04). CONCLUSIONS: IP port cytology is predictive of recurrence and survival in patients with ovarian cancer. This inexpensive test may serve as an adjunct to imaging and tumor markers to determine disease status at the completion of treatment. Further study should investigate how this may impact management.

Unraveling the etiology of ovarian cancer racial disparity in the deep south: Is it nature or nurture?

BACKGROUND: Our objective was to evaluate racial treatment and survival disparities in black women with ovarian cancer in the Deep South and to determine how environmental factors / socioeconomic status (SES) influence survival. METHODS: A retrospective study of ovarian cancer patients from 2007 to 2014 was performed. Socioeconomic status (SES) was obtained though U.S. Census block data and compared using Yost scores. Comparisons were performed using standard statistical approaches. RESULTS: A total of 393 patients were evaluated, 325 (83%) white and 68 (17%) black. Demographic information and surgical approach were similar in each racial group. However, compared to whites, black patients had lower rates of optimal debulking [89% vs. 71%, respectively (p=0.001)] and intraperitoneal chemotherapy (19% vs. 11%, p=0.01). Black women had lower SES parameters including education, income, and poverty. As a result, more black patients had the lowest SES (SES-1) when compared to white patients (17% vs. 41%, p<0.001). When controlling for these factors by cox regression analysis, a survival disadvantage was seen in black women for both progression free survival (16 vs. 27months, p=0.003) and overall survival (42 vs. 88months, p<0.001). CONCLUSIONS: Despite controlling for clinical and environmental factors, a survival disadvantage was still observed in black patients with ovarian cancer in the Deep South. Black women had lower optimal debulking rates and more platinum resistant disease. These data suggest other factors like tumor biology may play a role in racial survival differences, however, more research is needed to determine this causation.

mRNA detection in living cells: A next generation cancer stem cell identification technique.

Cancer stem cells (CSC) are a distinct subpopulation within a tumor shown to drive tumor progression, metastasis, and recurrence. A review of the literature reveals poor consensus, with the use of a wide variety of surface markers and functional assays to identify and isolate cancer stem cells. Utilizing a novel technology that enables live-cell mRNA quantitation, we have demonstrated the ability to identify and sort viable CSC based on markers associated with stemness in pluripotent cells. Fresh tumor samples from a variety of cancer types were examined by flow cytometry for Nanog expression. Levels of CSC detected ranged from 6% to 19%. This method of CSC detection was cross-validated with other commonly used surface markers with good correlation. Matrigel invasion assays confirmed that CSC isolated using this method are both highly motile and invasive. This approach simplifies the process of identifying viable CSC from fresh tumor tissue, providing a level of accuracy not previously available. This method may also provide a valuable tool for screening and validating new CSC biomarkers.

The trend towards minimally invasive surgery (MIS) for endometrial cancer: an ACS-NSQIP evaluation of surgical outcomes.

OBJECTIVE: Our objective was to evaluate the surgical trend towards increased MIS in the management of endometrial cancer in regard to improvements in patient outcomes. METHODS: Using the American College of Surgeons-National Surgical Quality Improvement Project's database, patients who underwent hysterectomy for endometrial cancer from 2006-2010 were identified and categorized into exploratory laparotomy (XLAP) or MIS. Comparative analyses were performed and stratified by year of surgery to evaluate demographics, surgical outcomes, and 30-day surgical morbidity. RESULTS: A total of 2076 patients (1269 XLAP and 807 MIS) underwent hysterectomy for endometrial cancer between 2006 and 2010. Longer operative times were seen in MIS compared to XLAP (192 vs. 148 min; p<0.001) as well as significant increase in mean hospital stay in the XLAP group of 3.8 days compared to 1.6 days in MIS (p<0.0001). When controlling for preoperative comorbidities, significant increases in postoperative complications were observed in XLAP compared to MIS group (total 396 vs. 91; p<0.0001). MIS increased from 16% in 2006 to 48% in 2010, which correlated to decreases in complications and hospital stays. Each 10% increase in MIS would save $2.8 million and 41 postoperative complications. If used exclusively, MIS would save 6434 hospital days and 416 complications. CONCLUSIONS: Despite increases in operative times, MIS for the treatment of endometrial cancer significantly reduces perioperative complications and hospital stay. Considering the improvements in patient outcomes and the potential savings to the health care system, MIS should be the preferred route for the surgical treatment of this disease when feasible.

Minority participation in Gynecologic Oncology Group (GOG) Studies.

OBJECTIVE: Participation of minority populations in clinical trials is paramount to understanding and overcoming cancer racial disparities. The goal of this project is to evaluate minority participation in published GOG clinical trials. METHODS: GOG publications from 1985 to 2013 were reviewed. Minority enrollment was stratified by tumor site, type of study, and year published. Based on Centers of Disease Control and Prevention (CDC) age-adjusted incidence for race, expected and observed ratios of racial participation were calculated. RESULTS: A total of 445 GOG publications involving 67,568 patients were reviewed. Racial breakdown was provided in 170 studies (38%) for a total of 45,259 patients: 83% White (n=37,617); 8% Black (n=3,686), and 9% Other (n=3,956). The majority of studies were Ovarian (n=202) and Phase 2 (n=290). When evaluating the quartiles of publication year, a steady decline in the proportion of Black patients enrolled was seen. Race was not reported in any publication prior to 1994. Compared to years 1994-2002, a 2.8-fold lower proportion of black enrollment was noted in years 2009-2013 (16% and 5.8%, respectively; p<0.01). Utilizing CDC age-adjusted incidence, observed enrollment of Black patients onto GOG clinical trials was significantly less than expected enrollment. Observed Black enrollment was 15-fold lower than expected for ovarian trials, 10-fold lower for endometrial, 4.5-fold for cervix, and 5.2-fold for sarcoma (each p<0.001). CONCLUSIONS: Based on age-adjusted incidence, observed enrollment of Black patients was lower than expected enrollment onto GOG studies. Despite national emphasis on minority enrollment on clinical trials, fewer Black patients were enrolled over time.

Validation of a venous thromboembolism risk assessment model in gynecologic oncology.

OBJECTIVES: Gynecologic oncology patients undergoing surgery are at an increased risk for venous thromboembolism (VTE). We attempted to validate a VTE risk assessment model in gynecologic oncology patients. METHODS: All gynecologic oncology patients who underwent a laparotomy for the diagnosis or suspicion of gynecologic malignancy from 2004 to 2010 were included. Demographic, surgicopathologic, and complication data were collected. VTE was based on the symptomatic diagnosis. Data for the Caprini risk assessment model (RAM) was used to score and stratify patients on their risk for VTE. RESULTS: 1123 gynecologic oncology patients were included within this study. Ovarian cancer was the most common diagnosis (39%) with a median age of 56.1. All patients received SCDs with 40% receiving double prophylaxis. The overall incidence of VTE was 3.3%, with lower extremity deep venous thrombosis (DVT) n=17 and pulmonary embolism (PE) n=20. Complication rates were similar in each group. Based on the Caprini scoring model 92% of patients scored in the "Highest Risk" category. The Caprini RAM accurately predicted all 37 VTEs, all of which scored in the "Highest Risk" category. The percentage of patients that received double prophylaxis increased with time from 12% in 2004 to 63% in 2010. Importantly, 25 of the 37 VTEs (68%) did not receive double prophylaxis. CONCLUSIONS: The use of the Caprini RAM accurately predicted patients at the highest risk of experiencing VTE. Considering accurate identification of patients allows proper administration of double prophylaxis, we recommend the use of this scoring model preoperatively in patients undergoing surgery for gynecologic malignancies.

Treatment of chemotherapy-induced anemia in ovarian cancer patients: does the use of erythropoiesis-stimulating agents worsen survival?

OBJECTIVE: Considering the paucity of data relating erythropoiesis-stimulating agent (ESA) use to ovarian cancer survival, our objective was to evaluate the effect of ESA as used for the treatment of chemotherapy-induced anemia (CIA) on survival in ovarian cancer patients. MATERIALS AND METHODS: A multi-institution retrospective chart review was performed on ovarian cancer patients. Data collection included patient demographic, surgicopathologic, chemotherapy, ESA, and survival data. Patients were stratified by ever-use of ESA and were compared using appropriate statistical methods. RESULTS: A total of 581 patients were eligible for analysis with 39% (n = 229) patients with ever-use of ESA (ESA-YES) and 61% (n = 352) never-use ESA (ESA-NO). Mean age was 60.4 years with most patients having stage IIIC (60%) of papillary serous histological diagnosis (64%) with an optimal cytoreduction (67%). Median follow-up for the cohort was 27 months. Both ESA-YES and ESA-NO groups were similar regarding age, body mass index, race, stage, histological diagnosis, and debulking status. Compared with the ESA-NO group, ESA-YES patients were significantly more likely to experience recurrence (56% vs 80%, P < 0.001) and death (46% vs 59%, P = 0.002). Kaplan-Meier curves demonstrated a significant reduction in progression-free survival for ESA-YES patients (16 vs 24 months, P < 0.001); however, overall survival was statistically similar between the 2 groups (38 vs 46 months, P = 0.10). When stratifying by ever experiencing a CIA, ESA-YES patients demonstrated a significantly worse progression-free survival (17 vs 24 months, P = 0.02) and overall survival (37 vs 146 months, P < 0.001). CONCLUSIONS: Our data evaluating the use of ESA as a treatment of CIA in ovarian cancer patients are similar to reports in other tumor sites. Considering that patients who used ESA were more likely to experience recurrence and death and to have decreased survival, the use of ESA in ovarian cancer patients should be limited.

Double prophylaxis for deep venous thrombosis in patients with gynecologic oncology who are undergoing laparotomy: does preoperative anticoagulation matter?

OBJECTIVE: Double prophylaxis for deep venous thrombosis (DVT) with thromboprophylaxis plus sequential compression devices (SCDs) is recommended for high-risk surgical patients with gynecologic oncology. Despite the use of preoperative thromboprophylaxis in clinical trials, the schedule of perioperative low molecular-weight heparin varies widely. We sought to determine the effectiveness and adverse effects of a preoperative dose of anticoagulation in patients with gynecologic oncology. METHODS: A multi-institutional chart review from January 2006 to July 2008 was performed. Patients with gynecologic oncology who received double prophylaxis for laparotomy were eligible. The patients were grouped according to whether they received preoperative anticoagulation (YES PREOP vs NO PREOP). All patients received postoperative low molecular-weight heparin for thromboprophylaxis and SCDs until discharge. Demographic, surgicopathologic, and complication data were collected. RESULTS: A total of 239 patients were identified: YES PREOP (n = 101) and NO PREOP (n = 138). Groups were similar with respect to demographics, diagnosis, and length of hospital stay. There were 2 DVTs in the YES PREOP group compared with 11 in the NO PREOP group (P = 0.04; relative risk, 0.77). There were also fewer DVT-attributable deaths in the YES PREOP group (0 vs 2; P < 0.001). Postoperative hematocrit (30.2% vs 31.4%; P = 0.42) and number of transfusions (26 vs 14; P = 0.31) were similar. CONCLUSION: The use of preoperative anticoagulation seems to significantly decrease the risk of DVT in this patient population, and complication rates are not increased. Patients receiving double prophylaxis should receive a preoperative dose of anticoagulation for maximum benefit.

Overcoming technical challenges with robotic surgery in gynecologic oncology.

BACKGROUND: The majority of data published on robotic surgery in gynecologic oncology has focused on patient outcomes and surgical data. We have found that technical challenges due to the complexity of the robotic technology create a separate set of issues, adding time and difficulty to the actual surgical procedure. This study focuses on these technical problems and identifies pitfalls and potential solutions in robotics. METHODS: All patients who underwent robotic surgery for gynecologic oncology indications from August 2006 through July 2008 were eligible for inclusion in the study. Data collected prospectively included demographics, surgical and clinicopathologic data, and technical problems with the robotic equipment. RESULTS: One hundred thirty-seven patients underwent robotic surgery during the study period. A total of 11 cases (8.02%) were associated with problems with robotic technology: 2/11 (18.2%) involved malfunction of robotic arms, 2/11 (18.2%) involved light or camera cords, and the remainder included a variety of problems, including malfunction of Maylard bipolar instrument [1/11 (9.1%)], power failure requiring reboot of robot [1/11 (9.1%)], port problems [2/11 (18.2%)], and 3/1 (27.3%) had miscellaneous problems. An estimated average of 25 min was added to each of these 11 cases in order to solve robot-related technological problems. No cases required conversion to laparotomy. All problems were solved by the robotic surgeon with the assistance of robotic surgery staff. CONCLUSIONS: Surgeons performing robotic surgery must become familiar with troubleshooting robotic technology. Several issues related to technical problems may arise, delaying progression of the case, and potential solutions were identified. As this technology is implemented, robotic surgeons must be trained to solve problems related to the robotic technology and associated equipment. Failure to do so may add time and technical difficulty to robotic cases.

Perioperative morbidity and mortality from major gynecologic surgery in the elderly woman.

OBJECTIVE: To report perioperative morbidity and mortality rates in elderly women who underwent major gynecologic surgery. STUDY DESIGN: The charts of 110 women between 80 and 91 years of age who underwent major gynecologic surgery between July 1995 and May 2003 were retrospectively reviewed. RESULTS: The mean age was 83.1 years. Forty-nine procedures (44.1%) were performed for cancer, 32 (28.8%) for a mass and 23 (20.7%) for pelvic organ prolapse or urinary incontinence. Sixty-nine (62.7%) procedures were performed abdominally, 36 (32.4%) vaginally and 5 (4.5%) laparoscopically. Fifty (44.6%) patients experienced a postoperative complication, and 9 (8.1%) experienced a major one. Major complications included serious morbidity, in 5 (4.5%) patients, and mortality, in 4 (3.6%). Advanced age (> 85 years) was not associated with any of the outcomes of interest, while prior surgical history was significantly associated with a decreased hospital stay (p < 0.001). Increased hospital stay was associated with a moderate or severe medical history (p < 0.05) and laparotomy/laparoscopy vs. vaginal surgery (p < 0.01). CONCLUSION: Postoperative complications occurred frequently among women > 80 years of age who underwent gynecologic surgery. The increased perioperative morbidity in the elderly should be considered when performing surgery on women in that age group.

Uterine weight as a predictor of morbidity after a benign abdominal and total laparoscopic hysterectomy.

OBJECTIVE: To determine if an enlarged uterus is associated with an increased rate of intraoperative and postoperative complications and prolonged hospital length of stay (LOS) after benign total abdominal hysterectomy (TAH) or total laparoscopic hysterectomy (TLH). STUDY DESIGN: Women who underwent TAH or TLH were stratified, according to uterine weight, into 3 groups: group 1, uterine weight < 200 g; group 2, 201-500 g; and group 3, > 500 g. Indications included uterine leiomyomas, chronic pelvic pain, prolapsed uterus, endometriosis and adenomyosis, dysfunctional uterine bleeding; all had benign final pathology. Statistical analysis compared risks of intraoperative and postoperative morbidity and prolonged hospital stay. RESULTS: Prolonged hospital stay risk increased for uterine weight > 500 g (p < or = 0.001). There was a significant association between postoperative complications and uterine size (p < or = 0.001). Mean estimated blood loss (EBL) also increased with uterine weight > 500 g (p < or = 0.001). TLH was associated with fewer postoperative complications, shorter LOS and reduced EBL (p < or = 0.001). CONCLUSION: Average LOS and risk of blood loss, blood transfusion and other postoperative complications after hysterectomy for benign disease increased with increasing uterine weight. TLH is an excellent alternative for enlarged uteri; it was strongly associated with decreased morbidity, shorter LOS, and reduced EBL and blood transfusion rate in all uterine weight groups when adjusted for other variables.

Endometrial cancer in women 45 years of age or younger: a clinicopathological analysis.

OBJECTIVE: The purpose of this study was to evaluate the experience with endometrial carcinoma in women < or =45 years of age at Ochsner Clinic Foundation, New Orleans, La. STUDY DESIGN: We evaluated the clinical history, treatment, and follow-up of 38 women < or =45 years of age diagnosed with endometrial cancer. RESULTS: Thirty-eight patients received primary treatment for endometrial cancer: stage I, 32 (84.2%); stage II, 1 (2.6%); stage III, 4 (10.5%); stage IV, 1 (2.6%). Tumors were well differentiated in 20 (52.6%), moderately differentiated in 10 (26.3%), and poorly differentiated in 8 (21.1%). At end of study period 32 women (84.2%) were alive with no evidence of disease, 5 had died of recurrent disease, and 1 died of metastatic breast cancer. CONCLUSION: Patients < or =45 years of age had lower incidence of advanced stage disease, higher degree of tumor differentiation, and better prognosis compared to patients older than 45 years.

Association between obesity and the trends of routes of hysterectomy performed for benign indications.

OBJECTIVE: To estimate the association between obesity and the recent trends of routes chosen for hysterectomy performed for benign indications in the United States. MATERIALS AND METHODS: Using the American College of Surgeons-National Surgical Quality Improvement Project's database, patients who underwent hysterectomy for benign indications from 2005 to 2011 were identified by International Classification of Diseases, 9th Revision codes and were categorized into total abdominal hysterectomy (TAH), total vaginal hysterectomy (TVH), laparoscopically assisted vaginal hysterectomy (LAVH), and total laparoscopic hysterectomy (TLH). The patients were divided into four subgroups according to body mass index (BMI) (less than 25, 25-29.9, 30-39.9, and 40 or greater). The data were analyzed using Student's t test or χ2 and Fisher's exact test. RESULTS: A total of 18,810 patients underwent hysterectomy for benign indications during the study period: 9,852 (52.4%) were TAH, 5,146 (27.4%) TVH, 2,296 (12.2%) LAVH, and 1,516 (8.0%) TLH. The rates of TAH increased from 45.7% in patients with ideal body weight to 62% in morbidly obese patients (P<.001). The rate of TVH and LAVH decreased from 32.7% and 13.3% in patients with ideal body weight to 17.1% and 11.7% in morbidly obese patients, respectively (P<.001 and 0.04). The rate of TLH performed was independent of BMI (P=.61). Higher BMI was associated with longer operative time (P<.001) in all routes of hysterectomy. The rates of superficial and deep wound infections were higher with increasing BMI in patients undergoing TAH (P<.001) but not with TVH (P=.26), LAVH (P=1.0), or TLH (P=.48). CONCLUSION: Regarding hysterectomy performed for benign indications, increasing BMI was associated with increased rate of TAH and decreased rate of TVH and LAVH, but not the rate of TLH. Increasing BMI was associated with increased operative time for all subgroups and increased surgical site infection in the TAH group.

Bartholin's gland carcinoma, malignant melanoma and other rare tumours of the vulva.

Non-squamous cancers of the vulva encompass an exciting and broad group of tumours, including Bartholin's gland carcinoma, malignant melanoma, Paget's disease, sarcomas and lymphoma. These tumours range from innocuous lesions treatable with simple local excision, such as basal-cell carcinoma, to cancers with very poor prognosis, such as Merkel-cell tumours. All of these tumours are thoroughly reviewed, with emphasis on presenting symptoms, pathological diagnosis and optimal management approaches. The literature supporting these recommendations is reviewed. Of the utmost importance in the management of these tumours is a thorough review of the pathological diagnosis by a specialist pathologist and a gynaecological oncologist. Establishing the correct diagnosis is essential to reaching appropriate treatment decisions. Frequently this will necessitate a second opinion by a referral centre.

Hysterectomy in women with cervical stenosis. Surgical indications and pathology.

OBJECTIVE: To evaluate indications for surgery and final pathology results in patients who underwent hysterectomy with a concurrent diagnosis of cervical stenosis. STUDY DESIGN: Retrospective chart review of 25 women who underwent hysterectomy after diagnosis of cervical stenosis. RESULTS: The average age was 59 years (range, 38-80). Indications for surgery included postmenopausal bleeding in 10 patients, previous dysplasia with inadequate Papanicolaou test follow-up in 4, recurrent high grade squamous intraepithelial lesion in 1, chronic pelvic pain in 5, acute pain in 2, dysfunctional uterine bleeding in 2 and thickened endometrial stripe in 1 patient on tamoxifen. An attempt to obtain an endometrial sample was unsuccessful in 14 patients. Twenty patients had undergone prior gynecologic surgery. The results of final cervical pathologic examination revealed severe cervical dysplasia or carcinoma in situ in 3. Final uterine pathology revealed 1 patient with uterine adenocarcinoma and 19 patients with benign pathology, including endometritis, fibroids, adenomyosis and endometrial hyperplasia. CONCLUSION: The majority of patients with cervical stenosis resulting in inadequate cancer screening and/or symptoms resulting from stenosis will have significant benign pathology (64%), cervical dysplasia (12%) or uterine cancer (4%). For these patients, hysterectomy is a reasonable option.

Necessity of endometrial biopsy in women with enlarged uteri and a preoperative diagnosis of uterine leiomyomata.

OBJECTIVE: To determine the necessity of a preoperative endometrial biopsy when evaluating a patient with symptomatic uterine fibroids. STUDY DESIGN: This was a retrospective study of 182 cases of hysterectomy for symptomatic uterine fibroids. The patients were stratified into 2 groups: those with uteri weighing between 280 and 500 g and with uteri weighing > 500 g. Charts were reviewed for all patients who did not have an endometrial biopsy and for all cases of malignancy. RESULTS: Of the patients with menorrhagia, 21-30% did not undergo a preoperative biopsy. In those who did, biopsy failed to detect 2.75% of malignancies. All patients diagnosed postoperatively with malignancy had presented with complaints of bleeding. CONCLUSION: With complaints other than bleeding, a preoperative endometrial biopsy may be omitted. However, any menstrual complaints warrant an investigation of the endometrium even though the incidence of endometrial carcinoma in these larger uteri is only 1.1%.

ALDH1A1 maintains ovarian cancer stem cell-like properties by altered regulation of cell cycle checkpoint and DNA repair network signaling.

OBJECTIVE: Aldehyde dehydrogenase (ALDH) expressing cells have been characterized as possessing stem cell-like properties. We evaluated ALDH+ ovarian cancer stem cell-like properties and their role in platinum resistance. METHODS: Isogenic ovarian cancer cell lines for platinum sensitivity (A2780) and platinum resistant (A2780/CP70) as well as ascites from ovarian cancer patients were analyzed for ALDH+ by flow cytometry to determine its association to platinum resistance, recurrence and survival. A stable shRNA knockdown model for ALDH1A1 was utilized to determine its effect on cancer stem cell-like properties, cell cycle checkpoints, and DNA repair mediators. RESULTS: ALDH status directly correlated to platinum resistance in primary ovarian cancer samples obtained from ascites. Patients with ALDHHIGH displayed significantly lower progression free survival than the patients with ALDHLOW cells (9 vs. 3 months, respectively p<0.01). ALDH1A1-knockdown significantly attenuated clonogenic potential, PARP-1 protein levels, and reversed inherent platinum resistance. ALDH1A1-knockdown resulted in dramatic decrease of KLF4 and p21 protein levels thereby leading to S and G2 phase accumulation of cells. Increases in S and G2 cells demonstrated increased expression of replication stress associated Fanconi Anemia DNA repair proteins (FANCD2, FANCJ) and replication checkpoint (pS317 Chk1) were affected. ALDH1A1-knockdown induced DNA damage, evidenced by robust induction of γ-H2AX and BAX mediated apoptosis, with significant increases in BRCA1 expression, suggesting ALDH1A1-dependent regulation of cell cycle checkpoints and DNA repair networks in ovarian cancer stem-like cells. CONCLUSION: This data suggests that ovarian cancer cells expressing ALDH1A1 may maintain platinum resistance by altered regulation of cell cycle checkpoint and DNA repair network signaling.

Ureteral transection repaired during robot-assisted surgery.

During robot-assisted surgery for endometrial cancer, a ureteral injury occurred in two women. Both injuries were repaired successfully with robot-assisted surgery. One of the injuries and its repair are shown in an edited video clip. Ureteral injury is a known complication of gynecologic surgery (Hoffman in OBG Manag 20:16-28, 2008). Transection of the pelvic ureter proximal to the parametrium may be repaired by reapproximation or reimplantation. Robot-assisted surgery has recently been established as useful for the performance of ureteral surgery (Kasturi et al. in Urology 79:680-683, 2012; Rehman et al. in Can J Urol 18:5548-5556, 2011; Patil et al. in Urology 72:47-50, 2008).

Signs of aging or the vague symptoms of ovarian cancer?

PURPOSE/OBJECTIVES: To explore the feelings that occurred at the same time as the vague physical symptoms of ovarian cancer. RESEARCH APPROACH: Qualitative, descriptive methodology. SETTING: University cancer institute in southeastern United States. PARTICIPANTS: 24 women (ages 39-78) diagnosed with ovarian cancer. Most were Caucasian, were diagnosed at stage II-III, had a college-level education, and had health insurance. Eighty-three percent did not know the signs and symptoms of ovarian cancer prior to diagnosis, and 91% had no family history of the cancer. METHODOLOGIC APPROACH: SPSS (version 18.0) was used to summarize the demographic characteristics and qualitative descriptive content analysis to identify and summarize themes in the narrative data. FINDINGS: Two themes were noted in the handwritten answers provided by the women: (a) "thought symptoms were aging" and (b) "felt or knew something was not right." CONCLUSIONS: Findings demonstrate and reinforce that a need exists for education regarding signs and symptoms of ovarian cancer among the general population as well as the common providers of women's health care. INTERPRETATION: Education campaigns on signs and symptoms of ovarian cancer and normal aging are necessary so women are empowered with knowledge and healthcare providers can suspect and evaluate the symptoms.