Epithelial Ovarian Cancer and Cancer Stem Cells.

Epithelial ovarian cancer is a lethal gynecological cancer. It is related to high mortality because the majority of the patients present in advanced stage and because of the high recurrence rates of the disease. Recurrent ovarian cancer is classified according to the time interval between the last platinum-based chemotherapy and the occurrence of recurrence, to platinum-sensitive and platinum-resistant. Many theories tried to explain development of resistance to platinum-based therapy. "Cancer stem cells" is one of these theories and is being currently under investigation by many groups. This chapter will demonstrate the suggested contribution of cancer stem cells to the development of recurrent ovarian cancer.

Correlation of elevated levels of lipoprotein(a), high-density lipoprotein and low-density lipoprotein with severity of preeclampsia: a prospective longitudinal study.

The aim of this study was to examine a possible association between the levels of total serum cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and lipoprotein(a), and the development of severe preeclampsia. We measured the levels of these lipoproteins in a prospective observational longitudinal cohort study that recruited 50 third-trimester pregnant women with mild preeclampsia at the time of recruitment. Two assessments were performed; the first measurement was at 29-31 weeks of pregnancy (at recruitment), and the second took place 4 weeks later. Patients with BMI 30, those < 20 years of age and those > 35 years of age were not included in the study. Eight mildly preeclamptic women developed severe preeclampsia within 4 weeks. In these patients, lipoprotein(a) level showed a twofold increase. A serum lipoprotein(a) level > 40.5 mg/dL in a mildly preeclamptic patient predicted the development of severe preeclampsia later on in the pregnancy, whereas a serum lipoprotein(a) level > 52.5 mg/dL was a marker of severity with high sensitivity and specificity. We suggest through our results that that lipoprotein(a) level correlates with the severity of the disease.IMPACT STATEMENTWhat is already known on this subject? Changes in blood lipids have been reported in preeclampsia. Abnormal lipoprotein levels are thought to play a role in the pathophysiology of the disease.What the results of this study add? In this study, we showed that a serum lipoprotein(a) level >40.5 mg/dL in a mildly preeclamptic patient predicted the development of severe preeclampsia later on in the pregnancy, whereas a serum lipoprotein(a) level >52.5 mg/dL was a marker of severity with high sensitivity and specificity.What the implications are of these findings for clinical practice and/or further research? Our results suggest that blood lipids, and especially lipoprotein(a), are involved in the pathogenesis of preeclampsia. The lipoprotein(a) level correlates with the severity of the disease. Hence, lipoprotein(a) could be used as a predictor of severe preeclampsia and a marker of the severity of preeclampsia. This should be validated through prospective studies recruiting an adequate sample size.

Peritoneal cancer index as a predictor of survival in advanced stage serous epithelial ovarian cancer: a prospective study.

OBJECTIVE: A numerical score, the peritoneal cancer index (PCI), was developed to reflect the extent of tumor growth in gastric and colorectal cancers and to tailor treatment. This study aimed to examine the value of the PCI score in advanced epithelial ovarian cancer (EOC) regarding completeness of surgical cytoreduction and survival. METHODS: This was a prospective observational cohort study. Patients with primary serous EOC at International Federation of Gynecology and Obstetrics (FIGO) stages IIIB or higher were included. Patients with FIGO stage IVB as well as those assigned to receive neoadjuvant treatment were excluded from the study. The PCI was obtained and registered intraoperatively. RESULTS: In the study period we recruited 96 patients with serous EOC stage IIIB-IVA. A PCI score cut-off value of 13 was calculated using a receiver operator characteristic (ROC) curve, above which worse survival is expected (area under the curve [AUC]=0.641; 95% confidence interval [CI]=0.517-0.765; sensitivity and specificity 80.6%, 45.0%, respectively; p=0.050). A multivariate analysis determined that suboptimal surgical cytoreduction was the only independent predictive factor for recurrence (odds ratio [OR]=7.548; 95% CI=1.473-38.675; p=0.015). A multivariate analysis determined that only suboptimal surgical cytoreduction (hazard ratio [HR]=2.33; 95% CI=0.616-8.795; p=0.005), but not PCI score >13 (HR=1.289; 95% CI=0.329-5.046; p=0.716), was an independent predictive factor for death. CONCLUSION: We conclude from this study that the PCI score is a reliable tool helping to assess the extent of disease in advanced serous EOC patients and may help predicting complete surgical cytoreduction but cannot qualify as a predictor of survival.

Neonatal blood rheological parameters at delivery in healthy neonates and in those with morbidities.

Rheological blood parameters of neonates are different form those of adults. Many authors have studied changes in blood rheology in neonates in different clinical disorders. To-date, no one set the normal values for blood rheological parameters in healthy neonates. The aim of this study is to set the norm for rheological blood parameters in healthy newborns and to describe the changes in those parameters in common clinical disorders that affect the newborns. We recruited all the neonates born to mothers experiencing un eventful pregnancies, blood was taken from the umbilical cord right after the delivery. In this time period we recruited 4985 neonate. From this huge database we were able to set the standards for blood rheology in neonates, namely plasma viscosity of 1.06±0.072 mPa, erythrocyte aggregation at stasis of 2.41±2.74 s-1 and erythrocyte aggregation under low shear forces of 8.51±6.38 s-1. These values changed significantly in some diseased neonates. This is the largest study investigating normal rheological parameters and deviations from the norm in common clinical disorders occurring in this early stage of life.

Pubic Hair Shaving Is Correlated to Vulvar Dysplasia and Inflammation: A Case-Control Study.

Objective: The risk factors for vulvar dysplasia and infections are not fully known. In this study, we aimed to investigate the correlation between pubic hair shaving and the occurrence of vulvar inflammation, dysplasia, and cancer. Methods: This study was performed between January 2013 and December 2016 in which a standardized questionnaire concerning genital hair shaving was administered to vulvar dysplasia and cancer patients and healthy participants. The presence of human papilloma virus (HPV) infection and the occurrence of genital inflammation were documented. Results: We recruited 49 patients with vulvar dysplasia or cancer and 234 healthy women as a control group. Smoking, HPV infection, genital inflammation, and complete pubic hair removal were significantly more common in the vulvar dysplasia/cancer group. Pubic hair shaving per se presented a clear association with vulvar dysplasia/cancer. Shaving the labia majora in particular showed also an association. Conclusion: Our findings suggest that partial or complete pubic hair shaving using a razor is correlated with and could be a potential risk factor for the development of genital inflammation, vulvar dysplasia, and malignancies. These results need to be confirmed in larger studies. HPV status and genital inflammation should be documented by medical personnel.

Clinical relevance of CD44 surface expression in advanced stage serous epithelial ovarian cancer: a prospective study.

PURPOSE: Cluster of differentiation (CD) 44 is a cell surface receptor that correlates with the development of drug resistance in epithelial ovarian cancer (EOC). Here, we prospectively investigated the clinical impact of CD44 expression on the development of chemoresistance, and on disease-free and overall survival in EOC. METHODS: This study included patients with primary serous EOC that was at International Federation of Gynecology and Obstetrics stages IIIB-IVA and tumors that were CD44 positive and negative in a 1:1 ratio. All patients underwent primary surgical cytoreduction, followed by six cycles of combined paclitaxel and carboplatin chemotherapy every 3 weeks. The treatment was considered complete after the chemotherapy had finished. All patients were followed up for 24 months after completing their chemotherapy. RESULTS: Of the 96 patients with serous EOC at stages IIIB-IVA, 51 % of the tumors were negative for the expression of CD44 and 49 % showed variable CD44 expression. Patients who had CD44-positive tumors had statistically significant shorter disease-free (p ≤ 0.001) and overall survival (p ≤ 0.001) intervals compared with patients with CD44-negative tumors. The hazard ratio for death was 6.8 (95 % confidence interval 2.4-19.2, p ≤ 0.001) among the patients with CD44-positive tumors. A multivariate analysis showed that carboplatin-resistant or carboplatin-refractory EOC was the only independent predictive factor for death. CONCLUSIONS: CD44 expression contributes to the development of carboplatin resistance in advanced serous EOC, and it may contribute to worse prognoses for patients, but it is neither an independent predictor of survival nor of recurrence.

Power Doppler flow mapping and four-dimensional ultrasound for evaluating tubal patency compared with laparoscopy.

OBJECTIVES: To study the accuracy of four-dimensional (4D) ultrasound and power Doppler flow mapping in detecting tubal patency in women with sub-/infertility, and compare it with laparoscopy and chromopertubation. STUDY DESIGN: A prospective study. The study was performed in the outpatient clinic and infertility unit of a university hospital. The sonographic team and laparoscopic team were blinded to the results of each other. Women aged younger than 43 years seeking medical advice due to primary or secondary infertility and who planned to have a diagnostic laparoscopy performed, were recruited to the study after signing an informed consent. All of the recruited patients had power Doppler flow mapping and 4D hysterosalpingo-sonography by injecting sterile saline into the fallopian tubes 1 day before surgery. Registering Doppler signals, while using power Doppler, both at the tubal ostia and fimbrial end and the ability to demonstrate the course of the tube especially the isthmus and fimbrial end, while using 4D mode, was considered a patent tube. RESULTS: Out of 50 recruited patients, 33 women had bilateral patent tubes and five had unilateral patent tubes as shown by chromopertubation during diagnostic laparoscopy. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for two-dimensional power Doppler hysterosalpingography were 94.4%, 100%, 100%, 89.2%, and 96.2%, respectively and for 4D ultrasound were 70.4%, 100%, 100%, 70.4%, and 82.6%, respectively. CONCLUSIONS: Four-dimensional saline hysterosalpingography has acceptable accuracy in detecting tubal patency, but is surpassed by power Doppler saline hysterosalpingography. Power Doppler saline hysterosalpingography could be incorporated into the routine sub-/infertility workup.

Impact of liver cirrhosis due to chronic hepatitis C viral infection on the outcome of ovarian cancer: a prospective study.

BACKGROUND: This study was designed to investigate the impact of liver cirrhosis due to chronic hepatitis C virus (HCV) infection on the disease-free and overall survival of ovarian cancer patients undergoing a standard primary operation followed by standard chemotherapy. Attainment of the operative goals, intra- and postoperative events, possible complications under chemotherapy necessitating the termination of treatment, and the impact of ovarian cancer treatment on liver function were assessed. METHODS: This was a prospective observational study that included only patients with primary epithelial ovarian cancer. Only patients with Child-Turcotte-Pugh classification class A disease were recruited. Patients were divided into two groups according to whether they had liver cirrhosis. All the patients underwent primary debulking surgery followed by 6 cycles of chemotherapy, and were followed-up for 24 months after chemotherapy was completed. RESULTS: We recruited 77 patients, 19 of whom had liver cirrhosis. There were no significant differences between patients with or without liver cirrhosis with respect to tumor stage, histopathological type, tumor grade, or optimal operative debulking. There was no registered liver dysfunction-related mortality in the follow-up period, and there were no statistically significant differences between the groups with respect to disease-free or overall survival (p = 0.719 and p = 0.524, respectively). CONCLUSION: From the results of this study, we conclude that compensated liver cirrhosis (Child-Turcotte-Pugh class A) due to chronic HCV infection affects neither the disease-free nor the overall survival of ovarian cancer patients, regardless of their stage. This study shows that it is possible to treat ovarian cancer patients with cirrhosis caused by HCV infection the same as any other patient; treatment does not have to be adjusted as long as the patients have Class A disease.

Rheologic results and their correlation to hemostatic changes in patients with moderate and severe preeclampsia: an observational cross-sectional study.

Previous study have shown an association between failure of physiological hemodilution during 2nd trimester and an increased risk for the development of subsequent pregnancy complications such as early birth, birth of a growth retarded newborn (IUGR), low fetal birth weight and preeclampsia. The latter complication in particular goes along with dramatic changes in the placental perfusion as well as systemic maternal blood flow. Severity of preeclampsia may be preceded by distinct impaired hemodilution and reflected by the results of rheological parameters. A subgroup analysis was performed in a community based retrospective study of 4,985 consecutively recorded singleton pregnant women of whom 423 had preeclampsia. Mean 2nd trimester hemoglobin levels and blood rheological results at the time of delivery were assessed and compared in women with moderate and severe preeclampsia. Mean 2nd trimester hemoglobin levels were calculated from the maternal records. Rheological variables included plasma viscosity (KSPV 1 Fresenius) and Red blood cell aggregation in stasis and under low shear conditions (MA1-Aggregometer; Myrenne). According to the definition of the German Society of Gynecology and Obstetrics (DGGG) 314 women had moderate preeclampsia (74.2%), while 109 had severe preeclampsia due to the presence of a blood pressure>170/110 mmHg (n=41; 9.7%), and/or IUGR<5th percentile (n=28; 6.6%), and/or HELLP-Syndrome (n=10; 2.4%), and/or proteinuria≥5 g/24 h (n=30; 7.1%). Age, BMI, smoking, and maternal weight were comparable in the groups, while gestational age at delivery as well as fetal outcome parameter were statistically significant unfavourable in patients with severe preeclampsia. Mean 2nd trimester hemoglobin level were statistically significantly higher in women who developed severe vs. moderate preeclampsia (m=12.75±0.99 g/dL vs. m=12.50±1.05 g/dL; p=0.033). However, in the ROC calculations a hemoglobin value of 12.05 g/dL revealed best sensitivity (78%) and specificity (33.8%) in women with subsequent diagnosis of severe preeclampsia, whereas sensitivity was 100% for a value>10.95 g/dL. There were no statistically significant differences for none of the rheological parameters at the time of delivery between groups of patient with moderate v.s severe preeclampsia. Severe preeclampsia and IUGR, however, was associated with statistically significantly higher RBC aggregation as compared to patients with moderate preeclampsia. Plasma viscosity was statistically significantly (p<0.05) correlated with Fibrinogen values (r=0.16), leukocyte-(r=0.11) and platelets-count (r=0.127), and hemoglobin/hematocrit values in particular (r=0.23/0.26). Although mean 2nd trimester hemoglobin concentration are higher in patients with subsequent development of severe preeclampsia, due to the low sensitivity and specificity of this parameter clinical use for identifying women at risk is of limited value. On the other hand, a hemoglobin value below 11.0 g/dL excluded the risk for severe preeclampsia to 100%. Blood rheological parameters at the time of delivery in the absence of IUGR are not markedly influenced by severity of preeclampsia.

Ultrasonographic examination of the endometrium and myometrium using acoustic radiation force impulse (ARFI) imaging technology: An initial experience with a new method.

PURPOSE: Acoustic radiation force impulse (ARFI) imaging technology provides measurable values of the elasticity/stiffness of the tissues examined. This work is a pilot study to determine the shear wave velocity values of normal endometrium and myometrium in healthy asymptomatic women. METHODS: In a prospective observational study that recruited asymptomatic women, we used the ARFI (Virtual Touch tissue quantification(™); Siemens Medical Solutions) to examine six different points in the uterus of each woman; two points in the endometrium and four points in the myometrium. Two readings were obtained at each of the examined points to test the intra-observer reproducibility. RESULTS: A total of 32 women were recruited. The age range was 19-68 years with a median age of 42 years. The menopausal status did not have any significant influence on the shear wave velocity measurements. The mean readings in the endometrium were 1.96, 2.03, 2.04 and 2.08 m/s while in the myometrium they were 2.78, 2.85, 2.87, 2.89, 2.91, 2.99, 3.2 and 3.23 m/s, respectively. CONCLUSIONS: The ARFI procedure is a novel, reproducible ultrasonographic modality that can provide information about tissue stiffness. Transvaginal transducers fitted with this technology are sought as well as larger studies validating our findings.

Correlation of rheological parameters in maternal and fetal blood at term.

OBJECTIVE: An association between maternal and fetal blood rheology has not yet been investigated nor is it known whether and to what extent fetal blood rheology may be affected by maternal conditions. METHODS: At delivery, blood was drawn from the cubital vein of 4985 consecutive mothers and from the umbilical cord during birth for determination of blood rheological parameters (erythrocyte aggregation stasis [E0], low shear [E1], plasma viscosity [Pv]) in addition to hemoglobin (Hb) values and hematocrit (Hct). RESULTS: Maternal and newborn Pv (r = 0.2; p < 0.0001) correlated statistically significant. There was a remarkable correlation between fetal Pv and gestational age (r = 0.197; p < 0.001). Iron supplementation during pregnancy led to increased fetal Hb, Hct as well as E0 and E1 (p < 0.0001), did not have a significant impact on neonatal Pv (p = 0.068). Smoking mothers gave birth to neonates with significantly higher Pv (p = 0.049), E0 (p = 0.016) and E1 (p = 0.013). CONCLUSIONS: The increase of fetal plasma viscosity at advanced delivery time-points refers to a more gaining protein synthesis by the fetal liver and thus maturity of the fetus. Iron supplementation as well as smoking during pregnancy is associated with a relative hyper-viscosity in the fetus at delivery.

A retrospective analysis of survival and prognostic factors of male breast cancer from a single center.

BACKGROUND: Less than 1% of all breast cancer cases are found in men, who reportedly have inferior outcomes compared with matched women patients. Ethnic differences may also affect their prognosis. Here, we investigated overall survival (OS) and major prognostic factors for male breast cancer (MBC) in a cohort of Egyptian patients. METHODS: We retrospectively analyzed OS in a cohort of 69 male patients with MBC who were surgically treated at the Mansoura Cancer Center, Egypt between 2000 and 2007. We registered demographic data, age, height, weight and body mass index, tumor size, histology, number of infiltrated axillary lymph nodes, hormone receptor (HR) status and metastatic presence, and TNM staging. Patients' OS was the primary endpoint. Patients received treatment to the medical standards at the time of their diagnosis. RESULTS: In the 69 patients who met the inclusion criteria and had complete stored patient data, tumors ranged from T1c to T3. We could gather cancer-related survival data from only 56 patients. The collective 5-year survival in this cohort was 46.4%. Only five patients had distant metastasis at diagnosis, but they showed a null percent 5-year survival, whereas those with no lymph node infiltration showed a 100% 5-year survival. Lymph node status and tumor grading were the only prognostic factors that significantly affected OS. CONCLUSIONS: Lymph node status and tumor grade are the most important prognostic factors for overall survival of MBC in Egyptian male patients; whereas even remarkably low HR expression in MBC did not significantly affect OS. Further research is needed to understand the factors that affect this disease.

Sonographic features of triple-negative and non-triple-negative breast cancer.

OBJECTIVES: Triple-negative breast cancer (TNBC) is known to have unique molecular, clinical, and pathologic characteristics. The growth pattern of this cancer may also affect its appearance on sonography. Our study evaluated the sonographic features of TNBC according to the American College of Radiology Breast Imaging Reporting and Data System sonographic classification system and compared these features with those of non-TNBC. METHODS: Data from 315 consecutive breast cancer cases were collected. The images were reevaluated by an examiner blinded to the patients' characteristics and histologic results according to the Breast Imaging Reporting and Data System. The sonographic features of TNBC (n = 33) and non-TNBC (n = 282) were compared. RESULTS: Triple-negative breast cancer was significantly correlated with a younger patient age (P = .002) and was associated with higher tumor grades (P < .001), more lymph node involvement (P = .014), and a trend toward a larger tumor size. With regard to sonographic features, the margin of TNBC was more frequently described as lobulated or microlobulated (75.8% versus 49.5% in non-TNBC; P = .005). The echoic halo was observed significantly less often in TNBC than in non-TNBC(39.4% versus 62.8%; P = .014). Cooper ligaments were displaced rather than disrupted in TNBC compared to non-TNBC (P = .003). Regarding the posterior acoustic features, enhancement was observed significantly more often in TNBC (36.4% versus 13.0% in non-TNBC; P = .031). CONCLUSIONS: Triple-negative breast cancer and non-TNBC have different sonographic features. This finding can be explained by the pathologic profile of this breast cancer subtype. Some of the distinct sonographic criteria for TNBC are more likely to be associated with benign masses. Knowledge of the distinct sonographic features of TNBC would help the examiner avoid false-negative classification of this tumor type.

Variations in the Elasticity of Breast Tissue During the Menstrual Cycle Determined by Real-time Sonoelastography.

OBJECTIVES: The purpose of this study was to determine the dependence of breast tissue elasticity on the menstrual cycle of healthy volunteers by means of real-time sonoelastography. METHODS: Twenty-two healthy volunteers (aged 18-33 years) were examined once weekly during two consecutive menstrual cycles using sonoelastography. Group 1 (n= 10) was not taking hormonal medication; group 2 (n = 12) was taking oral contraceptives. RESULTS: The breast parenchyma appeared softer than the dermis and harder than the adipose tissue, and elasticity varied over the menstrual cycle and between groups. Group 1 (no hormone intake) showed continuously increasing elasticity with relatively soft breast parenchyma in the menstrual and follicular phases and harder parenchyma in the luteal phase (P = .012). Group 2 (oral contraceptives) showed no statistically significant changes in breast parenchymal elasticity according to sonoelastography. The parenchyma was generally softer in group 1 compared with group 2 throughout the menstrual cycle (P = .033). The dermis, the subcutaneous adipose tissue, and the pectoralis major muscle showed no changes in elasticity. Comparison of measurements made during the first and the second menstrual cycles showed similar patterns of elasticity in both groups. CONCLUSIONS: Sonoelastography is a reproducible method that can be used to determine the dependence of breast parenchyma elasticity on the menstrual cycle and on the intake of hormonal contraceptives.

Degenerated huge retroperitoneal leiomyoma presenting with sonographic features mimicking a large uterine leiomyoma in an infertile woman with a history of myomectomy: a case report.

INTRODUCTION: Retroperitoneal leiomyomata are rare. They are either mistaken preoperatively for malignant retroperitoneal tumors or dealt with as cases of subserous leiomyomata that turn out intraoperatively to be huge retroperitoneal masses of unknown nature. CASE PRESENTATION: We report the case of a 46-year-old nulligravid female patient of Middle Eastern ethnicity who presented to our university hospital with lower abdominal as well as pelvic pain along with a bloated sensation. She also reported noticing an unusual increase in her abdominal girth. These symptoms developed over the previous two months. Preoperative investigation by means of an ultrasound suggested a degenerated subserous huge uterine leiomyoma. An abdominal hysterectomy was planned. Intraoperatively, a normal sized uterus was found, the surface of which was studded with multiple variable sized pedunculated subserous leiomyomata. Another huge retroperitoneal soft to firm mass was found extending from her left pelvic wall to the level of her spleen, with no connections to her uterus. The mass was excised and a histopathological examination revealed a degenerated leiomyoma. CONCLUSION: Some unusually located extra-uterine leiomyomata have been reported; retroperitoneal leiomyoma being among them. The origin of such tumors is still obscure; a parasitic origin as well as Müllerian cell rests or smooth muscle cells in the retroperitoneal vessels wall have been suggested. An 'iatrogenic' origin for such growths is also a possible theory. The origin of uncommonly located leiomyomata is an unexplored issue that merits more investigation.

The Automated Breast Volume Scanner (ABVS): initial experiences in lesion detection compared with conventional handheld B-mode ultrasound: a pilot study of 50 cases.

The idea of an automated whole breast ultrasound was developed three decades ago. We present our initial experiences with the latest technical advance in this technique, the automated breast volume scanner (ABVS) ACUSON S2000(™). Volume data sets were collected from 50 patients and a database containing 23 women with no detectable lesions in conventional ultrasound (BI-RADS(®)-US 1), 13 women with clearly benign lesions (BI-RADS(®)-US 2), and 14 women with known breast cancer (BI-RADS(®)-US 5) was created. An independent examiner evaluated the ABVS data on a separate workstation without any prior knowledge of the patients' histories. The diagnostic accuracy for the experimental ABVS was 66.0% (95% confidence interval [CI]: 52.9-79.1). The independent examiner detected all breast cancers in the volume data resulting in a calculated sensitivity of 100% in the described setting (95% CI: 73.2%-100%). After the ABVS examination, there were a high number of requests for second-look ultrasounds in 47% (95% CI: 30.9-63.5) of the healthy women (with either a clearly benign lesion or no breast lesions at all in conventional handheld ultrasound). Therefore, the specificity remained at 52.8% (95% CI: 35.7-69.2). When comparing the concordance of the ABVS with the gold standard (conventional handheld ultrasound), Cohen's Kappa value as an estimation of the inter-rater reliability was κ = 0.37, indicating fair agreement. In conclusion, the ABVS must still be regarded as an experimental technique for breast ultrasound, which definitely needs to undergo further evaluation studies.