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Ovarian Cancer

Cancer of the ovaries are the second most common group of gynaecologic cancers, and account for about 5% of all women's cancers. There are two main types; (i) epithelial tumours (carcinomas) which account for 90% of ovarian cancers, and (ii) non-epithelial tumours (eg. Stroma cell and germ cell tumours of the ovary). The epithelial ovarian cancers are usually found in women aged over 40, while the non-epithelial tumours are more common in girls and young women. Epithelial ovarian cancer has few early symptoms, a risk factor is having a family history of the disease. Taking the contraceptive pill is known to be protective against ovarian cancer.

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    MeSH term: Ovarian Neoplasms
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Kilic Sakarya D, Yetimalar MH
Is there a current change of maintenance treatment in ovarian cancer? An updated review of the literature.
J BUON. 2016 Mar-Apr; 21(2):290-300 [PubMed] Related Publications
Maintenance therapy in ovarian cancer has been introduced and evaluated in many large randomized trials; however, its efficacy is still unclear and includes concerns for both short-term and longer-term side effects. Thus far, some therapies that have been studied in this setting showed a delay in tumor progression but unfortunately no improvement in overall survival has been noticed. The introduction of new chemotherapeutic agents redirected research efforts. Assessing benefits of prolonged therapy and its impact in terms of toxicity is considerably important for the decision to administer such treatments. The purpose of this article was to provide an update on the randomized trials and review the role of maintenance therapy in the treatment of ovarian cancer.

Manea E, Munteanu A
Rev Med Chir Soc Med Nat Iasi. 2016 Jan-Mar; 120(1):192-6 [PubMed] Related Publications
Bilateral breast cancer incidence is appreciated to be between 0.3 to 12% and is determined either by a hereditary load associated with chromosomal instability under the effect of environmental factors, or by the evolution in a particular hormonal context which gives biological aggressiveness. We present the case of a patient, aged 38 years, clinically, imagistic and bioptic diagnosed with left axillary lymph node metastases of breast carcinoma NST invasive G3, IHC-RE = 60%, RP = 30%, HER2neu = 2 +, Ki67 = 20%, in August 2013. Patient followed neoadjuvant chemotherapy treatment during September-October 2013. In December 2013 she was clinically and imaging diagnosed with bilateral breast cancer, for which surgical intervention was done which consisted of bilateral radical Madden mastectomy with bilateral axillary lymphadenectomy. BAP-invasive carcinoma NST: left breast-pT2mN3a G2, right breast--pT3mN3a G2, IHC-RE = 90%, RP =70% HER2neu = 2 +, Ki67 = 50%. During the period of January-March 2014, the patient followed adjuvant chemotherapy and Herceptin. Bilateral breast ultrasound assessment in April 2014 revealed: left axilla--liquid blade 29 / 6mm; right axilla--oval ganglion 9/5 mm. Abdominal and pelvic ultrasound: empty uterine cavity, bosselated contour; at left ovary level multiple cystic formations. During the period of May-June 2014, adjuvant radiation therapy and ovarian irradiationwas administered to the patient. Subsequently hormone therapy was initiated. Following CHT / ovarian irradiation patient continues to experience intermittent uterine bleeding, which is why a total hysterectomy with bilateral ovariectomy was done, and BAP: cervical, endometrialand left ovary with tumor multifocal infiltration with histopathological aspect of invasive breast carcinoma NST. Periodic imaging evaluations do not reveal local or distant recurrence. The particularity of this case is synchronous bilateral breast cancer diagnosis in a young patient complicated in its evolution by ovarian metastases. This form of metastasis is rare in young women and occurs in advanced stages of the disease.

Zhai DK, Liu B, Bai XF, Wen JA
Identification of biomarkers and pathway-related modules involved in ovarian cancer based on topological centralities.
J BUON. 2016 Jan-Feb; 21(1):208-20 [PubMed] Related Publications
PURPOSE: The present study was designed to explore the significant biomarkers and pathway-related modules for predicting the effects of eribulin relative to paclitaxel in ovarian cancer.
METHODS: The gene expression data E-GEOD-50831 were downloaded from the European Bioinformatics Institute (EBI) database. Differentially expressed genes (DEGs) were screened. Subsequently, differential coexpression network was constructed. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and pathway-related modules mining were conducted. Topological centralities (degree, betweenness, closeness and stress) analyses for coexpression network and pathway-related modules were performed to explore hub genes and the most significant pathways. Then, we verified our findings in an independent sample set via RT-PCR and Western blotting.
RESULTS: Centralities results of ESCO1, CDC27and MCM4 ranked the top five. Moreover, among the top 10% hub genes, CDC27, MCM4 and SOS1 were pathway-enriched genes in two networks. A total of 5 and 6 pathway-related modules were obtained under two drugs treatment. Based analyses of degree, betweenness and other centralities, DNA replication pathway-related module was the most significant under paclitaxel treatment, while cell cycle pathway-related module was the most significant under eribulin treatment. RT-PCR and Western blotting results were consistent with the bioinformatics results. The expression level of MCM4 was remarkably decreased under eribulin treatment relative to paclitaxel.
CONCLUSIONS: The inhibition of ovarian cancer growth by paclitaxel and eribulin might be connected with downregulation of cell cycle and DNA replication pathway. Moreover, MCM4 signature might be a potential biomarker to predict the effect of eribulin in ovarian cancer.

Zhou LY, Shi LY, Xiao Y
Changes of HMGB1 expression on angiogenesis of ovarian cancer and its mechanism.
J Biol Regul Homeost Agents. 2016 Jan-Mar; 30(1):233-8 [PubMed] Related Publications
This study was designed to investigate the changes of high-mobility group box-1 (HMGB1) expression and its effects on regulating the angiogenesis of ovarian cancer. HMGB1 eukaryotic expression plasmid and artificially synthesized small interfering ribose nucleic acid (siRNA) were constructed to transfer SKOV3 cell, respectively. Western blot was adopted to investigate the changes of HMGB1, CXCL12 and vascular endothelial growth factor (VEGF) before and after the transfection and flow cytometry (FCM) was applied to detect SKOV3 apoptosis. Results revealed that the apoptosis rates of SKOV3 cell were 32.8±2.2%, 33.9±1.9% and 11.7±1%, respectively, in the control group, no-load group and transfection group after 2-d cisplatin treatment (10 μg/mL). The apoptosis rate in the transfection group was obviously lower than that in the control group and no-load group (p = 0.00) while no significant difference was found in the apoptosis rate in the other two groups (p = 0.75). Furthermore, the apoptosis rates of SKOV3 cell in the SKOV3 group, negative control group, SKOV3-ribose nucleic acid interfere (RNAi) group were 7.9±0.5%, 8.3±0.8% and 29.5±1.3% respectively. The apoptosis rate was notably higher in SKOV3-RNAi group than in the SKOV3 group and negative control group (p < 0.001) while no significant difference was found in the apoptosis rate in the other two groups (p = 0.89). Thus, it can be concluded that HMGB1 interference can reduce VEGF and CXCL12 expression in ovarian cancer cells, but increase the apoptosis of ovarian cancer cells. Moreover, HMGB1 is highly expressed in cytoplasm and karyon.

Moszynski R, Szubert S, Tomczak D, et al.
Solitary fibrous mass of the omentum mimicking an ovarian tumor: case report.
Eur J Gynaecol Oncol. 2016; 37(1):144-7 [PubMed] Related Publications
There are some pelvic masses which are difficult to correctly classify as malignant or benign. The decision concerning method and choice of surgical intervention is not simple in this situation. Some tumors are extremely rare and need to be presented in the literature. The authors report a rare case of fibrous tumor of the omentum simulating a malignant ovarian tumor, which ultimately resulted to be a primary solitary fibrous tumor of the omentum. Ultrasound findings are mostly precise prognostic tools according ovarian masses. However, from time to time, Doppler blood flow examination may present false positive results.

Sofoudis C, Kouiroukidou P, Louis K, et al.
Enormous ovarian fibroma with elevated Ca-125 associated with Meigs' syndrome. Presentation of a rare case.
Eur J Gynaecol Oncol. 2016; 37(1):142-3 [PubMed] Related Publications
In medicine, Meigs' syndrome is the triad of ascites, pleural effusion, and benign ovarian tumor (fibroma, Brenner tumour, and occasionally granulosa cell tumour). It resolves after the resection of the tumor. Because the transdiaphragmatic lymphatic channels are larger in diameter on the right, the pleural effusion is classically on the right side. The etiologies of the ascites and pleural effusion are poorly understood. Atypical Meigs' syndrome,characterized by a benign pelvic mass with right-sided pleural effusion but without ascites, can also occur. As in Meigs syndrome, pleural effusion resolves after removal of the pelvic mass. The authors would like to share their own experience of a case of Meigs' syndrome associated with an enormous ovarian fibroma and elevated Ca-125.

Kuno I, Hashiguchi Y, Kasai M, et al.
Krukenberg tumor in a 18-year-old-female: a rare case.
Eur J Gynaecol Oncol. 2016; 37(1):139-41 [PubMed] Related Publications
BACKGROUND: Krukenberg tumors mostly occur after 40 years. Metastatic ovarian tumors in young age are very rare.
CASE: A 18-year-old female presented with colon cancer which was accompanied by Krukenberg tumor. The present case was a very rare case of metastatic ovarian tumor in very young age. The present patient presented with abdominal pain. On examination, colon tumor was detected and bilateral ovary were almost normal with only slight swelling. During the operation for colon tumor, biopsy of bilateral ovary was performed for histopathological evaluation. Although there were no specific findings in bilateral ovary, microscopic examination revealed poorly differentiated adenocarcinoma, diffusely invading the ovarian parenchyma. Diagnosis of colon cancer was made postoperatively and ovarian Krukenberg tumor was confirmed.
CONCLUSION: In case of suspecting colon cancer even in very young patient with normal ovary, biopsy of ovary should be considered for the diagnosis of Krukenberg tumor.

Li X, Yang J, Wang X, et al.
Role of TWIST2, E-cadherin and Vimentin in epithelial ovarian carcinogenesis and prognosis and their interaction in cancer progression.
Eur J Gynaecol Oncol. 2016; 37(1):100-8 [PubMed] Related Publications
UNLABELLED: Globally, most patients are at late-stage when they have been diagnosed with ovarian cancer. Investigating the potential mechanisms involved in tumor progression and prognosis is essential for improving treatment options, outcomes, and survival.
OBJECTIVE: This study elucidated the clinico-pathological significance of TWIST2 and the relationship of TWIST2, E-cadherin, and Vimentin expression in the progression and prognosis of epithelial ovarian cancer (EOC).
MATERIALS AND METHODS: Immunohistochemical staining was used to quantify the expression and relevance of TWIST2, E-cadherin, and Vimentin in 103 ovarian specimens, including 30 cases of benign ovarian tumors, 30 cases of borderline ovarian tumors, and 43 cases of EOC.
RESULTS: The expression of TWIST2 in the cytoplasm may help to maintain characteristics of epithelial cancer cells with E-cadherin normal membranous expression, while nuclear TWIST2 induces tumor translation front with membranous expression of Vimentin, which eventually promotes cancer metastasis. Moreover, the upregulation of TWIST2 was also related to the aberrant expression of E-cadherin and the increased expression of Vimentin, which were reported as important indicators of epithelial-mesenchymal transition (EMT).
DISCUSSION: The data suggested that co-expression of TWIST2/Vimentin was an independent prognostic indicator for both overall survival and disease-free survival by multivariate Cox proportional hazards model. TWIST2 regulates EMT by depriving the epithelial cell phenotype of E-cadherin and endowing the mesenchymal cell phenotype with Vimentin, which may be involved in the progression and prognosis of ovarian cancer, and TWIST2/Vimentin co-expression might be a novel indicator with prognostic potential in EOC patients.

Ma X, Hui Y, Lin L, et al.
Possible relevance of tumor-related genes mutation to malignant transformation of endometriosis.
Eur J Gynaecol Oncol. 2016; 37(1):89-94 [PubMed] Related Publications
OBJECTIVE: Despite studies have suggested that endometriosis has malignant potential, the molecular mechanism underlying the malignant transformation of endometriosis is poorly understood so far. Endometriosis-associated ovarian cancer (EAOC) or ovarian cancer arising from endometriosis (OCEM) may provide an ideal model for genetic studies. To investigate the genetic alterations during transformation of ovarian endometriosis into cancer, the authors analysed mutations of tumour-related genes (PTEN and p53) in EAOC cases (n=23, group 1), including 19 cases which were detected co-existence of endometriosis and cancer and four cases which fulfilled the histological criteria in malignant transformation of endometriosis (OCEMs), and in atypical hyperplasia ovarian endometriosis (aEMs) (n = 10, group 2), as well as in solitary ovarian endometriosis (EMs) (n = 20, group 3), simultaneously, to study the correlation of the two genes in the development and progression of the ovarian endometriosis malignancy.
MATERIALS AND METHODS: Each paraffin block was sliced into serial ten-µm-thick sections. Extracted DNA was amplified by nested PCR. Mutations of PTEN and p53 were examined by bidirectional DNA sequencing.
RESULTS: It was acknowledged by experiments that the PTEN and p53 mutation frequency in EAOCs were significantly higher than that in aEMs and EMs. There was significant difference to compare EAOCs with EMs (p < 0.01, p < 0.05), and converse to compare with aEMs (p > 0.05), respectively. No definite involvement between the frequency of PTEN and p53 mutations in EAOCs and age difference, histological type, clinical stage, pathological grade, and whether accompanied by metastasis (p > 0.05); however, a decreasing trend of PTEN mutation with the increased age, decreased clinical stage and pathological grade, and when accompanied by metastasis was detected. Adversely, an increasing trend of p53 mutation was represented. In EAOCs group, the authors detected eight PTEN and four p53 mutation events, respectively. Moreover, one case occurred PTEN and p53 mutation simultaneously. With 23 EAOCs, two cases which fulfilled the histological criteria in malignant transformation of endometriosis, which may be a specific entity distinct from non-endometriosis-associated ovarian cancer, the authors named them the OCEMs, occurred PTEN or p53 mutation, respectively.
CONCLUSION: The present study suggested that the mutation and functional incapacitation of certain tumor-related genes may be involved in malignant transformation of endometriosis. PTEN mutation is the pristine event, but p53 mutation is the late.

Kanis MJ, Kolev V, Getrajdman J, et al.
Carcinosarcoma of the ovary: a single institution experience and review of the literature.
Eur J Gynaecol Oncol. 2016; 37(1):75-9 [PubMed] Related Publications
PURPOSE: To evaluate the management and outcome in patients with advanced stage primary carcinosarcoma (CS) of the ovary in a single institution.
MATERIALS AND METHODS: The authors performed a retrospective analysis of all patients treated for CS of the ovary between 1994 and 2011. The medical records, operative reports and pathology records were abstracted for baseline characteristics, surgical staging, degree of cytoreduction and chemotherapy regimens used. Standard statistical methods for analysis of the data were used.
RESULTS: A total of 33 patients with ovarian CS were identified. Of these, 28 records were available for analysis. One patient was Stage I (3.5%), two were Stage II (11.1%), 20 were Stage III (71.4%), and five (17.9%) were Stage IV. The early stage (Stage I and II) patients were excluded from analysis. Of the 25 advanced stage (III and IV) patients, 21 (84.0%) were optimally cytoreduced to a residual disease of < one cm and four (16.0%) were suboptimally cytoreduced. The median progression free survival (PFS) and overall survival (OS) were ten and 21 months, respectively, for advanced stages. Twenty-one (75%) patients received adjuvant chemotherapy and 62% (13 of 21) of treated patients received paclitaxel/carboplatin (T/C) as first-line chemotherapy. The median PFS and OS were 15.6 and 31.7 months, respectively, for those treated with T/C. There was no.difference in PFS (p = 0.42) and OS (p = 0.91) between the patients who received T/C vs. other chemotherapy regimens as a first-line adjuvant chemotherapy. Patients with optimal cytoreduction had an improved PFS compared to those with suboptimal cytoreduction (ten vs. four monthsp = 0.015); however, there was no difference in OS (21 vs. 13 p = 0.117). The two-year OS was 48.0%. In the preset study, PFS was improved in patients who were optimally cytoreduced at the time of diagnosis.
CONCLUSION: T/C is an active regimen in the treatment of ovarian CS and has the potential to be the backbone for addition of biologic targeted therapies in the future. For advanced ovarian CS the authors recommend optimal cytoreductive surgery followed by T/C chemotherapy.

Nieuwenhuyzen-de Boer GM, Gerestein CG, Eijkemans MJ, et al.
Nomogram for 30-day morbidity after primary cytoreductive surgery for advanced stage ovarian cancer.
Eur J Gynaecol Oncol. 2016; 37(1):63-8 [PubMed] Related Publications
PURPOSE OF INVESTIGATION: Extensive surgical procedures to achieve maximal cytoreduction in patients with advanced stage epithelial ovarian cancer (EOC) are inevitably associated with postoperative morbidity and mortality. This study aimed to identify preoperative predictors of 30-day morbidity after primary cytoreductive surgery for advanced stage EOC and to develop a nomogram for individual risk assessment.
MATERIALS AND METHODS: Patients in The Netherlands who underwent primary cytoreductive surgery for advanced stage EOC between January 2004 and December 2007. All peri- and postoperative complications within 30 days after surgery were registered and classified. To investigate predictors of 30-day morbidity, a Cox proportional hazard model with backward stepwise elimination was utilized. The identified predictors were entered into a nomogram. The main outcome was to identify parameters that predict operative risk.
RESULTS: 293 patients entered the study protocol. Optimal cytoreduction was achieved in 136 (46%) patients. Thirty-day morbidity was seen in 99 (34%) patients. Morbidity could be predicted by age (p = 0.033; OR 1.024), preoperative hemoglobin (p = 0.194; OR 0.843), and WHO performance status (p = 0.015; OR 1.821) with a optimism-corrected c-statistic of 0.62. Determinants co-morbidity status, serum CA125 level, platelet count, and presence of ascites were comparable in both groups.
CONCLUSIONS: Thirty-day morbidity after primary cytoreductive surgery for advanced stage EOC could be predicted by age, hemoglobin, and WHO performance status. The generated nomogram could be valuable for predicting operative risk in the individual patient.

Santotoribio JD, Garcia-de la Torre A, Cañavate-Solano C, et al.
Cancer antigens 19.9 and 125 as tumor markers in patients with mucinous ovarian tumors.
Eur J Gynaecol Oncol. 2016; 37(1):26-9 [PubMed] Related Publications
PURPOSE OF INVESTIGATION: To determine the accuracy of carcinoembryonic antigen (CEA), cancer antigen (CA) 15.3, CA 19.9, and CA 125 for diagnosis of mucinous ovarian cancer (MOC).
MATERIALS AND METHODS: Samples were collected preoperatively from patients with mucinous ovarian tumor. The following variables were analysed: CEA, CA 15.3, CA 19.9, and CA 125. After surgery, histology and stage were determined according to FIGO-classification. Patients were classified into two groups according to the diagnosis of ovarian biopsy: NOT MOC and MOC.
RESULTS: The authors studied 94 patients with ages between 15 and 80 years (median = 43). Eighty-two patients were NOT MOC (68 mucinous ovarian cystadenomas and 14 mucinous borderline ovarian tumors) and 12 were MOC. All MOC patients were in FIGO Stages I or II. No statistically significant differences were found between MOC and NOT MOC patients according to CEA and CA 15.3 (p > 0.05). All MOC patients had abnormal serum CA 19.9 and/or CA 125 levels. Using CA 19.9 and CA 125, we performed a linear regression formula CA 19.9+125 = 0.00102 x CA 19.9 + 0.00057 x CA 125. AUCs values were 0.862 (p = 0.0002), 0.829 (p = 0.0021), and 0.911 (p = 0.0001) for CA 19.9, CA 125, and CA 19.9 + 125, respectively. CA 19.9 + 125 exhibited 95.1% specificity and 66.7% sensitivity, increased by 16.7% sensitivity compared with using only CA 19.9 or CA 125.
CONCLUSIONS: Preoperative CA 19.9 and CA 125 levels showed high diagnosis efficacy to predict whether a mucinous ovarian tumour is benign or malignant. Using both markers simultaneously increases the sensitivity for diagnosis of MOC.

Bonilla-Musoles F, Cadete C, Raga F, et al.
HDLive ultrasound images of ovarian dermoid cysts: diagnostic accuracy.
Clin Exp Obstet Gynecol. 2016; 43(1):16-24 [PubMed] Related Publications
OBJECTIVE: To demonstrate that the use of 3D/4D HDLive increases the image quality in the diagnosis of benign cystic ovarian teratomas.
MATERIALS AND METHODS: 3D/HDLive ultrasound (US) was used in 31 cases of suspected ovarian cystic teratoma using vaginal 2D US. The following pathognomonic images of mature cystic teratomas were considered for diagnosis: 1) a cystic, unilocular lesion with a densely echogenic tubercle (Rokitansky nodule); 2) a diffuse or partially echogenic mass usually demonstrating sound attenuation; 3) fluid-fluid/fat-fluid levels; 4) dermoid mesh with hyperechogenic calcifications indicating the presence of bone, teeth, or other ectodermally-derived structure; 5) multiple mobile spherical structures (fat globules).
RESULTS: Dermoids present a wide spectrum of images depending on the predominant tissue type. In the vast majority of cases there are dense echogenic structures that correspond to complex masses of fatty tissue, sebum, hair, epithelial remnants, along with cartilage or bone. If we catalogue all the images together, the pathognomonic of dermoid are: 1) cystic or solid cystic lesions with a Rokitansky nodule, with bone, teeth or cartilage (six cases, 22.2%); 2) a solid mass with or without attenuation that corresponds with pure sebum (five cases, 18.5%); 3) a diffuse mass with fine bands that correspond with hair inside sebum (four cases, 12.9%) and that may form meshes or plugs corresponding with a mixture of fat, sebum, and hair (three cases, 11.5%).
CONCLUSIONS: HDLive U.S. provides some images of exceptional quality that enhance the definition of the structures of these tumors (fat, hair, cartilage, bone, etc.) compared to 2D/3D/4D.

Appel SJ, Cleiment RJ
Identifying Women at Risk for Hereditary Breast and Ovarian Cancer Syndrome Utilizing Breast Care Nurse Navigation at Mammography and Imaging Centers.
J Natl Black Nurses Assoc. 2015; 26(2):17-26 [PubMed] Related Publications
Approximately 5-10% of breast cancer cases appear in families at a higher rate and at an earlier onset than in the average population. Two known gene defects, BRCA1 and BRCA2, account for the majority of these hereditary related breast cancers. Additionally, BRCA1 and BRCA2 are related to the Hereditary Breast and Ovarian Cancer syndrome (HBOC), where risk for other related cancers are increased. Various health-care professional organizations provide guidelines that speak to the need for conducting risk assessments, but little research has been conducted focusing on the initial screening for this syndrome. This quality improvement project attempts to determine if Nurse Navigators can effectively perform the initial education and screening for HBOC syndrome within a mammography and women's breast imaging setting using a simplified patient history tool. E. M. Rodgers' Diffusion of Innovation model, a map of how new ideas and programs have become adopted and accepted, guided this project's development and implementation. Over the course of 8 weeks, 1,420 women seeking service at 3 mammography and imaging sites were given a new risk assessment tool for HBOC. Additionally, the use of Nurse Navigation to identify women who may be at risk for HBOC was implemented. Two populations seeking service at the study sites were evaluated: (1) women obtaining breast screening/imaging services and (2) women receiving breast biopsy results. Patients identified as "at-risk" were defined by evidence-based practice guidelines from the National Comprehensive Cancer Network and were referred for further genetic evaluation by a genetic professional. During this initial implementation of the HBOC risk assessment program, low participation of screening/imaging patients requesting HBOC education and evaluation occurred (129 screening patients or 9%). High rates of positive biopsy patients (5 patients or 34.7%) werefound to be at risk for HBOC compared to similar studies. Identifying HBOC risk at the time of breast biopsy results gave the opportunity to impact the timing and kind of surgical management of patients at risk for this syndrome.The Commission on Cancer (CoC), an arm of the American College of Surgeons, provides practice guideline standards and accreditation for cancer programs. Patients will become more familiar with being assessed for HBOC and other hereditary cancers during their annual health-care visits and more identification of patients at riskfor HBOC should occur as new CoC 2012 standards requiring hereditary cancer risk assessments for a cancer program's certification are enacted.

Ledermann JA, Embleton AC, Raja F, et al.
Cediranib in patients with relapsed platinum-sensitive ovarian cancer (ICON6): a randomised, double-blind, placebo-controlled phase 3 trial.
Lancet. 2016; 387(10023):1066-74 [PubMed] Related Publications
BACKGROUND: Angiogenesis is a validated clinical target in advanced epithelial ovarian cancer. Cediranib is an oral antiangiogenic vascular endothelial growth factor receptor 1-3 inhibitor that has shown antitumour activity in recurrent ovarian cancer. We assessed efficacy and safety of cediranib in combination with platinum-based chemotherapy and as continued maintenance treatment in patients with first relapse of platinum-sensitive ovarian cancer.
METHODS: In this randomised, three-arm, double-blind, placebo-controlled phase 3 trial, we randomly assigned patients aged 18 years or older with relapsed platinum-sensitive ovarian cancer at 63 centres in Australia, Canada, New Zealand, Spain, and the UK. Participants received up to six cycles of platinum-based chemotherapy (once every 3 weeks) then entered a maintenance phase. Participants were randomly allocated (2:3:3), with five stratification factors and in alternating blocks, to receive placebo alongside chemotherapy and then placebo only maintenance (arm A; reference), cediranib 20 mg once-daily alongside chemotherapy then placebo only maintenance (arm B; concurrent), or cediranib 20 mg once-daily alongside chemotherapy then cediranib 20 mg once-daily maintenance (arm C; maintenance). Patients continued treatment to progression or excessive toxic effects. The primary efficacy endpoint was progression-free survival between arms A and C. Efficacy analysis was by intention to treat. Safety was assessed in all patients who received the allocated study drug. This trial is registered with ClinicalTrials.gov, number NCT00532194; the ISRCTN registry, number ISRCTN68510403; and ANZ Clinical Trials Registry, number ACTRN1261000016003.
FINDINGS: We randomly assigned 486 [corrected] women between Nov 13, 2007, and Dec 23, 2011; results presented are for 456 patients randomly assigned subsequent to the 30mg safety phase. During a median of 19·5 months (IQR 14-26) follow-up, 113 (96%) of 118 women assigned to arm A and 141 (86%) of 164 assigned to arm C had disease progression. Median progression-free survival was 11·0 months (95% CI 10·4-11·7) in arm C and 8·7 months (7·7-9·4) in arm A (hazard ratio 0·56, 0·44-0·72, p<0·0001). 156 (90%) of 174 patients in arm B had disease progression, and median progression-free survival was 9·9 months (95% CI 9·4-10·5). Diarrhoea, neutropenia, hypertension, and voice changes were significantly more common, during chemotherapy with cediranib, and diarrhoea, hypothyroidism and voice changes were more common during maintenance. Poor compliance with cediranib was noted during maintenance treatment with toxic effects being the most common cause for discontinuation.
INTERPRETATION: Cediranib, when given orally with chemotherapy and continued as maintenance, yielded a meaningful improvement [corrected] in progression-free survival in women with recurrent platinum-sensitive ovarian cancer, albeit with added toxic effects. The positive results in ICON6 could provide women with a new therapeutic option for recurrent ovarian cancer. Assessment of the secondary endpoint of overall survival will need longer follow-up.
FUNDING: Medical Research Council, Cancer Research UK, Canadian Cancer Society Research Institute, Cancer Australia, National Gynecological Cancer Centre, and AstraZeneca.

Stanculeanu DL, Mosoiu D, Mihnea A, et al.
Actualities in Ovarian Cancer in the Perspective of 2015 (ASCO and ECCO).
Chirurgia (Bucur). 2016 Jan-Feb; 111(1):9-11 [PubMed] Related Publications
Ovarian cancer represents the 4-th reason of cancer related death in women, the majority of patients being diagnosed in advanced stages of the disease, (III-IV). The loco-regional advanced ovarian cancer should be considered a chronic disease, with multiple evolutionary relapses and where the adjuvant treatment is mandatory.The treatment of the disease is multidisciplinary and the oncologist is the centerpiece.

Postmenopausal hormone replacement therapy: ovarian cancer.
Prescrire Int. 2016; 25(167):16 [PubMed] Related Publications
About 1 additional ovarian cancer per 1000 women exposed to post- menopausal hormone replacement therapy for 5 years.

Bornstein E, Jimeno A
Olaparib for the treatment of ovarian cancer.
Drugs Today (Barc). 2016; 52(1):17-28 [PubMed] Related Publications
Olaparib, an oral poly(ADP-ribose) polymerase (PARP) inhibitor, is the first FDA-approved drug in its class for patients with ovarian cancer, specifically in a subset of patients with BRCA mutations and prior chemotherapy treatments. PARP inhibitors have had other implications in different solid tumor types including breast, gastric and pancreatic malignancies. In light of the recent FDA approval of olaparib for the treatment of ovarian cancer, this article aims to outline the mechanisms and implications of the drug. With a favorable adverse event profile and improved outcomes, including progression-free survival, olaparib has demonstrated augmentation to therapeutic options in the treatment of ovarian cancer.

Chan JK, Brady MF, Penson RT, et al.
Weekly vs. Every-3-Week Paclitaxel and Carboplatin for Ovarian Cancer.
N Engl J Med. 2016; 374(8):738-48 [PubMed] Related Publications
BACKGROUND: A dose-dense weekly schedule of paclitaxel (resulting in a greater frequency of drug delivery) plus carboplatin every 3 weeks or the addition of bevacizumab to paclitaxel and carboplatin administered every 3 weeks has shown efficacy in ovarian cancer. We proposed to determine whether dose-dense weekly paclitaxel and carboplatin would prolong progression-free survival as compared with paclitaxel and carboplatin administered every 3 weeks among patients receiving and those not receiving bevacizumab.
METHODS: We prospectively stratified patients according to whether they elected to receive bevacizumab and then randomly assigned them to receive either paclitaxel, administered intravenously at a dose of 175 mg per square meter of body-surface area every 3 weeks, plus carboplatin (dose equivalent to an area under the curve [AUC] of 6) for six cycles or paclitaxel, administered weekly at a dose of 80 mg per square meter, plus carboplatin (AUC, 6) for six cycles. The primary end point was progression-free survival.
RESULTS: A total of 692 patients were enrolled, 84% of whom opted to receive bevacizumab. In the intention-to-treat analysis, weekly paclitaxel was not associated with longer progression-free survival than paclitaxel administered every 3 weeks (14.7 months and 14.0 months, respectively; hazard ratio for disease progression or death, 0.89; 95% confidence interval [CI], 0.74 to 1.06; P=0.18). Among patients who did not receive bevacizumab, weekly paclitaxel was associated with progression-free survival that was 3.9 months longer than that observed with paclitaxel administered every 3 weeks (14.2 vs. 10.3 months; hazard ratio, 0.62; 95% CI, 0.40 to 0.95; P=0.03). However, among patients who received bevacizumab, weekly paclitaxel did not significantly prolong progression-free survival, as compared with paclitaxel administered every 3 weeks (14.9 months and 14.7 months, respectively; hazard ratio, 0.99; 95% CI, 0.83 to 1.20; P=0.60). A test for interaction that assessed homogeneity of the treatment effect showed a significant difference between treatment with bevacizumab and without bevacizumab (P=0.047). Patients who received weekly paclitaxel had a higher rate of grade 3 or 4 anemia than did those who received paclitaxel every 3 weeks (36% vs. 16%), as well as a higher rate of grade 2 to 4 sensory neuropathy (26% vs. 18%); however, they had a lower rate of grade 3 or 4 neutropenia (72% vs. 83%).
CONCLUSIONS: Overall, weekly paclitaxel, as compared with paclitaxel administered every 3 weeks, did not prolong progression-free survival among patients with ovarian cancer. (Funded by the National Cancer Institute and Genentech; GOG-0262 ClinicalTrials.gov number, NCT01167712.).

Ratnavelu ND, Brown AP, Mallett S, et al.
Intraoperative frozen section analysis for the diagnosis of early stage ovarian cancer in suspicious pelvic masses.
Cochrane Database Syst Rev. 2016; 3:CD010360 [PubMed] Related Publications
BACKGROUND: Women with suspected early-stage ovarian cancer need surgical staging which involves taking samples from areas within the abdominal cavity and retroperitoneal lymph nodes in order to inform further treatment. One potential strategy is to surgically stage all women with suspicious ovarian masses, without any histological information during surgery. This avoids incomplete staging, but puts more women at risk of potential surgical over-treatment.A second strategy is to perform a two-stage procedure to remove the pelvic mass and subject it to paraffin sectioning, which involves formal tissue fixing with formalin and paraffin embedding, prior to ultrathin sectioning and multiple site sampling of the tumour. Surgeons may then base further surgical staging on this histology, reducing the rate of over-treatment, but conferring additional surgical and anaesthetic morbidity.A third strategy is to perform a rapid histological analysis on the ovarian mass during surgery, known as 'frozen section'. Tissues are snap frozen to allow fine tissue sections to be cut and basic histochemical staining to be performed. Surgeons can perform or avoid the full surgical staging procedure depending on the results. However, this is a relatively crude test compared to paraffin sections, which take many hours to perform. With frozen section there is therefore a risk of misdiagnosing malignancy and understaging women subsequently found to have a presumed early-stage malignancy (false negative), or overstaging women without a malignancy (false positive). Therefore it is important to evaluate the accuracy and usefulness of adding frozen section to the clinical decision-making process.
OBJECTIVES: To assess the diagnostic test accuracy of frozen section (index test) to diagnose histopathological ovarian cancer in women with suspicious pelvic masses as verified by paraffin section (reference standard).
SEARCH METHODS: We searched MEDLINE (January 1946 to January 2015), EMBASE (January 1980 to January 2015) and relevant Cochrane registers.
SELECTION CRITERIA: Studies that used frozen section for intraoperative diagnosis of ovarian masses suspicious of malignancy, provided there was sufficient data to construct 2 x 2 tables. We excluded articles without an available English translation.
DATA COLLECTION AND ANALYSIS: Authors independently assessed the methodological quality of included studies using the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2) domains: patient selection, index test, reference standard, flow and timing. Data extraction converted 3 x 3 tables of per patient results presented in articles into 2 x 2 tables, for two index test thresholds.
MAIN RESULTS: All studies were retrospective, and the majority reported consecutive sampling of cases. Sensitivity and specificity results were available from 38 studies involving 11,181 participants (3200 with invasive cancer, 1055 with borderline tumours and 6926 with benign tumours, determined by paraffin section as the reference standard). The median prevalence of malignancy was 29% (interquartile range (IQR) 23% to 36%, range 11% to 63%). We assessed test performance using two thresholds for the frozen section test. Firstly, we used a test threshold for frozen sections, defining positive test results as invasive cancer and negative test results as borderline and benign tumours. The average sensitivity was 90.0% (95% confidence interval (CI) 87.6% to 92.0%; with most studies typically reporting range of 71% to 100%), and average specificity was 99.5% (95% CI 99.2% to 99.7%; range 96% to 100%).Similarly, we analysed sensitivity and specificity using a second threshold for frozen section, where both invasive cancer and borderline tumours were considered test positive and benign cases were classified as negative. Average sensitivity was 96.5% (95% CI 95.5% to 97.3%; typical range 83% to 100%), and average specificity was 89.5% (95% CI 86.6% to 91.9%; typical range 58% to 99%).Results were available from the same 38 studies, including the subset of 3953 participants with a frozen section result of either borderline or invasive cancer, based on final diagnosis of malignancy. Studies with small numbers of disease-negative cases (borderline cases) had more variation in estimates of specificity. Average sensitivity was 94.0% (95% CI 92.0% to 95.5%; range 73% to 100%), and average specificity was 95.8% (95% CI 92.4% to 97.8%; typical range 81% to 100%).Our additional analyses showed that, if the frozen section showed a benign or invasive cancer, the final diagnosis would remain the same in, on average, 94% and 99% of cases, respectively.In cases where the frozen section diagnosis was a borderline tumour, on average 21% of the final diagnoses would turn out to be invasive cancer.In three studies, the same pathologist interpreted the index and reference standard tests, potentially causing bias. No studies reported blinding pathologists to index test results when reporting paraffin sections.In heterogeneity analyses, there were no statistically significant differences between studies with pathologists of different levels of expertise.
AUTHORS' CONCLUSIONS: In a hypothetical population of 1000 patients (290 with cancer and 80 with a borderline tumour), if a frozen section positive test result for invasive cancer alone was used to diagnose cancer, on average 261 women would have a correct diagnosis of a cancer, and 706 women would be correctly diagnosed without a cancer. However, 4 women would be incorrectly diagnosed with a cancer (false positive), and 29 with a cancer would be missed (false negative).If a frozen section result of either an invasive cancer or a borderline tumour was used as a positive test to diagnose cancer, on average 280 women would be correctly diagnosed with a cancer and 635 would be correctly diagnosed without. However, 75 women would be incorrectly diagnosed with a cancer and 10 women with a cancer would be missed.The largest discordance is within the reporting of frozen section borderline tumours. Investigation into factors leading to discordance within centres and standardisation of criteria for reporting borderline tumours may help improve accuracy. Some centres may choose to perform surgical staging in women with frozen section diagnosis of a borderline ovarian tumour to reduce the number of false positives. In their interpretation of this review, readers should evaluate results from studies most typical of their population of patients.

Akcay T, Yasar O, Kuseyri MA, et al.
Significance of serum c-erbB-2 oncoprotein, insulin-like growth factor-1 and vascular endothelial growth factor levels in ovarian cancer.
Bratisl Lek Listy. 2016; 117(3):156-60 [PubMed] Related Publications
OBJECTIVES: Our aim was to determine the predictive values of serum levels of several growth factors in ovarian cancer, including soluble c-erbB-2 oncoprotein, insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF).
BACKGROUND: Previous studies have shown that growth factors play an important role in carcinogenesis.
METHODS: Two groups were established. One of them was the malignant group which included 41 patients with ovarian carcinoma and the other was the control group that was made up of 28 healthy volunteers. Preoperative serum samples were obtained from the patients, and c-erbB-2, IGF-1 and VEGF levels were measured in these samples using ELISA. Serum CA-125 levels were also determined, by chemiluminescent microparticle immunoassay.
RESULTS: VEGF levels of the malignant group were significantly higher than those of the control group (p < 0.01). CA-125 levels were also significantly higher than the in control group (p < 0.001). Area under the ROC curve (AUC) was 0.982 for CA-125, 0.780 for VEGF, 0.603 for c-erbB-2, and 0.467 for IGF-1 in differentiating cancers from controls.
CONCLUSION: Serum VEGF levels might be a predictor for diagnosis in ovarian cancer patients, while serum c-erbB-2 and IGF-1 levels do not have a clinical significance in terms of ovarian cancer (Tab. 1, Fig. 1, Ref. 46).

Stemberger-Papić S, Vrdoljak-Mozetic D, Ostojić DV, et al.
Expression of CD133 and CD117 in 64 Serous Ovarian Cancer Cases.
Coll Antropol. 2015; 39(3):745-53 [PubMed] Related Publications
The cancer stem cells (CSCs) represent a minority of tumor cells that are able to proliferate and self-renew and might be responsible for tumor initiation and maintenance. The CD133 and CD117 are the most commonly used markers for the putative CSCs, especially for the ovarian CSCs, but its clinical significance remains uncertain. The aim of this study was to compare the immunohistochemical expression of CD133 and CD117 in 64 primary ovarian high grade serous carcinoma and peritoneal metastasis, and to examine their potential clinical role. CD133 expression was mainly seen in the apical/endoluminal cell surface of tumor cells and was found in 61% of the carcinoma samples and 41% of the metastasis. The median of CD133 positive cells in tumors was 1 (0.1-7)%, and in metastases was 0.6 (0.1-6)%. CD117 expression appeared as a cytoplasmic and/or membranous stain and was found in 81% of the carcinoma samples and 77% of the metastasis. The median of CD117 positive cells in tumors was 1 (0.1-8)%, and in metastases was 0.1 (0.1-7)%. Multivariate analysis has shown that patients with high CD133 expression in tumor cells have significantly shorter disease free survival and overall survival (p=0.025 and p=0.014, respectively). Patients with high CD117 expression in tumor cells have significantly shorter disease free survival (p=0.031). Cox's proportional hazards model identified expression of CD133 protein in tumor as an independent prognostic factor. Our study indicates that the immunohistochemical assessment of CD133 and CD117 expression may have potential clinical value in predicting disease progression and prognosis in the high grade serous ovarian cancer. CD133 proved to be an independent prognostic factor in the high grade serous ovarian cancer patients.

Ramalingam P
Morphologic, Immunophenotypic, and Molecular Features of Epithelial Ovarian Cancer.
Oncology (Williston Park). 2016; 30(2):166-76 [PubMed] Related Publications
Epithelial ovarian cancer comprises a heterogeneous group of tumors. The four most common subtypes are serous, endometrioid, clear cell, and mucinous carcinoma. Less common are transitional cell tumors, including transitional cell carcinoma and malignant Brenner tumor. While in the past these subtypes were grouped together and designated as epithelial ovarian tumors, these tumor types are now known to be separate entities with distinct clinical and biologic behaviors. From a therapeutic standpoint, current regimens employ standard chemotherapy based on stage and grade rather than histotype. However, this landscape may change in the era of personalized therapy, given that most subtypes (with the exception of high-grade serous carcinoma) are relatively resistant to chemotherapy. It is now well-accepted that high-grade and low-grade serous carcinomas represent distinct entities rather than a spectrum of the same tumor type. While they are similar in that patients present with advanced-stage disease, their histologic and molecular features are entirely different. High-grade serous carcinoma is associated with TP53 mutations, whereas low-grade serous carcinomas are associated with BRAF and KRAS mutations. Endometrioid and clear cell carcinomas typically present as early-stage disease and are frequently associated with endometriosis. Mucinous carcinomas typically present as large unilateral masses and often show areas of mucinous cystadenoma and mucinous borderline tumor. It must be emphasized that primary mucinous carcinomas are uncommon tumors, and metastasis from other sites such as the appendix, colon, stomach, and pancreaticobiliary tract must always be considered in the differential diagnosis. Lastly, transitional cell tumors of the ovary, specifically malignant Brenner tumors, are quite uncommon. High-grade serous carcinoma often has a transitional cell pattern, and adequate sampling in most cases shows more typical areas of serous carcinoma. Immunohistochemical markers are routinely employed in the diagnosis of epithelial ovarian carcinomas. However, molecular testing of these tumors, unlike in endometrial carcinoma, is not routinely used in clinical practice.

Li S, Liu Z, Dong C, et al.
Growing Teratoma Syndrome Secondary to Ovarian Giant Immature Teratoma in an Adolescent Girl: A Case Report and Literature Review.
Medicine (Baltimore). 2016; 95(7):e2647 [PubMed] Related Publications
Growing teratoma syndrome (GTS) is a rare clinical entity first described by Logothetis et al in 1982. Although it is unusual for GTS to be located in the ovary, this report is of a case of an adolescent girl who underwent a complete surgical resection of the mass. Histopathology confirmed only an immature teratoma had originated from the ovary and so she received adjuvant chemotherapy with blemycin, etopside, and cisplatin over 4 cycles. Results from an abdominal enhanced CT (computed tomography) 9 years later revealed a giant mass had compressed adjacent tissues and organs. Laparotomy was performed and a postoperative histopathology showed the presence of a mature teratoma, and so the diagnosis of ovarian GTS was made. One hundred one cases of ovarian GTS from English literature published between 1977 and 2015 were collected and respectively analyzed in large samples for the first time. The median age of diagnosis with primary immature teratoma was 22 years (range 4-48 years, n = 56). GTS originating from the right ovary accounted for 57% (27/47, n = 47) whereas the left contained 43% (20/47, n = 47). Median primary tumor size was 18.7 cm (range 6-45 cm, n = 28) and median subsequent tumor size was 8.6 cm (range 1-25 cm, n = 25). From the primary treatment to the diagnosis of ovarian GTS, median tumor growth speed was 0.94 cm/month (range 0.3-4.3 cm/month, n = 21). Median time interval was 26.6 months (range 1-264 months, n = 41). According to these findings, 5 patients did have a pregnancy during the time interval between primary disease and GTS, making our patient the first case of having a pregnancy following the diagnosis of ovarian GTS. Because of its high recurrence and insensitiveness to chemotherapy, complete surgical resection is the preferred treatment and fertility-sparing surgery should be considered for women of child-bearing age. Anyhow GTS of the ovary has an excellent prognosis. Patients with GTS had no evidence of recurrence or were found to be disease free during a 40.3-month (range 1-216 months, n = 48) median follow-up. Moreover, regular follow-ups with imaging and serum tumor markers are important and must not be neglected.

Altman AD, Bentley JR, Rittenberg PV, Murray SK
Luteinized Thecomas ("Thecomatosis") with Sclerosing Peritonitis (LTSP): Report of 2 Cases and Review of an Enigmatic Syndrome Associated with a Peritoneal Proliferation of Specialized (vimentin+/keratin+/CD34+) Submesothelial Fibroblasts.
J Obstet Gynaecol Can. 2016; 38(1):41-50 [PubMed] Related Publications
OBJECTIVE: To present the clinicopathologic features of two cases of luteinized thecomas with sclerosing peritonitis (LTSP), characterize the cellular proliferation in the sclerosing peritonitis (SP), and review the literature.
METHODS: The clinical, laboratory, and imaging data, operative findings, and pathology materials were reviewed and summarized. Samples of the SP were stained with keratin AE1/AE3, vimentin, CD34, calretinin, smooth muscle actin, ER/PR, CD10 and desmin. A literature search was performed to identify cases of LTSP for comparison.
RESULTS: A total of 43 cases of LTSP syndrome were identified. Frequent clinical features included ascites (74%), abdominal pain (35%), bowel obstruction (42%), and bilateral masses (84%). We isolated a distinct form of ovarian luteinized thecoma (thecomatosis) and peculiar sclerosing peritonitis (SP). IHC analysis shows a proliferation of specialized (vimentin+/keratin+/CD34+) submesothelial fibroblasts (SMF) with patchy expression of calretinin and hormone receptors.
CONCLUSION: LTSP syndrome is a rare entity presenting with abdominal pain, bowel obstruction, ascites, ovarian masses, and SP containing specialized (vimentin+/keratin+/CD34+) SMF. LTSP must be distinguished from abdominal cocoon, isolated SP, Meigs' syndrome, and peritoneal carcinomatosis. The importance of recognizing the diagnosis is stressed, as failure to manage this disease conservatively leads to significant morbidity and mortality. The SP and bowel obstruction may persist for months, even after resection of the tumours, resulting in extended medical therapy. Based on the immunophenotype of the peritoneal lesions, strategies to elucidate 'targeted' pharmacologic agents that could inhibit the proliferation of specialized (vimentin+/keratin+/CD34+) SMF may be of benefit.

Wright JD, Tergas AI, Hou JY, et al.
Trends in Periodic Surveillance Testing for Early-Stage Uterine Cancer Survivors.
Obstet Gynecol. 2016; 127(3):449-58 [PubMed] Article available free on PMC after 01/03/2017 Related Publications
OBJECTIVE: To examine the use of periodic surveillance testing for early-stage endometrial cancer survivors.
METHODS: We performed a population-based analysis using the Surveillance, Epidemiology, and End Results-Medicare database, which was used to identify patients with stage I-II endometrioid endometrial cancer treated from 1992 to 2011. Three surveillance periods (7-18, 19-30, 31-42 months) after hysterectomy were examined. Use of vaginal cytology and imaging were quantified.
RESULTS: We identified 17,638 patients. From 1992 to 2011, the use of chest radiography decreased (46.3-34.2%) during the first surveillance period, whereas imaging with chest computed tomography (CT) (0.9-12.6%), abdominopelvic CT (11.7-24.8%), and positron emission tomography (0-2.9%) increased (P<.001 for all). The use of cytology increased from 68.5% in 1992 to 72.3% in 2007 and then decreased to 66.9% in 2011 (P=.02). The mean number of cytologic samples obtained per patient increased from 1.3 in 1992 to 1.6 in 2008 and then declined to 1.3 in 2011, whereas the mean per patient number of chest CTs (0.02-0.2), abdominopelvic CTs (0.2-0.4), and positron emission tomographies (0-0.03) rose from 1992 to 2011. In 2011, 49.3% underwent radiologic surveillance 7-18 months after diagnosis, whereas 11.9% underwent two or more radiologic assessments in combination with cytology. These findings were similar for surveillance periods 2 and 3.
CONCLUSION: The use of chest radiography has decreased and use of cytology has started to decline. However, the use of more costly imaging modalities is increasing despite a lack of evidence for the efficacy of these tests for early-stage endometrial cancer survivors.

Karamanou M, Tsoucalas G, Laios K, et al.
Uterine cancer in the writings of Byzantine physicians.
J BUON. 2015 Nov-Dec; 20(6):1645-8 [PubMed] Related Publications
Byzantine physicians recognized uterine cancer as a distinct disease and tried to suggest a therapeutic approach. The work of Oribasius, Aetius of Amida, Paul of Aegina, Cleopatra Metrodora and Theophanes Nonnus reflects the Hippocratic-Galenic scientific ideas as well as their own concept on this malignancy. According to their writings uterine cancer was considered an incurable disease and its treatment was based mainly on palliative herbal drugs.

Gao Y, Rankin GO, Tu Y, Chen YC
Inhibitory Effects of the Four Main Theaflavin Derivatives Found in Black Tea on Ovarian Cancer Cells.
Anticancer Res. 2016; 36(2):643-51 [PubMed] Article available free on PMC after 01/02/2017 Related Publications
BACKGROUND: Some polyphenols induce apoptosis and inhibit angiogenesis. Consumption of black tea, rich in polyphenols, has been found to reduce ovarian cancer risk. Theaflavin (TF1), theaflavin-3-gallate (TF2a), theaflavin-3'-gallate (TF2b) and theaflavin-3, 3'-digallate (TF3) are four main theaflavin derivatives found in black tea.
MATERIALS AND METHODS: Cell proliferation assay, Hoechst 33342 staining assay, Caspase-Glo Assay, western blot, human umbilical vein endothelial cell tube formation assay and vascular endothelial growth factor (VEGF) enzyme-linked immunosorbent assay were performed.
RESULTS: All four theaflavin derivatives reduced viability of ovarian cancer cells at lower concentrations than with normal ovarian cells. TF1 mainly mediated apoptosis via the intrinsic pathway, while the others via the intrinsic and extrinsic pathways. TF1 inhibited tube formation via reducing VEGF secretion in a hypoxia-inducible factor 1α-independent manner, while the others in a HIF1α-dependent way.
CONCLUSION: All four theaflavin derivatives inhibited ovarian cancer cells. Some of the effects and mechanisms of TF1 are different from those of the other three theaflavin derivatives.

Yan H, Guo BY, Zhang S
Cancer-associated fibroblasts attenuate Cisplatin-induced apoptosis in ovarian cancer cells by promoting STAT3 signaling.
Biochem Biophys Res Commun. 2016; 470(4):947-54 [PubMed] Related Publications
One of the main reasons for treatment failure in ovarian cancer is acquired drug resistance. Cancer associated fibroblasts (CAFs) are known to enhance chemoresistance in many human tumors. However, its contributions to chemoresistance acquisition in ovarian cancer are not well understood. Here, we provide the first evidence that the conditioned medium of CAFs (CAFs-CM) could attenuate the sensitivity to Cisplatin in A2780 and ES2 ovarian cancer cells and protect them from Cisplatin-induced apoptosis. We found the expression level of two anti-apoptotic proteins, Bcl-2 and Survivin, as well as their upstream controller p-STAT3 were significantly increased when ovarian cancer cells were exposed to CAFs-CM. Furthermore, inhibition of STAT3 signaling with Cryptotanshinone could down-regulate the expression of Bcl-2 and Survivin, thus weaken the post-target resistance to Cispaltin mediating by CAFs-CM in ovarian cancer cells. In conclusion, our data suggested that CAFs could activate the anti-apoptotic STAT3 signaling, thereby decrease the Cisplatin-induced apoptosis and promote chemoresistance in ovarian cancer.

Yoshida A, Derchain SF, Pitta DR, et al.
Comparing the Copenhagen Index (CPH-I) and Risk of Ovarian Malignancy Algorithm (ROMA): Two equivalent ways to differentiate malignant from benign ovarian tumors before surgery?
Gynecol Oncol. 2016; 140(3):481-5 [PubMed] Related Publications
AIM: To evaluate the prediction of malignancy in women with pelvic masses using the Copenhagen Index (CPH-I) and Risk of Ovarian Malignancy Algorithm (ROMA).
PATIENTS AND METHODS: Three hundred eighty four women operated due to an ovarian mass were enrolled between January 2010 and June 2015. All patients had histopathological diagnosis, HE4 and CA125 measurement. CPH-I and ROMA were calculated and their performances compared in two distinct scenarios: 1) for the discrimination of benign ovarian disease from epithelial ovarian cancer (EOC), non-epithelial ovarian cancer, borderline ovarian tumors (BOT) and ovarian metastases, and 2) for the discrimination of benign disease from EOC. Receiver Operator Characteristics' Areas Under the Curves (AUC) were calculated for CPH-I and ROMA and compared.
RESULTS: Of the 384 women, 224 presented a benign ovarian tumor, 32 BOT, 87 EOC, 26 non-epithelial ovarian cancer, and 15 had ovarian metastases. The best AUCs were obtained for the discrimination of EOC from benign tumors. CPH-I performed slightly better than ROMA, and both approached 89% sensitivity and 85% specificity. When all malignant tumors (EOC, BOT, ovarian metastases and non-epithelial ovarian cancer - entire cohort) were included, the performance of CPH-I and ROMA declined to nearly 72%, although the specificity remained close to 85%.
CONCLUSION: CPH-I and ROMA performed similarly well for the discrimination of EOC from benign ovarian tumors. However, caution is necessary since, in practical situations, where all the histological possibilities for malignant ovarian tumors must be considered, the sensitivity of CPH-I and ROMA may not surpass 70%.

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