Macit Arvas

Prevalence of endometriosis in malignant epithelial ovary tumours

Abstract Objective : To determine the prevalence of ovarian endometriosis in malignant epithelial ovarian tumours. Study design : A retrospective analysis of 160 malignant and 23 borderline ovarian tumours during the period 1995–2001. Results : Fourteen (7.7%) of the tumours contained endometriosis. This affected 22% of the endometrioid and 10.8% of the mixed adenocarcinomas. The mean age of the ovarian endometriosis patients was 43±13 range 26–70 years. The incidence in borderline tumours 13% (3/23) was higher than that in ovarian cancer 6.9% (11/160) ( P >0.05). Eight (57%) of cases were classified as atypical and six (43%) as typical endometriosis. Nine cases were FIGO (International Federation of Gynaecology and Obstetrics) stage I and 5 stage III. Conclusions : Both malignant and borderline ovarian tumours are associated with ovarian endometriosis. In addition, atypical endometriosis was found associated with endometrioid and mixed epithelial ovarian tumours.

Comparison of total plasma lysophosphatidic acid and serum CA-125 as a tumor marker in the diagnosis and follow-up of patients with epithelial ovarian cancer

OBJECTIVE To evaluate the role of lysophosphatidic acid (LPA) as a tumor marker in diagnosis and follow-up of patients with epithelial ovarian cancer. METHODS Eighty-seven epithelial ovarian cancer patients, 74 benign ovarian tumor patients, and 50 healthy women were enrolled in the study. Twenty-nine of 87 epithelial ovarian cancer patients were followed up for 6 cycles of paclitaxel-carboplatin chemotherapy. CA-125 and total plasma LPA levels were measured preoperatively and before each chemotherapy cycle. RESULTS Preoperative total plasma LPA and serum CA-125 levels were significantly higher in patients with epithelial ovarian cancer compared to patients with benign ovarian tumors and healthy women. Cut-off value for LPA was determined as 1.3 µmol/L and sensitivity, specificity, positive predictive value and negative predictive value were 95%, 92%, 95% and 92%, respectively. Mean total plasma LPA level of 29 patients who received chemotherapy was 7.21±6.63 µmol/L preoperatively and 6.84±6.34 µmol/L, 6.34±5.92 µmol/L, 6.14±5.79 µmol/L, 5.86±5.68 µmol/L, 5.23±5.11 µmol/L and 5.21±5.32 µmol/L in measurements held just before the 1st, 2nd, 3rd, 4th, 5th and 6th chemotherapy cycles, respectively (ANOVA, p=0.832). Total plasma LPA levels decreased slightly with chemotherapy administration and there was a weak negative correlation (Spearman, r(s)=-0.151, p=0.034), compared to a significant negative correlation in CA-125 (Spearman, r(s)=-0.596, p<0.001). CONCLUSION LPA is a better biomarker for diagnosis of epithelial ovarian cancer compared to CA-125. However, measurement of total plasma LPA levels during chemotherapy administration have no superiority to the serum CA-125 levels.

Ultrasonographic appearance of endometrium in postmenopausal breast cancer patients receiving tamoxifen.

OBJECTIVES To assess the ultrasonographic appearance and associated pathological changes of the endometrium in postmenopausal breast cancer patients with tamoxifen therapy. STUDY DESIGN Forty-eight postmenopausal breast cancer patients receiving 20 mg/day tamoxifen for 6-84 months (mean 29) and 38 control breast cancer patients without any hormonal treatment were examined by transvaginal ultrasonography and endometrial biopsy. Any thickening of the endometrium with cystic formations or homogeneous endometrial thickening > 10 mm detected by ultrasonography was defined as abnormal endometrial appearance. Homogeneous endometrial thickening < 10 mm without cystic formations was accepted as normal. Statistical analysis was performed using the Students t-test and Mann-Whitney U test. RESULTS The two groups were similar in age and menopausal period. The patients on tamoxifen therapy had a thicker endometrium (8.6 +/- 6.6 mm) than the non-treated women (4.8 +/- 3.1 mm), which was found to be a statistically significant difference (P < 0.01). The sonographic evaluations showed abnormal endometrial appearance in 8 cases of tamoxifen treated women while the others revealed homogeneous thickness < 10 mm without cystic formations or a thin linear echo with or without fluid in the endometrial cavity. All 8 patients with cystic appearance had endometrial thickness > 10 mm. Only 1 patient had endometrial cancer on biopsy and no pathology was observed in the remaining 7 patients. In the control group, only 1 patient had abnormal ultrasonographic finding who had insufficient endometrial tissue on biopsy. CONCLUSIONS Tamoxifen can produce a sonographic image of the endometrium that resembles endometrial neoplasia. It is suggested that the discrepancy between the sonographic findings and histology may be the result of the stromal edema of the endometrium from tamoxifen treatment. Until more data are gathered, all postmenopausal breast cancer patients who are being treated with tamoxifen should have a periodic ultrasonographic examination and those presenting with a sonogram suggestive of endometrial pathology should undergo biopsy.

The magnitude of gonadotoxicity of chemotherapy drugs on ovarian follicles and granulosa cells varies depending upon the category of the drugs and the type of granulosa cells

STUDY QUESTION Do different chemotherapy drugs exert the same magnitude of cytotoxicity on dormant primordial follicles and the growing follicle fraction in the ovary in vivo and on mitotic non-luteinized and non-mitotic luteinized granulosa cells in vitro? SUMMARY ANSWER Cyclophosphamide (alkylating agent) and cisplatin (alkylating like) impacted both primordial and pre-antral/antral follicles and both mitotic and non-mitotic granulosa cells, whereas the anti-metabolite cancer drug gemcitabine was detrimental only to pre-antral/antral follicles and mitotic non-luteinized granulosa cells. WHAT IS KNOWN ALREADY It is already known that anti-metabolite cancer drugs are less detrimental to the ovary than alkylating and alkylating like agents, such as cyclophosphamide and cisplatin. This assumption is largely based on the results of clinical reports showing lower rates of amenorrhea in women receiving anti-metabolite agent-based regimens compared with those treated with the protocols containing an alkylating drug or a platinum compound. But a quantitative comparison of gonadotoxicity with a histomorphometric proof of evidence has not been available for many chemotherapy drugs. Therefore, we combined in this study in vivo and in vitro models of human and rat origin that allows a comparative analysis of the impact of different chemotherapy agents on the ovary and granulosa cells using real-time quantitative cell indices, histomorphometry, steroidogenesis assays, and DNA damage and cell death/viability markers. We also aimed to investigate if there is a difference between mitotic and non-mitotic granulosa cells in terms of their sensitivity to the cytotoxic actions of chemotherapy drugs with different mechanisms of action. This issue has not been addressed previously. STUDY DESIGN, SIZE, DURATION This translational research study involved in vivo analyses of ovaries in rats and in vitro analyses of granulosa cells of human and rat origin. PARTICIPANTS/MATERIALS, SETTING, METHODS For the in vivo assays, 54 4- to 6-week old Sprague-Dawley young female rats were randomly allocated into four groups of 13 to receive a single IP injection of: saline (control), gemcitabine (200 mg/kg), cisplatin (50 mg/kg) or cyclophosphamide (200 mg/kg). The animals were euthanized 72 h later. Follicle counts and serum AMH levels were compared between the groups. In vitro cytotoxicity studies were performed using mitotic non-luteinized rat (SIGC) and human (COV434, HGrC1) granulosa cells, and non-mitotic luteinized human (HLGC) granulosa cells. The cells were plated at a density of 5000 cells/well using DMEM-F12 culture media supplemented with 10% FBS. Chemotherapy agents were used at their therapeutic blood concentrations. The growth of mitotic granulosa cells was monitored real-time using xCelligence system. Live/dead cell and apoptosis assays were also carried out using intravital Yo-Pro-1 staining and cleaved caspase-3 expression, respectively. Estradiol (E2), progesterone (P) and anti-Mullerian hormone (AMH) levels were assayed with ELISA. MAIN RESULTS AND THE ROLE OF CHANCE Cyclophosphamide and cisplatin caused massive atresia of both primordials and growing follicles in the rat ovary whereas gemcitabine impacted pre-antral/antral follicles only. Cyclophosphamide and cisplatin induced apoptosis of both mitotic non-luteinized and non-mitotic luteinized granulosa cells in vitro. By contrast, cytotoxicity of gemcitabine was confined to mitotic non-luteinized granulosa cells. LIMITATIONS, REASONS FOR CAUTION This study tested only three chemotherapeutic agents. The experimental methodology described here could be applied to other drugs for detailed analysis of their ovarian cytotoxicity. WIDER IMPLICATIONS OF THE FINDINGS These findings indicate that in vivo and in vitro cytotoxic actions of chemotherapy drugs on the ovarian follicles and granulosa cells vary depending upon the their mechanism of action and the nature of the granulosa cells.

Radical versus conservative surgery for vulvar carcinoma

The comparison of the radical and conservative surgical approaches for vulvar carcinoma in relation to the rate of recurrence and complications.

A Turkish Gynecologic Oncology Group study of fertility-sparing treatment for early-stage endometrial cancer.

To analyze the results of fertility‐sparing treatment of early‐stage endometrial cancer (EC) in patients treated at Turkish gynecologic oncology centers, and to present a review of the literature.

Vascular endothelial growth factor in adnexal masses

Objectives: To determine cyst fluid and serum vascular endothelial growth factor (VEGF) concentrations in patients with ovarian masses and to investigate the efficiency of this modulator in the clinical management of cystic pelvic masses. Methods: Needle puncture for cyst fluid aspiration were performed on 88 cystic ovarian masses intraoperatively. Forty‐five patients with benign and 43 patients with malignant ovarian pathology were analyzed for cyst fluid and serum VEGF concentrations. Both cystic fluid and serum VEGF concentration were determined by enzyme‐linked immunosorbent assay (ELISA). Results: Cyst fluid VEGF levels of malignant cysts (40.65±17.69 ng/ml) were significantly higher than those of benign cysts (12.53±6.13 ng/ml; P<0.001). Similarly, higher serum VEGF concentrations were found in patients with malignant disease (0.72±0.17 ng/ml) compared with benign cysts (0.33±0.11 ng/ml; P<0.001). A statistically significant correlation was observed between cyst fluid and serum VEGF levels in both malignant and benign cysts. For serum VEGF, at a cut‐off value of 0.41 ng/ml; sensitivity, specificity, PPV, and NPV were 95%, 78%, 80% and 95%, respectively. No significant correlation between cyst fluid VEGF concentration and tumor stage or grade could be found. Conclusions: Significantly higher concentrations of VEGF are present in cyst fluid and serum of patients with malignant ovarian cysts compared with benign ovarian ones. There is no relation between VEGF and tumor stage or grade.

A strong prognostic variable in endometrial carcinoma

The purpose of this study was to determine the role of flow cytometric S‐phase fraction as a prognostic factor in patients with endometrial adenocarcinoma.

Synchronous Primary Cancers of the Endometrium and Ovary With the Same Histopathologic Type Versus Endometrial Cancer With Ovarian Metastasis: A Single Institution Review of 72 Cases.

Objective The purpose of this study was to evaluate the clinicopathological characteristics and survival outcomes of women with simultaneous endometrial and ovarian carcinomas having the same histopathologic type. Materials and Methods A review of medical records from 1997 to 2015 identified 72 patients with simultaneous carcinomas of the endometrium and ovary with the same histopathologic type. Patients with synchronous primary cancers of endometrium and ovary (SCEOs) were compared with patients with primary endometrial cancer with ovarian metastasis (ECOM). Clinical and pathological data were obtained from the patients’ medical records. Clinicopathological variables including categorical data were analyzed by &khgr;2 or Fisher exact test and continuous data by a Student t test. A Kaplan-Meier survival analysis was performed and compared by using the log-rank test. Results A univariate and multivariate analysis of 72 patients with SCEO with the same histopathologic type revealed that SCEO is an independent prognostic factor of 10-year overall survival. There were 31 patients in the SCEO group and 41 patients in the ECOM group. With a mean follow-up time of 68.2 months, the 10-year overall survival rates were 61.3% and 36.6% in SCEO and ECOM groups, respectively (P = 0.029). Age, menopausal status, stage of ovarian cancer, performing lymphadenectomy, grade of endometrial tumor, omental metastasis, and residual tumor were found to be significant risk factors for recurrence in the synchronous group. Conclusions The differentiation between SCEO and ECOM is of great clinical importance while our results showed a better prognosis for patients with SCEO compared with patients with ECOM. More aggressive therapeutic approaches may be considered for patients with SCEO who are older, postmenopausal, and/or have advanced grade of endometrial tumor, omental metastasis, and residual tumor. Lymphadenectomy should be performed in every patient with SCEO.

Serum levels of epidermal growth factor, transforming growth factor, and c-erbB2 in ovarian cancer.

Objective This study aimed to investigate serum levels of epidermal growth factor (EGF), transforming growth factor α (TGF-α), and c-erbB2 in patients with ovarian cancer. Materials and Methods In this retrospective cohort study, the study and control groups were composed of 43 women with a prediagnosis of ovarian cancer and 43 healthy women, respectively. Blood samples from all women were obtained and studied by enzyme-linked immunosorbent assay kits for EGF, TGF-α, and c-erbB2. After surgery of the study group, ovarian cancer was confirmed and compared with control group. Stage, grade, and histological types were defined after histopathologic examination, and subgroups were constructed and compared. Results Serum EGF, TGF-α, and c-erbB2 levels were significantly increased in study group compared with those in the control group (P < 0.001). There were no differences in serum levels of EGF, TGF-α, and c-erbB2 among all stages, grades, and histological types of ovarian cancer. If 47.90 pg/mL was selected as the cutoff value, EGF has an 80% sensitivity and a 65% specificity for detecting ovarian cancer. The cutoff value of 41,095.00 pg/mL for TGF-α has a 90% sensitivity and a 72% specificity for detecting ovarian cancer. The c-erbB2 level of 4.63 pg/mL as the cutoff value has an 83% sensitivity and a 76% specificity for predicting ovarian cancer. Conclusions Serum levels of EGF, TGF-α, and c-erbB2 may be used for diagnosing ovarian cancer.