Impact of cytoreductive surgery on survival of patients with low-grade serous ovarian carcinoma: A multicentric study of Turkish Society of Gynecologic Oncology (TRSGO-OvCa-001).

BACKGROUND AND OBJECTIVES: The aim of this study was to analyze the factors affecting recurrence-free (RFS) and overall survival (OS) rates of women diagnosed with low-grade serous ovarian cancer (LGSOC). METHODS: Databases from 13 participating centers in Turkey were searched retrospectively for women who had been treated for stage I-IV LGSOC between 1997 and 2018. RESULTS: Overall 191 eligible women were included. The median age at diagnosis was 49 years (range, 21-84 years). One hundred seventy-five (92%) patients underwent primary cytoreductive surgery. Complete and optimal cytoreduction was achieved in 148 (77.5%) and 33 (17.3%) patients, respectively. The median follow-up period was 44 months (range, 2-208 months). Multivariate analysis showed the presence of endometriosis (p = .012), lymphovascular space invasion (LVSI) (p = .022), any residual disease (p = .023), and the International Federation of Gynecology and Obstetrics (FIGO) stage II-IV disease (p = .045) were negatively correlated with RFS while the only presence of residual disease (p = .002) and FIGO stage II-IV disease (p = .003) significantly decreased OS. CONCLUSIONS: The maximal surgical effort is warranted for complete cytoreduction as achieving no residual disease is the single most important variable affecting the survival of patients with LGSOC. The prognostic role of LVSI and endometriosis should be evaluated by further studies as both of these parameters significantly affected RFS.

The relationship between hypertension and plasma allantoin, uric acid, xanthine oxidase activity and nitrite, and their predictive capacity in severe preeclampsia.

It is controversial that uric acid (UA) levels are related to the severity of hypertension in preeclampsia (PE). Our aim in this study was to determine whether UA, xanthine oxidase activity (XOA), allantoin and nitrite levels are related to arterial blood pressure (BP) in PE. We formed a control group (n = 20) and a PE group (n = 20) for the study. Their BPs and plasma UA, XOA, allantoin and nitrite levels were measured. The values from the control and PE pregnant women were assessed via a Wilcoxon matched-pairs test. A Pearson correlation test was also performed. In addition, the diagnostic value of these tests was evaluated via receiver operating characteristic (ROC) analysis. The BP, UA, XOA and allantoin levels in the PE patients were found to be higher when compared with those of the pregnant controls. The UA, XOA and allantoin levels showed high correlations with BP in cases of PE. However, there was no superiority among the correlations. No differences were observed between the groups in terms of nitrite levels and the relationship between nitrite and BP. UA, XOA and allantoin levels may be high due to placental cell death because of abnormal trophoblastic activity observed in PE. Moreover, the reactive oxygen products that are created during the genetic material degradation may explain how UA, XOA and allantoin levels are related to BP. According to ROC analysis, UA, XOA and allantoin assays are reliable predictors for the determination of PE.

Prognostic Significance of Retroperitoneal Lymphadenectomy, Preoperative Neutrophil Lymphocyte Ratio and Platelet Lymphocyte Ratio in Primary Fallopian Tube Carcinoma: A Multicenter Study.

PURPOSE: The purpose of this study is to evaluate the prognostic role of preoperative neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) and the need for para-aortic lymphadectomy in patients with primary fallopian tube carcinoma (PFTC). MATERIALS AND METHODS: Ninety-one patients with a diagnosis of PFTC were identified through the gynecologic oncology service database of six academic centers. Clinicopathological, surgical, and complete blood count data were collected. RESULTS: In univariate analysis, advanced stage, suboptimal surgery, and NLR > 2.7 were significant prognostic factors for progression-free survival, whereas in multivariate analysis, only advanced stage and suboptimal surgery were significant. In addition, in univariate analysis, cancer antigen 125 ≥ 35 U/mL, ascites, advanced stage, suboptimal surgery, NLR > 2.7, PLR > 233.3, platelet count ≥ 400,000 cells/mm(3), staging type, and histological subtype were significant prognostic factors for overall survival (OS); however, in multivariate analysis, only advanced stage, suboptimal surgery, NLR > 2.7, and staging type were significant. Inclusion of pelvic and para-aortic lymphadenectomy in surgery showed significant association with longer OS, with a mean and median OS of 42.0 months and 35.5 months (range, 22 to 78 months), respectively, vs. 33.5 months and 27.5 months (range, 14 to 76 months), respectively, for patients who underwent surgery without para-aortic lymphadenectomy (hazard ratio, 3.1; 95% confidence interval, 1.4 to 5.7; p=0.002). CONCLUSION: NLR (in both univariate and multivariate analysis) and PLR (only in univariate analysis) were prognostic factors in PFTC. NLR and PLR are inexpensive and easy tests to perform. In addition, patients with PFTC who underwent bilateral pelvic and para-aortic lymphadenectomy had longer OS.

Multicenter analysis of gestational trophoblastic neoplasia in Turkey.

BACKGROUND: To evaluate the incidence, diagnosis and management of GTN among 28 centers in Turkey. MATERIALS AND METHODS: A retrospective study was designed to include GTN patients attending 28 centers in the 10-year period between January 2003 and May 2013. Demographical characteristics of the patients, histopathological diagnosis, the International Federation of Gynecology and Obstetrics (FIGO) anatomical and prognostic scores, use of single-agent and multi-agent chemotherapy, surgical interventions and prognosis were evaluated. RESULTS: From 2003-2013, there were 1,173,235 deliveries and 456 GTN cases at the 28 centers. The incidence was calculated to be 0.38 per 1,000 deliveries. According to the evaluated data of 364 patients, the median age at diagnosis was 31 years (range, 15-59 years). A histopathological diagnosis was present for 45.1% of the patients, and invasive mole, choriocarcinoma and PSTTs were diagnosed in 22.3% (n=81), 18.1% (n=66) and 4.7% (n=17) of the patients, respectively. Regarding final prognosis, 352 (96.7%) of the patients had remission, and 7 (1.9%) had persistence, whereas the disease was mortal for 5 (1.4%) of the patients. CONCLUSIONS: Because of the differences between countries, it is important to provide national registration systems and special clinics for the accurate diagnosis and treatment of GTN.

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

OBJECTIVE: 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. METHODS: Thirteen healthcare centers in Turkey were contacted to determine if they were eligible to participate in the study. Centers that were eligible and agreed to participate were sent a database form to record the demographic characteristics, clinicopathologic findings, and follow-up results for their EC patients. RESULTS: Eleven Turkish healthcare centers provided data on 43 EC patients. Mean duration of treatment was 5 months and mean follow-up was 49 months. In total, 35 (81.4%) patients were tumor free following primary progesterone therapy. Mean time from the end of progesterone therapy to pregnancy was 10.6 ± 4.3 months (range, 3-18 months). Two patients had tumor recurrence during follow-up. The pregnancy rate among the 31 women who actively sought pregnancy was 41.9% (n=13). CONCLUSION: Conservative management of early-stage EC in women of reproductive age using oral progestins was effective and did not compromise oncological outcome. Pregnancy in the study patients was achieved spontaneously and artificially.

Neoangiogenesis and expression of hypoxia-inducible factor 1alpha, vascular endothelial growth factor, and glucose transporter-1 in endometrioid type endometrium adenocarcinomas.

OBJECTIVE: Hypoxia Inducible Factor-1alpha (HIF-1alpha) is a transcriptional factor that activates multiple genes including Vascular Endothelial Growth Factor (VEGF) and glucose transporter-1 (GLUT-1) in response to hypoxia and promotes neoangiogenesis. METHODS: Expression of HIF-1alpha VEGF, and GLUT-1 were analyzed by immunohistochemistry and microvessel density (MVD) was determined by CD 34 immunostaining in 100 endometrioid type endometrial adenocarcinoma, FIGO Stages I-IV. RESULTS: High expression of HIF-1alpha, VEGF and GLUT-1 were significantly more prevalent in advanced stages than early stages (p<0.001). High expression of HIF-1alpha was found in 100% of Stage III-IV patients, whereas 50% of Stage II and 9% of Stage I patients had high HIF-1alpha expression. Similarly, high VEGF expression was determined in 4% of Stage I and 30% of Stage II patients, however 90% of Stage III-IV patients had high expression of VEGF. Comparing the GLUT-1 scores, it was found that increasing stages correlated with high GLUT-1 expression. Additionally, a statistically significant difference was also noted in MVD between stages (p<0.001). The average MVD of Stage I patients was 31.87+/-7.73. It was found 49.24+/-7.60 in Stage II, and 78.74+/-14.48 in Stage III-IV patients. On analyzing expression of HIF-1alpha, VEGF and GLUT-1 and MVD in pairs, statistically significant correlations were found between each other (p<0.001). CONCLUSION: HIF-1alpha was increasingly expressed from early stages through advance stages of endometrioid adenocarcinoma, paralleled by activation of its downstream genes such as GLUT-1, VEGF and increased angiogenesis. These results highlight the importance of hypoxia and related pathways in progression of endometrial carcinoma.

C-kit protein expression in uterine and ovarian mesenchymal tumours.

The protooncogene c-kit encoding transmembrane tyrosine kinase receptor protein plays an important role in the signal transduction pathway that regulates cellular growth and repair. Gene product KIT overexpression has been shown in a number of different neoplasms, particularly in mastocytosis and gastrointestinal stromal tumours (GIST). The morphologic similarity of uterine mesenchymal tumours and GIST, and the presence of KIT protein in normal uterine tissue, suggests that uterine sarcomas may have the same c-kit overexpression. The purpose of this study was to determine the overexpression of c-kit protein in uterine and ovarian sarcomas. Immunohistochemical staining using a polyclonal anti-c-kit antibody was performed on tissue blocks from 12 carsinosarcomas, 14 leiomyosarcomas, 8 endometrial stromal sarcomas, 2 adenosarcomas, 1 atypical leiomyoma, 1 leiomyoma with limited experience, and 10 leiomyomas. The slides were evaluated by a semiquantitative method. C-kit was positive in 10 of 12 (83%) carcinosarcomas, 10 of 14 (71%) leiomyosarcomas, 6 of 8 75(%) endometrial stromal sarcomas, 1 of 2 (50%) adenosarcomas, 1 leiomyoma with limited experience, and 1 of 10 (10%) leiomyomas. The uterine sarcomas express c-kit, like GISTs. It seems that KIT may have a significant role in the oncogenesis of mesenchymal tumours of the uterus and ovary.

Serous papillary adenocarcinoma and adult granulosa cell tumor in the same ovary. An unusual case.

Surface epithelial-stromal cell tumors are the most common neoplasms of the ovary but occurrence of a serous adenocarcinoma and an adult granulosa cell tumor in the same ovary is an unusual incident. In the present case report we describe this very uncommon occurrence in the ovary of a 50-year-old woman. The patient suffered abdominal distention and was referred to the state hospital where a 5x3 cm multilocular cystic lesion was observed on abdominal CT. Total abdominal hysterectomy with salpingo-oophorectomy and omentectomy was performed. Microscopy revealed an adult granulosa cell tumor and a serous papillary adenocarcinoma in the left ovary. Immunohistochemical staining with inhibin alpha and pancytokeratin confirmed the diagnosis.

Expression of heat-shock proteins hsp27, hsp70 and hsp90 in malignant epithelial tumour of the ovaries.

Recently, considerable attention has been focused on the role of the small heat-shock protein group hsp27, hsp70 and hsp90 in the clinical outcome of several malignancies. However, conflicting data exist regarding the prognostic role of hsp27 expression in ovarian carcinoma, and the prognostic significance of hsp70 and hsp90 expression still remains unknown in these tumours. The purpose of this study was to investigate immunohistochemically whether hsp27, hsp70 and hsp90 expression was associated with clinicopathological parameters and survival in 52 epithelial ovarian carcinomas. Chi-square test, Kaplan-Meier and Cox regression analysis were used for statistical analysis. Among clinicopathological parameters, hsp27, hsp70 and hsp90 expression was only correlated with FIGO stage; hsp70 and hsp90 positivity failed to detect survival. However, the overall survival rate of patients with hsp27 expression was 13%, which was significantly worse than that of patients without hsp27 expression (47%) (p<0.01). The prognosis was also adversely affected by FIGO stage (p<0.01) and presence of ascites (p<0.01). In multivariate analysis, hsp27 expression and FIGO stage were independent prognostic variables. Our results indicate that hsp70 and hsp90 expression had no prognostic relevance in epithelial ovarian carcinomas. However, hsp27 expression and FIGO stage in these tumours could be reliable indicators of prognosis.

Tenascin expression in normal, hyperplastic, and neoplastic endometrium.

Tenascin (TN) is an extracellular matrix glycoprotein (ECM) that participates in embryogenesis and carcinogenesis. The aim of this study was to investigate immunohistochemically the expression of TN in the normal, hyperplastic, and neoplastic endometrium (endometrial adenocarcinoma). In the adenocarcinomas, the results were correlated with patient age, menopausal status, stage, grade, myometrial invasion, and vascular invasion. TN expression was studied in the following cases: proliferative endometrium (10 cases), early secretory endometrium (10), secretory endometrium (10), simple hyperplasia (15), complex hyperplasia (15), atypical hyperplasia (15), and endometrial adenocarcinomas (25). Staining of basal membranes and the cytoplasm of the stromal and epithelial cells was evaluated semiquantitatively. Positive staining was observed in the vascular and glandular basal membranes, stromal cells, and epithelial cells of proliferative, hyperplastic, and neoplastic endometrium. The difference in percentage of stained stromal cells between the neoplastic and the nonneoplastic (proliferative and hyperplastic) endometrium was significant (p<0.005). However, the percentage of stained epithelial cell area in hyperplasia was significantly higher than that of adenocarcinoma and functional endometrium (p<0.005). We conclude that TN is an extracellular matrix glycoprotein that plays a role in proliferation and possibly endometrial carcinogenesis.