Comparison of the effectiveness of liposomal doxorubicin and gemcitabine in patients with platinum-sensitive recurrent ovarian cancer receiving third-line chemotherapy.

OBJECTIVE: In this retrospective study, we compared the effectiveness and reliability of the third-line chemotherapies gemcitabine and liposomal doxorubicin, in patients with platinum-sensitive ovarian cancer (OC). PATIENTS AND METHODS: The retrospective study included platinum-sensitive epithelial ovarian cancer patients who had previously received paclitaxel and carboplatin therapy. Between 2013-2021, cross-matched 45 patients who received gemcitabine and 48 who received liposomal doxorubicin as third-line therapy were compared based on clinicopathological characteristics, biomarkers, and blood cancer antigen (CA) 125 levels. Time to treatment failure, survival, and quality of life were additional objectives. RESULTS: The study included a total of 93 patients. The reported mean survival durations for treatments, 19.45 months for gemcitabine and 17 months for liposomal doxorubicin, did not statistically significantly differ (p=0.398). The mean CA 125 levels for the liposomal doxorubicin and gemcitabine groups after treatment were 54.4±11.4 U/ml and 54.7±11.1 U/ml, respectively. There was no noticeable difference between the treatments when comparing the postop CA 125 value (p=0.37). CONCLUSIONS: For both pegylated liposomal doxorubicin (PLD) and gemcitabine as single agents in the third line, our data revealed comparable effectiveness results, and there was no substantial difference in progression-free survival (PFS) for recurrent ovarian cancer. These therapies were tolerated with an expected incidence of hematological toxicities.

Assessment of primary radical hysterectomy and neoadjuvant chemotherapy followed by radical hysterectomy in Stage IB2, IIA bulky cervical cancer.

OBJECTIVE: Uncertainty concerning the treatment of Stage IB2-IIA (bulky) cervical cancer is still continuing. In this study, an analysis of Stage IB2-IIA (bulky) cervical cancer was performed. The efficacy of primary radical surgery and neoadjuvant chemotherapy followed by a radical surgery was investigated. MATERIALS AND METHODS: Medical data of 50 patients who were diagnosed with Stage 1B2-IIA (bulky) cervical cancer and treated between 2002-2009 were retrospectively assessed. In the radical surgery group, radical hysterectomy + bilateral pelvic + para-aortic lymphadenectomy were performed. In the neoadjuvant chemotherapy group, a combination of cisplatin/topotecan or paclitaxel/carboplatin was given to the patients and then radical surgery was performed. Each group was evaluated individually. Prognostic factors were determined and survival rates were compared between the groups. Ap value was taken < 0.05 for the statistical significance level for all results. RESULTS: Radical surgery after neoadjuvant chemotherapy was performed in 21 and primary radical surgery in 29 patients. Median follow-up time was 36.0 +/- 14.0 months. Average of the tumor size before treatment was 50.2 +/- 7.6 mm. In the radical surgery after neoadjuvant chemotherapy group, lymphovascular space invasion (LVSI) and tumor size (before and after treatment) were determined to be significant factors for each of disease-free survival (DFS) and overall survival (OS). On multivariate analysis, tumor size (before treatment) was found to be an independent prognostic factor for both of DFS (p = 0.006) and OS (p = 0.010). No significant difference in survival periods was observed among the groups. CONCLUSION: There was no significant superiority among the two treatment options. Nonetheless, further studies are needed to compare the multimodal approaches in these stages of cervical cancer.

The relationship between ovarian volume and serum CA-125 levels.

PURPOSE: The aim of this study was to investigate the relationship between ovarian volume and serum CA-125 levels. MATERIALS AND METHODS: Serum CA-125 levels and ovarian volume were compared among the cases with benign ovarian neoplasms, primary epithelial ovarian cancer (EOC), controlled ovarian hyperstimulation, and ovarian hyperstimulation syndrome (OHSS). Also, the correlation between CA-125 levels and ovarian volume were evaluated in the presence of peritoneal fluid and/or peritoneal carcinomatosis. RESULTS: Although ovarian volume was not different among the groups, CA-125 levels were higher in the cases with EOC than with benign ovarian tumors (p = 0.001). Baseline CA-125 levels were not found to have increased while ovarian volume went up with controlled hyperstimulation in the infertile group (p = 0.555). However, uncontrolled hyperstimulation of the ovaries and the presence of peritoneal fluid caused an increase in the levels of CA-125 (p = 0.001). There was no correlation between ovarian volume and CA-125 levels in the cases with malignant ovarian tumors (r = 0.083). CONCLUSIONS: The results of this study have confirmed that CA-125 is a peritoneal marker and increased ovarian volume with benign ovarian neoplasms or controlled hyperstimulation does not increase CA-125 levels in the same way. The presence of peritoneal carcinomatosis and/or peritoneal fluid seems to be an important factor for high CA-125 levels in patients with epithelial ovarian cancer (EOC).

Serum neutrophil gelatinase associated lipocalin and plasma nitric oxide levels in healthy and preeclamptic pregnants.

AIMS: The authors aimed to evaluate serum neutrophil gelatinase associated lipocalin (NGAL) and plasma nitric oxide (NO) levels in preeclamptic and healthy pregnant women above 24 gestation weeks. MATERIALS AND METHODS: Forty-nine healthy and 21 preeclamptic (total 70) pregnant women participated voluntarily in the study. Presence of 140 mmHg and above systolic and 90 mmHg and above diastolic blood pressure which emerges after 20th gestation week, proteinuria more than 300 mg/24 hour, and edema were used as diagnostic criterion for preeclamptic pregnant women. Measurements of serum NGAL and plasma NO were performed with enzyme linked immunosorbent assay (ELISA) and photometric method, respectively. RESULTS: Serum NGAL and plasma NO levels of healthy and preeclamptic groups did not show a statistical difference. In preeclamptic group, a statistically meaningful correlation was found between level of NGAL and body mass index (BMI) of sampling time, creatinine and NGAL, total protein and NO, and albumin and NO. CONCLUSIONS: Serum NGAL levels, correlated with serum creatinine levels in this study, may be the early marker of renal damage which may develop mainly due to inflammation and endothelial damage. The authors could not find a statistical difference for serum NGAL and plasma NO levels between healthy pregnant and preeclamptic groups. Varieties peculiar to humans in preeclampsia, impossibility of obtaining first trimester tissue material as an evidence of inadequate trophoblast invasion, and different appearance of maternal reaction to underlying main pathology in every case may restrict clarification of etiopathogenesis.

Clinicopathological features and prognostic factors of the uterine sarcomas: 20 years of experience at Cukurova University.

OBJECTIVE: Uterine sarcomas (US) are rare, malignant, and aggressive tumors of the uterus. In this study the authors aimed to evalu- ate retrospectively the clinical and pathologic features and to investigate the prognostic factors of the U.S. patients who were treated in their department in the last 20 years. MATERIALS AND METHODS: The archive files, medical, and pathological records of the 132 US patients who were operated on and regularly followed up in the clinic between March 1991-March 2011 were reviewed. Clinical features, operation characteristics, pathological findings, adjuvant therapies, and follow-up data of the patients and their effects on survival were investigated. Analysis of disease-free survival (DFS) and overall survival (OS) were calculated using Kaplan-Meier and Cox regression tests. Thep value was taken <0.05 to maintain the statistical significance level for all results. Results: Seventy of the patients were diagnosed with leiomyosarcomas (LMS), 33 were with carcinosarcomas, 12 were with endometrial stromal sarcomas (ESS), nine were with undifferentiated endometrial sarcomas, five were with adenosarcomas, and three were with botryoid rhabdomyosarcomas. The average patients' age was 53.7 +/- 12.6 (17-78). About two-thirds of the patients were in postmenopausal and one-third were in pre- menopausal period. Vaginal bleeding was detected as the most common reason for patients' admission (68.9%). All cases underwent surgery and a procedure of total abdominal hysterectomy + bilateral salpingo-oophorectomy (TAH + BSO) was performed for most of them (88%). The mean duration of follow-up was 36 months (4-198). The two- and five-year OS rates were 65% and 36%, respectively, with a median time of 37 months (95% CI, 28-45). The two- and five-year DFS rates were 59% and 33%, respectively, with a median time of 29 months (95% CI, 18-40). CONCLUSION: As a result of multivariate analysis, while age, stage, lymphovascular space invasion (LVSI), and lymphadenectomy were found to be independent prognostic factors affecting DFS, only stage was detected as an independent prognostic factor for OS.

Mature cystic teratoma of the fallopian tube.

Teratoma of the fallopian tube (cystic or solid) is a rarely encountered tumour and, to date, only 73 cases have been reported in the literature. A comprehensive review has not been done since 1972, when Mazzarella and colleagues reviewed 44 cases of tubal teratomas. This situation has prompted us to survey the literature to update the data on tubal teratoma cases. The majority of the tumours were benign. The tumour was cystic in nature in 50 cases. Patients' ages ranged between 17 and 67 years. None of them was diagnosed preoperatively. Half of the tumours were ≤ 5 cm, whereas the other half were > 5 cm in diameter. About two-thirds of the patients were associated with two or fewer gravidity. To the best of our knowledge, the present case included in our paper is the first tubal cystic teratoma reported from Turkey.

Preoperative evaluation, clinical characteristics, and prognostic factors of nongenital metastatic ovarian tumors: review of 48 patients.

OBJECTIVE: To evaluate the clinicopathologic characteristics, methods for preoperative evaluation, prognostic factors, and overall survival of nongenital ovarian metastases (NGOM). MATERIAL AND METHODS: Forty-eight patients with NGOM followed between January 2001 and January 2009 in Cukurova University Department of Gynecologic Oncology were included in the study. Clinical characteristics including demographics, preoperative imaging methods, endoscopic evaluations, tumor markers, histopathologic findings, prognostic factors, types of surgery, modalities for adjuvant therapy and survival were analyzed. RESULTS: The gastrointestinal tract is the most common location of the primary tumor; colonic origin was found in 41% of the patients (n = 20). All metastatic lesions were adenocarcinoma with 23% of these classified as Krukenberg and 29% as mucinous type adenocarcinoma. When the whole group was evaluated, median survival time was 15.7 months in patients and there were significant differences between the groups according to primary site. Histopathological subtypes and presence of peritoneal carcinomatosis affected the median survival. The significant prognostic factors were primary site and histopathologic subtypes of the NGOM. CONCLUSIONS: NGOM should be kept in mind to avoid inappropriate management and therapy in patients with surgically managed ovarian tumor, especially young patients with gastrointestinal complaints.

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.

Prognostic factors determining recurrence in early-stage endometrial cancer.

OBJECTIVE: This study aimed to determine the clinically important prognostic factors for loco-regional or distant recurrence in early-stage endometrial cancer. MATERIALS AND METHODS: This study complied with the Declaration of Helsinki, and the local ethics committee approved the study. Cases who underwent primary surgery of early-stage endometrial cancer at the Institution from 2000 to 2012 were reviewed retrospectively. Patients who did not detect recurrence were classified as group 1 (n = 200); those who detected recurrence were classified as group 2 (n = 23). Clinically prognostic factors were evaluated by univariate analyses. RESULTS: The average age for group 2 (LUSI) was 63.8 years (p = 0.0001). Patients with grade 3 histology were all detected within group 2 (p = 0.0001). Endometrioid adenocarcinoma displaying squamous differentiation was found with a rate of 58.3% in group 2 (p = 0.0001). Lower uterine segment involvement (LUSI) and lymphovascular space invasion (LVSI) rates were 86.9% in group 2 (p = 0.0001). The rate of tumor size > 2 cm was 56.6% in group 2 (p = 0.0001). The median depth of myometrial invasion (DMI) was 5.1 mm (p = 0.034) and the average in myometrial thickness was 14.5 mm in group II (p = 0.0001). The percentage of myometrial invasion was 35.8% in Group II (p = 0.0001). Tumor free-distance was 9.4 mm in group II (p = 0.0001). CONCLUSION: Age and clinicopathological parameters of the tumours are significant predictors for recurrence in early-stage endometrial cancer.

Heterogeneity in recurrent complete hydatidiform mole: presentation of two new Turkish families with different genetic characteristics.

Subsequent pregnancy outcomes following complete hydatidiform moles (CHM) are usually favorable and the risk of a second CHM less than 2%. However, a small number of women have a rare autosomal recessive condition that predisposes them to CHM. Unlike typical CHM, that are androgenetic (AnCHM), the CHM in these women are diploid and biparental (BiCHM) with a contribution from each parent to the nuclear genome. To date most women with recurrent CHM have been found to have BiCHM and to have a wide variety of mutations in the causative gene, NLRP7. Our objectives were to genotype the molar tissue and identify the NLRP7 mutations in two unrelated Turkish women with recurrent CHM. Fluorescent microsatellite genotyping of molar tissue and screening of patient DNA for NLRP7 mutations was carried out in two women with five and four CHM respectively. The first case was confirmed to have BiCHM. In addition the patient was found to have a novel homozygous mutation in exon 8 of NLRP7. All CHM examined in the second case were AnCHM and no NLRP7 mutations were identified in DNA from the patient. This report describes a further individual with BiCHM and a novel mutation in NLRP7. A second patient with similar clinical history had no mutations in NLRP7 and is the first report of a patient with four CHM where the CHM are androgenetic. This study highlights the heterogeneity of recurrent CHM and the need to investigate women with recurrent molar pregnancies for appropriate clinical management.

Mullerian adenosarcoma of the uterine cervix in an adolescent girl.

BACKGROUND: Cervical adenosarcoma is a rare gynecological tumor which is prone to recur locally. A case of cervical adenosarcoma in a 14-year-old girl treated in order to preserve fertility. CASE: A 14-year-old girl presented with a pedunculated mass protruding from the vagina. Simple excision was performed. Histological evaluation revealed adenosarcoma. Her clinical course has been uneventful for fifteen months. SUMMARY AND CONCLUSION: Adenosarcoma is a low malignant potential tumor of the female genital tract. A simple excision may be an option for young women who need to preserve their fertility. It is mandatory to monitor regularly the cervical base of the lesion for the purpose of the high potential of the local recurrence.

Fallopian tube carcinoma metastatic to the pericardium and breast.

INTRODUCTION: Fallopian tube carcinoma is a rare gynecological tumor and simultaneous pericardial and breast metastasis of this cancer is an extremely exceptional event. CASE: A 46-year-old woman with FIGO Stage IIIc, grade 3 adenocarcinoma of the fallopian tube received cyclophosphamide and carboplatin subsequent to surgery. The disease had been completely silent for 41 months and then it relapsed with pericardial and breast metastasis consecutively. She expired one year after the relapse. CONCLUSION: Although clinical and biological behavior and response to the treatment of fallopian tube carcinoma is quite similar to epithelial ovarian carcinoma, breast and pericardium are unusual sites of metastasis for each malignancy. As survival is prolonged with new chemotherapeutics these atypical cancer metastases will be observed more frequently.

A case with diffuse uterine leiomyomatosis and review of the literature.

Leiomyomas and diffuse uterine leiomyomatosis are smooth muscle tumors of the uterus. Diffuse uterine leiomyomatosis is a benign and extremely rare condition in which the uterus is symmetrically enlarged as a result of the almost complete replacement of the myometrium by innumerable poorly defined, confluent nodules. The etiology of these neoplasms is not completely understood. Initial symptoms of the diffuse uterine leiomyomatosis usually are abdominal pain and abnormal uterine bleeding. Similar to uterine leiomyomas, patients with leiomyomatosis present with menorrhagia, dysmenorrhea, abdominal pain, infertility, and pelvic pressure. Hormonal treatment usually fails to control the symptoms, anemia, or tumor growth after treatment is stopped. As a result, despite patients being in the third or fourth decades of life, hysterectomy has been the only permanent treatment option offered to patients for treatment of the symptoms related to uterine fibroids in diffuse leiomyomatosis. A case of a patient with a huge uterine mass (2,650 g in weight) who underwent hysterectomy due to diffuse uterine leiomyomatosis is presented together with a review of the literature.

Maspin overexpression correlates with increased expression of vascular endothelial growth factors A, C, and D in human ovarian carcinoma.

The vascular endothelial growth factor (VEGF) family, including VEGFA, VEGFC, and VEGFD, plays an essential role in the angiogenesis of both pathologic and nonpathologic conditions. Maspin belongs to the serpin superfamily and has been identified as a tumor suppressor because it inhibits motility, invasion, and angiogenesis. Few studies have compared maspin with VEGF in ovarian carcinoma. Therefore, we investigated the expression and correlation of maspin, VEGFA, VEGFC, and VEGFD with the tumorigenesis of the ovary and clinicopathologic variables. Using immunohistochemistry, we examined maspin, VEGFA, VEGFC, and VEGFD expression in 60 ovarian carcinoma tissues (35 serous papillary carcinomas, 18 endometrioid carcinomas, and 7 primary ovarian mucinous carcinomas). Staining of cells was scored as +2 if more than 50% of the cells were positive, as +1 if less than 50% of the cells were positive, and as negative if none of the cells stained positive. Overexpression of maspin, VEGFC, and VEGFD was significantly associated with high tumor grade (P<.001, P=.004, P<.001, respectively), clinical stage (P=.002, .01, and .001, respectively), the presence of ascites (P<.001, P=.03, and P=.001, respectively), and the presence of metastatic lymph nodes (P=.002, P<.001, and P<.001, respectively). Maspin was correlated with VEGFA (P=.01), VEGFC (P<.001), and VEGFD (P<.001). The VEGFA score was positively correlated with high tumor grade (P=.04), lymphovascular space invasion (LVSI) (P<.001), International Federation of Gynecology and Obstetrics (FIGO) stage (P=.009), maspin, VEGFC (P=.003), and VEGFD (P=.003), but it was not correlated with the presence of ascites and metastatic lymph nodes. Maspin, VEGFC, and VEGFD are expressed in ovarian tumors with a poor prognostic parameters, and seem to play a role in ovarian cancer angiogenesis, progression, and lymph node metastases. Our results indicate that in contrast to most other carcinomas, maspin expression is directly associated with the biological aggressiveness of ovarian carcinoma. These results may offer new insights regarding the role of maspin in ovarian cancer and might also affect the diagnosis and treatment strategies.

Nitric oxide, lipid peroxidation and antioxidant defence system in patients with active or inactive Behçet's disease.

BACKGROUND: One of the prominent features of Behçet's disease (BD) is vasculitis and thrombosis as a result of endothelial dysfunction. Nitric oxide (NO) is responsible for endothelial vasorelaxation and inhibition of platelet adhesion. OBJECTIVES: To assess serum total NO, erythrocyte superoxide dismutase (SOD), whole blood glutathione peroxidase (GSH-Px), plasma total antioxidant status (TAS) and plasma malondialdehyde (MDA) in patients with BD and to correlate their levels with disease activity. METHODS: The study group consisted of 49 patients with BD and 26 healthy control subjects. None of the subjects was given a standardized diet. Patients with any systemic disease were excluded. Patients with BD were randomized to two groups according to their disease activity (active/inactive, 26/23). We measured serum total NO levels using the enzyme-linked immunosorbent assay method, and SOD, GSH-Px, TAS and MDA levels by spectrophotometric methods. RESULTS: In patients with active disease (n = 26), serum total NO levels were found to be significantly decreased when compared with the inactive (n = 23) and control (n = 26) groups. Levels were also significantly lower in patients with inactive disease and in total BD patients (n = 49) than in the controls. GSH-Px activities and TAS levels were significantly lower in total BD patients than those in the controls. Patients with active disease and total BD patients exhibited markedly higher MDA levels than the control subjects. MDA levels in the patients with active disease were also found to be elevated compared with the patients with inactive disease. CONCLUSIONS: We conclude that changes in parameters associated with oxidative stress such as NO-related processes, activities of antioxidant enzymes in the bloodstream and erythrocytes and total plasma antioxidant capacity are involved in the aetiopathogenesis of the vasculitis seen in BD.

Fine needle aspiration cytology of ovarian lesions.

OBJECTIVE: To assess the diagnostic value of fine needle aspiration cytology (FNAC) in ovarian lesions. STUDY DESIGN: Sixty-two fine needle aspirations of varied ovarian masses were performed between January 2000 and February 2003. Aspiration material was obtained from fresh tissues at the time of frozen section before dissection of the specimens. The slides were evaluated by a pathologist who was blinded to the gross findings and histopathologic diagnosis. RESULTS: A total of 62.9% of cases were assessed as malignant and 30.6% as benign. Two false positive and 2 false negative cases occurred. In our series the overall sensitivity and specificity were 95.1% and 90.4%, respectively. Seven benign and 15 malignant lesions could be subclassified specifically. CONCLUSION: We studied excised specimens, but since ovarian masses are reachable by laparoscopically and ultrasonographically guided aspiration, FNAC can be used for diagnoses of these lesions. If a multidisciplinary approach can be carried out in patients with ovarian lesions, cytopathologic interpretation can provide optimum benefits.

Efficacy of gemcitabine in heavily pretreated advanced ovarian cancer patients.

Single agent gemcitabine was used in recurrent epithelial ovarian cancer patients after standard treatment with debulking surgery and platin-paclitaxel based chemotherapy. Response rates and toxicity results were evaluated retrospectively. Gemcitabine was given in 1000 mg/m2 intravenous infusion over 30 minutes at 1, 8, 15 days of every 28 days. Clinical response was evaluated with clinical findings, serum CA 125 levels, and computerized tomography. Twenty-two patients--ten as second-line, 11 as third-line, and one as fourth line--received gemcitabine. Seven patients received six courses, nine cases three, five cases two and one case one course of treatment. There were four (18.2%) partial and two (9.1%) complete responses with an overall response rate of 27.3%. Stable disease was also observed in three more cases. The progression-free interval was found to be a median of three months. Grade 3-4 neutropenia was seen in two (9.1%) and grade 3-4 thrombocytopenia was seen in four (18.2%) cases. Pancytopenia was observed in one (4.5%) patient. There was no grade 3-4 non-hematological toxicity. Antitumoral activity is encouraging in heavily pretreated ovarian cancer patients. A short progression-free interval is noticeable in responding cases. Toxicity is mainly hematologic and moderate.

Central nervous system involvement in gestational trophoblastic neoplasia.

OBJECTIVE: To evaluate characteristics of patients with central nervous system (CNS) lesions of gestational trophoblastic disease and determine prognostic and therapeutic implications applicable to management. METHODS: Nine patients among 56 cases of malignant gestational trophoblastic neoplasia (GTN) were analyzed prospectively in a single institution between the years 1990 and 1997 with at least two years of follow-up. Brain metastases were documented by physical exam and computed tomography scan or magnetic resonance imaging. In terms of therapy, all of the patients received an etoposide, methotraxate, actinomycin, cyclosphamide and vincristine (EMA-CO) regimen for 5 to 9 courses. To prevent unexpected intracranial hemorrhage, all patients received radiation therapy. No intrathecal chemotherapy was given. Remission was defined as three weekly beta-hCG levels below assay sensitivity (<5 mIU/ml). RESULTS: The mean age of the patients at diagnosis was 29.6 years. While two of the patients initially presented with symptoms related to cranial involvement, five were diagnosed during routine investigation for metastasis in malignant GTD and the remaining two developed cerebral metastases during the therapy. Besides central nervous system involvement, six had additional lung, two had hepatic and splenic and one had pelvic metastases. Overall survival was 66.6%. Two patients had a fulminant clinical course and were lost one month after initial diagnosis. CONCLUSION: Early diagnosis via computed tomography of the head and beta-hCG serum testing along with aggressive, multiagent intervention (EMA-CO) have greatly improved patient prognosis of this once highly fatal condition.