Diagnostic and prognostic role of TFF3, Romo-1, NF-кB and SFRP4 as biomarkers for endometrial and ovarian cancers: a prospective observational translational study.

PURPOSE: This study aimed to evaluate trefoil factor 3 (TFF3), secreted frizzled-related protein 4 (sFRP4), reactive oxygen species modulator 1 (Romo1) and nuclear factor kappa B (NF-κB) as diagnostic and prognostic markers of endometrial cancer (EC) and ovarian cancer (OC). METHODS: Thirty-one patients with EC and 30 patients with OC undergone surgical treatment were enrolled together with 30 healthy controls in a prospective study. Commercial ELISA kits determined serum TFF-3, Romo-1, NF-кB and sFRP-4 concentrations. RESULTS: Serum TFF-3, Romo-1 and NF-кB levels were significantly higher in patients with EC and OC than those without cancer. Regarding EC, none of the serum biomarkers differs significantly between endometrial and non-endometrioid endometrial carcinomas. Mean serum TFF-3 and NF-кB levels were significantly higher in advanced stages. Increased serum levels of TFF-3 and NF-кB were found in those with a higher grade of the disease. Regarding OC, none of the serum biomarkers differed significantly among histological subtypes. Significantly increased serum levels of NF-кB were observed in patients with advanced-stage OC than those with stage I and II diseases. No difference in serum biomarker levels was found between those who had a recurrence and those who had not. The sensibility and specificity of these four biomarkers in discriminating EC and OC from the control group showed encouraging values, although no one reached 70%. CONCLUSIONS: TFF-3, Romo-1, NF-кB and SFRP4 could represent new diagnostic and prognostic markers for OC and EC. Further studies are needed to validate our results.

YKL-40 in the diagnosis, prediction of prognosis, and platinum sensitivity in serous epithelial ovarian cancer.

OBJECTIVE: To evaluate the use of YKL-40 in the discrimination between benign and malignant adnexal mass and to determine its prognostic value in assessing residual tumor after primary cytoreduction and platinum sensitivity in serous epithelial ovarian carcinoma (EOC). MATERIALS AND METHODS: During the three years from January 2015 to December 2017, a nonconsecutive series of 100 patient (60 malignant, 40 benign) who underwent surgery for an adnexal mass were enrolled in the study. Preoperatively, serum samples were collected for YKL-40 level analysis. RESULTS: YKL-40 [receiver operator characteristics (ROC)-area under curve (AUC)=0.83] was a significantly better predictor of EOC than cancer antigen-125 (ROC-AUC=0.75). Using a cut-off for YKL-40 of 47.7 ng/mL had a sensitivity of 80% and a specificity of 70%. Higher serum YKL-40 levels were associated with advanced stage, higher grade, residual tumor after primary cytoreduction and recurrence. Platinum-sensitive patients had significantly elevated levels of YKL-40 compared with platinum-resistant or refractory patients. CONCLUSION: The results obtained from our study support the use of serum YKL-40 for the discrimination between malignant and benign ovarian tumors. YKL-40 levels in patients with serous EOC may also predict disease residual disease after primary cytoreduction and recurrence. Further studies are needed to understand the relationship between YKL-40 and platinum sensitivity.

Ykl-40 and cancer antigen 72-4 as new and promising diagnostic and prognostic markers for endometrial cancer.

OBJECTIVE: To determine the predictive role of serum levels of YKL-40 and cancer antigen (CA) 72-4 in the diagnosis of endometrial cancer (EC). MATERIALS AND METHODS: Forty-one patients with EC and 21 women with uterine polyps were evaluated between January and December 2015 in a prospective study. RESULTS: Age, body mass index, preoperative serum YKL-40 and CA 72-4 levels were significantly higher in the malignant group compared with the control group. Serum YKL-40 levels were significantly higher in patients with superficial myometrial invasion and no lymph node involvement (p=0.042; p=0.004). No relationship between clinicopathologic factors and serum CA 72-4 levels was found. CONCLUSION: Serum CA 72-4 and YKL-40 levels are increased in women with EC compared with uterine polyps. Preoperative serum YKL-40 levels may be associated with favorable prognostic factors. The determination of YKL-40 before surgery may be helpful in the evaluation of the regional lymph nodes.

Effects of Apigenin on Experimental Ischemia/Reperfusion Injury in the Rat Ovary.

BACKGROUND: Apigenin is a plant-derived compound belonging to the flavone class, which possess antioxidant, free-radical-scavenging and anti-inflammatory properties. AIMS: To address the effects of apigenin on serum anti-mullerian hormone levels, tissue oxidative stress parameters and histopathological changes in ovarian ischemia/reperfusion injury. STUDY DESIGN: Animal experiment. METHODS: Twenty-eight female Wistar albino rats were randomly separated into four sections: Sham operation (group 1), ischemia/reperfusion plus saline (group 2), ischemia/reperfusion plus dimethyl sulfoxide (group 3) and ischemia/reperfusion plus apigenin (group 4). In all ischemia/reperfusion groups, a bilateral adnexal 3-h period of ischemia was performed, followed by 3-h of reperfusion. A single dose of 15 mg/kg apigenin was given intraperitoneally 60 min before reperfusion in group 4. After 3-h of reperfusion, both ovaries were removed, and blood samples were collected. The main outcome measures were serum anti-mullerian hormone levels, ovarian tissue malondialdehyde, total nitric oxide, Cu/Zn superoxide dismutase, catalase and glutathione levels and histopathological damage scores. RESULTS: The ovarian tissue nitric oxide level was significantly lower, and the glutathione level was significantly higher in group 4 compared with groups 2 and 3. There was no significant difference in anti-mullerian hormone levels among the three ischemia/reperfusion groups. The histopathological damage score was lower in group 4 than in groups 2 and 3 (p>0.05). CONCLUSION: Administration of apigenin has no significant protective effect on ovarian reserve and tissue damage in ovarian ischemia/reperfusion injury.

Is serum level of nestin useful in detecting epithelial ovarian cancer?

AIM: The aim of the present study was to evaluate the usefulness of nestin as a discriminative marker between benign and malignant ovarian tumors. METHODS: During the 1 year from January 2015 through December 2015, a nonconsecutive series of 80 patients (40 malignant, 40 benign) who underwent surgery for an adnexal mass were enrolled in the study. Intraoperative frozen section evaluation was performed if there was a suspicion in diagnosis. Statistical analyses were performed using spss ver. 16.0, while clinicopathological variables, including the categorical data, were analyzed using the χ2 -test or Fisher's exact test. A P-value < 0.05 was defined as statistically significant. RESULTS: Preoperative serum carbohydrate antigen (CA)-125, CA-15-3, and nestin levels were significantly higher in the malignant group compared to patients with benign ovarian tumors (P < 0.001, respectively). Serum nestin levels did not differ significantly on the basis of histologic subtypes. Serum nestin levels had specificity of 89.7%, which demonstrates nestin's sufficiency to distinguish benign from malignant epithelial ovarian tumors. The positive likelihood ratio of nestin was found to be superior to that of CA-125 and CA-15-3. CONCLUSION: The results obtained from our study suggest that measurement of nestin level, alongside physical examination, transvaginal ultrasound, and serum CA-125 and CA-15-3 levels, can help differentiate benign ovarian tumors from malignant epithelial ovarian tumors. The findings of our study need to be supported with additional studies.

Postoperative upper extremity deep vein thrombosis in a gynecologic oncology patient: A case report.

INTRODUCTION: Upper extremity deep vein thrombosis (UEDVT) represents approximately 10% of all thromboembolic events. It is a rare condition after a gynecologic surgery and highly related with pulmonary embolism. PRESENTATION OF CASE: Herein, we present a very rare case of a unilateral left upper extremity deep vein thrombosis in a morbidly obese patient with synchronous primary cancers of endometrium and ovary. DISCUSSION: Our aim was to underline the relationship between the presence of gynecologic malignancy, oncologic surgery and UEDVT. CONCLUSION: Upper extremity deep vein thrombosis should be kept in mind in the presence of any symptom on upper extremity during postoperative period even in patients without central venous catheter.

The Combination of Preoperative Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography and Sentinel Lymph Node Mapping in the Surgical Management of Endometrioid Endometrial Cancer.

OBJECTIVE: The goal of this study was to evaluate the combination of sentinel lymph node (SLN) mapping and F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) scan in detection of lymph node involvement in patients with endometrioid endometrial cancer (EEC). METHODS/MATERIALS: Ninety-five patients with EEC who had preoperative PET/CT imaging and underwent SLN mapping were retrospectively analyzed. Methylene blue dye was used and injected to the cervix at 3- and 9-o'clock positions (a total of 4 mL). Pelvic lymphadenectomy was performed on all of the patients after SLN mapping. If the SLN was negative in the initial hematoxylin and eosin staining, an ultrastaging study was performed for the SLNs. RESULTS: Sentinel lymph nodes were detected in 77 (81.1%) of 95 patients, with a mean of 2.95 SLNs. There was only 1 case (1.4%) with a positive SLN in the intraoperative frozen section examination in those patients with negative PET/CT findings and in whom SLNs were detected (n = 70). Among the remaining 69 patients with negative preoperative PET/CT findings and negative frozen section results for the SLNs, there were 2 patients with SLN involvement in the final ultrastaging pathology. In the patient-based analyses, the sensitivity, specificity, and positive and negative predictive values of the PET/CT and SLN frozen section were 33%, 100%, 100%, and 97.1%, respectively. CONCLUSIONS: As no metastases in the nonsentinel pelvic lymph nodes were found in patients with EEC who had both negative PET/CT findings and frozen section results of the SLNs in both hemipelvises, we suggest using both methods to reduce the incidence of unnecessary systematic lymphadenectomy.

Risk factors for recurrence of borderline ovarian tumours: A tertiary centre experience.

The aim of this study was to evaluate the risk factors for recurrence of borderline ovarian tumours. This study investigated 127 women who were finally diagnosed with borderline epithelial ovarian tumours. Most of them were diagnosed in stage I (83.4%). With a median follow-up of 81.8 months (range: 14-205), the median time to recurrence was 22.4 months (range: 3-74). Five-year recurrence-free survival (RFS) and overall survival (OS) rates were 85.8% and 97.6%, respectively. In multivariate analysis, invasive implants and fertility-sparing surgery were found to be independent prognostic factors for 5-year RFS. Overall, 20 patients (15.7%) experienced relapse within the observation period. Although there is no consensus about high-risk category of borderline ovarian tumours, invasive implants and conservative surgery were closely related to the recurrence. Patients presenting these risk factors should undergo closer follow-up.

Post-coital vaginal cuff dehiscence with small bowel evisceration after laparoscopic type II radical hysterectomy: A case report.

INTRODUCTION: Vaginal cuff dehiscence after hysterectomy can be life-threating condition. Vaginal evisceration of bowel may lead to intestinal ischemia and intraabdominal infection. Immediate recognition and surgical repair are crucial for succesful management. CASE REPORT: Herein, we report a case of vaginal cuff dehiscence with small bowel evisceration in a 32-year old woman who underwent laparoscopic type II hysterectomy for stage IA2 cervical cancer. CONCLUSION: Patients who have undergone hysterectomy should be advised about when to restart coitus. Vaginal repair of vaginal cuff dehiscence is recommended if intestinal ischemia is excluded.

Comparison of Diagnostic Accuracies of Serum HE-4 Levels and 3D Power Doppler Angiography Parameters between Benign Endometrial Pathologies and Endometrial Cancer.

PURPOSE: To study the diagnostic accuracies of serum human epididymis protein 4 (HE-4) levels, virtual organ computer-aided analysis (VOCAL) parameters and endometrial volume in endometrial cancer cases. MATERIALS AND METHODS: One hundred and seven patients (37 with endometrial cancer and 70 with benign endometrial pathology) were included in this study. VOCAL parameters and serum HE-4 levels were compared between the groups. RESULTS: Area under the curve (AUC) values were 0.702, 0.658, 0.706 for vascularization index (VI), the flow index (FI) and the vascularization flow index (VFI), respectively. A cut off value of 0.568 for VI demonstrated 70% sensitivity, 72% specificity, 56% positive predictive value (PPV) and a81% negative predictive value (NPV). A cut off value of 25.8 for showed a senitivith of 70% and a specificity of 58% with aPPV of 46% and NPV of 78%, and with a cut off value of 0.12 for VFI 70%, 69%, 54% and 81%, respectively. The area under the curve for HE-4 was 0.814. A cut off value of 458 pmol/L was predictive of malignancy with 86% sensitivity and 63% specificity. CONCLUSIONS: VOCAL parameters and serum HE-4 levels were statistically significantly higher in the endometrial cancer patients. Serum HE-4 levels provided a greater sensitivity compared to power doppler angiography for predicting malignancy or benign endometrial pathology.

Tertiary Cytoreduction for Recurrent Epithelial Ovarian Cancer: a Multicenter Study in Turkey.

BACKGROUND: The purpose of this study was to determine the benefit of tertiary cytoreductive surgery (TC) for secondary recurrent epithelial ovarian cancer (EOC), focusing on whether optimal cytoreduction has an impact on disease-free survival, and whether certain patient characteristics could identify ideal candidates for TC. MATERIALS AND METHODS: Retrospective analysis of secondary recurrent EOC patients undergoing TC at three Turkish tertiary institutions from May 1997 to July 2014 was performed. All patients had previously received primary cytoreduction followed by intravenous platinum-based chemotherapy and secondary cytoreduction for first recurrence. Clinical and pathological data were obtained from the patients' medical records. Survival analysis was caried out using the Kaplan Meier method. Actuarial curves were compared by the two tailed Logrank test with a statistical significance level of 0.05. RESULTS: Median age of the patients was 49.6 years (range, 30-67) and thirty-eight (72%) had stage III-IV disease at initial diagnosis. Twenty six (49%) had optimal and 27 (51%) suboptimal cytoreduction during tertiary debulking surgery . Optimal initial cytoreduction, time to first recurrence, optimal secondary cytoreduction, time interval between secondary cytoreduction and secondary recurrence, size of recurrence, disease status at last follow-up were found to be significant risk factors to predict optimal TC. Optimal cytoreduction in initial and tertiary surgery and serum CA-125 level prior to TC were independent prognostic factors on univariate analysis. CONCLUSIONS: Our results and a literature review clearly showed that maximal surgical effort should be made in TC, since patients undergoing optimal TC have a better survival. Thus, patients with secondary recurrent EOC in whom optimal cytoreduction can be achieved should be actively selected.

Isolated adnexal torsion in a 20-week spontaneous twin pregnancy.

BACKGROUND: Adnexal torsion can be a life-threatning condition in pregnancy, while the risk of late diagnosis is increased, in second and third trimester in particular. Laparoscopy is an effective approach in diagnosis and treatment of adnexal torsion. However, entry to abdomen may be challenging in more advanced pregnancies. CASE REPORT: Herein, we report a case of adnexal torsion during 20th week of twin pregnancy, which was detorsioned laparoscopically. The woman delivered healthy infants at her 36th week of pregnancy. DISCUSSION: Adnexal torsion as a cause of acute abdomen may be kept in mind in pregnants, even if there is no predisposing factor. Laparoscopy may be performed safely in 2nd trimester for acute abdomen.

Surgical Treatment of Metastatic Ovarian Tumors From Extragenital Primary Sites.

OBJECTIVE: The purpose of this study was to investigate the outcomes and prognostic factors of metastasectomy in patients with metastatic ovarian tumors from extragenital primary sites. MATERIALS AND METHODS: All patients with pathologically confirmed metastatic ovarian tumors between January 1997 and June 2015 were included in this study. A total of 131 patients were identified. The data were obtained from the patients' medical records. Clinicopathological features were evaluated by both univariate and multivariate analyses. RESULTS: The primary sites were colorectal region (53.4%), stomach (26%), and breast (13%). Preoperative serum CA 125 and CA 19-9 levels were elevated in 29.4% and 39.8% of the patients, respectively. Cytoreductive surgery was performed in 41.2% of the patients. Seventy-three (55.7%) patients had no residual disease after surgery. Sixty-six (49.6%) patients had combined metastases at the time of the surgery to sites including the liver, pancreas, lung, bone, lymph nodes, bladder, or the intestine. With a median follow-up of 33 months, the median survival time was 22 months. The estimated 5-year survival probability is 0.26. On univariate analysis, primary cancer site, combined metastasis outside the ovaries, residual disease, preoperative serum CA 125 and CA 19-9 levels, and histologic type were significant parameters for overall survival. Furthermore, residual disease, preoperative serum CA 19-9 level, and primary cancer site were found to be independent prognostic factors on multivariate analysis. CONCLUSIONS: The most common primary sites for ovarian metastasis are gastrointestinal tract. Metastasectomy may have beneficial effects on survival, especially if the residual disease is less than 5 mm. Prospective studies warranted to evaluate the value of metastasectomy in patients with ovarian metastasis.

Expression of PTEN and ß-Catenin and Their Relationship With Clinicopathological and Prognostic Factors in Endometrioid Type Endometrial Cancer.

OBJECTIVE: The aim of this study was to investigate rates of expression of PTEN (phosphatase and tensin homolog deleted on chromosome 10) and ß-catenin and their relationship with clinicopathological and prognostic factors in endometrioid type endometrial cancer (EC). METHODS AND MATERIALS: PTEN and ß-catenin expressions of 59 operated patients with EC between January 2000 and December 2008 and followed-up until December 2014 in Cerrahpasa School of Medicine, Gynecologic Oncology Division, were evaluated retrospectively. Clinical data were obtained from patient files, and pathological data were obtained from pathology records. Each patient had 4 paraffin sections of tumoral tissue. These sections were stained by immunohistochemical methods. Clinical features and postoperative histopathologic findings were analyzed using Fisher exact test or the χ(2) test as appropriate. The Kaplan-Meier method was used to generate the survival curves. RESULTS: During median follow-up of 102 months, tumor recurrence and disease-related mortality were observed in 10 (16.9%) and 7 (11.9%) cases, respectively. Immunohistochemical staining of PTEN and ß-catenin were positive in 61% and 69.5% of all cases, respectively. Positive staining of PTEN was positively correlated with myometrial invasion (P= 0.02). There was no correlation between ß-catenin and clinicopathological factors. PTEN or ß-catenin positivity were not significant prognostic factors for 5-year overall survival (P = 0.37, P = 0.62, respectively) and 5-year disease-free survival (P = 0.28, P = 0.58, respectively). CONCLUSIONS: PTEN and ß-catenin expressions cannot be used to determine prognosis in patients with EC as PTEN and ß-catenin staining status were found to have no significant effect on 5-year overall survival and disease-free survival. Positive staining of PTEN may be associated with increased myometrial invasion. Meta-analyses and broader studies are needed to evaluate the prognostic value of PTEN and ß-catenin in EC.

Primary signet ring cell carcinoma of the cervix: A case report and review of the literature.

INTRODUCTION: Primary signet cell carcinoma of the cervix has been reported only in 18 cases to date. PRESENTATION OF CASE: A 48-year-old woman was seen at our Gynecologic Oncology Unit, because she complained postcoital bleeding during the last three months. She had 1-2 cm cervical mass, originating from the endocervical canal. A biopsy revealed a signet ring cell-type adenocarcinoma. Suspected primary sites were excluded after gastroscopy, colonoscopy and mammography. The patient underwent a laparoscopic type-3 radical hysterectomy with bilateral salpingo-oophorectomy, pelvic lymph node dissection and paraaortic lymph node dissection with a presumed diagnosis of primary signet ring cell carcinoma of the cervix. Microscopically, the tumour consisted of 70% signet ring cell type and 30% endocervical adenocarcinoma. She did not receive any adjuvant treatment. Follow-up at 18 months after surgery showed no evidence of recurrence. DISCUSSION: Nineteenth case of a primary signet ring cell carcinoma of the cervix was presented. Immunohistochemical studies and HPV DNA positivity may help in diagnosis. CONCLUSION: It is crucial to differentiate primary tumour from metastatic signet cell carcinoma, while treatment and prognosis differ significantly.

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 χ(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.

Intravenous leiomyoma with extension to the heart: a case report and review of the literature.

Introduction. Intravenous leiomyomatosis with cardiac extension is an extremely rare uterine tumor. We report here a case of intravenous leiomyoma extending to the right atrium, diagnosed in a patient having leiomyoma. Case Presentation. A 39-year-old woman with no symptoms and a past medical history of two myomectomy operations (7 and 3 years previously) was admitted to our clinic for routine control. We detected a uterine fibroid of 8 centimeters and 4 small solid masses of 1-2 centimeters near the uterus and ovaries at vaginal ultrasonography. Computed tomography (CT) was performed to investigate the abdominal cavity. It revealed a mass originating from the left common iliac vein, which invaded the inferior vena cava (IVC) and extended to the right atrium in addition to the uterine fibroids and pelvic masses. The operation was performed with a combined team of gynecologists and cardiac surgeons and a one-stage operation was accomplished. The postoperative course was uneventful. Conclusion. Abdominal CT is a useful imaging technique for the diagnosis of unusual pathology in a patient with uterine fibroid having suspicious pelvic masses. Also, when a right atrial mass is identified in a female with a prior history of hysterectomy because of leiomyoma or in whom there is a uterine myoma, then intravenous leiomyomatosis should be considered.

Randomized trial of oral misoprostol treatment for cervical ripening before tandem application in cervix cancer.

PURPOSE: To investigate the efficacy of oral misoprostol administered to facilitate tandem application to the cervix as a part of brachytherapy in patients with cervical cancer. METHODS AND MATERIALS: Eighty patients with cervical cancer who had been planned to undergo brachytherapy at Dr. Lütfi Kirdar Kartal Training and Research Hospital were evaluated in a double-blind, prospective, randomized trial. Patients were divided randomly into two groups of 40 patients. The first and second groups received 400 µg of misoprostol orally and placebo, respectively, 3 h before tandem application. The two groups were compared in terms of age, diameter of tumor, parity, age at first intercourse, amount of bleeding and pain at first tandem application, length of endometrial cavity measured by hysterometer, and size of Hegar dilators used for cervical dilatation. RESULTS: Of all cases, 63.6%, 16.3%, 10%, 6.3%, 2.5%, and 1.3% were Stage IIB, IIIB, IIIA, IVA, IIA and IIC, respectively. Mean (±SD) age (range) was 49.3 ± 13.1 (25-83) years and 56.6 ± 13.2 (30-78) years in the study and control groups, respectively (p = 0.015). Age at first intercourse, diameter of tumor, parity, amount of bleeding at first tandem application, and length of endometrial cavity measured by hysterometer were not significantly different between the two groups. Pain score was significantly higher in the control group (p < 0.001). Application was significantly easier in the study group compared with controls (p < 0.001). Average size of initial Hegar dilators used for cervical dilatation was significantly higher in the study group compared with controls (p = 0.017). CONCLUSION: Administration of misoprostol 400 µg orally for cervical ripening before tandem application facilitates the procedure, increases patient tolerability and comfort, and may decrease complication rates.