Investigation of resistin 420 and 62 gene polymorphism in patients with endometrial cancer.

OBJECTIVE: We aimed to assess resistin gene polymorphisms, namely 420C > G and 62G > A and their effect on the risk of endometrial cancer (EC). MATERIALS AND METHODS: Between January 2012 and January 2015, of the total of 183 patients diagnosed with EC, 94 patients were enrolled into the study. Patients with diabetes mellitus, hypertension and history of any other cancer were excluded. To identify the importance of nucleotide polymorphism including 420C > G and 62G > A in the resistin gene, 94 healthy volunteers were included as the control group. RESULTS: Among the Resistin 420 gene polymorphism profiles, 420 GC (47.9%) was the most common gene polymorphism in the EC group. Also, the polymorphism of 420 CC (57.7%, p: 0.002) lead the list in the control group followed by the 420GC (37.5%) polymorphism. Resistin 62 gene polymorphism analysis demonstrated that the 62GC polymorphism was significantly more common in the EC group (p < 0.01), while 62 AG (52.9%) was observed most frequently in the control group bringing about a reduction in the risk of EC (p < 0.01, Odds Ratio:0.37). Additionally, the alleles of 420G+ and 62A + were significantly more common in the EC group and the control group, respectively (p:0.02 and p<:0.01). Multivariate regression analysis revealed that the presence of 420G + allele increased the EC risk 1.99 fold while the presence of 62A + allele was shown to decrease the risk of EC (p<:0.01 Odds Ratio:0.038). CONCLUSION: Our study for the first time had demonstrated that Resistin 420G > C and 62G > A gene polymorphisms play a role in EC development.

Clinicopathological analysis of borderline ovarian tumours and risk factors related to recurrence: experience of single institution.

This study was conducted to determine the demographic and clinicopathologic characteristics and evaluate the prognostic value of various factors, such as the extensiveness of surgery, related to the tumour itself and the clinical features in the recurrence of borderline ovarian tumours (BOT). We retrospectively evaluated the data of 103 patients with a borderline ovarian tumours treated at our institution between the years 2000 and 2012. The median age was 37 (16-79) years and the majority of the patients were premenopausal (76.7%). During the follow-up, 16 recurrences were observed (15.5%). The multivariate analysis showed that the micropapillary architecture and fertility sparing surgery were the only significant independent predictors for the development of a recurrence amongst all of the demographic and clinicopathological features. In our study group, we identified that the micropapillary architecture itself and the fertility sparing surgery had a significant impact on the development of a BOT recurrence. The patients who possess these features should be followed up more closely for a long time period. Impact statement What is already known on this subject? A borderline ovarian tumour is known as a recurrent disease. The recurrence rate varies between 5 and 20%. It is well known in the literature that patients treated by an oophorectomy have a relatively lower risk of development of a recurrence compared to the patients treated by cystectomy. What do the results of this study add? Although some of the clinicopathological features are shown to be risk factors for the development of a recurrence in many studies, some of the pathological-clinical and the demographic features have not been described as yet, or have been considered to be equivocal regarding the development of a recurrence. In this study, we investigate all possible demographic, pathological, and clinical factors associated with a recurrence. Not only the well-known pathological characteristics but also the new pathological parameters and clinical approaches have been investigated. For instance, microinvasion architecture and lymphadenectomy speculated in the literature as the risk factors for the development of a recurrence, have not been identified as risk factors in our study. On the other hand, our statistical analyses have revealed that micropapillary architecture should be described as a risk factor for the development of a recurrence. What are the implications of these findings for clinical practice and/or further research? We hope our study becomes influential in the literature on the field of a micropapillary architecture and the development of a recurrence. The patients carrying this feature have to be followed up very closely and carefully. Furthermore, our findings have indicated no significant relation between the performing of a lymphadenectomy and the rate of a recurrence. This result might be encouraging for the gynaecological surgeons to refrain from a lymphadenectomy for the borderline ovarian tumours.

The Use of Human Epididymis 4 and Cancer Antigen 125 Tumor Markers in the Benign or Malignant Differential Diagnosis of Pelvic or Adnexal Masses.

BACKGROUND: Ovarian cancer is one of the highest mortality cancers in gynaecology. Discrimination of benign masses from malignant ones may sometimes become a challenge for the clinician since there is not a reliable tumour marker, thus some unnecessary, highly morbid operations can be performed. AIMS: To explore the efficacy of human epididymis 4 (HE 4) and cancer antigen 125 (CA 125) markers in differentiating malignant and benign pelvic masses of ovarian origin and to identify the cut-off points for those markers. STUDY DESIGN: Prospective study. METHODS: Fifty-one patients who were diagnosed and planned to undergo surgery for ovarian mass between June 2008 and December 2008 were enrolled into this study. Preoperative venous blood samples were taken and frozen for marker investigation and final diagnoses were concluded by histopathological examination. After recruitment of all cases CA 125 and HE 4 levels were evaluated. RESULTS: The statistical analysis did not indicate any statistically significant difference between the CA 125 levels of the patients with malignant and benign adnexal masses (p=0.105). The HE 4 levels of the patients with malignant adnexal masses were higher at a statistically significant level compared to the patients with benign adnexal masses (p=0.002). For HE 4 tumour marker and at the cut-off point of >25 pM, sensitivity was 1, specificity 0.40, positive cut-off value 0.19, negative cut-off value 1, accuracy 0.47 and positive likelihood ratio 1.65. CONCLUSION: Human epididymis 4 is a better diagnostic tool than CA 125 in benign-malignant discrimination of adnexal masses. The cut-off value of 25 pmol/L for human epididymis 4 will contribute to providing proper guidance to patients with adnexal masses and applying the proper treatment method.

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.

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.

Perioperative complications in abdominal sacrocolpopexy, sacrospinous ligament fixation and prolift procedures.

BACKGROUND: Pelvic organ prolapse is an important problem for women. To overcome this issue, different operational technics are in use, such as abdominal sacrocolpopexy, sacrospinous fixation, and the total Prolift procedure. AIMS: This study assessed perioperative complications in abdominal sacrocolpopexy, sacrospinous fixation, and the total Prolift procedure. STUDY DESIGN: Retrospective comparative study. METHODS: Perioperative complications were defined as any complication occurring during surgery or the first 6 weeks postoperatively. Forty-five patients underwent abdominal procedures, 60 patients underwent sacrospinous fixation, and 43 patients underwent the total Prolift procedure. RESULTS: In the abdominal group, one bladder injury, four hemorrhages, and three wound dehiscences occurred. In the sacrospinous group, one rectal injury and one postoperative vault infection occurred. In the Prolift group, one bladder injury and one hemorrhage occurred. Minor complications were more frequent in the abdominal group than the others. The operating time and hospital stay of the abdominal group were significantly longer than the others. The Pro-lift procedure had less operating time and hospital stay than other procedures. CONCLUSION: The total Prolift may be a novel alternative for apical prolapse with low perioperative morbidities and complications.

Management and follow-up results of an incidental thyroid carcinoma in a young woman with ovarian teratoma.

Thyroid cancer in ovarian teratoma is reported to be rare and experiences are limited. A 26-year-old woman had undergone bilateral cystectomy and omentectomy for bilateral cystic adnexial masses. Pathological examination showed 1.5 cm follicular variant papillary thyroid carcinoma on the basis of unilateral mature cystic teratoma. Increased CA-125 and CA19-9 levels decreased to normal reference ranges after surgery, but postoperative magnetic resonance imaging indicated multiple abdominal cystic loci. After total thyroidectomy, high dose I-131 was administered to ablate thyroid tissue. Thereafter, levothyroxine was started to achieve subclinical hyperthyroidism. No iodine uptake was detected in post-therapeutic whole body scan (WBS) other than thyroid bed. This finding supported that tumor did not show dissemination to abdomen. No uptake on the first-year evaluation with low-dose I-131 WBS suggested the complete ablation of the thyroid gland. It is recommended that thyroid carcinoma arising from ectopic thyroid tissue in a teratoma should be managed as thyroid carcinoma in thyroid. However, direct dissemination to contiguous regions in abdomen and hematogenous dissemination to distant organs should be in mind. Radical surgery including total abdominal hysterectomy, bilateral salphingo-oopherectomy, pelvic and paraaortic lymph node excision and thyroidectomy is recommended. Fertility preserving surgery may be the surgical procedure as in the present case.

Hepatic hydatid disease requiring urgent treatment during pregnancy.

BACKGROUND: Pregnant women may experience an acute presentation of hepatic hydatid disease. The available literature is limited to case reports. METHODS: The charts of 7 patients who underwent urgent treatment for hepatic hydatid disease during pregnancy between 1992 and 2010 were reviewed. RESULTS: The median patient age was 27 (range 23-39) years and median gestational age was 18 (range 13-24) weeks. The symptoms were severe abdominal pain (4), vomiting (2), jaundice (2), pruritus (2) and severe dyspepsia (1); in the asymptomatic patient, a closed intraperitoneal rupture had been detected during gynecologic ultrasonography. Surgical drainage of the cysts was performed in all cases. The two patients with frank biliary rupture underwent choledochoduodenostomy or Roux-Y hepaticojejunostomy. Four patients required postoperative tocolysis. Albendazole was not used. All mothers gave birth to healthy babies at term. The patients were followed for a median of 9 (range 4-19) years. Two patients developed recurrences at 2 and 7 years; these were treated with surgical drainage and albendazole. CONCLUSION: This entity entails the responsibility of two human beings. Although it imposes limitations on the routine diagnostic and therapeutic options due to risk of premature labor or teratogenicity, acceptable results can be obtained in collaboration with the department of obstetrics and gynecology.

Diagnostic value of PET/CT is similar to that of conventional MRI and even better for detecting small peritoneal implants in patients with recurrent ovarian cancer.

OBJECTIVE: The aim of this study was to evaluate the diagnostic value of 2-(fluorine-18)-fluoro-2-deoxy-D-glucose ((18)F-FDG) PET/CT in comparison with MRI for the detection of recurrent ovarian cancer. METHODS: Forty-seven patients with suspected ovarian cancer recurrence after total ablative or cytoreductive surgery, as well as neoadjuvant or adjuvant chemotherapy, who had undergone (18)F-FDG PET/CT imaging were recruited for the present study. All patients also underwent MRI within a month of (18)F-FDG PET/CT for the same purpose. Recurrent cancer in the abdomen and pelvis was evaluated in each of the 47 patients and classified as either distant metastasis or local pelvic recurrence involving the vaginal stump, peritoneal implants, supradiaphragmatic region, and/or abdominal and pelvic lymph nodes. Special attention was paid to peritoneal implants. These were divided into five groups according to size of the implants: less than 0.5 cm (group 1), 0.5-1 cm (group 2), 1-2 cm (group 3), 2-3 cm (group 4), and larger than 3 cm (group 5). PET/CT findings were compared with abdominopelvic MR findings. Statistical analysis was carried out using the Wilcoxon signed rank test. RESULTS: Thirty-nine of 47 patients were found to have recurrent ovarian cancer. Both PET/CT and MRI were negative for recurrence in six patients. Overall sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of PET/CT were 97.5, 100, 100, 87.5, and 97.8%, respectively, whereas those of MRI were 95, 85.7, 97.4, 75, and 93.6%, respectively. For the peritoneal implants in groups 2 and 3, the sensitivity, negative predictive value, and diagnostic accuracy values of PET/CT were significantly better than those of MRI (P<0.05). CONCLUSION: The present study revealed that PET/CT is similar to conventional MRI for the detection of recurrent ovarian cancer. PET/CT has greater accuracy in the detection of small-to-medium-sized (<2 cm) peritoneal implants compared with MRI. This may affect surgical decision making.

Sentinel lymph node biopsy in endometrial cancer: description of the technique and preliminary results.

OBJECTIVE: To measure the feasibility of sentinel lymph node technique in endometrial cancer. MATERIAL AND METHODS: The study was designed as a prospective non-randomized case-control trial. Between 2010-2011, in Istanbul University, Istanbul Medical Faculty, Gynecologic Oncology department, 26 patients who were preoperatively evaluated as endometrial cancer enrolled in the study. Patients' detailed informed consent and ethics committee approval were obtained. Sentinel lymph node (SLN) detection rate was determined as the primary outcome. Sensitivity, specificity, positive and negative predictive values and particularly false negative results were determined as secondary outcomes. As a technique of SLN, injection of methylene blue to the subserosal myometrium of the uterine fundus via 5 cc syringe following peritoneal aspiration cytology procedure was obtained. Surgery was made after injection for an average of 5 minutes due to the physiological spread of the blue dye. Then, the standard protocol of hysterectomy was performed and the retroperitoneum was opened to perform lymphadenectomy. The presence of lymph node regions, and presence of a sentinel node was recorded on the trial record form. Positive staining nodes were sent separately for pathological examination. In the course of the study due to insufficient rate of staining, the technique has been changed to cervical and multiple uterine injections. RESULTS: As the primary outcome, an SLN positivity rate of 23% in 6 patients with a total of 8 lymph nodes were found. The remarkable finding was that in the first technique, the rate was 1/16 (6%), while the second technique, 5/10 (50%), respectively. The difference is statistically significant (p=0.001). In endometrial cancer stage I and II, secondary outcomes for sensitivity, specificity, positive predictive value, negative predictive value were 23%, 0%, 100%, 43%, respectively. Because there were no metastatic lymph nodes found, false negative rate was 0%. CONCLUSION: SLN approach is not valuable enough to eliminate the need for lymphadenectomy. On the other hand, it facilitates scanning micrometastases and ultrastaging, while its clinical value has not yet been established. However, according to the recent pilot studies, it provides a means for assessing micrometastases for the medium-risk group for local recurrence.

HOXA methylation in normal endometrium from premenopausal women is associated with the presence of ovarian cancer: a proof of principle study.

DNA methylation of polycomb group target (PCGT) genes is an early step in carcinogenesis and could potentially be assayed to determine cancer risk prediction. To assess whether methylation changes in PCGT genes in normal tissue is able to predict the presence of cancer, we studied HOXA gene methylation in normal endometrium from premenopausal ovarian cancer patients and age-matched healthy controls without ovarian cancer. DNA methylation of HOXA9 and HOXA11 genes in normal endometrium was associated with ovarian cancer in an initial test set and this was subsequently confirmed in independent validation sample sets. The overall risk of ovarian cancer was increased 12.3-fold by high HOXA9 methylation for all stages, and 14.8-fold for early stage ovarian cancers, independent of age, phase of the menstrual cycle and histology of the cancer. The results of this proof of principle study demonstrate the potential to detect ovarian cancer via analysis of normal endometrial cells and provide insight into the possible contribution of this novel approach in ovarian cancer risk prediction and prevention.

Malignant ovarian germ cell tumors: a single-institution experience.

OBJECTIVE: To evaluate the clinicopathologic prognostic factors in malignant ovarian germ cell tumors. METHODS: We reviewed the medical records of 70 patients treated from 1990 to 2006 at our center. Clinical data including demographics, stage, surgery, chemotherapy, survival, menses status, and fertility were collected from patients' charts. RESULTS: Median age was 22 years (range, 9-68). The histologic subtypes included 36 dysgerminomas, 11 yolk sac tumors, 3 immature teratomas, 1 embryonal carcinomas, and 19 mixed types. The most striking clinicopathologic finding was a history of concomitant immunosuppressant therapy, which was observed in 2 patients. Two patients had contralateral sex-cord tumors at presentation and follow-up. During a median follow-up period of 4.6 years, 11 patients had recurrence. The median time to recurrence was 8 months (6-28 months). Recurrences appeared in the abdominopelvic cavity in 9 out of 11 patients. Only one could be salvaged with second-line chemotherapy. Cumulative survival rate was 97% and 60% in patients with dysgerminoma and nondysgerminoma, respectively. Nondysgerminoma histology and residual tumor after surgery were unfavorable prognostic factors (P < 0.001 and P = 0.015). Fertility-sparing surgery was as effective as radical surgery among all eligible patients. Of patients with known menstrual status, 96% had regular menses. Of the 8 patients who opted for conception among these patients, 7 delivered healthy infants. CONCLUSIONS: Nondysgerminomas have an aggressive clinical course. New treatment strategies are needed for eradication of abdominopelvic disease at initial diagnosis and recurrent setting. Occurrence of malignant ovarian germ cell tumors may be associated with immunosuppression in some patients. Sex-cord stromal tumors may present with bilateral involvement. It is possible to maintain fertility after fertility-sparing surgery followed by chemotherapy.

Perioperative complications in abdominal sacrocolpopexy and vaginal sacrospinous ligament fixation procedures.

This study assessed perioperative complications in abdominal sacrocolpopexy and vaginal sacrospinous ligament fixation procedures. Perioperative complications were defined as any complication occurring during surgery or the first 6 weeks postoperatively. Forty-five patients underwent abdominal procedures (20 sacrohysteropexy and 25 sacrocolpopexy) and 60 patients underwent vaginal sacrospinous fixation. Of the 105 patients, 13 had vaginal vault prolapse. In the abdominal group, one bladder injury, four hemorrhages, and three wound dehiscences occurred. In the vaginal group, one rectal injury and one postoperative vaginal vault infection occurred. Major and minor complications were more frequent in the abdominal group than in the vaginal group. Blood loss was not significantly different. The operating time and hospital stay in the abdominal group were significantly longer than in the vaginal group. In conclusion, abdominal sacrocolpopexy had a higher rate of perioperative complications and longer hospital stay and operating time.

The expression of Ki-67, p53, estrogen and progesterone receptors affecting survival in uterine leiomyosarcomas. A clinicopathologic study.

OBJECTIVES: To evaluate the level of expression of estrogen receptor (ER), progesterone receptor (PR), p53 and Ki-67 in patients with leiomyosarcoma and to investigate the effect of these and to identify the clinical parameters on prognosis. MATERIALS AND METHODS: Twenty-four patients operated for LMS of uterine origin between 1994 and 2003 at Istanbul Medical School, Department of Obstetrics and Gynecology and Division of Gynecologic Oncology constituted our study group. The data of all patients were updated via mail or phone. The effects of stage, grade, chemotherapy, radiotherapy, number of mitoses, presence of necrosis, Ki-67 and p53 expression, presence of estrogen and progesterone receptors on survival were evaluated. RESULTS: The mean follow-up period of patients is 30.42 +/- 25.15 months. The mean overall survival for all LMS patients was estimated to be 48.4 +/- 10.38 months. The cumulative survival ratio in the 33rd month was 33.08. Age, menopausal status, history of prior radiotherapy, number of mitoses had no statistically significant effect on overall survival in our study although stage had a significant effect. Finding of greater than 10% steroid receptor expression has a positive effect on survival ([ER P = 0.019; log rank = 5.49] and [PR P = 0.023; log rank = 5.14]). The median value of Ki-67 was calculated to be 30. There was a survival advantage in patients with Ki-67 expression (P = 0.034; log rank = 4.49) below the median value. p53 levels had no significant effect on survival (P = 0.336; log rank = 0.92). CONCLUSION: Surgical staging is an important prognostic factor in LMS patients, while number of mitoses and grade of the tumor also seem to affect prognosis. Contrary to the current literature, our findings suggest that estrogen and progesterone receptor positivity greater than 10% may be associated with a better prognosis.

Therapeutic amniocentesis for treatment of twin-twin transfusion syndrome.

OBJECTIVE: The objective was to determine whether therapeutic amniocentesis may improve outcomes in patients with twin-twin transfusion syndrome. STUDY DESIGN: Eleven patients were managed aggressively with repetitive serial amniocenteses, and six patients were managed conservatively. RESULTS: The time interval between diagnosis and delivery was 17.4 days more in the amniodrainage group, but the difference between the groups was not significant (68.3+/-41.9 days in the therapeutic amniocentesis group and 50.83+/-29.7 days in the expectant management group [p=0.384]). The overall survival rate of the two groups was 38.2%, and was not significantly different between groups (40.9% in the amniocentesis group and 33.3% in the expectant management group; p=1.00). Two of nine (22.2%) infants in the amnioreduction group, and one of four (25.0%) infants in the expectantly managed group had neurological symptoms. CONCLUSION: Our results did not show a significant benefit of aggressive therapeutic amniocentesis. A slight improvement in perinatal outcome was observed.