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A Ayhan

Publications and source records attributed to A Ayhan.

At least 19 recordsLinked to original sources

Genetic intra-tumour heterogeneity in epithelial ovarian cancer and its implications for molecular diagnosis of tumours.

Genetic analysis of solid tumours using DNA or cDNA expression microarrays may enable individualized treatment based on the profiles of genetic changes that are identified from each patient. This could result in better response to adjuvant chemotherapy and, consequently, improved clinical outcome. So far, most research studies that have tested the efficacy of such an approach have sampled only single areas of neoplastic tissue from tumours; this assumes that the genetic profile within solid tumours is homogeneous throughout. The aim of this study was to evaluate the extent of genetic intra-tumour heterogeneity (ITH) within a series of epithelial ovarian cancers. Several different regions (five to eight regions) of tumour tissue from 16 grade 3, serous epithelial ovarian cancers were analysed for genetic alterations using a combination of microsatellite analysis and single nucleotide polymorphism (SNP) analysis, in order to establish the extent of ITH. Maximum parsimony tree analysis was applied to the genetic data from each tumour to evaluate the clonal relationship between different regions within tumours. Extensive ITH was identified within all ovarian cancers using both microsatellite and SNP analysis. Evolutionary analysis of microsatellite data suggested that the origin of all tumours was monoclonal, but that subsequent clonal divergence created mixed populations of genetically distinct cells within the tumour. SNP analysis suggested that ITH was not restricted to random genetic changes, but affected genes that have an important functional role in ovarian cancer development. The frequent occurrence of ITH within epithelial ovarian cancers may have implications for the interpretation of genetic data generated from emerging technologies such as DNA and mRNA expression microarrays, and their use in the clinical management of patients with ovarian cancer. The basis of genetic ITH and the possible implications for molecular approaches to clinical diagnosis of ovarian cancers may apply to other tumour types.

Adenocarcinoma, Papillary↗

Medical treatment of vulvar squamous cell hyperplasia.

OBJECTIVE: To evaluate symptomatic response and recurrence rates of graduated topical fluorinated corticosteroid in patients with vulvar squamous cell hyperplasia. METHODS: Nine hundred seventy-six patients with biopsy-proven vulvar squamous cell hyperplasia from 1990 to 2003 were reviewed in this retrospective study. All patients were treated with graduated topical fluorinated corticosteroid. Data were obtained from hospital records. Symptomatic remission and recurrence rates were noted following six months local therapy. RESULTS: The mean age was 42.55+/-10.93 (15-85). The remission rate was 93.8% in six months. The remission rate was non-significantly higher in postmenopausal patients than that in their premenopausal counterpart (94.9% vs 93.0%, p=0.15). The disease recurred in 6.9% of patients. Of the patients that suffered recurrence 47.5% had persistent disease initially. The patients with following factors older ages (>40 years), postmenopausal period had significantly higher recurrence rates. Four patients with recurrent disease and six patients with persistent disease in the form of vulvar intraepithelial neoplasia I-II or atypical squamous hyperplasia, were treated with skinning vulvectomy. CONCLUSION: Corticosteroid in the treatment of vulvar squamous cell hyperplasia yielded excellent response rates. In the evaluation of patients without symptomatic relief, the first step should be a vulvar biopsy to exclude the presence of atypical components.

Adolescent↗

The Manchester operation for uterine prolapse.

OBJECTIVE: To evaluate the clinical characteristics, complications, and satisfaction scores of patients who underwent the Manchester operation. METHODS: This retrospective observational study evaluated data from 204 women who underwent the Manchester operation at the Department of Obstetrics and Gynecology of Hacettepe University School of Medicine, Ankara, Turkey, from January 1985 to April 2004. RESULTS: Mean age was 34.68+/-4.24 years and parity 2.47+/-0.96; 85.8% of the patients were premenopausal; 176 patients (86.28%) had grade 3 and 28 (13.72%) had grade 2 uterine prolapse; 95.1% of the patients had associated cystoceles and 51.3% had associated rectoceles; and 81.4% had urinary incontinence. Regarding early postoperative complications, 27 patients (13.23%) had febrile morbidity; retroperitoneal hematoma occurred in 1 patient (0.49%); urinary retention occurred in 45 patients (22.05%), and cervical stenosis occurred in 23 patients (11.27%). At 1 year, 1 patient had undergone abdominal hysterectomy because of unsuccessful cervical dilatation; and a mean of 3.6 years following the operation, 8 patients (3.9%) had undergone the tension-free vaginal tape procedure plus a vaginal hysterectomy for recurrent stress urinary incontinence and uterine prolapse. The mean satisfaction/acceptance score for the operation was 8.52+/-2.13 (range, 2-10). CONCLUSION: A high degree of acceptance/satisfaction and a low morbidity rate show the Manchester operation to be a good option for the treatment of uterine prolapse in women who wish to keep their uterus.

Adolescent↗

Vaginal hysterectomy: results and complications of 886 patients.

The aim of this study was to determine the feasibility, results and complications of vaginal hysterectomy. A total of 886 consecutive patients who had undergone vaginal hysterectomy for benign gynecological diseases were retrospectively analysed. Vaginal hysterectomy was successfully performed in 96.1% of the nulliparous and 99.9% of the parous patients. The mean duration (min) of the operation was 89.1+/-29.1. The operation time (min) of the nulliparous women was significantly higher than that of the primiparous and multiparous women (109.3+/-40.2 vs 81.1+/-33.2 and 85.1+/-28.3, respectively). The overall complication rate was 14.6%. The intraoperative and postoperative complication rates were 4.1% and 10.5%, respectively. The most common intraoperative complication was bladder injury (2.5%). Vaginal hysterectomy for benign gynaecological diseases has high feasibility with acceptable complication rates.

Female↗

Neoadjuvant chemotherapy in gynecological cancers.

Neoadjuvant chemotherapy in gynecological cancers is an approach that is shown to have positive effects on survival. It increases the rate of resectability in ovarian and cervical cancers and thus contributes to survival. However, there are studies reporting that despite increasing operability, the approach does not make any changes in terms of survival. Nevertheless, no negative effects have been reported in studies conducted till today. Prospective and randomized well-designed studies that encompass a high number of cases and parameters, including cost-effectiveness, are needed in both types of cancers. Until the results of such studies are obtained, neoadjuvant chemotherapy may be taken into consideration as an alternative when conventional methods do not suffice. The number of studies concerning endometrial, vulvar and vaginal cancers are few in the area of neoadjuvant chemotherapy.

Adult↗

The role of cytoreductive surgery in nongenital cancers metastatic to the ovaries.

OBJECTIVE: To investigate the role of cytoreductive surgery in patients with nongenital cancers metastatic to the ovaries. PATIENTS AND METHODS: One hundred and fifty-four patients with nongenital cancers metastatic to the ovaries treated in Hacettepe University Hospital, Gynecologic Oncology Unit between 1982 and 2004 years were retrospectively evaluated. Data were obtained from patients' records and pathology reports. Demographic characteristics, prognostic factors, 5-year and median survivals were analyzed in all patients. RESULTS: During study period, nongenital cancers metastatic to the ovaries constituted 9% of all malignant ovarian neoplasms. Primary cancers were breast (35), stomach (35) and colorectal (33) cancers, lymphoma (17), undetermined origin (16), appendix (7), ileum (4), pancreas (3), gallbladder cancer (2) and mesothelioma (2). Of patients, 67% were premenopausal and 33% were postmenopausal. Although most common presenting symptoms were abdominal distension with dyspeptic complaints in 46%, abdominal mass in 22%, and pressure symptoms in 8.4%, 15 patients (10%) were asymptomatic and were diagnosed in routine control examinations. Total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH + BSO), omentectomy, and bilateral pelvic and para-aortic lymphadenectomy (BP-PALND) with cytoreduction were performed in 102 patients (66%), TAH + BSO + omentectomy in 21 patients (14%), TAH + BSO in 23 patients (15%), minimal surgical effort including BSO or biopsy in 8 patients (5%). Eighty-four percent of patients received adjuvant treatment according to the primary origins. Mean follow-up was 47.3 +/- 5.9 months. Overall, 5-year survival was 36% and median survival was 42 months. Comparison of median survival times for the primary sites showed a significant overall differences (P = 0.0001) and were as follows: breast 54 months, stomach 18 months, colorectal 48 months, lymphoma 181 months, unknown primary 16 months, appendix 18 months, ileum 40 months, pancreas 3 months, gallbladder 8 months and mesothelioma 20 months. Median survival time of patients who underwent cytoreductive surgery was 48 months, compared with 26 months for patients with suboptimal cytoreductive surgery (P = 0.0039). The 5-year survival rate was 47% and 23%, respectively. Multivariate analysis identified age, menopausal status, primary site, diffuse peritoneal involvement and type of operation as prognostic factors. CONCLUSION: Presence of ovarian metastasis is associated with a poor prognosis in nongenital cancers. Surgery is essential for diagnosis of primary tumor and necessary for relief of symptoms. Cytoreductive surgery seems to have a beneficial effect on survival of selected patients, especially for patients with colorectal cancer metastatic to the ovary.

Adolescent↗

Pregnancy following intracytoplasmic sperm injection and preimplantation genetic diagnosis after the conservative management of endometrial cancer.

A rare case of a patient with conservatively treated endometrial carcinoma who conceived and delivered a healthy baby after the transfer of embryos with intracytoplasmic sperm injection (ICSI) and preimplantation genetic diagnosis (PGD) is presented. A 41-year-old woman had an office hysteroscopy in the infertility work-up and stage I endometrial adenocarcinoma was diagnosed. After conservative treatment, the patient underwent ICSI and PGD. She achieved pregnancy with two normal embryos. Two gestational sacs were observed but one of them was blighted. The patient subsequently delivered a healthy female infant. Repeated office hysteroscopy and endometrial sampling was performed after delivery. The appearance of the endometrium was normal on hysteroscopy, and the histology report was normal. The principal concern with medical therapy is that the lesion cannot be fully evaluated until the hysterectomy is performed, the nodes palpated, and the uterus is sectioned. The patient was referred to a gynaecological oncologist for definitive surgery.

Adenocarcinoma↗

Restaging in gynaecological cancers.

Regardless of recent technical developments in the scientific arena, stage is still the most important prognostic factor in gynaecological cancers. Surgical staging is performed in all types of gynaecologic cancers except for cervical cancer. Adjuvant therapies that contribute to survival are planned in the light of information obtained from staging procedures. Therefore, necessary information for further therapeutic management should be revealed by the end of surgical staging. A staging surgery that is not completed for any reason will not only deprive the patient of necessary treatments, but can also cause administration of unnecessary adjuvant treatments. This is especially important, given the undesired effects and cost of both chemotherapy and radiotherapy. A particularly relevant case in point is tumours that look like early stage; this is because upstaging up to 30% has been reported in ovarian and endometrial cancers. As for vulvar cancer, clinical staging has been reported to lead to about 15% over-diagnosis in comparison to surgical staging. Thus, the first step in all gynaecological cancers, except cervical cancer, should be to perform surgical staging when possible and unveil all surgical-pathological prognostic factors in the light of data obtained. Accordingly, restaging surgery should be considered in all cases that had incomplete staging. However, care should be taken to evaluate the benefits to be reaped together with the operative morbidity risk associated with the restaging procedure. This will both ensure accurate planning of postoperative treatment and provide a universal standard of approaching cancer patients and their treatments.

Female↗

Quantitative telomerase activity in malignant, benign and normal gynecological tissues.

OBJECTIVE: The aim of this study was to evaluate quantitative telomerase activity in malignant, benign and normal gynecological tissue samples by using the Telomerase-PCR ELISA kit, and to determine a cut-off level for malignancy by this quantitative method. MATERIALS AND METHODS: Fifty gynecological tumors, 27 benign gynecological disorders and 29 normal tissues were analyzed by the Telomerase-PCR ELISA kit. All tissues were confirmed by a pathologist. A ROC (receiver operator characteristic) curve was drawn to determine a threshold level best discriminating malignant tissues from benign pathologies and normal tissues. Telomerase activity was compared in malignant, benign and normal tissues. RESULTS: The mean level of telomerase activity of the malignant tumor samples (1.03 +/- 0.53 units) was significantly (p < .001) higher than the normal tissues (0.13 +/- 0.07 units) and benign pathologies (0.37 +/- 0.25 units). The cut-off point to differentiate malignant samples from benign samples was set at 0.42 units, where the sensitivity was 93.8% and the specificity was 89.3%. Positive predictive value was 84% and negative predictive value was 89.3%. There was a significant difference in telomerase activity between malignant, benign and normal tissues within each histological group. CONCLUSION: In this preliminary study, the telomerase-PCR ELISA method was found to have a high sensitivity and specificity to differentiate malignant gynecological tissues from benign tissues.

Biomarkers, Tumor↗

Combined effect of epirubicin and lymphokine-activated killer cells on the resistant human breast cancer cells.

Accumulating evidence suggests the concept that epirubicin and lymphokine-activated killer (LAK) cells cytotoxicity may be mediated by free radicals generation and P-glycoprotein-positive (Pg-p+) cancer cells are more sensitive for LAK cells than their drug-sensitive parental lines. We tested this hypothesis further by exposing drug-sensitive (WT) and epirubicin-resistant MCF-7 human breast tumor cells to epirubicin and LAK cells. Subsequently, we monitored cell proliferation as a measure of cytotoxicity. The cytotoxicity of epirubicin, LAK, and LAK + epirubicin (1/10 of IC50) was evaluated in 400-fold epirubicin resistant MCF-7 EPI(R) (P-glycoprotein overexpressing) and drug-sensitive MCF-7 WT cells. IC50 values were measured using the MTT cytotoxicity test. The MCF-7 EPI(R) cells exhibited an increased susceptibility to LAK cells than did the MCF-7 WT cells. P-gp+ MCF-7 EPI(R) cells were lysed by human LAK cells to a greater extend than were their drug-sensitive counterparts. LAK + epirubicin combined treatment increased susceptibility of MCF-7 WT and MCF-7 EPI(R) cells to LAK cells cytotoxicity. For both cell lines, cytotoxicity was dependent upon the concentration of the epirubicin and effector cell/target cell (E/T) ratio. The resistance of MCF-7 EPI(R) cells to epirubicin appears to be associated with a developed tolerance to superoxide, most likely because of a tree-fold increase in superoxide dismutase (SOD) activity and 13-fold augmented selenium dependent glutathione peroxidase (GSH-Px) activity. Acting in concert, these two enzymes would decrease the formation of hydroxyl radical from reduced molecular oxygen intermediates. The addition of SOD decreased cytotoxicity of epirubicin and LAK cells. Taken together, these observations support the role of oxygen radicals in the cytotoxicity mechanism of epirubicin and suggest further that the development of resistance to this drug by the MCF-7 EPI(R) tumor cells may have a component linked to oxygen free radicals. It is proposed that production of reactive oxygen species by the treatment of epirubicin and LAK cells can cause cytotoxicity of MCF-7 WT and MCF-7 EPI(R) cells. SOD, catalase, GSH-Px, GST (glutathione S-transferase), and GSH (reduced glutathione) must be considered as part of the intracellular antioxidant defense mechanism of MCF-7 WT and MCF-7 EPI(R) cells against reactive oxygen species.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Clinical value of immunohistochemically detected lymphovascular invasion in endometrioid endometrial cancer.

INTRODUCTION: Lymphovascular Invasion (LVSI) of tumour cells is marked as an important step in the process of tumour metastases and is an important prognostic factor in Endometrial Cancer (EC). Currently, the standard method for assessing LVSI is light microscopic examination of H&E stained sections. Tumour cells within lymphovascular spaces can evade detection on H&E staining if they are present in very small numbers or surrounded by a greater number of circulating cells. Dual immunostaining for epithelial and endothelial cell markers cell markers has been shown to increase detection rate of LVSI significantly. OBJECTIVES: To investigate the clinical significance of LVSI as detected by H&E (LVSI-H&E) and immunohistochemically (LVSI-IHC) in clinically stage I endometrioid EC patients. Methods. Single representative section of 90 patients with stage I endometriod EC were immunostained in accordance with established streptavidin-biotin peroxidase method using a mouse monoclonal pancytokeratin (PCK), clone AE1/AE3 and CD31 endothelial cell marker. The H&E sections and their corresponding immunostained sections were re-examined to identify LVSI. Clinical records were available on 72 patients. The following data were collected: age, race, parity, presentation, associated medical disorders (obesity, diabetes and hypertension), use of Tamoxifen or HRT, menopausal state, recurrence and survival. RESULTS: Overall, LVSI was present in 45 (50%) cases and absent in 45 (50%) cases on IHC, as compared with 17 (19%) and 73 (81%) cases, respectively, on H&E. Statistical analysis revealed significant association between LVSI-H&E and depth of myometrial invasion (P < 0.0001). The median follow-up period was 161 months (range 5-207 months). During the follow-up period, six of 14 cases with evidence of LVSI-H&E presented with recurrence as opposed to six of 58 patients with no evidence (OR = 6.26, 95%: CI = 1.3-30.6). There was a significant association between tumour recurrence rate and LVSI-H&E (P = 0.01). The 5-year recurrence-free survival was 54% for the group with H&E evidence of LVSI (95%: CI = 44-64%) compared with 89% for the group without (95%: CI = 82-97%). There was a significant difference in the recurrence-free survival between the two groups (Chi-square = 6.96, P = 0.008). In contrast, LVSI-IHC was found to be significantly associated only with high-grade tumours (P = 0.01) and survival analysis revealed no statistically significant association with recurrence or survival. CONCLUSIONS: LVSI-H&E in stage I EC remains an important predictive factor of recurrent disease and reduced disease-free interval. Immunohistochemically detected LVSI is a common event, associated with tumour grade and appears to be of no statistically significant clinical value.

Adult↗

Prognostic and therapeutic importance of lymphadenectomy in gynecological cancers.

Lymphadenectomy has been a matter of interest for years because of the increased morbidity rates in gynecological cancers due to the procedure itself and because the procedure requires experience. Although a number of alternative methods have been developed to find out the prevalence of gynecological cancers, dissection and histopathological evaluation of lymph nodes is still the gold standard in detecting disease. Even though there are opposing views regarding this approach, since the morbidity rate has decreased over the years many studies in the literature report that lymphadenectomy has prognostic and therapeutic value. Its contribution to survival can be attributed both to its being determinant in postoperative treatment modifications and to debulking and lymphadenectomy itself. In order to reap the prognostic and therapeutic benefit expected from lymphadenectomy, a sufficient number of lymph nodes must be dissected. Surgical experience is important both for the procedure itself and to reduce the morbidity due to the procedure. This study discusses the prognostic and therapeutic importance of lymphadenectomy in ovarian, endometrial, cervical and vulvar cancers.

Female↗