The effect of long-term use of progesterone therapy on proliferation and apoptosis in simple endometrial hyperplasia without atypia.

The aim of this study was to evaluate the effect of long-term use of progesterone treatment on proliferation and apoptosis in simple endometrial hyperplasia without atypia. In this prospective control study, endometrial tissue samples of 19 patients with simple endometrial hyperplasia without atypia (group 1), posttreatment biopsy materials of the patients after 3 months of cyclic progesterone treatment with noretisterone for 10 days (group 2), and 18 endometrial biopsy materials of the control group (group 3) were examined for proliferative and apoptotic activities. There was a statistically significant difference between the median values of the proliferative index of the three groups (P = 0.000). The proliferative index was significantly higher in the endometrial hyperplasia group than in posttreatment group (P = 0.000). But there was no significant difference between posttreatment group and control group. The median value of apoptotic activity was significantly different between three groups (P = 0.000). Apoptotic index was highest in hyperplasia group. A significant decrease in apoptosis was observed after the progesterone treatment (P = 0.002). The lowest apoptotic activity was detected in the control group. In conclusion, 3 months of cyclic progesterone treatment reduces both proliferative and apoptotic activities in endometrial tissue with simple hyperplasia.

Skin metastasis in ovarian carcinoma.

We report a case of 69-year-old woman who presented with pleural metastasis of a serous papillary adenocarcinoma of the ovary. After chemotherapy and surgery, she had 2 years disease-free survival. After this period of time, she presented with a swollen leg, a cellulitis-like syndrome and erythematous nodules at lower abdominal wall and upper leg skin. The skin biopsy revealed metastasis of adenocarcinoma in the dermis. She died after 4 months of the diagnosis of the skin metastasis. In 20 years experience in our unit, it is the first time that we recognize a cutaneous metastasis in ovarian cancer.

Radical versus conservative surgery for vulvar carcinoma.

OBJECTIVE: The comparison of the radical and conservative surgical approaches for vulvar carcinoma in relation to the rate of recurrence and complications. METHODS: The records of invasive vulvar carcinoma cases were retrospectively reviewed in Istanbul University, Cerrahpasa School of Medicine, Gynecologic Oncology Division and Social Insurance Institution, Ankara Maternity Hospital, Gynecologic Oncology Department. Surgically treated cases with squamous histology were divided into radical vulvectomy and conservative procedures groups and were compared with respect to recurrence, complications, and disease-free survival. RESULTS: One hundred thirteen cases of invasive vulvar carcinoma cases were of squamous histopathology and 92 of these were surgically treated. The rate of local recurrence was lower in the radical vulvectomy group (25%) compared to conservative procedures groups (42.5%; p>0.05). The complication rates were comparable between the radical vulvectomy and conservative procedures groups (32.7% versus 35%, respectively; p>0.05). At the end of five years of the follow-up, the disease-free survival rates were 51.5% in radical vulvectomy group versus 35.7% in conservative procedures group (p>0.05). CONCLUSION: The rate of recurrence, complication, and disease-free survival are similar for the radical vulvectomy and the conservative procedures. Deciding the surgical strategy for vulvar carcinoma should depend on the experience of the surgeon for the short-term adequate results.

Primary fallopian tube carcinoma: a retrospective multicenter study.

PURPOSE: This retrospective multicenter study aimed to assess the survival and prognostic factors of primary fallopian tube carcinoma. METHODS: The medical records of 29 patients with fallopian tube carcinoma from two centers were reviewed for age, stage, surgical intervention, relapse and survival. RESULTS: The mean age of the patients was 56 years (range, 37-76). Six patients were in Stage I (20.7%), eight cases in Stage II (27.6%), nine cases in Stage III (31%) and two cases in Stage IV (6.9%). Data on stage was not available in four cases (13.8). Fifteen patients underwent lymph node evaluation. The median follow-up was 29 months (range, 3-122). The median survival was 95 months with a 5-year survival rate of 69.7%. The median progression-free survival was 76 months with a 5-year survival rate of 51.8%. CONCLUSION: Age, stage and lymphadenectomy were found to be significant prognostic factors on overall survival.

Vascular endothelial growth factor in adnexal masses.

OBJECTIVES: To determine cyst fluid and serum vascular endothelial growth factor (VEGF) concentrations in patients with ovarian masses and to investigate the efficiency of this modulator in the clinical management of cystic pelvic masses. METHODS: Needle puncture for cyst fluid aspiration were performed on 88 cystic ovarian masses intraoperatively. Forty-five patients with benign and 43 patients with malignant ovarian pathology were analyzed for cyst fluid and serum VEGF concentrations. Both cystic fluid and serum VEGF concentration were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Cyst fluid VEGF levels of malignant cysts (40.65+/-17.69 ng/ml) were significantly higher than those of benign cysts (12.53+/-6.13 ng/ml; P<0.001). Similarly, higher serum VEGF concentrations were found in patients with malignant disease (0.72+/-0.17 ng/ml) compared with benign cysts (0.33+/-0.11 ng/ml; P<0.001). A statistically significant correlation was observed between cyst fluid and serum VEGF levels in both malignant and benign cysts. For serum VEGF, at a cut-off value of 0.41 ng/ml; sensitivity, specificity, PPV, and NPV were 95%, 78%, 80% and 95%, respectively. No significant correlation between cyst fluid VEGF concentration and tumor stage or grade could be found. CONCLUSIONS: Significantly higher concentrations of VEGF are present in cyst fluid and serum of patients with malignant ovarian cysts compared with benign ovarian ones. There is no relation between VEGF and tumor stage or grade.

A huge abdominal mass mimicking ovarian cancer: p53-negative but aneuploid myxoid leiomyosarcoma of the uterus.

OBJECTIVE: Less than 20 myxoid leiomyosarcoma cases were reported in literature. Since, these tumors are very rare and may exhibit highly malignant behavior despite their low mitotic index, clinical course and optimum type of therapy of myxoid variant of leiomyosarcoma were not well understood. The goal of this report is to contribute the better understanding of this rare type of tumor. METHODS: A 39-year-old woman presented with a huge abdominal cystic mass. Laparotomy was performed and frozen section diagnosis was low-grade uterine leiomyosarcoma. TAH-BSO, omentectomy, pelvic lymph node and peritoneal samplings were carried out. No chemotherapy was performed after surgical therapy. RESULTS: Final histopathological diagnosis was uterine myxoid leiomyosarcoma. The tumor was p53-negative and had aneuploid DNA content. The patient tolerated well the operation and she is alive and free of disease after 24 months of primary surgical treatment. CONCLUSION: Uterine myxoid leiomyosarcoma may present a huge abdominal cystic mass and can be treated successfully with surgery alone.

A strong prognostic variable in endometrial carcinoma: flow cytometric S-phase fraction.

BACKGROUND: The purpose of this study was to determine the role of flow cytometric S-phase fraction as a prognostic factor in patients with endometrial adenocarcinoma. METHODS: The study included 80 patients with endometrial adenocarcinoma of endometrioid type who were followed regularly between 1984-1995 in the Department of Obstetrics and Gynecology at Cerrahpasa Faculty of Medicine in Istanbul, Turkey. The method employed for the flow cytometric analysis was modified from Hedley et al. RESULTS: The S-phase fraction was identified as the most significant variable associated with death from endometrial carcinoma of endometrioid type by the Cox proportional hazards model. The risk of death was significantly higher in patients with S-phase values greater than 20%. Aneuploidy and DNA indexes were also significant prognostic variables. CONCLUSIONS: The S-phase fraction is considered to be a significant prognostic variable in identifying those patients with endometrial carcinoma who have a poor prognosis. The authors believe that S-phase fraction distinguishes those patients who may benefit from additional treatment approaches.

What should be the cut-off level of serum CA125 to evaluate the disease status before second-look laparotomy in epithelial ovarian carcinoma?

To assess the predictive value of serum CA125 level prior to second-look laparotomy in epithelial ovarian carcinoma, 45 patients who were clinically or radiologically tumor-free prior to a second-look laparotomy were studied. Serum CA125 levels were measured 10 days prior to the operation, and were compared with the surgico-pathological results. Twenty-eight (62%) patients were found to have tumor at surgery. The serum CA125 levels were > or = 35 U ml-1 (42%) patients. Tumors were found in 14 (74%) of these 19 patients. Although a serum CA125 level > or = 35 U ml-1 was a strong predictor of the presence of an intraperitoneal tumor, a level <35 U ml-1 was not predictive of a tumor-free state. When the cut-off level was accepted as 20 U ml-1, 28 patients (62%) were found to have elevated CA125 level. The sensitivity, the specificity, the positive and negative predictive value and the false negative ratio were calculated as 79%, 65%, 79%, 65% and 21% respectively. The threshold value for a raised CA125 level was considered and a lower level of 20 U ml-1 was suggested as a cut-off level prior to second-look laparotomy in evaluating patients with known epithelial ovarian cancer.

Ultrasonographic appearance of endometrium in postmenopausal breast cancer patients receiving tamoxifen.

OBJECTIVES: To assess the ultrasonographic appearance and associated pathological changes of the endometrium in postmenopausal breast cancer patients with tamoxifen therapy. STUDY DESIGN: Forty-eight postmenopausal breast cancer patients receiving 20 mg/day tamoxifen for 6-84 months (mean 29) and 38 control breast cancer patients without any hormonal treatment were examined by transvaginal ultrasonography and endometrial biopsy. Any thickening of the endometrium with cystic formations or homogeneous endometrial thickening > 10 mm detected by ultrasonography was defined as abnormal endometrial appearance. Homogeneous endometrial thickening < 10 mm without cystic formations was accepted as normal. Statistical analysis was performed using the Student's t-test and Mann-Whitney U test. RESULTS: The two groups were similar in age and menopausal period. The patients on tamoxifen therapy had a thicker endometrium (8.6 +/- 6.6 mm) than the non-treated women (4.8 +/- 3.1 mm), which was found to be a statistically significant difference (P < 0.01). The sonographic evaluations showed abnormal endometrial appearance in 8 cases of tamoxifen treated women while the others revealed homogeneous thickness < 10 mm without cystic formations or a thin linear echo with or without fluid in the endometrial cavity. All 8 patients with cystic appearance had endometrial thickness > 10 mm. Only 1 patient had endometrial cancer on biopsy and no pathology was observed in the remaining 7 patients. In the control group, only 1 patient had abnormal ultrasonographic finding who had insufficient endometrial tissue on biopsy. CONCLUSIONS: Tamoxifen can produce a sonographic image of the endometrium that resembles endometrial neoplasia. It is suggested that the discrepancy between the sonographic findings and histology may be the result of the stromal edema of the endometrium from tamoxifen treatment. Until more data are gathered, all postmenopausal breast cancer patients who are being treated with tamoxifen should have a periodic ultrasonographic examination and those presenting with a sonogram suggestive of endometrial pathology should undergo biopsy.

Appendectomy in the surgical staging of ovarian carcinoma.

OBJECTIVES: Extensive debulking is accepted as the primary method of operative management for carcinoma of the ovary. However, there is no consensus regarding the role of appendectomy in primary surgical treatment. The aim of this study was to assess the role of appendectomy in the surgical staging and cytoreduction of ovarian carcinoma. METHODS: The study was a retrospective review of 90 primary malignant ovarian carcinoma patients who had an appendectomy in addition to primary cytoreductive surgery. RESULTS: Out of 90 patients, 10 (11.1%) had metastasis to the appendix. The rate of metastasis to the appendix was 11.5% (9/78) in malignant epithelial ovarian carcinomas and 8.3% (1/12) in non-epithelial ovarian tumors. Of the patients with metastasis in the appendix, malignant epithelial ovarian tumors were identified in 90% (serous: 70%; clear cell: 20%), and non-epithelial malignant ovarian tumor were disclosed in 10% (granulosa cell carcinoma). There were no metastases to the appendix in the other histological types. Although metastasis to the appendix was not observed in early stage ovarian carcinomas, it was detected in 21.4% (9/42) of stage III and 50% (1/2) of stage IV. Macroscopic tumor metastasis in the abdomen was noted in all patients with metastasis to the appendix. CONCLUSION: Appendectomy for stage I and II patients was not beneficial and did not affect final staging. As a result, for the proper staging of ovarian carcinoma there is no advantage to the addition of routine appendectomy to primary cytoreductive surgery in early stage (stage I and II) malignant epithelial ovarian tumors. Appendectomy would contribute to the cytoreduction of advanced stage disease if it is macroscopically involved.

The prognostic significance of cervico-vaginal cytology in endometrial cancer.

In patients with endometrial cancer, preoperative identification of certain poor prognostic factors is helpful in planning therapy. To determine the place of cervico-vaginal cytology in this respect, we have studied the relationship between cervico-vaginal cytology and the well-known prognostic factors of endometrial cancer such as grade, myometrial invasion, peritoneal cytology, stage and histological subtype. A hundred and sixty two patients, all of whom underwent surgical therapy in our clinic, were included in this study in order to correlate the cytological results with the pathological findings. Cervico-vaginal cytology was negative in 88 patients (54%), suspicious in 26 patients (16%) and malignant in 48 patients (30%). Twenty four per cent of cases with adenocarcinoma and adenoachantoma, and fifty two per cent of patients with adenosquamous carcinoma, papillary adenocarcinoma and clear cell carcinoma had positive cervicovaginal cytology (p < 0.001). Seventy four per cent of patients with negative cervico-vaginal cytology had grade I tumor, while 5% of patients with negative cytology had grade III tumor. On the other hand, only 9% of patients with positive cervico-vaginal cytology had grade I tumor, while 55% had grade III tumor (p < 0.001). 8% of patients with inner 1/2 myometrial invasion had positive cytology, whereas 51% of patients with 1/2 outer myometrial invasion had malignant cells in their smear (p < 0.001). As for the staging of the endometrial cancer according to FIGO, 19% of patients with Stage I disease had positive cervico-vaginal cytology while 60% of patients in Stage II and 66% of patients in Stage III-IV had positive cytology (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The role of prolactin in luteal inadequacy: treatment of hyperprolactinaemia with bromocriptine.

Endometrial biopsy carried out in 628 women presenting for routine investigation of infertility showed that 268 had luteal phase deficiency and 46 of them also had hyperprolactinaemia, without evidence of any other cause of their infertility. These 46 patients were given treatment with bromocriptine, starting with a dose of 1.25 mg/day and increasing to 5 mg/day, depending on how well the drug was tolerated. Serum prolactin levels were assayed every month in all women who had not conceived and endometrial biopsy was repeated in those who had still not conceived after 3-months' treatment. The levels were shown to have decreased to within normal limits in all patients and 18 (39%) of the women had become pregnant, 13 of them during the first 3 months of treatment. No abnormality was detected in any of the babies. The remaining patients who did not become pregnant had normal prolactin levels and normal endometrial secretion after bromocriptine treatment.

Hyperprolactinemia and its effect on female sterility.

Starting with the isolation and purification of human prolactin, several studies have been conducted in order to understand prolactin (PRL) physiology and pathology in the human. Results of research effected since then have shown that high levels of PRL could cause sterility either through its effects on ovulation at the hypothalamic, hypophyseal or gonadal level or through the inhibition of steroid synthesis in the ovaries which leads to amenorrhea. In parallel with these findings, bromocriptine, a dopamin agonist inhibiting PRL secretion has been used in the clinic for the treatment of hyperprolactinemic states and the positive results obtained confirmed the role of PRL in human reproduction. The aim of our study is to investigate the causative mechanisms of sterility in hyperprolactinemic patients. For this purpose, in hyperprolactinemic cases with sterility a possible correlation between the PRL values and endometrial changes is investigated. Our findings indicate that effects of PRL on the receptors of distal organs show individual variations and depend on the degree of receptor sensitivity. It is believed that the effects of PRL through receptor mediation deserve further investigation.