Effects of hormone replacement therapy regimens on mammographic breast density: the role of progestins.

AIM: To evaluate the effects of different regimens of hormone replacement therapy (HRT) on mammographic breast density. METHODS: Mammograms of 113 healthy postmenopausal women who were on different HRT regimens were evaluated retrospectively. All women had a baseline mammography and at least one mammogram after at least 12 months of HRT. Four parenchymal patterns were considered mammographically. Quantification of density changes that occurred on follow-up mammograms was done qualitatively and with reference to densities on baseline mammograms. RESULTS: Sixty women were treated with a continuous estrogen-progestin combination; 16 with a cyclic estrogen-progestin combination and 37 were with estrogen only. Twenty-six women had increased mammographic density after HRT. Mammographic density increase was detected in 23 women (38.3%) of the continuous estrogen-progestin combination group, two women (12.5%) of the cyclic estrogen-progestin combination group and one woman (2.7%) of the estrogen-only group. Mammographic density increase was more common among women in the continuous estrogen-progestin combination group than the other groups and this difference was found to be statistically significant (P < 0.001). Breast density increase was observed in 18 of 30 women (60%) with higher doses of progestin compared to 5 of 30 women (16.7%) with lower dose (P < 0.05). CONCLUSIONS: Postmenopausal HRT may increase mammographic breast density. Breast density appears to be mostly affected by higher doses and continuous administration of progestin.

Expression of cyclin D1 in normal, hyperplastic and neoplastic endometrium and its correlation with Ki-67 and clinicopathological variables.

METHODS: We investigated cyclin D1 expression in proliferative endometrium, endometrial hyperplasia and endometrioid adenocarcinoma, and examined the correlation of cyclin D1 expression with Ki67 as a cell proliferation associated marker. Immunohistochemical expression of cyclin D1 and Ki67 were studied in 30 cases with endometrial carcinoma, 14 cases with atypical hyperplasia, 15 cases with simple hyperplasia and 30 cases with proliferative endometrium. RESULTS: One out of 30 patients (3.3%) with proliferative endometrium, 1 out of 14 patients (7.1%) with atypical hyperplasia, and 8 out of 30 patients (26.6%) with endometrial carcinoma were found to have immunoreactivity to cyclin D1. All cases of simple hyperplasia had negative staining for cyclin D1. A positive immunoreaction for Ki67 was obtained in all cases. Statistically significant difference was found in cyclin D1 immunoreactivity between both proliferative endometrium and adenocarcinoma, and simple hyperplasia and adenocarcinoma (p<0.05). In patients with adenocarcinoma, cyclin D1 immunoreactive cases had higher mean Ki67 values compared with the non-immunoreactive ones (p<0.05). Ki67 and cyclin D1 immunoreactivity had no impact on overall survival. Univariate analysis revealed a significant relationship between survival and grade and stage (p<0.01). Cyclin D1 expression was not correlated with age, depth of myometrial invasion, lymphovascular space involvement, grade, lymph node metastasis and stage. CONCLUSION: Cyclin D1 expression in endometrial carcinoma is higher than proliferative endometrium and simple hyperplasia. These findings support that cyclin D1 may play a role in endometrial carcinogenesis.

Splenectomy in cytoreductive surgery for advanced ovarian cancer.

METHODS: To evaluate the series of advanced ovarian cancer patients who underwent splenectomy as part of their surgery, a retrospective file review of 258 ovarian cancer cases were examined. RESULTS: There were 13 cases that underwent splenectomy. These patients constitute 5% of all and 8.8% of the advanced ovarian cancer patients. Seven cases had splenectomy as part of their initial cytoreductive surgery while 6 had surgery for recurrent disease. Splenectomy was performed to resect hilar and/or capsular involvement in 9 (69%) cases, while in 3 cases (23%) splenic injury during adjacent tumoral resection required splenectomy. One patient had splenectomy for infarcts and died after the surgery with systemic complications nonrelated to the surgery. No other serious morbidity was detected. Median survival of the patients was 34 months (1-120 months) from the initial diagnosis. Median survival was 18 months (1-78 months) after the splenectomy. Three patients were still alive with no evidence of disease 2, 5 and 6.5 years after the splenectomy. CONCLUSION: Splenectomy is a feasible and safe procedure. However, it should be reserved for patients in whom optimal cytoreductive results could be achieved.

A comparison of three histological grading systems in endometrial cancer.

METHODS: To compare the architectural, nuclear and International Federation of Gynecology and Obstetrics (FIGO) grading systems in endometrial cancer 70 consecutive patients with endometrial cancer were retrospectively reevaluated with three grading systems. RESULTS: Twenty-eight (40%), 27 (38.6%) and 14 (20%) cases were reported to have different grades when architectural vs nuclear, architectural vs. FIGO and nuclear vs. FIGO grading systems were compared in evaluation, respectively. Only 3 (42.8%) of the seven died patients had grade 3 in all three grading systems. Five-year survival rates were 95.7, 80, and 78.6% for architectural grade 1, 2 and 3, respectively. Same rates were 96.7, 90.5, and 78.9% for nuclear and 96, 91.7 and 81% for FIGO grading systems, respectively. CONCLUSIONS: Grades of the tumors often change when different grading systems are used. Postoperative treatment should be considered when at least one of the grading systems indicates poor differentiation.

The influence of timing of systemic ketamine administration on postoperative morphine consumption.

STUDY OBJECTIVE: To determine the influence of timing of systemic ketamine administration on postoperative morphine consumption. DESIGN: Prospective randomized study. SETTING: Operating rooms, postanesthesia care unit, and gynecology service of a university hospital. PATIENTS: Forty-five patients undergoing laparotomy for benign gynecologic pathologies were randomized into 3 groups. INTERVENTIONS: In Group 1, before surgical incision, patients received 0.5 mg/kg ketamine IV, followed by normal saline infusion and normal saline IV at wound closure in group 1 (n = 15). In group 2 (n = 15), patients received 0.5 mg/kg ketamine IV before surgery, followed by ketamine infusion 600 mug . kg(-1) . h(-1), until wound closure and normal saline IV at that time. In the other group (group 3, n = 15), patients received normal saline IV before surgery, followed by saline infusion and then 0.5 mg/kg ketamine IV at wound closure. In the postoperative period, patient-controlled analgesia IV morphine was used for postoperative pain relief. First requested analgesic medication time was recorded. Postoperative pain was assessed by measuring morphine consumption at 0 to 2, 0 to 4, and 0 to 24 hours and visual analog scale (VAS) pain scores in response to cough at 2nd, 4th, and 24th hours and during rest at 0 to 2, 0 to 4, and 0 to 24 hours after surgery. MEASUREMENT AND MAIN RESULTS: First requested analgesia was shorter in group 1 than the others (P < .01). Mean VAS pain scores in response to cough at 24th hour in groups 2 and 3 were significantly lower than in group 1 (P < .001 and P < .01, respectively). Mean VAS pain scores during rest at 0 to 24 hours in groups 2 and 3 were significantly lower than in group 1 (P < .01 and P < .05, respectively). Morphine consumption was lower in groups 2 and 3 at 0 to 2 hours (P < .001 and P < .01). Moreover, morphine consumption at 0 to 4 hours in group 2 was significantly lower (P < .01). CONCLUSIONS: Lower pain scores and morphine consumption in groups 2 and 3 may be related to higher plasma ketamine concentrations caused by the higher doses and later administration. Our findings suggest that a single preoperative dose of ketamine provided less analgesia compared with other dosing regimens that included intraoperative infusions or postoperative administration.

Coexisting endometrial cancer in patients with a preoperative diagnosis of atypical endometrial hyperplasia.

AIM: To investigate the possibility of coexisting endometrial cancer (EC) in patients with atypical endometrial hyperplasia (AEH). METHODS: Forty-six consecutive women who underwent hysterectomy for AEH were analyzed. RESULTS: Final histopathological evaluation of hysterectomy specimens revealed EC in 11 patients (23.9%). Preoperative diagnosis of AEH was established by pipelle biopsy in eight patients and curettage was performed in the remaining patients. Of the patients with pipelle biopsy, two had a diagnosis of EC (25%), whereas nine women who underwent curettage, were further diagnosed as having EC (23.7%) (P > 0.05). Four (13.3%) of 30 women who had frozen sections at hysterectomy, were diagnosed with EC. Diagnosis of EC was missed in two patients (50%) at frozen section. In contrast, seven of 16 women (43.7%) who did not have frozen section, had EC. CONCLUSION: A relatively high incidence of EC is seen in patients with a diagnosis of AEH. Diagnostic results of pipelle biopsy and curettage were comparable. Frozen sections of hysterectomy specimens does not guarantee to exclude the possibility of EC, especially in patients with no myometrial invasion.

The endometrium in asymptomatic breast cancer patients on tamoxifen: value of transvaginal ultrasonography with saline infusion and Doppler flow.

OBJECTIVE: To define by transvaginal ultrasonography an optimal cutoff for endometrial thickness measurements to be used in screening for endometrial pathologies in asymptomatic breast cancer patients on tamoxifen, and to evaluate the incorporation of saline infusion sonohysterography and Doppler studies into the diagnostic scheme. METHODS: Sixty tamoxifen-treated women examined by transvaginal ultrasonography with saline infusion were included in this retrospective study. Variables of interest were endometrial thickness and texture, and the presence of intracavitary fluid at ultrasonography, total endometrial thickness, defined as the sum of the two endometrial layers and the presence of polypoid masses at sonohysterography, and uterine artery flow indices at Doppler ultrasonography. The dilatation and curettage performed after the sonographic scan detected pathological endometrial changes in nine cases, including six endometrial polyps, two endometrial hyperplasias, and one endometrial cancer. All parameters evaluated were compared between patients with benign and pathological endometria. Continuous variables that differed significantly between the groups were investigated further by receiver operating characteristics curve analyses and the diagnostic value of combinations of various parameters by binary logistic regression. RESULTS: The endometrial thickness in patients with proven endometrial pathologies was significantly greater compared with women with benign endometria, both by transvaginal ultrasonography (12.7 +/- 5.5 vs. 7.0 +/- 4.5 mm; P = 0.003) and by sonohysterography (6.3 +/- 2.8 vs. 4.1 +/- 1.7 mm; P = 0.036). While saline infusion sonohysterography also revealed a significantly higher frequency of polypoid masses in the former group (67% vs. 2%; P < 0.001), no other significant differences were defined between the groups in regard to any other sonographic or Doppler parameter evaluated. For the diagnosis of any endometrial pathology, the optimal cutoffs of endometrial thickness at ultrasonography and total endometrial thickness at sonohysterography were 9.5 and 5.5 mm, with sensitivities of 89% and 78% and specificities of 78% and 84%, respectively. A logistic regression model including polypoid lesions (B = -4.935; P < 0.001) and total endometrial thickness at sonohysterography (B = 0.432; P = 0.027) as the only two independent variables had a sensitivity of 100% and specificity of 84%. CONCLUSION: Saline infusion sonohysterography does, yet Doppler ultrasonography does not, add to the value of endometrial thickness measurements by transvaginal ultrasonography in the screen for endometrial pathologies in asymptomatic breast cancer patients on tamoxifen.

Successful salvage therapy of resistant gestational trophoblastic disease with etoposide, methotrexate, actinomycin-D, etoposide, cisplatin (EMA/EP).

A 26-year-old woman who had been treated for nonmetastatic gestational trophoblastic tumor with three courses of methotrexate with folinic acid rescue and had been lost to follow up for 4 years was referred with the fractional curettage diagnosis of choriocarcinoma that had been performed for abnormal vaginal bleeding. Her serum beta human chorionic gonadotropin (betahCG) was 706000 mIU/mL and there were multiple pulmonary metastatic foci. The uterus was 12 weeks pregnant-size and a 6 x 6-cm tumor mass was seen within the anterior uterine wall at ultrasonography. Following total abdominal hysterectomy etoposide, methotrexate, actinomycin-D, vincristine and cyclophosphamide (EMA/CO) regimen was given. Whole brain radiation of 30 Gy in 3 weeks for brain metastasis, discovered in magnetic resonance imaging was given after the first course. Since serum betahCG levels plateaued after three courses of chemotherapy and multiple pulmonary metastases persisted, treatment was shifted to etoposide, methotrexate, actinomycin-D, etoposide, cisplatin (EMA/EP) regimen. She was in remission after three courses of chemotherapy.

Ovarian endodermal sinus tumor in a 76-year-old woman.

A 76-year-old woman underwent surgery for pelvic mass, during which a 13 x 8-cm right ovarian tumor was discovered. On histopathological examination, she was diagnosed with an endodermal sinus tumor with right tubal metastasis. The patient was treated with four cycles of Bleomycin, Etoposide and Cisplatin. She died of disseminated disease four years later.

Transvaginal ultrasonography and uterine artery Doppler in diagnosing endometrial pathologies and carcinoma in postmenopausal bleeding.

Routine dilatation and curettage (D&C) in all patients with postmenopausal bleeding (PMB) is debatable, as 70%-80% will eventually receive benign diagnoses. Endometrial thickness (ET) measurements by transvaginal ultrasonography (TVUS) are used with high sensitivity to detect patients who would benefit from D&C, yet they suffer from low specificity that fails to reduce undue invasive procedures. The aim of this study was to define optimal cutoffs for ET in diagnosing endometrial pathologies in PMB and to assess a possible complementary role for Doppler ultrasonography. The study population consisted of 97 women with PMB; 39, 22 and 36 of whom had endometrial cancer (EC), benign endometrial pathologies and normal endometrial findings, respectively, defined by D&C performed after TVUS, which was used to measure uterine dimensions and ET, together with pulsatility and resistance indices (PI and RI, respectively) of the uterine arteries. Receiver operating characteristics curves revealed ET to be the most valuable parameter to prognosticate both EC and any endometrial pathology (sensitivities of 90% and 89%, and specificities of 79% and 94% with optimal cutoffs of 9.6 and 7.7 mm, respectively). Binary logistic regression revealed uterine artery RI to be the only independent variable that could be used together with ET, which increased the sensitivity of ET to 97% and 93% for EC and any endometrial pathology, but caused its specificity to regress to 58% and 53%, respectively. Same levels of sensitivity, yet better levels of specificity of 60% and 89%, respectively, were attained by using a cutoff of 6.3 mm for ET alone. Assessing uterine artery Doppler indices has no complementary role for measuring ET in evaluating PMB.

Angiogenesis in endometrial carcinoma: correlation with survival and clinicopathologic risk factors.

Association among angiogenesis, survival and clinicopathologic parameters in endometrial carcinoma was evaluated. Sixty patients who had been diagnosed as endometrial carcinoma, from 1993 to 1998, were included in the study. All patients had been surgically staged with bilateral pelvic and para-aortic lymph node dissection. All hysterectomy specimens were stained immunohistologically for factor VIII-related antigen. The area with the most intensified microvasculature was determined under low-power (x100) magnification, and the microvessel count of this area under high-power (x200) magnification was determined as the microvessel density (MVD) of the tumor. The mean MVD was 26.2 +/- 13.0 (range 6-68), and it was considered as high (n = 24; 40%), moderate (n = 19; 31.7%) and low (n = 17; 28.3%) when the MVD was >30, between 15-30 and <15, respectively. Statistical analysis included Mann-Whitney, Kruskal-Wallis and Spearman rank correlation tests. The Kaplan-Meier method was used to evaluate the difference between angiogenesis and survival. Multivariate analysis with the Cox regression model was used in MVD values and different clinicopathological parameters. There was positive correlation between MVD increase and surgicopathological stage (p < 0.05). A significant difference was seen between MVD increase and lymph node metastasis (p < 0.05). There were no differences between MVD and age, histological type, grade and lymphovascular invasion. MVD did not change in association with myometrial invasion depth. There was a significant difference in means of survival between the low and high MVD groups (p = 0.01). However, MVD was not an independent prognostic factor in multivariate analysis. Increased angiogenesis was found to be associated with advanced stage and decreased survival in endometrial carcinoma.