Tuula Salmi

Prognostic Value of flow cytometric DNA content analysis in granulosa cell tumor of the ovary

The nuclear DNA content and S‐phase fraction of 23 ovarian granulosa cell tumors were measured from paraffin‐embedded tissue with flow cytometry. Crude survival of the patients with a euploid tumor (17 diploid, one tetraploid) was more favorable than that of the patients with an aneuploid tumor (n = 5, P = 0.02). The percentage of S‐phase cells was a good predictor of survival. If more than 6% S‐phase cells were present in the DNA histogram, both crude survival (P = 0.0001) and survival corrected for intercurrent deaths (P = 0.0001) were clearly inferior as compared with tumors with less than 6% S‐phase cells. The results indicate that DNA flow cytometric study may provide a rapid and valuable method to predict the biological behavior of granulosa cell tumors of the ovary.

Long-term effects of hormone replacement therapy on the uterus and on uterine circulation

OBJECTIVE Our purpose was to study the effects of postmenopausal hormone replacement therapy on the uterus and uterine circulation. STUDY DESIGN The study population consisted of 432 women, 58 to 59 years of age. Color Doppler ultrasonography with a transvaginal probe was used to measure the size of the uterus and the uterine artery pulsatility index. RESULTS The mean endometrial thickness in group 1 (controls without hormone replacement therapy) was significantly thinner compared with group 2 hormone replacement therapy and with group 3 after discontinuance of hormone replacement therapy. The mean uterine artery pulsatility index was lower both in group 2 and 3 compared with group 1. When hormone replacement therapy was initiated 2 to 10 years after menopause, the endometrial thickness did not differ from that among those who had started hormone replacement therapy earlier, but the pulsatility index was significantly higher. There was positive correlation between the size of the uterus and the pulsatility index in group 1, but the correlation was negative in group 2. In general, the duration of hormone replacement therapy had no effect on the pulsatility index. Estrogen users had a significantly thicker endometrium compared with estrogen-progestogen users. The pulsatility index was highest in the estrogen users with progestogen added every month. CONCLUSION The duration, onset of treatment in relation to menopause, discontinuance of hormone replacement therapy, and mode of treatment modify both the normal postmenopausal endometrial thickness and the uterine vascular resistance.

Impairment of heart rate variability during paclitaxel therapy

Paclitaxel, which has been reported to be effective in treating metastatic breast carcinoma and advanced ovarian carcinoma, has been associated with cardiac side effects. Therefore, the effect of paclitaxel on cardiovascular autonomic regulation was studied.

Radiation sensitivity of endometrial carcinoma in vitro

The role of radiation therapy is essential in the treatment of endometrial carcinoma. The present knowledge of the radiation sensitivity of endometrial carcinoma is mostly empirical and based on clinical trials. To study the inherent radiation sensitivity of endometrial carcinoma, we tested two long-established cell lines (RL95-2, KLE) and four new, low-passage cell lines (UM-EC-1, UM-EC-2, UM-EC-3, UT-EC-1) by using a 96-well plate clonogenic assay. This method has proved to be suitable for clonogenic studies of both squamous cell carcinomas (SCC) and adenocarcinomas in our recent works. Plating efficiencies of the cell lines tested varied from 0.005 to 0.45. Cells were irradiated in suspension with a 4-MeV linear accelerator at a dose rate of 2.0 Gy/min. Survival data were fitted by the linear quadratic function F = exp (-(alpha D + beta D2)). Radiation sensitivity was expressed as the area under the curve (AUC), equivalent to the mean inactivation dose. UM-EC-1 and UT-EC-1 were the most radiation-resistant cell lines tested (AUC greater than 1.6 Gy), while UM-EC-3 was the most sensitive (AUC = 1.0 Gy). The difference in radiation sensitivity between these cell lines was statistically significant (P less than 0.001). As a group, endometrial carcinoma cell lines were clearly more radiosensitive than most SCC lines of head and neck and vulva earlier tested by us. However, our results showed also great variance in the inherent radiation sensitivity between individual cell lines derived from endometrial carcinomas.

Transdermal estrogen for female stress urinary incontinence in postmenopause

OBJECTIVE To evaluate the effect of transdermal estrogen for stress urinary incontinence in postmenopause. STUDY DESIGN An open within patient, dose-finding study with transdermal 17-beta-estradiol combined with cyclic medroxyprogesterone acetate was conducted over 9 months in 21 patients (mean age 57.3 years) suffering from urodynamically verified mild to moderate stress incontinence without detrusor instability. RESULTS Subjective improvement was noted in 16 out of 21 patients (76%). The dose level of 50 micrograms was better tolerated than 100 micrograms and sufficient enough to achieve continence. CONCLUSION Transdermal estrogen therapy plays an adjuvant role in conservative therapy for mild to moderate stress urinary incontinence in postmenopausal women.

Endobrush Sampling for Endometrial Cancer

The two intra‐uterine cytological sampling methods Endobrush and Pistolet were compared for clinical applicability in 66 premenopausal and 47 postmenopausal women. The taking of the specimens succeeded in 94% of the cases with the Endobrush method and in 99% with the Pistolet method. The two intra‐uterine sampling methods were both almost painless. The Endobrush and the Pistolet specimens were filtered and stained by the Papanicolaou method. The Endobrush specimens were also used to make smears, which were also stained by the Pap method. According to the separate evaluations of two cytologists the Endobrush smear yielded specimens with a large or moderate number of cells in 59.0 to 71.4%, the Endobrush filter method in 73.6 to 76.5% and the Pistolet filter method in 71.4 to 76.8%. Specimens with good or moderate quality were found in 83.3%, 86.8 to 89.6% and 93.7 to 99.1%, respectively. Unsatisfactory specimens accounted for only 2.8–0.9% of the cases. All four endometrial carcinomas were placed in Pap classes 3 to 5 on the basis of the Endobrush and Pistolet filter specimens. The diagnostic quality of the smears was inferior to that of the filter specimens. The results suggest that the Endobrush filter method yields cytological endometrial samples which are similar in cell number, quality and diagnostic value to those obtained by the Pistolet method. Endobrush method is also simple, quick and painless, and therefore well acceptable to patients and suitable for clinical use.

High-dose chemotherapy with autologous stem cell support in advanced ovarian cancer.

Since 1981, over 300 patients reported with advanced or refractory ovarian cancer have been treated with high-dose chemotherapy supported by autologous bone marrow or peripheral blood stem cell transplantation. Partial or complete clinical response has been reported in 54-100% of the cases, but the median duration of the response in the majority of patients has been only a few months. It is obvious from the available data that high-dose regimens supported by autologous stem cell transplantation (ASCT) are not capable of inducing long-term survival in patients with heavy tumour burden or chemoresistant ovarian cancer. Recent reports on nearly 100 patients have described results of the use of high-dose chemotherapy as first-line treatment for patients with optimally debulked disease or negative second-look laparotomy. Response rates and survival have been better when compared to historical controls, but the efficacy of this treatment modality in inducing durable remission has not been tested in randomized trials. Most of the ongoing trials presented briefly in this review have been designed to evaluate the potential of high-dose therapy as first-line treatment in preventing the development of resistant tumour clones and recurrence. The role of sequential high-dose chemotherapy with ASCT as a part of primary treatment or as salvage therapy for chemosensitive recurrent disease is also under investigation.

Response of estrogen receptor-positive intraabdominal fibromatosis to aromatase inhibitor therapy

BACKGROUND Intraabdominal fibromatosis is a rare tumor-like lesion of uncertain etiology. CASE A 49-year-old woman underwent abdominal hysterectomy and bilateral salpingooophorectomy in 1997 to treat uterine leiomyomata and ovarian fibromatosis. Postoperatively, she received estradiol 2 mg daily as hormone replacement therapy (HRT). In 2000, laparotomy performed for a large pelvic tumor revealed inoperable intra-abdominal fibromatosis. The tumor, which was positive for estrogen and progesterone receptors, resolved during aromatase inhibitor therapy. The first follow-up computed tomographic (CT) scan revealed that the tumor masses were significantly reduced in size, and successive CT scans revealed stable disease. CONCLUSION Intraabdominal fibromatosis that expresses estrogen and progesterone receptors may respond favorably to treatment with aromatase inhibitors.

A longitudinal study of screening for endometrial cancer by endometrial biopsy in diabetic females.

Diabetics are at high risk of developing endometrial cancer; the relative risk of endometrial cancer in diabetics is fourfold in comparison to non-diabetic controls. The purpose of this longitudinal study was to evaluate the effectiveness of screening asymptomatic diabetic females in terms of the premalignant and malignant endometrial findings, and to try to determine the optimal screening interval. In 1980–1981, a group of 462 diabetic females was identified and registered. One half of them (237) was invited to be screened. Endometrial samples were taken by using Vabra aspiration. The results of this first randomized screening in 1980–1981 have been published elsewhere. At that time 124 females participated. The remaining 225 females acted as an unscreened control group. Eight years later (1988–1989), both groups were invited to be screened. The Pistolet aspiration method was used. At this stage, group 1 (screened in 1980–1981) consisted of 78 females, and group 2 (not screened in 1980–1981) consisted of 148 females. In 85% (193/226) of the females, the uterine cavity was reached with the Pistolet instrument; 96% of the females found the pain acceptable. In the group screened twice (group 1), no pathologic lesions of the endometrium were found in the second screening. In the group screened for the first time (group 2), one female had endometrial adenocarcinoma (0.8%), one had complex hyperplasia without atypia (0.8%) and four had endometrial polyps (3.3%). In 165 cases of 193, both a cytologic and a histologic specimen were available. In 130 cases (79%) the cytology was of class I, including the one endometrial adenocarcinoma. In three cases (2%) it was of class II and in one case (1%) of class III. Endometrial biopsy by Pistolet aspiration was a method highly acceptable by the patients for examining the endometrium. However, cytologic examination was not able to show the existing endometrial adenocarcinoma. One endometrial sampling of asymptomatic diabetic females during early menopause could detect the bulk of the occult, slowly progressing lesions of the endometrium. Such screeening might be most efficient in terms of cost-benefit ratio.

The Role of Cul-de-Sac Aspiration Cytology in the Follow-up of Ovarian Cancer

The methods most often used for follow-up of ovarian cancer are physical examination, CA-125 measurement and ultrasonography or computed tomography. In the present study the role of cul-de-sac aspiration cytology as a supplementary method was evaluated. We analyzed the records of 110 stage I-IV ovarian cancer patients who had undergone cul-de-sac aspiration as a part of their follow-up schedule after the primary treatment. During the median follow-up of 5 years altogether 577 cul-de-sac aspirations were performed with a median interval of 9 months. Only in 2 cases the obtained sample was insufficient for evaluation. Twenty patients had cul-de-sac cytology > or = class III at some point during the follow-up. In 12 cases the preceding or subsequent CA-125 values taken within 3 months were < 35 U/l. In 7 cases CA-125 values increased later, but in 5 cases the tumour marker values remained within normal range during the entire follow-up. Nine out of these 12 patients had a clinical recurrence later on, but 3 patients had no evidence of the disease. Twenty-seven recurrences were detected during the follow-up. Cul-de-sac aspiration cytology was the first or the only indication of recurrence in 9 cases (33%) and is a useful supplementary method in the follow-up of ovarian cancer.