[Effectiveness of aromatase inhibitors in comparison with metformin for neoadjuvant treatment in patients with endometrial cancer].

We compared the efficacy of endometrial cancer neoadjuvant treatment in 38 patients receiving nonsteroid (letrozol, anastrozol) or steroid (ekzemestan) aromatase inhibitors and 12 patients receiving metformin. The changes in glucose metabolism were revealed in 26.3% of patients treated with aromatase inhibitors and 16.7% of patients treated with metformin. However, comparison of endometrial thickness (M-echo signal) data, postoperative data on favorable differentiation grade changes rate and proliferative activity (Ki-67 expression) revealed the superiority of 2-4 weeks aromatase inhibitors course in comparison with 2-9 (average 5.3 +/- 0.7) weeks metformin treatment.

[Criteria for evaluating the effectiveness of aromatase inhibitors in the neoadjuvant treatment of patients with endometrial carcinoma].

Clinical and experimental effects of neoadjuvant treatment of endometrial cancer patients with non-steroidal aromatase inhibitors: letrozole (femara, n=10, 2.5 mg/day, 14 days), anastrozole (arimidex, n=15,1 mg/day, 28 days) and exemestane (aromazine, n=13, 25 mg/day, 14 days) were compared. Administration of anastrozole was mostly frequently followed by pain relief in the lower abdomen and/or decreased rates of uterine discharge. Endometrial wall thickness (M-echo signal) decreased significantly in 60% of patients receiving anastrozole, exemestane - 58.3% and letrozole - 40%. Substantial drop in intratumoral aromatase and blood estradiol levels occurred more frequently after anastrozole and letrozole while progesterone receptor levels in tumor were markedly lower after exemestane administration. Assay of blood LH (except letrozole), FSH and cholesterol appeared to be of less relevance. On the contrary, significance of assessment of marker Ki-67 expression, which, in the case of anastrozole, dropped in 6 out of 12 patients after a 28-day course, could hardly be underestimated.

[Features of ultrasound diagnosis of non-epithelial ovarian carcinoma].

Ultrasound examination using color Doppler imaging was used in 70 patients with non-epithelial ovarian carcinoma and 23 patients with subserous nodes of uterine myoma. Diagnosis was confirmed by histological assay of resected material. The procedure can be used for differentiated diagnosis between non-epithelial ovarian carcinoma and subserous nodes of uterine myoma, as well as for appraisal of individual features of tumor so that adequate treatment might be selected.

[Comparison of letrozole and exemestane used in non-adjuvant therapy of endometrial carcinoma].

The clinical and endocrine-related effects of 2-week preoperative treatment of endometrial carcinoma patients with a non-steroid inhibitor of letrozole aromatase (femara 2.5 mg/day, n=10) and a steroid inactivator of the enzyme (exemestane 25 mg/day, n=13) were compared. In the first group, pain relief in the lower part of the belly and/or decreased uterine discharge were reported in two cases, as well as a 31% drop in the mean endometrial M-echo (ultrasound) signal. In the exemestane group, two patients revealed moderate uterine discharge decrease matched by a 15.6% decrease in M-signal intensity; no tumor was detected in another patient on completion of the course. Letrozole effect was relatively greater when such parameters as tumor-tissue aromatase level, estrogen concentration in vaginal smear and blood-cholesterol, FSH and LH levels were taken into consideration. However, exemestane therapy involved a relatively sharper drop in the levels of tumor receptors of progesterone and a significantly higher estrogen/progesterone receptor ratio. Hence, no matter how short treatment duration was, both steroid and non-steroid aromatase inhibitors induced effects predominantly associated with lowering estrogen production in endometrial carcinoma patients. This makes a case for further clinical trials of these drugs to deal with the pathology.

[Risk of endometrial hyperplasia and carcinoma in breast cancer patients receiving adjuvant tamoxifen]. / Risk vozniknoveniia giperplasticheskikh protsessov i raka éndometriia u bol'nykh rakom molochnoi zhelezy, podvergshikhsia ad''iuvantnomy lecheniiu tamoksifenom.

The antiestrogen drug tamoxifen, which is widely used in adjuvant hormone therapy of breast cancer, presents certain risk of causing hyperplasia and endometrial carcinoma. Our clinical data on 1,969 breast cancer patients (stage I-III) (tamoxifen--947; control--1,022) showed a double rise in endometrial carcinoma risk in cases receiving hormone therapy. Endometrial carcinoma incidence in tamoxifen-treated patients was 3% while in the untreated ones--1.6% (p < 0.05). According to the endometrial tissue study in 439 breast cancer patients, proliferative effect of tamoxifen in the form of endometrial hyperplasia was 5--6 times in tamoxifen users. Meanwhile, endometrial carcinoma and hyperplasia risk increased during a much longer exposure to tamoxifen and in combination with such factors as obesity, diabetes mellitus, uterine myoma and estrogen-type colpocytological response. Hence, breast cancer patients need to undergo dynamic follow-up of the endometrium including ultrasonic examination of the small-pelvis organs and cytological study of ecto- and endocervical smears and endometrial aspirates.

[Doppler investigation of blood flow in uterine vessels of patients with endometrial cancer]. / Dopplerometricheskoe issledovanie krovotoka v matochnykh sosudakh u bol'nykh rakom éndometriia.

125 suspects for endometrial pathology were examined to evaluate clinical significance of color Doppler sonography for comprehensive diagnosis of endometrial carcinoma. This pathology was identified in 114; atypical hyperplasia--11. The data on combined application of traditional ultrasound and color Doppler sonography were compared with those on clinical and postoperative histological examinations. The combined method proved the most informative both in primary diagnosis of endometrial carcinoma and assessment of invasion into the myometrium. The specific features of blood supply to carcinoma are discussed.

[Neoadjuvant use of the aromatase inhibitor letrozole in uterine cancer: endocrine and clinical effects]. / Neoad''iuvantnoe primenenie ingibitora aromatazy letrozola pri rake tela matki: éndokrinnye i klinicheskie éffekty.

Endometrial cancer (EC) is estrogen-dependent tumor in the hormonal treatment of which mostly progestins are used. During last 5-7 years feasibility of aromatase inhibitors use in EC is discussed without any special practical move in this direction. To evaluate possible biological response of tumor and patients to such treatment, we conducted a short pilot study involving 10 primary postmenopausal EC patients, mostly stage Ia,b (average age 59) who received letrozole (Femara, Novartis) 2.5 mg/day during 14 days before operation. Clinical, sonographical, morphological, cytological and hormonal-metabolic (blood estradiol, FSH, LH, glucose, lipid fractions by RIA or enzyme-colorimetric methods; tumor progesterone receptors by LBA and aromatase activity by 3H-water release assay) studies were included into the protocol before and after treatment. Tolerability of letrozole was satisfactory in all patients. 2 patients reported decrease of pain and pathological secretions from uterine cavity. In 3 patients, decrease in M-sonographical endometrial signal was registered; average value after treatment was 31.1% lower than before it. Tendency to the decrease in estrogenicity of vaginal smears was revealed. Average decrease in blood estradiol was 37.8% and in progesterone receptor level and aromatase activity 34.4% and 17.5% respectively. Decrease of aromatase activity in tumor tissue was registered mostly in normal weight patients. A more detailed and longer randomized study of aromatase inhibitors in EC performed in neoadjuvant setting deserves consideration.

[Diagnostic potential of ultrasound examination for tumor recurrence and metastasis]. / Vozmozhnosti èkhografii v diagnostike retsidivov i metastazov u onkoginekologicheskikh bol'nykh.

Ultrasound examination was carried out in 252 patients following specific treatment of uterine and ovarian malignancies. To compare the effectiveness of diagnostic procedures, transabdominal and transvaginal examinations were performed in succession in all the patients using ultrasound (Doppler) technique. Transvaginal study proved relatively more sensitive (98.9%) and diagnostically accurate (97.2%) in detecting relapse. Transabdominal examination carried out in conjunction with color Doppler imaging was best for metastasis detection.

[Comparative study of the ploidy and cell proliferation of malignant epithelial neoplasms of various origin (flow cytometric assay)]. / Sravnitel'noe issledovanie ploidnosti i proliferativnoi aktivnosti kletok zlokachestvennykh épitelial'nykh novoobrazovanii razlichnogo proiskhozhdeniia (protochno-tsitometrichenkikh analiz)

Flow cytometry was used for measure DNA content of tumor cells of squamous-cell carcinoma of the tongue and mucosa of the oral cavity fundus, invasive ductal breast carcinoma, endometrial, colonic and rectal adenocarcinomas. Frequency of aneuploidy is characteristic of tumor. Frequency of aneuploidy is high in the oral cavity and breast cancer, colonic and rectal carcinomas and low in cancer of the tongue and endometrium Aneuploidy is associated with nonfavorable clinical and morphological signs of breast cancer, carcinomas of the oral cavity, corpurus uteri and rectum. High DNA index is typical of aggressiveness of carcinomas of the tongue, breast and endometrium. High proliferative activity prognostic factor of endometrial adenocarcinoma. We also found aneuploid cells in normal epithelium of the corpurus uteri, colon and rectum of patients with aneuploid tumors of the same organ. It is possible to suggest that these cells is an unfavorable cause recurrence.

[Flow-cytometric study of aneuploidy and proliferative activity of endometrial cancer cells as indicators of tumor aggressiveness]. / Protochno-tsitometricheskoe issledovanie aneuploidii i proliferativnoi aktivnosti kletok raka éndometriia kak pokazatelei agressivnosti opukholi.

DNA level and proliferative activity of malignant cells (89), atypical (7), glandular and glandular-cystous hyperplasia (15) of the endometrium and normal endometrium (28) have been assayed by flow cytometry. The results were evaluated versus degree of cell differentiation, depth of invasion and expected clinical prognosis. A reverse relationship was established between aneuplody frequency on the one hand, and cell differentiation degree and poor prognosis, on the other. However, a direct correlation was observed between DNA index and tumor aggressiveness. It was demonstrated that proliferative processes are much more active in non-differentiated cell carcinoma of the endometrium.