[Hyperthermic intraperitoneal chemotherapy in the treatment for recurrent ovarian cancer].

There are presented data of literature and own observations of the treatment for recurrent ovarian cancer using hyperthermic intraperitoneal chemoperfusion. The possible complications during hyperthermic chemoperfusion are discussed and the effectiveness of the method is analyzed. Further studies are needed to obtain more certain criteria for abdominal chemotherapy in these patients.

[Effectiveness of platinum-based chemotherapy in ovarian cancer patients with BRCA1/2 mutations].

The purpose of this study was to examine the clinical significance of mutations in BRCA1/2 in the formation of response to neoadjuvant platinum-based chemotherapy for ovarian cancer (OC). All patients who had had neoadjuvant chemotherapy (NCT) in our Institute from January 2000 till January 2013 were tested for carrier of mutations in BRCA1/2. In accordance with the BRCA-status we formed two groups--a group with hereditary advanced OC and a group with non-hereditary advanced OC. In the formed groups there was studied the effectiveness of chemotherapy. Patients carriers of mutations in BRCA1/2 showed a complete clinical response in 34% of cases, compared to 4% in the non-hereditary OC. Analysis of the results of cytoreductive surgery showed that in the group of hereditary cancer it was significantly higher the percentage of performing optimal cytoreductive operations (71% vs 48%). We analyzed the cases of complete pathologic response in all patients NCT and found that full pathomorphosis significantly associated with BRCA-status and the type of ongoing chemotherapy. It was important to note that all carriers of mutations in BRCA1/2 responded to cisplatin chemotherapy.

[Neoadjuvant chemoradiotherapy in the combined treatment of patients with stage IB2-III cervical cancer].

There are provided own observations on the use of cisplatin and capecitabine in schemes of combined treatment of patients with cervical cancer. Their efficiency as radiosensitizing agents is showed. There are discussed possible indications for the use of cisplatin and capecitabine in cervical cancer patients with metastatic lymph nodes.

[The role of laparoscopic interventions in diagnosis and treatment of patients with locally advanced cervical cancer].

The efficiency of laparoscopic para-aortic lymphadenectomy and radiodiagnostic methods in pre-treatment clarification of tumor lesion extent in stage IB2-III cervical cancer patients was compared. The Magnetic Resonance or sonographic imaging data was found to be inferior to lymph nodes morphological investigation followed by morphological study of distant lymph nodes. The results demonstrate the adequacy of surgical staging by laparoscopic para-aortic lymphadenectomy in patients with locally advanced cervical cancer for therapy tactics decision making.

[Laparoscopic surgery for treatment of endometrial cancer].

Surgery is the cornerstone of the treatment of endometrial cancer. With introduction of new technologies the laparoscopic intervention becomes increasingly popular for treatment of endometrial cancers. Forty five patients with endometrial cancer were operated in N.N. Petrov Research Institute of Oncology from September 2011 to March 2011. Laparoscopic hysterectomy with appendages was performed in 30 patients (66.7%), in 14 (66.7%) patients was also performed pelvic lymphadenectomy and in 1 (2.2%) case additional omentectomy was required. There were no intraoperative complications. The postoperative period was characterized by early mobilization, satisfactory intestinal peristaltic in the first 24 hours, minimal complication rate and absence of contraindications for adjuvant radiotherapy.

[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.

[Results of treatment for recurrent cancer of the uterine cervix].

The investigation involved 285 patients suffering from recurrences and distant metastases of uterine carcinoma cases of 24% of all (primary tumor). All recurrences generally occurred 12-20 months after the beginning of specialized therapy in 3.3-40%, with 78.3% detected within the first 24 months. Relapse was reported mostly in groups in which a single modality was used: surgery (32.4%) or radiotherapy (24.7%). Local recurrence rate for primary squamous cell tumor was 53.6%, adenocarcinoma - 6.3% and poorly-differentiated cell carcinoma - 4.9%. Complete regression of relapse following combined treatment was reported in 19% versus 14% and 4% after radiotherapy and chemotherapy, respectively. Moreover, more apparent responses were registered as a result of combinations of modalities (69%) as compared with 26% and 20% for radio- and chemotherapy, respectively.

[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.

[Prognostic significance of tumor cell ploidy in advanced ovarian carcinoma].

A micro-imaging retrospective investigation of tumor cell ploidy using exudates smears from 52 patients with serous ovarian adenocarcinoma (stage III-IV) showed survival in those with diploid tumor to be significantly longer (38 months) than in cases of aneuploid malignancies (16 months). Significant differences in survival versus ploidy, stage, residual tumor size, therapy modality and age were established with the aid of univariate analysis (Caplan-Meyer) of 5-year survival. Multivariate step-by-step regressive analysis (Cox) was carried out on the prognostic significance of such factors as residual tumor size (p=0.013), stage (p=0.019) and tumor ploidy (p=0.035). Further study showed ploidy to be a fully independent factor like any other factors of ovarian carcinoma development.

[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.

[The modern organ- and function-sparing surgical treatment in oncology]. / Sovremennoe organosokhraniaiushchee i funktsional'no shchadiashchee khirurgicheskoe lechenie v onkologii.

The results of organ-sparing treatment of patients with cancers of the breast, uterine cervix, endometrium and ovary are described in the paper. A prospective randomized clinical study launched in 1995 at Petrov's Research Institute of Oncology comprised cases of above 700 patients with breast cancer, around 300 women with cancer in situ and with microinvasive cancer of the uterine cervix and 83 patients with initial endometrial cancer. The results of the above treatment (segment resection + axillar dissection + radiotherapy) were shown to be similar to those obtained after Petey-Dyson mastectomy (5-year survival of 86.7% versus 88.8%, p = 0.81). The risk of local recurrence was increasing in patients with the tumors' diameter of more than 1 cm who were not treated by radiotherapy. The total regression of tumors was registered in 70% of patients with initial endometrial cancer after hormone therapy by progestagens and antiestrogens; 20% of them maintained the reproductive function.

[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.

[Tumor tissue aromatase and estrogen levels versus clinical course of endometrial cancer]. / Aktivnost' aromatazy, tkanevoe soderzhanie éstrogenov i osobennosti techeniia raka éndometriia.

Levels of aromatase, a key enzyme in estrogen biosynthesis, were assayed in tumor tissue sampled from 25 patients with endometrial cancer. In addition, estradiol concentrations were compared in normal and altered endometrial tissue from 78 patients suffering uterine cancer. Unlike breast cancer, aromatase was not detectable in altered endometrium unless tissue estrogens could be identified in both normal and tumor tissue. Hence, aromatase presence served as an indicator of malignant transformation. Its concentration in samples of uterine tissue varied 0-28.4 fM/mg protein/hr (an average of 12.9(1.7 fM/mg protein/hr). There was hardly any correlation between this level, on the one hand, and menopause and body mass, on the other. Yet, it tended to increase in step with stage of disease and cell differentiation decline. Estradiol concentrations in malignant endometrium in both reproductive and menopausal patients were higher than in macroscopically normal ones, while still cycling women tended to show higher values than menopausal ones. Although there was no significant difference in estradiol levels in the altered endomentrium of patients with pathogenetical patterns of uterine cancer stage I and II, they did show a direct correlation with clinical stage of tumor process and depth of invasion into the underlying myometrium. Hence, unlike estrogens circulating in blood, those contained in tissue ("intratumor") ones did enhance the aggressiveness of endometrial cancer course. It will be for further investigations to show whether it is due to an estrogen fraction being carried away by tumor from the circulation, or estrogens being synthesized by aromatase in tumor itself.

[Comparative characteristics of hormonal status in patients with receptor-negative cancers of the breast and of the endometrium]. / Sravnitel'nye osobennosti gormonal'no-metabolicheskogo statusa u bol'nykh s retseptor-negativnymi novoobrazovaniiami molochnoi zhelezy i éndometriia.

2,429 breast cancer patients and 478 patients with endometrial carcinoma were examined. It was suggested that the absence of estrogen receptors (ER) and/or progesterone receptors (PR) should be accounted for by peculiar endocrine features (including those of reproductive function) of the patients' medical history and/or hormonal metabolic status (body weight, estrogenemia, insulinemia, etc.) at clinical detection of tumor. The differences between breast and endometrial cancer in receptor-negative (R-) incidence were related to age (decade of lifespan) and menstrual cycle. Indices describing hormone-metabolic status were used for identification of receptor-negative or receptor-positive status of tumor (reliability of 65-70% for breast cancer and 75-80%--endometrial carcinoma) when it was not feasible under laboratory conditions.

[Frequency of infertility in endometrial cancer]. / Chastota besplodiia pri rake éndometriia.

A retrospective study included 1,559 patients with endometrial carcinoma who had received surgical and combined treatment (1968-1995). It was found that infertility was at the background of practically all cases under the age of 30 (92.3%). Moreover, high rates of infertility were discovered in the histories of patients with light-cell (mesonephroid) carcinoma which developed in menopause.

[Effect of neoadjuvant therapy with neovir on the level of steroid hormone receptors in endometrial cancer tissue]. / Vliiane neoad''iuvantnoi terapii neovirom na soderzhanie retseptorov steroidnykh gormonov v tkani raka tela matki.

The effects of neoadjuvant therapy with neovir, provera and their combinations on endometrial tumor morphology, progesterone (PR) and estradiol (ER) receptor levels were studied in 50 patients, aged 40-78, with primary tumors stage I-III, and without concomitant pathology. A 19-day course of neovir did not alter tumor morphological status but was followed by a significant rise in PR and ER concentrations. After neoadjuvant therapy in combination with provera, which generally lowers cytoplasmic receptor levels, mean values of receptors dropped in PR+ tumors while, in PR- tumors, they increased significantly. Our findings suggest that neovir may be used in clinic to stimulate endometrial tumor sensitivity to specific hormonal therapy, particularly, for hormone-independent neoplasia.

[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.