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Tumors of female reproductive system

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Vol 11, No 1 (2015)
View or download the full issue PDF (Russian)
https://doi.org/10.17650/1994-4098-2015-11-1

MAMMOLOGY. TOPICAL ISSUE

8-11 1818
Abstract

Breast cancer (BC) heads a list of diseases of women in Russia, almost one fourth of all patients are in reproductive age. In 2009 BC was diagnosed in 23 % of all women younger than 45 y. o., who were diagnosed the malignant neoplasm for the first time. Polychemotherapy has a gonadotoxic effect, when the disturbance of ovarian function may vary from transient amenorrhea to development of premature menopause. The article considers the condition of reproductive function in women with BC: possibility of pregnancy during and after chemotherapy at the background of hormonotherapy and intervals safe for pregnancy. It sets out the results of research of pregnancy and birth in the BC patients. Operative treatment of phase I and phase II of BC may be carried out during any trimester of pregnancy. Modified radical mastectomy is more preferable. It is advisable to refrain from organ-preserving surgical interventions as the radiotherapy of pregnant women shall be suspended till the end of pregnancy. In case of relevant indications, the polychemotherapy may be carried out beginning from trimester II of the pregnancy. The last course of chemotherapy shall be completed at least 4 weeks before the delivery. The chemotherapy is contraindicative during trimester I of the pregnancy, as the teratogenic effect of antineoplastic drugs is very high especially during this period. Hormonotherapy is not recommended today for BC treatment in pregnant women. Tamoxifen exerts strong teratogenic effect and in 20 % of cases leads to impaired development of facial bones and genitourinary system. The article sets out the results of observations children of patients treated by chemotherapy during the pregnancy. Using of assisted reproduction helps to preserve the genetic material in BC patients. Multifollicular ovarian stimulation in patients with hormone-dependent breast cancer, which may entail the potential risk of recurrence, is still quite controversial matter.

12-17 996
Abstract

Despite the considerable progress in research of breast cancer (BC), taking into consideration the division into molecular subtypes, the mechanics of metastasis development in BC patients are not definitely investigated, especially at favorable prognosis. Research of new informative diagnostic and prognostic markers represents the modern problems of BC pathology in a new way.

This paper is devoted to study of osteoprotegerin (OPG) expression levels in tumor cells in BC patients. The study covered 83 female patients with regional BC (T2–4N0–3M0), treated from 2003 to 2010. The inclusion criteria were histologically proved diagnosis of invasive BC, age over 18 y. o., ECOG 0 or 1. In order to study OPG levels, we carried out immune histochemical test, which was carried out according to standard protocol on the sections of biopsy material. The OPG antibody from GeneTex, used in the study, was rabbit polyclonal, dilution 1:1000, incubation time – 30 minutes. Vizualization system was Real EnVision, anti-rabbit (by DAKO, Denmark). Immunohistochemical staining was studied by counting of number of positive cells in reference to total number of malignant cells. Expression over 50 % of cells was regarded as high, less than 50 % – as low. Average value of OPG expression level was 49 %, median – 50 %. Minimal value – 0 %, maximum value – 90 %. The patients were divided into 2 groups according their expression levels: Group 1 – OPG (high) expression (more than median), Group 2 – OPG (low) expression (less than median). OPG (high) Group was made by 47 patients, OPG (low) Group – by 36. When analyzing clinical and pathological characteristics of BC patients, taking into consideration OPG expression, there were noticed no reliable differences with respect to availability  or absence of affected regional lymph nodes, category T and Ki-67 indice. The group with positive estogen-progesteron receptors showed reliably more often the high values of OPG than the group with negative receptors (p < 0,05). When analyzing the duration till the progression and overall survival, a difference between the survival and time to progression (rise of metastases) in patients with low OPG levels and the same exponents in patients with high OPG levels was established.

MAMMOLOGY. DIAGNOSIS

18-26 1202
Abstract

Every year more than 1 million new cases of breast cancer are being recorded worldwide. Choice of appropriate tactics of treatment depends on the timely diagnosis and correct assessment of the prevalence of cancer.

The algorithm of patient»s examination includes clinical examination, X-ray mammography and ultrasonic diagnosis of breast. However, this is not sufficient for a complete interpretation of the patient»s condition in case of non-palpable breast formations, ambiguous interpretation of imaging under structural changes, increased density of breast tissue, etc.

In this regard, the introduction of new technologies and their evaluation in terms of practicality is a logical and developing method of early diagnosis of breast pathology.

One of the methods that enables enhancing the information capability of ultrasonic diagnosis of breast is elastography. It allows for the differential diagnosis of benign and malignant changes not only in the breast tissue, but also in the areas of regional lymph drainage.

Promising method of modern diagnostic breast care is digital mammography tomosynthesis. However, in spite of the first and very optimistic

data, this technique is still far from standard.

Complex diagnostics of breast pathology, in addition to clinical data and imaging results, are based on information obtained from biopsies. At the present stage core-biopsy is considered as the best way of verification, where the resulting material is subjected to immunohistochemical studies.

Thus, the spectrum of diagnostic capabilities is constantly expanding. Highly informative techniques included in the daily practice today enable clinicians to achieve optimal results in curing even greater number of patients.


27-34 2623
Abstract

Breast cancer (BC) is the most common female cancer type and the leading cause of female cancer mortality in Russia and in majority countries of the world. Along with the most common type of BC – ductal carcinoma, there are a lot of histological types, distinguished by structure features, which lead to a variable clinical and instrumental semiotics.

These histological types of BC in the group marked out special types of BC, including medullary carcinoma. The concept of medullary cancer includes typical medullary BC, atypical medullary BC and invasive ductal BC with evidence of medullary morphology.

Based on the current literature data, the authors discuss the main epidemiological, clinical and morphological diagnostic features of medullary BC. The authors pay special influence pathological picture, forming the characteristic diagnostic features of medullary cancer detected using X-ray mammography and ultrasound of the breast – the basic techniques of BC and other breast diseases detection.

In 2003–2013 diagnosed 19 medullary BC cases in women aged 18–56 years, with 18 of them were recorded in patients aged 34–56 years. The authors describe in detail the features of clinical, mammographic and ultrasound semiotics of medullary BC. Article is focused on the main X-ray and ultrasound characteristics, such as mass shape and margin features, as well as its internal structure, and also the results of power Doppler. One of the main features of this article is description of ultrasound elastography pattern of medullary BC, which could be find in only a small number of scientific articles.

Typical medullary BC, atypical medullary cancer and ductal carcinoma with medullary signs have different prognosis. This problem leads to necessity find reliable distinguishing features in mammograpic and ultrasound semiotics. It is seems important to reveal sites with indistinct margin. We have found the indistinct margin detection is not statistically significant for the differential diagnosis of typical forms of medullary BC from atypical forms and invasive ductal BC with evidence of medullary structure.

The authors conclude that the mammographic and ultrasound semiotics of medullary BC makes accurate differential diagnosis with benign breast pathology by X-ray mammography as well as breast ultrasound impossible. There are no statistically significant differences in the results of the mammography and breast ultrasound in different histological types of medullary BC. So these diagnostic features are not reliable for the differential diagnosis. However, the application of a comprehensive usage of mammography and breast ultrasound using modern technology of ultrasound diagnosis allows to suspect BC.

35-42 973
Abstract

Based on the scientific materials of domestic and foreign authors as well as on own observations, the results of the ultrasonic and mammographic research of the man’s mass pathology in the mammary gland projection being found in the process of differential diagnosis between malignant and benign tumors with similar clinical picture are presented in the article. Methodologically there has been carried out the analysis of the distinctive and rare signs of the benign process and malignant transformation of the man’s mass pathology in the mammary gland projection. In order to compare X-Ray and ultrasonic characteristics of the mass pathology in the patients’ mammary gland projection similar visual effects in the process of the prebiopsy clinical diagnosis forming has been studied in pairs. Mammography pictures and visualization in B-regime have been studied critically: shape correctness, localization, irregularity and obscurity of contours, presence of pathological inclusions), data of the colour and spectral Doppler sonography and 3D-regime scanning. According to the results of visual examinaion objective indications for needle biopsy of the man’s mass pathology in the mammary gland projection have been presented to the reader. The calculation of operation characteristics of different research methods of the mammary gland and combination of these methods has been done. The regularity of the information increase with an increase of the methods applied has been revealed. Based on the catamnesis examples of 317 men, the analysis of the necessity to make a combined examination variants of the mammary gland as the only definite opportunity to get a clinical diagnosis has been done.

61-68 890
Abstract

This article assesses the disturbance degree of apoptotic program in patients with preinvasive and invasive cervical cancer by investigating the expression level of genes of caspases-3, -6, -8 и -9 in mononuclear cells of periphery blood and in tumor tissue on the two regulating levels – on mRNA level (transcriptional) and proteolytic activity (post transcriptional). 75 patients with stage III of cervical intraepithelial neoplasias (CIN) III  (middle age of 32,9 ± 7,4),45 patients with stage IA (31,3 ± 6,0), 21 – with stage II (43,6 ± 13,2), 15 – with stage III–IV (46,9 ± 11,1) have been examined. The control group has been formed from 30 almost healthy donors without any cervical pathology and papilloma human virus (control 1) and 30 patients with a preinvasive and microinvasive cervical cancer (control 2). It has been found that in proportion of progress of cervix cancer, the membranous expression of CD95 increases in MPB – fraction (peripheral blood monocytes) when the a CIN and initial stages of cervix cancer, more than two times. Herewith number CD95+-lymphocytes is positively correlated with stage of cervical cancer (r = 0,91; R2  = 0,82; p << 0,01). It has been found out that the activity gain of caspase-8 (r = 0,92; R2  = 0,86; p << 0,01), caspase-6 (r = 0,77; R2 = 0,59; p << 0,01) and reduction activity of caspase-9 (r = –0,60;  R2 = 0,36; p < 0,01) in mononuclear cells of peripheral blood pointed out on the sensitivity increase to Fas-induced apoptosis. Opposite, in tumor tissue, beginning from CIN stage III, apoptosis-resistant phenotype is formed, it were defined by the expression of caspase-3 (r = –0,72; R2 = 0,52, p < 0,01), caspase-6 (r = –0,59; R2 = 0, 38; p < 0,01) и caspase-9 (r = –0,67; R2 = 0,45; p < 0,01) by mRNA level and proteolytic activity. It has been shown, that the cervical cancer development is accompanied by multilateral disturbances of apoptotic processes, which are realized in decreased function of caspases and multilateral resistance of tumor cells in against signals of apoptosis. The obtained results give an opportunity to examine the genes of caspase as a probable prospective biomarkers in complex diagnostic of a CIN and early diagnosis of a cervical cancer (in combination with morphological criteria and other molecular markers of viral origin)

MAMMOLOGY. CLINICAL OBSERVATIONS

48-52 2148
Abstract

Multifocal malignant tumors (MMT) represent a comprehensive and multifaceted problem of clinical oncology.

Today, as far as observations are accumulated, there are attempts to determine a real incidence rate of multifocal tumors. Research of MMT problem becomes more and more actual and significant in oncology. Several dozen thousands of MMT observations have been described all over the world for the recent 30 years. There is a stable trend towards the increase of the number of patients with such pathology. This is primarily concerned with the improvement of diagnostics, medical treatment and increased expectation of life.

The increase in incidence of MMT is due to such factors as increased average expectation of life, increased intensity of carcinogenic effects, urbanization, accumulation of hereditary loading and improved diagnostics of oncologic diseases. Detection and record of such pathology are based first on detection of simultaneous tumors, second – on diagnostics of tumor and retrospective determination according to life record data of the first neoplasm, third – on determination of further tumor at regular follow-up, which requires prolonged and high quality examination of the patients.

MMT most commonly develop in patients elder than 50 y. o., even in elder age in men than in women. The article describes a case of bilateral breast cancer in man. Clinicopathologic and immunohistochemical characteristics of the tumor were studied, the genetic polymorphisms were investigated by the method of polymerase chain reaction, associated with the risk of breast cancer development, genetic analysis of BRCA1 and BRCA2, blood cancer markers was done. Full equivalence of clinicopathologic and biological properties of tumor of the right and left mammae, witnessing the common etiology and pathogenesis of neoplastic process, was established. Each case of bilateral breast cancer in men shall be studied with particular care and referred in international medical literature for analysis of pathogenesis of such disease.

MAMMOLOGY. TREATMENT

43-47 1096
Abstract

Breast cancer heads the list of malignant neoplasms in women. In this connection the regional forms of cancer are diagnosed in one fourth of the patients. The treatment of regional cancer begins with systemic therapy and aimed at gaining of state fit for operation. The choice of modern treatment strategy is based on determination of molecular subtype of the tumor. One of them is referred to HER-2-positive cancer, requiring the administration of additional targeted therapy. This form of cancer is referred to prognostically pejorative tumors, as it’s more aggressive, leads to fast metastasis and early death of the patients. The “golden standard” of systemic chemotherapy is defined as administration of docetaxel and trastuzumab,  and antracyclic drugs, which also prove to be efficient. However concomitant administration of trastuzumab and antracyclines is limited due to their cardiotoxicity. Chemotherapy is not always efficient and, upon recommendations both of Russian and international oncologists, radiotherapy is the next stage of treatment. The question about radiosensibility of HER-2-positive tumors is still open and worth studying. Addition of radiotherapy to regional cancer treatment regimen in combination with the targeted therapy and chemotherapy may contribute to obtaining better survival rate and disease control. There are still no clearly defined standard for the sequence of chemo-radiation therapy. Simultaneous  chemo-radiatiojn  therapy results in  reliably better loco-regional control of tumor and  enables to gain a  higher degree of pathomorphological response on the one hand, and it may result in development of serious adverse effects on the other hand. Striving for improvement of immediate results of antineoplastic therapy, including that of regional cancer, by combining various methods, one should keep in mind the increasing action toxicity, which may have a considerable impact on the patients’ quality of living. Continuation of experiments and clinical trials in this direction is rather actual, as it allows getting new data for treatment of regional breast cancer.

GYNECOLOGY. DIAGNOSIS

53-60 1822
Abstract

Introduction. Ovarian cancer (OC) in Russia is ranked the seventh within the structure of general cancer diseases and the third within the gynecological tumors, due to such reasons the problem of early diagnostics is still actual. New technologies, such as color Doppler ultrasonography,

3D power Doppler ultrasonography contribute to increasing of opportunities of ultrasound analysis to detect any malignancy signs.

Materials and methods. The paper sets out the results of comprehensive ultrasound study of 68 patients with morphologically verified OC at stages IА–В, IIА–В. The control group was made of 100 female patients with morphologically verified ovarian tumors (serosal cystadenomas, thecomas, fibromas). A complex of the following ultrasound methods was used during the study: 2D and 3D ultrasonography in B mode, in color Doppler and power mapping mode, 3D angiography, spectrum Doppler imaging.

Results. Maximum size of tumor varied within a range between 37 and 300 mm (108 ± 61.2 mm). It worth noting that no direct dependence between the size of neoplasm and process phase was established. When assessing the echostructure, all ovarian tumors were divided into 3 structure types: cystic type (57.8 % of cases), cystic and solid type (33.3 % of cases), solid type (8.9 % of cases). The conducted analysis of types of small pelvis neoplasm echostructures enabled to evolve the sonographic types of ovarian tumors, more or less associated with the malignant transformation. The most relevanl Doppler ultrasonography exponents characteristic for benignant and malignant processes: resistance index in benignant tumors was 0.56, at OC – 0.32 (р < 0.001); average arterial blood velocity in benignant tumors – 7.8 cm/s, at OC – 20.1 cm/s (р < 0.001); average maximum venous flow velocity in benignant tumors – 3.2 cm/s, at OC – 9.3 cm/s (р < 0.001).

Conclusion. Therefore modern ultrasonography can detect and differentiate rather efficiently the localized variants of OC, provided that the main part of diagnosis is formed in mode of color and power Doppler mapping, which shall be taken into consideration during the primary diagnostics of OC.

 

69-75 1417
Abstract

A review article presents the modern methods of screening and early diagnosis of primary ovarian cancer (OC). This issue is still relevant in view of the continuing upward trend in incidence rate ratios along with a slight decrease in mortality and 5-year survival rate, as well as the lack of clear definition of the concept of pathogenesis. The diagnostic value of tumor markers and their potential, advantages and disadvantages are discussed. In light of this the need becomes evident for combination of tumor markers with radiological method of imaging, such as transvaginal sonography as the most affordable, safe and multi-reproducible method enabling to most accurately determine the nature of the process, its nosology belonging, as well as to carry out the required dynamic monitoring within a short time. More advanced imaging techniques such as computer tomography or magnetic resonance imaging proved too expensive for widespread use in view of their limited sensitivity and specificity. Attempt to assess the performance of marker screening on the base of CA-125 in groups, divided by clinical and pathogenic way of OC development also proved to be ineffective. Currently, none of the presented algorithms can meet the criteria of economic efficiency, even in the most developed countries. In view of the above, possible options to enhance their performance by developing reliable multimarker panels, the use of ultrasound color power doppler mapping, and others are considered. In addition, the feasibility and application prospects of ultrasound elastometry, mass-spectrometry, IVDMIA tests, OVA dx-test as part of screening programs are discussed. The data of recent studies on the direct comparison of diagnostic tests is given. The importance of genetic counseling for persons at high risk of cancer development process is noted. In case of mutation detection in the BRCA1, BRCA2 genes, in some countries a wide range of preventive activities is recommended: from regular «targeted» preventive examinations to the prophylactic oophorectomy and mastectomy. Increased survival rate of patients with OC is the main aim of all scientific research.

76-82 972
Abstract

Ovarian cancer (OC) is one of the most common malignant tumors of the reproductive system. The five-year survival rate is extremely low. This disease is difficult to verify due to lack of pathognomonic symptoms and timely diagnosis. The key issue to increase survival in ovarian cancer is finding new methods for early diagnosis. Thus, the development of new methods for diagnosis of ovarian cancer is one of the most urgent problems in modern oncology. The basic approach in this matter is searching for new biomarkers of ovarian cancer, which will be characterized by such concepts as sensitivity and specificity. Biomarkers present in modern oncology, including CA-125, have insufficient specificity and have low sensitivity. The advantage of using a combination of several diagnostic biomarkers instead of one or panels of markers has been proved. Modern proteomic technologies such as two-dimensional electrophoresis, mass spectrometric methods are a valuable tool for finding new biomarkers for various malignancies, particularly ovarian cancer. The best results are achieved by using SELDI-TOF technology (Surface-enhanced laser desorption/ionization time-of-flight), combining the use of chromatographic protein chips with mass spectrometric detection. Serum amyloid A1 deserves the greatest attention between all of the biomarkers identified using mass spectrometric methods, as its ability to have a direct influence on the development of the tumor has been proved. Also its increase by hundreds of times during the disease has been found compared to the other candidate biomarkers identified by mass spectrometry. The main characteristics of serum amyloid 1A have been analyzed and found as one of the most promising markers for the combined determination for prompt diagnosis of ovarian cancer.



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ISSN 1994-4098 (Print)
ISSN 1999-8627 (Online)