A clinical case of diagnosis of breast cancer in patients with family history of BRCA mutations 1.

BACKGROUND: The incidence of breast cancer is growing rapidly worldwide (1.7 million new cases and 600,000 deaths per year). Moreover, about 10% of breast cancer cases occur in young women under the age of 45. The aim of the study was to report a rare case of BRCA 1-mutated breast cancer in a young patient with multiple affected relatives. Breast cancer is due to a genetic predisposition with BRCA1 and BRCA2 representing a significant proportion of families with a very high risk of developing the disease over a lifetime of up to 50-80%. CASE PRESENTATION: In this paper we report a case of a 29-year-old woman with a confirmed diagnosis of left breast carcinoma. CONCLUSIONS: Mutations of the BRCA1 gene were revealed in the patient, in two of her sisters, brother and brother's daughter.

Severe adenomyosis with unexpectedly high CA-125: report of a rare case.

A 46-year-old woman presented to the emergency department with abdominal pain and abnormal uterine bleeding over the last year. She had a history of failed cyclic progesterone with tranexamic acid over the last 3 months to control her bleeding attacks. She had a tender pelvi-abdominal mass of 28 weeks' gestation size. Therapeutic curettage was performed, followed by correction of her iron deficiency anemia with intravenous iron. The trans-abdominal ultrasound of the pelvi-abdominal mass showed asymmetrical myometrial thickening, predominantly its anterior wall, with myometrial hyperechoic regions surrounded by hypoechoic areas suggestive of adenomyosis uterus for magnetic resonance imaging (MRI) evaluation. The MRI evaluation confirmed the diagnosis of adenomyosis uterus and showed diffuse asymmetrical uterine adenomyosis, predominantly its anterior myometrial wall, with an ill-defined endo-myometrial junction. Total abdominal hysterectomy with bilateral salpingectomy and bilateral ovarian conservation was performed after departmental approval and the patient's consent. The routine pre-operative investigations were completely normal except the cancer antigen (CA-125) which was unexpectedly high (1658 and 1046 IU/ml repeated twice two days apart). The histological examination of the surgical removed uterus confirmed the diagnosis of adenomyosis uterus and the pre-operative high CA-125 decreased to 22 IU/ml (normal range 0-35 IU/ml) one week after surgery. CONCLUSIONS: Unexpectedly high CA-125 over 1000 IU/ml can be seen in benign gynecologic conditions such as severe adenomyosis. The high CA-125 level is positively correlated to the uterine size in severe adenomyosis.

Postmenopausal adnexal torsion: rare case report.

Most ovarian and/or adnexal torsions occur in reproductive age and are less common in postmenopausal age. A 49-year-old menopausal woman presented to the Emergency Department with abdominal pain. She had a palpable pelvi-abdominal mass and abdominal tenderness on examination. Departmental ultrasound and magnetic resonance imaging (MRI) showed a large multilocular right adnexal cyst (15 × 12 cm) containing fluid with variable signal intensities on both T1 and T2 sequences (stained glass appearance) - most probably mucinous cystadenoma. The studied woman signed an informed consent form and agreed to exploratory laparotomy and adnexectomy. After the pre-operative investigations, which were done according to the hospital protocol, including CA-125 (26 IU/ml) and anaesthesia consultation, she was scheduled for laparotomy. At laparotomy an ovarian cyst originating from the right ovary was found with evidence of torsion of the infundibulopelvic and utero-ovarian ligaments (adnexal torsion). The right adnexa including the right ovary containing the ovarian cyst and the right fallopian tube was excised (adnexectomy). The histological examination of the excised adnexa confirmed the diagnosis of mucinous cystadenoma of the ovary. This report represents a rare case of an adnexal torsion in postmenopausal woman, to highlight that adnexal torsion can occur at any age and that the presence of ovarian mass or cyst predispose to adnexal torsion at any age.

The outcome of hypertensive disorders with pregnancy.

BACKGROUND: Hypertensive disorders (HTDs) with pregnancy remain a major health problem because of the associated adverse maternal and perinatal adverse outcomes. OBJECTIVES: To evaluate the outcomes of HTDs with pregnancy. PATIENTS AND METHODS: Four hundred and five (405) hypertensive women included in this retrospective multicenter study. Data of the studied women including maternal age, parity, gestational age at delivery, pregnancy outcome [preterm delivery (PTD), birth weight (LBW), Apgar scores, neonatal intensive care unit admission (NICU), intrauterine fetal death (IUFD), intrapartum and/or early neonatal deaths] were collected. Collected data analyzed statistically to evaluate the outcome of HTDs with pregnancy. RESULTS: Preeclampsia (PE)/superimposed PE group had significantly high relative risk (RR) and Odds ratio (OR) for PTD (RR 2.1; OR; 3.3; P = 0.0001 and P = 0.0001, respectively), LBW (RR 2.01; OR; 3.17; P = 0.0001 and P = 0.0001, respectively), and low Apgar score at 1st min (RR 1.7; OR 1.9; P = 0.01 and 0.01, respectively) and at 5th min (RR 2.2; OR; 2.36; P = 0.2 and 0.2; respectively). In addition, PE/superimposed PE group had significantly high RR and OR for NICU admission (RR 1.6; OR 2.2; P < 0.0002 and P < 0.0001, respectively) and IUFD (RR 2.9; OR 3.1; P = 0.01 and 0.01, respectively). CONCLUSION: women with PE/superimposed PE have high RR and OR for PTD, LBW, and low Apgar score at 1st and 5th min, NICU, and IUFD compared to the gestational and chronic hypertension with pregnancy.

Elevated and diagnostic androgens of polycystic ovary syndrome.

INTRODUCTION: A genetic variation at the level of aromatase enzyme and/or androgen receptors was suggested in polycystic ovary syndrome (PCOS). AIM OF THE STUDY: To determine the androgens elevated and diagnostic for PCOS. MATERIAL AND METHODS: A total of 120 PCOS women were compared to non-PCOS controls in this study. The studied women were evaluated thoroughly, including: day 2-3 hormonal profile and any hormonal change confirmed by two laboratory results eight weeks apart. Collected data were analysed to determine the androgens elevated and diagnostic for PCOS. RESULTS: The luteinising hormone (LH) and LH/follicle stimulating hormone (FSH) ratio were significantly high in the studied PCOS group compared to controls (p = 0.02 and 0.01, respectively). In addition, total and free testosterone and androstenedione were significantly high in the studied PCOS group compared to controls (p = 0.001, 0.003, and 0.02, respectively).The studied PCOS group had higher relative risk (RR) and odds ratio (OR) of elevated total testosterone (2.4 and 5.7, respectively), elevated free testosterone (2.9 and 4.9, respectively), and elevated androstenedione (3.0 and 4.8, respectively), compared to controls. CONCLUSIONS: Testosterone (both total and free testosterone) and androstenedione were the main elevated androgens and were diagnostic for excess ovarian androgens in the studied PCOS women, whereas dehydroepiandrosterone (DHEA) was not elevated and/or diagnostic for excess ovarian androgens in the studied PCOS women.

Gastric Cancer in Aktobe Region of Western Kazakhstan from 2009 to 2018: Incidence Rates, Trends, and Five-Year Survival.

OBJECTIVE: to assess the current state of gastric cancer (GC) incidence and its five-year survival across Aktobe region of western Kazakhstan from 2009 to 2018 by presenting key indicators and analyzing the most significant features. METHODS: Rough incidence rates (per 100,000) and average annual percent changes (aAPCs) were estimated for each age group at diagnosis with respect to gender, ethnicity, residence, the disease stages, tumor subsite, and histology type using linear regression analysis, including the prognostic index for 2019-2020. Overall five-year survival rates were estimated by the Kaplan-Meier method. RESULTS: Overall GC incidence increased from 19.2 to 29.3, and averaged 25.8 (R2 0.65) with aAPC of 3.2%, with a potential to further rise (30.4 by 2020, p<0.001). Non-cardia location (17.8, p<0.001, aAPC 6.4%) and intestinal type of the tumor (17.0, p<0.001, aAPC 7.35%) were predominant. The observed overall five-year survival rate was 28.4% (95% CI 24.5;32.3) with a median survival time of 8.0 months (95% CI 6.6;9.4). Groups aged 40-49 and ≥70 had the lowest rates (24.4% and 22.1%, respectively, log-rank p 0.008), but the youngest individuals (18-39 years) showed the shortest median survival time, 5.0 months after diagnosis at the survival rate of 29.4%. Resectional surgery contributed significantly to the median survival time, 23.0 months vs. 6.0 in non-operated patients (log-rank p<0.001). CONCLUSION: GC in Aktobe region was featured by growing incidence and unsatisfactory five-year survival rates. Indigenous males of 60-69 years old with intestinal histology type, as well as the youngest patients irrespective of their gender, ethnicity, and other characteristics were recognized as high risk groups. Besides, relatively high aAPC 5.1% in the youngest revealed their further expected vulnerability. Further research is suggested to focus on risk factors, including gene expression profiling, to find out an accessible preventive strategy.
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Is transvaginal ultrasound an appropriate screening tool for endometrial cancer in asymptomatic postmenopausal women? A case report.

A 55-years-old woman menopausal for the last 6 years discovered to have an endometrial thickness (ET) > 12 mm (suspected endometrial polyp) during routine evaluation in the gynaecology clinic using the transvaginal ultrasound (TVS). Departmental ultrasound confirmed the same TVS findings and suggested the presence of endometrial polyp as the main cause of the ET. Based upon the patient's risk factors (diabetic, hypertensive, obese with family history of endometrial cancer), a departmental decision was taken to proceed for diagnostic hysteroscopy and polypectomy after informed written consent. Large endometrial polyp and submucosal fibroid were found and excised during hysteroscopy. The histopathological results confirmed the intraoperative diagnosis of the endometrial polyp and submucosal fibroid. This report supports the American College of Obstetricians and Gynecologists recommendations and highlights that the TVS is not an appropriate screening tool for asymptomatic postmenopausal women. In addition, the ET > 4 mm in asymptomatic postmenopausal women does not need evaluation.

Interdisciplinary Approaches to Assessing the Health of People Living in Environmentally Adverse Conditions.

BACKGROUND: The health status of the population of different ages was examined. Since children are very vulnerable to environmental factors, our goal was to examine their health status and compare them with those of the older population. Also one of the important tasks of our study was the installation of carcinogenic and non-carcinogenic risks for children and adults of different sexes. METHODS: During our research, we calculated the air pollution index, investigated the incidence statistics of the population, and calculated the lifetime average daily dose (LADD). We investigated the content of sulfur dioxide, hydrogen sulfide, nitrogen oxide, ammonium and hydrogen carbonates and compared it with safe level of exposure. RESULTS: In Aktobe, the Republic of Kazakhstan the external environment is polluted with boron and chromium, and in Aktau - with organic hydrocarbons. High morbidity rates in adolescents were found for endocrine disorders, digestive system diseases, and musculoskeletal system disorders. Estimating the prevalence and incidence of newly diagnosed diseases among women in Aktau showed that the overall incidence rate, as well as the incidence of respiratory and skin diseases, declines with age. The incidence of the genitourinary system and the number of nervous disorders increase, and the number of neoplasms increases in men population. A study of carcinogenic risks showed that children with Aktau, especially boys, have the greatest risk of cancer. CONCLUSION: The conducted research shows that environmental factors have a big impact on the health of the population.

Metabolic and immunologic aspects of fetoplacental insufficiency.

PROBLEM: The chronic placental insufficiency is the most common cause of intrauterine hypoxia, retardation of fetal growth, and other threatening conditions. Immune disturbances may occur in the system "mother-placenta-fetus." METHOD OF STUDY: Biochemical blood indicators were studied on an automated biochemical analyzer. Pattern of lymphocyte subpopulations was detected by direct membrane immunofluorescence. RESULTS: Study revealed imbalance of immune parameters, caused by placental insufficiency (increase natural killers (CD16(+) , CD56(+) ), B lymphocytes (CD19(+) CD3(-) ), T and B lymphocytes with HLA-DR(+) antigen, and early activation of immune cells (by CD25(+) ), as well as disorders in apoptotic mechanisms (by CD95(+) )). CONCLUSION: Placental insufficiency leads to abnormalities of the immune system in pregnant, parturient women and maternity patients which were evaluated by localization of activation markers CD25(+) CD95(+) on the CD3(+) , CD4(+) , CD8(+) , CD16(+) , CD56(+) lymphocytes. This is reflected in the change of lymphocyte functions in newborns.

Thymic emigration patterns in patients with type 2 diabetes treated with metformin.

Recent data suggest that thymic output, which provides the naive T cells necessary for the normal functioning of T-cell-dependent immunosurveillance cellular immunity including anti-cancer protection, can be disturbed in the course of type 2 diabetes. Metformin, an anti-diabetic drug commonly confirmed as an agent with many potential anti-cancer activities, might be helpful in this immune correction. The profile of thymic output was evaluated in the current study on the basis of the signal-joint T-cell receptor excision circle (sjTREC) concentration in peripheral blood polymorphonuclear cells and thymic emigrant content in peripheral blood evaluated from CD127 and/or CD132 antigen expression. It was revealed that recent thymic emigrants and more differentiated CD127(+) CD132(+) cell populations were decreased among naive T cells and CD8(+) T cells, whereas RTE count was increased in CD4(+) T cells, and the CD127(+) CD132(+) cell population was less numerous than in non-diabetic participants. Terminally differentiated thymic emigrants, i.e. CD127(-) CD132(+) cells, were increased in naive T cells and in CD8(+) T cells. Metformin affects mainly the early phases of thymic export, increasing CD127(+) CD132(-) and CD127(+) CD132(+) cell populations in naive T cells and the CD127(+) CD132(-) population in CD4(+) T lymphocytes. It could be concluded that type 2 diabetes deteriorates thymic immunostasis. The decreased thymic output could be compensated by metformin, especially with regard to CD4(+) naive T cells. It is the first time that therapy with metformin has been documented by us as particularly useful in the control and normalization of thymus function, regarding correction of early populations of thymic emigrants.

Cancer incidence and mortality data in Aktobe, west Kazakhstan, 2000-2010.

The article provides an assessment of the dynamics of cancer incidence and mortality in the territory of Aktobe city for the period 2000-2010. The most common cancers were found in the lungs, stomach, esophagus and breast throughout the period, with slight increase in colon cancer and decrease in esophageal cancer being apparent. In an attempt to cast light on effects of environmental pollution, the authors also compared data on total emissions of chemicals into the air. While preliminary, the findings provide a basic picture of cancer burden in this industrialised city in Kazakhstan which should be followed up by more comprehensive monitoring.

Malignant Neoplasm Prevalence in the Aktobe Region of Kazakhstan.

An oncopathological state assessment was conducted among adults, children and teenagers in Aktobe region for 2004-2013. Overall the burden of mortality was in the range of 94.8-100.2 per 100,000 population, without any obvious trend over time. Ranking by pathology, the highest incidences among women were registered for breast cancer (5.8-8.4), cervix uteri (2.9-4.6), ovary (2.4-3.6) and corpus uteri, stomach, esophagus, without any marked change over time except for a slight rise in cervical cancer rates. In males, the first place in rank was trachea, bronchus and lung, followed by stomach and esophagus, which are followed by bladder, lymphoid and hematopoietic tissues pathology. Agian no clear trends were apparent over time. In children, main localizations in cancer incidence blood (acute lymphocytic leukemia, lymphosarcoma, acute myeloid leukemia, Hodgkin's disease), brain and central nervous system, bones and articular cartilages, kidneys, and eye and it's appendages, in both sexes. Similarly, in young adults, the major percentage was in blood and lymphatic tissues (acute myeloid leukemia, acute lymphocytic leukemia, Hodgkin's disease) a significant percentage accruing to lymphosarcoma, lymphoma, other myeloid leukemia and hematological malignancies as well as tumors of brain and central nervous system, bones and articular cartilages. This initial survey provides the basis for more detailed investigation of cancer epidemiology in Aktobe, Kazakhstan.

Increased circulating RANTES in type 2 diabetes.

AIM: The pro-atherogenic role of RANTES, a chemokine expressing pleiotropic activities, in the course of type 2 diabetes-related atherosclerosis has been well documented. However, it is not known which of the diabetes-related factors primarily influence serum RANTES levels in patients with type 2 diabetes. Our aim was to investigate relationships between several factors known to be related to an increased risk of atherosclerosis and serum RANTES levels in type 2 diabetic patients. METHODS: A total of 168 subjects were examined, which included 138 patients with type 2 diabetes and 30 non-diabetic controls. Measurements of venous, fasting, plasma glucose, HbA1c, lipid profile, 1,5-anhydro-D-glucitol (1,5-AG) plasma levels, homocysteine and the fasting, serum C-peptide levels were performed. Serum concentrations of RANTES were assayed using BD(TM) Cytometric Bead Array tests. Peripheral insulin resistance was expressed according to a new index defined by Ohkura et al. RESULTS: RANTES levels in type 2 diabetic patients correlated with 1,5-AG, fasting glycaemia, HbA1c and the Ohkura index. Multivariate regression analysis was performed taking into consideration several factors related to the inflammatory process and atherosclerosis, namely the patient's age, diabetes duration, waist circumference, 1,5-AG, HbA1c, lipid profile parameters, serum homocysteine levels and Ohkura index, as independent variables potentially influencing serum RANTES levels in type 2 diabetic patients. It is shown that RANTES concentrations in the serum is primarily dependent upon 1,5-AG plasma levels. CONCLUSION: Our results suggest that increased serum levels of RANTES in type 2 diabetic patients are closely related to postprandial (acute) hyperglycaemia.

In vitro maturation is slowed in prepubertal lamb oocytes: ultrastructural evidences.

BACKGROUND: In vitro maturation (IVM) of immature oocytes retrieved from unstimulated ovaries may avoid side effects connected to hyperstimulation during IVF procedures, including the risk of cancer recurrence. In humans, the scarce availability of immature oocytes limits morphological studies. The monovular ovine may represent an experimental model for IVM studies. METHODS: To assess if the scarce developmental competence of prepubertal oocytes (PO) is related to morphological changes we analyzed, by light and transmission electron microscopy, cumulus-oocyte-complexes (COCs) from lambs (30-40 days old) and sheep (4-6 years old) at sampling and after 7 h, 19 h, 24 h of IVM. Meiotic progression was determined at the same time points. RESULTS: At sampling, the germinal vesicle (GV) of PO was round and centrally or slightly eccentrically located, whereas in adult oocytes (AO) it was irregularly shaped and flattened against the oolemma. PO, differently from AO, showed numerous trans-zonal projections. Organelles, including cortical granules (CGs), were more abundant in AO. After 7 h, the percentage of AO that underwent GVBD-MI transition increased significantly. In PO, the oolemma was juxtaposed to the ZP; in AO, it showed several spikes in correspondence of cumulus cells (CC) endings. In PO, organelles and isolated CGs were scattered in the ooplasm. In AO, groups of CGs were also present under the oolemma. After 19 h, PO underwent GVBD-MI transition; their oolemma showed several spikes, with CC projections retracted and detached from the ZP. AO underwent MI-MII transition; their oolemma regained a round shape. CGs were located beneath the plasmalemma, arranged in multiple, continuous layers, sometime discontinuous in PO. After 24 h, both groups reached the MII-stage, characterized by a regular oolemma and by expanded CCs. PO showed CGs distributed discontinuously beneath the oolemma, while AO showed a continuous monolayer of CGs. CONCLUSIONS: Even if PO were able of reaching morphological maturation after 24 h of IVM, our ultrastructural analysis allowed detecting the presumptive sequence of cytoplasmic alterations connected with the delay of nuclear maturation, that might explain the reduced developmental competence of such oocytes. Data from the sheep model are of interest for zootechny, and provide an experimental basis for improving human IVM technology.