Analysis of informativeness of immunohistochemical and flow cytometric methods for estrogen receptor α assessment.

Informative capacity analysis of immunohistochemistry (IHC) and flow cytometry (FCM) in the assessment of estrogen receptor α (ERα) expression in breast cancer tissue was performed. Similar frequencies of expression were shown by both methods: 27% of ERα-negative and 73% ERα-positive cases. However, IHC evaluation detected low levels in only 20% of ERα-positive cases, whereas low levels of ERα detected by FCM were 2 times more often (48%). Moreover, FCM revealed positive expression (23-60%) in 33% of IHC ERα-negative cases. Among IHC ER-positive cases, zero ERα expression was detected by FCM in 12.5%. The approaches to minimize errors in routine clinical determination of the estrogen receptor status were proposed.

[NOMOGRAM AS A PROGNOSTIC TOOL FOR LYMPH NODE METASTASIS IN PATIENTS WITH BREAST CANCER].

It was retrospectively analyzed clinicopathological features of 529 breast cancer patients treated at the Ulyanovsk Oncology Center. Of 529 patients 235 (44.4%) had at least one positive axillary lymph node. Tumor size (p = 0,0005), histological grade (p = 0004), lymphovascular invasion (p < 0,0001), HER2-status (p = 0,014) and total score of malignancy (p < 0,0001) were significant independent predictors for lymph nodes metastases. By univariate and multivariate regression analysis it was created the graphic variant of nomogram which could predict the risk of lymph nodes metastases in breast cancer patients. An area under ROC-curve in our nomogram reached 0,737 that demonstrated high prediction level of accuracy of the developed model. Thus new nomogram is a useful tool in planning axillary surgery in breast cancer patients.

[Lipidomic markers of breast cancer malignant tumor histological types]. / Lipidomnye markery gistologicheskikh tipov zlokachestvennoi opukholi molochnoi zhelezy.

The molecular profile of a tumor is associated with its histological type and can be used both to study the mechanisms of tumor progression and to diagnose it. In this work, changes in the lipid profile of a malignant breast tumor and the adjacent tissue were studied. The potential possibility of determining the histological type of the tumor by its lipid profile was evaluated. Lipid profiling was performed by reverse-phase chromato-mass-spectrometric analysis the tissue of lipid extract with identification of lipids by characteristic fragments. Potential lipid markers of the histological type of tumor were determined using the Kruskal-Wallis test. Impact of lipid markers was calculated by MetaboAnalyst. Classification models were built by support vector machines with linear kernel and 1-vs-1 architecture. Models were validated by leave-one out cross-validation. Accuracy of models based on microenvironment tissue, were 99% and 75%, accuracy of models, based on tumor tissue, were 90% and 40% for the positive ion mode and negative ion mode respectively. The lipid profile of marginal (adjacent) tissue can be used for identification histological types of breast cancer. Glycerophospholipid metabolism pathway changes were statistically significant in the adjacent tissue and tumor tissue.

[Lipidomic markers of tumor progress in breast cancer patients]. / Lipidomnye markery opukholevoi progressii u bol'nykh rakom molochnoi zhelezy.

Research of cancer progression mechanisms and their impact on metabolism of tumor cells and tumor microenvironment cells is an important element in drug development for cancer target therapy. In this study, changes in tumor tissue and margin tissue lipid profiles, were associated with the following clinical and morphological characteristics: tumor size, cancer stage, multifocalite, tumor grade, number of lymph node metastasis, Nottingham prognostic index, total malignancy score, level of Ki67 protein. Lipid profiling was performed by reverse-phase chromato-mass spectrometry analysis of lipid tissue extract with lipid identification by characteristic fragments. In the lipid profile of tumor tissue 13 characteristic lipids were selected. Their levels significantly correlated with at least 5 clinical and morphological features. Eight of 13 belonged to phosphatidylcholines. In lipid profile of tumor microenviroment tissue 13 lipid features were selected. Their levels significantly correlated with at least 5 clinical and morphological features. Four of 13 belonged to oxidized lipids, 4 lipid features belonged to sphingomyelins, four of 13 belonged to phosphatidylethanolamines. The tumor microenvironment tissue lipid profile correlated with tumor size, cancer stage, tumor grade, number of axillary metastases, Nottingham prognostic index. The tumor tissue lipid profile correlated with tumor size, tumor grade, total malignant score, and number of axillary metastases.

[Methylation profiles of genes in breast cancer luminal HER2-negative primary tumor during regional lymphnode metastasis]. / Profil' metilirovaniia genov pervichnoi opukholi u bol'nykh liuminal'nym HER2-negativnym rakom molochnoi zhelezy pri metastazirovanii v regionarnye limfaticheskie uzly.

Aberrant methylation is strongly associated with development of cancer, but limited data exist on correlation between methylation and regional lymph node metastasis (RLNM). The aim of this research was to study using of methylation levels of WIF1, RASSF1A, CDO1 and MEST aberrant methylated genes in a primary breast cancer for prediction of regional lymph node metastases. We used MS-HRM (Methylation Sensitive High Resolution Melting) to assess methylation levels. The results were confirmed by pyrosequencing. The study included 66 women with LumA and 46 women with HER2- (LumB-), 22 and 26 of them had metastasis in at least one lymph node respectively. It was found that methylation levels between LumA and LumB subtypes differed significantly in genes: WIF1 (p<0.001), CDO1 (p=0.002) and MEST (p=0.033). In the Lum A subtype statistically significant differences in level of methylation of WIF1 gene between patients with metastases in RLNM and patients without metastases were found (p=0.03). Analysis of tumors longer than 2 cm in the LumA subtype, revealed an increase of statistical significance of WIF1 gene - p=0.009 (AUC (95%CI) = 0.76 (0.59-0.93)). In LumB- subtype RASSF1A, CDO1 and MEST had statistically significant differences in methylation level between groups (p=0.03, p=0.048 and p=0.045 respectively). ROC analysis showed that combining of three genes by logistic regression, AUC (95%CI) was 0.74 (0.6-0.88). Analysis of tumors longer than 2 cm, did not increase statistical significance for these genes (p=0.046; p=0.089 and p=0.076, respectively). Thus, the study of methylation in primary tumors may be useful for prediction of lymph node metastasis, as well as for better understanding of biological process inside breast cancer.

Expression of micrornas in molecular genetic breast cancer subtypes.

BACKGROUND: It is shown that each type of human malignancies has a unique set of expressed miRNAs, and tumor-specific miRNAs in biological tissues of a patient are stable. The aim of this study was to determine the differences in the expression of miRNAs in tumor tissue of invasive breast carcinoma compared to normal tissue, as well as to analyze the variable expression of miRNAs in molecular genetic subtypes of breast cancer. METHODS: We determined differences in mRNA expression in 35 biopsies of tumor tissue of various molecular genetic subtypes of breast cancer and 35 biopsies of adjacent conventionally normal breast tissue by RT-PCR in real time. We assessed the expression levels of miRNA-21, 221, 222, 155, 205, 20a , 125b and 200a. RESULTS: A significant increase in the level of expression of the oncogenic miRNA-20a (p=0.000141) and miRNA-221 (p=0.037777) in the triple negative cancer in comparison with the luminal A and luminal B/HER2/neu-negative breast cancer subtypes was established. Assessment of significance of the results was conducted using ROC analysis. For miRNA-221 AUC value was 0.772, for miRNA-20a AUC value was 0.949. The obtained results suggest the possibility of using the levels of miRNA-21, 155, 205, 125b expression in tumor tissue to assess a malignant potential of a breast carcinoma. The levels of expression of oncogenic miRNA-221 and miRNA-20a are increased in TNBC compared with luminal A and luminal B/HER2/neu-negative breast cancer subtypes, supporting the characteristic of TNBC as the most aggressive subtype of breast cancer. MiRNA-20a is a marker of TNBC compared with luminal subtypes of breast cancer. MICRO ABSTRACT: To identify markers for breast cancer with triple-negative phenotype, we evaluated expression levels of siRNA-21, 221, 222, 155, 205, 20a, 125b, 200a and 146b in the tumor tissue of 35 patients by RT-PCR. AUC value equal to 0.949 in the ROC-analysis allows us to recommend the miRNA-20a as a marker of triple negative breast cancer to differentiate it from the luminal subtypes.

[Value of the isometric exercise test in objectively evaluating the effectiveness of hyperbaric oxygenation in ischemic heart disease]. / Znachenie proby s izometricheskoi nagruzkoi v ob''ektivnoi otsenke éffektivnosti giperbaricheskoi oksigenatsii pri ishemicheskoi bolezni serdtsa.

The isometric test was conducted prior to and after a hyperbaric oxygenation (HBO) session in 31 coronary heart disease (CHD) patients. The results were compared with the findings provided by the examination of 138 coronary patients and 23 normal subjects receiving no HBO treatment. It was shown that the isometric test makes it possible to objectively assess the HBO effect in CHD patients. The results of the test reflect reduction in the severity of angina pectoris or cardiac failure following hyperbarotherpy. The results obtained justify the recommendation of the isometric test for the individual evaluation of the hyperbaric treatment in CHD.

[Effect of hyperbaric oxygenation on the circulatory function in rheumatic mitral valve disease]. / Vliianie giperbaricheskoi oksigenatsii na funktsiiu krovoobrashcheniia u bol'nykh revmaticheskim mitral'nym porokom.

The effect of a hyperbaric oxygenation course (10-14 exposures, one exposure daily at 0.7-1.0 ATA) upon the circulation function was studied in 61 patients with rheumatic mitral valve disease combined with systemic circulation insufficiency. The obtained results (reduction of the heart volume, acceleration of the blood stream within the heart and the body, increase of the stroke index, of the blood flow in the muscles of the extremities, reduction of the arterial and central venous pressure) demonstrate that the contractility of the myocardium and redistribution of the cardiac output between separate vascular regions is improved under the effect of hyperbaric oxygenation. The authors suggest that the increase of contractility in the right or left heart predominantly depends on the prevalence of mitral stenosis or circulatory insufficiency.

[Hyperbaric oxygenation in the overall therapy of chronic ischemic heart disease]. / Giperbaricheskaia oksigenatsiia v kompleksnoi terapii khronicheskoi ishemicheskoi bolezni serdtsa.

Seventy-seven patients with chronic ischemic heart disease were treated in single-seater oxygen hyperbaric chambers; 52 patients had angina pectoris of effort or angina of effort and at rest while 25 patients with macrofocal postinfarction cardiosclerosis had insufficiency of pulmonary or systemic circulation. Treatment consisted of 12--15 procedures. The use of hyperbaric oxygenation in a complex with drug therapy makes it possible to alleviate or arrest the attack of angina pectoris and relieve considerably the symptoms of cardiac decompensation. The initial condition of central hemodynamics affects greatly the results of barotherapy. Normal parameters of hemodynamics hardly change after treatment. At the same time, in patients with markedly reduced myocardial contractility hyperbaric oxygenation causes evident positive changes in hemodynamics. The combination of hyperbaric oxygenation with drug therapy improves the effect of treatment significantly.

[Effect of hyperbaric oxygenation on pulmonary function, acid-base state and the blood gas composition in mitral heart defect patients]. / Vliianie giperbaricheskoi oksigenatsii na funktsiiu legkikh, kislotno-shchelochnoe sostoianie i gazovyi sostav krovi u bol'nykh mitral'nym porokom serdtsa.

Improvement of external respiration, acid-base balance and gas composition of blood was noted after application of a complex of therapeutic measures in combination with hyperbaric oxygenation. The fact that positive changes in external respiration were less pronounced in patients with stenosis of the left venous orifice than in those with mitral incompetence may evidently be explained by the presence of long-term and high pulmonary hypertension and certain increase in the volume of blood in pulmonary circulation in noncorrected stenosis of the left venous orifice. A decrease in metabolic acidosis is noted, which is a complication leading to deterioration of systemic and peripheral hemodynamics, inhibition and myocardial function and blood supply to the brain.

[Effect of hyperbaric oxygenation on central hemodynamics and oxygenating function of the lungs in open-heart surgery]. / Vliianie giperbaricheskoi oksiganatsii na tsentral'nuiu gemodinamiku i oksigeniruiushchuiu funktsiiu legkikh pri operatsiiakh na otkrytom serdtse.

The dynamics of some oxygenating pulmonary function (OPF) indices has been studied in 33 patients with coronary cardiac disease and rheumatic lesions of cardiac valves 4-6 hours after surgery in response to a single hyperbaric oxygenation (HBO) session (1.5 ata, 45 min) in the immediate postoperative period. It is found that in the presence of slight or, on the contrary, pronounced arterial hypoxemia, no significant negative OPF changes were observed. At the same time, a temporary increase in the alveolo-arterial gradient has been found in some patients. The comparison of data on the systemic blood flow with the OPF indices permits suggesting the prevalent role of the membrane component in a PaO2 decrease in patients after using assisted circulation.

[Preoperative instrumental diagnosis of postoperative choledocholithiasis]. / Dooperatsionnaia instrumentalnaia diagnostika posle operatsionnogo choledokholitiaza.

Experience in examination of 221 patients with postoperative cholangiolithiasis is discussed. Analysis of the results of instrumental examination ERPCG to surpass all the existing methods of diagnosis of stones in the bile ducts in informativeness and safety. A diagnostic algorithm of examination is suggested by means of which the necessary tactical problems connected with the forthcoming operation were solved in 98.2% of cases.

[Surgical tactics in cholangitis in middle-aged and elderly patients]. / Khirurgicheskaia taktika pri kholangite u bol'nykh pozhilogo i starcheskogo vozrasta.

The authors analysed the results of examination and treatment of 399 elderly and old-aged patients in the period between 1971 and 1981. At that time cholangitis was managed in 146 (36.6%) patients mainly by surgical intracavitary operations, in 21.2% with a fatal outcome. The results showed the high risk of surgical methods for treatment of cholangitis. Since 1982 the authors have introduced into every-day practice endoscopic methods for the management of this disease. It was found that endoscopic papillosphincterotomy (EPST) is the most physiological and safe method for the treatment of choledocholithiasis, stenosis of the major duodenal papilla, and acute cholangitis. EPST undertaken in 253 (63.4%) patients ensured adequate decompression of the bile ducts in 187 (73.9%) of them and facilitated removal of cholangitis and recovery. With the use of EPST in the treatment of acute cholangitis not only was the number of surgical operations on patients of the older age group reduced, but the mortality decreased to 5.5% (which was 3.9 times lower than the mortality in management of cholangitis by surgical operations).

[Diagnosis and treatment of acute cholecystitis complicated by local peritonitis]. / Diagnostika i lechenie ostrogo kholetsistita, oslozhnennogo mestnym peritonitom.

The article analyses 610 patients with acute cholecystitis complicated by circumscribed peritonitis which determines the results of surgical treatment in many patients. The clinical manifestations of circumscribed peritonitis complicating destructive cholecystitis are discussed. It is shown that laparoscopy plays a role in the early diagnosis of atypical or asymptomatic course of this complication, particularly in elderly and old-aged patients. Data on the surgical treatment of acute cholecystitis complicated by localized circumscribed and ++non-circumscribed peritonitis are presented. The authors show the possibility of choosing the optimal operation--laparoscopic drainage of the gallbladder and abdominal cavity--in the first stage of treatment of patients with phlegmonous cholecystitis and localized ++non-circumscribed peritonitis in the presence of serious concomitant diseases.

[Late results of the surgical treatment of patients with biliary calculi]. / Otdalennye rezul'taty khirurgicheskogo lecheniia bol'nykh s kamniami zhelchnykh protokov.

The authors analyse the late results of surgical treatment of 463 patients who underwent operation for stones in the bile ducts. The late results were found to be determined by the character of the affection of the bile excreting system and the rational choice of the operative method. The indications and contraindications for various methods of treating cholelithiasis were determined more precisely from study of the late results.

[Treatment of nontumorous obstructive jaundice and cholangitis in middle-aged and elderly patients]. / Lechenie neopukholevoi obturatsionnoi zheltukhi i kholangita u bol'nykh pozhilogo i starcheskogo vozrasta.

On the basis of examination and treatment of 364 elderly and senile patients with obstructive jaundice and cholangitis, the authors conclude that the frequency of these complications is high and that cholangitis takes an atypical course in patients over 60 years of age. They determine the significance of the respiratory insufficiency syndrome in manifestation of the severity of the disease. In view of the high risk of surgery at the peak of jaundice and cholangitis, the authors suggest the wide use of endoscopic papillosphincterotomy according to indications for correcting biliary hypertension. It proved to be one of the most effective methods in the treatment of jaundice and cholangitis, contributed to reduction of the number of surgical operations on cavities and to a 4.4-fold decrease of postoperative death rates among this contingent of patients.

[Acute cholecystitis and its complications]. / Ostryi kholetsistit i ego oslozhneniia.

The results of operative treatment of 4,011 patients with acute complications of cholecystitis are analysed. Problems of diagnosis and tactics and the results of treatment are discussed. It is pointed out that the management of patients with acute complicated cholecystitis is a great and urgent problem in abdominal surgery in view of the diffuse character of the process.

[The forme-fruste clinical symptoms of peritonitis in acute destructive cholecystitis]. / O stertoi klinicheskoi simptomatike peritonita pri ostrom destruktivnom kholetsistite.

Among 894 patients with acute destructive cholecystitis complicated by peritonitis there were 478 patients with slight clinical symptoms of peritonitis. In 125 of these patients (26.1%) the clinical symptoms of peritonitis were completely absent, extremely slight manifestations being observed in 353 patients (73.9%). The percentage of patients with acute destructive cholecystitis having slight clinical symptoms of peritonitis was considerably higher in elderly and senile patients (72.3%) than in the group of young patients (27.7%). The slight clinical symptoms of this complication was observed more often in patients with a local peritonitis.

[Choosing a method of treating suppurative lactational mastitis]. / Vybor metoda lecheniia gnoinogo laktatsionnogo mastita.

The abscessing form of lactation mastitis as well as subaureolar abscesses with small foci (not more than 3-4 cm) should be expediently treated by a puncture method. In large foci permanent drainage should be used. Limited foci (up to 1-1.5 quadrants) in phlegmonous-abscessing form of mastitis must be carefully dissected. Treatment by incisions is indicated in cases with infiltrative-abscessing form of mastitis. Local treatment must be supplemented by antibacterial and detoxication therapy and by the means enhancing the organism resistance.

[Our 15 years' experience using lobectomy with resection and plastic surgery of the bronchi in lung cancer]. / Nash piatnadtsatiletnii opyt primeneniia lobektomii s rezektsiei i plastikoi bronkhov pri rake legkogo.

An experience with the treatment of 303 patients with lung cancer subjected to lobectomies with resections and plasty of bronchi is generalized. The immediate results were as follows: postoperative complications in 6,5% +/- 2,0; postoperative lethality in 5,9% +/- 1,3. More than a five year survival was noted in 41,2% of the patients.