Pathomorphological Parameters Research Articles

Tumour budding, MELF-pattern and tumour-infiltrating lymphocytes as possible pathomorphological parameters of the course of endometrioid adenocarcinoma of the uterine corpus

Aim. To evaluatethe role tumour budding (TB), MELF-pattern and tumour-infiltrating lymphocytes (TILs) as possible prognostic factors of endometrioid adenocarcinoma of the uterine corpus.Materials and methods. A single-centre, retrospective, observational study was conducted involving 188 patients with endometrioid adenocarcinoma of the uterine body. 40 patients who had disease recurrence or died directly from progression of endometrioid adenocarcinoma of the uterine body were the unfavourable outcome group, 148 patients without progression and death from this tumour were the favourable outcome group. Fisher, Yates exact two-sided criteria were used to analyze the data. Survival analysis was performed using log-rank test. The hazard ratio (HR) and its 95 % confidence interval (CI) were estimated using single-factor analysis with log-rank test and multivariate Cox proportional hazards analysis. p <0.05 was considered statistically significant.Results. TB was observed predominantly in the group of patients with unfavourable outcome (р <0.0001) Survival analysis revealed statistically significant decreased survival in cases with TB (HR 5.3; 95 % CI 2.2–12.7; р <0.0001). MELF-pattern was statistically significantly more frequent in the group of patients with unfavourable outcome (р <0.0001), a decreased survival of patients was observed in the presence of MELF-pattern (HR 5.8; 95 % CI 2.1–16.2; р <0.0001). Comparison of groups according to the number of TILs revealed statistically significant differences (р = 0.0242). When analyzing survival relative to the threshold value of the number of TILs, statistically significant differences were also observed (HR 3.7; 95 % CI 1.7–7.9; р = 0.021). Multivariate Cox proportional hazards analysis revealed that only TB and MELF-pattern had prognostic significance for recurrence-free survival (HR 3.7; 95 % CI 1.8–7.4; р <0.001).Conclusion. TB and MELF-pattern are specific changes in the stroma of endometrioid adenocarcinoma stroma of the uterine corpus that can be used as pathomorphological predictors of clinical outcome.

Correlations of pathomorphological parameters between lesions at the invasive front and lymph node metastases in colorectal cancer: a retrospective clinical study

BackgroundLymph node (LN) metastasis is one of the most important indicators to evaluate stage, choose treatment strategy, and predict outcome of colorectal cancer (CRC). The morphological correlation between primary tumors and LN metastases can help predict the incidence of LN metastasis in CRC more accurately and assist with more individualized risk-stratification management decisions.MethodsA retrospective study was devised with paired tissue specimens from the invasive front of primary tumors and LN metastases in 426 patients after a radial surgery for CRC. According to the presence (N +) or absence (N-) of regional LN metastasis and the number of LN metastases (pN1a/1b/1c/2a/2b), comparisons were performed regarding tumor budding (TB) and poorly-differentiated clusters (PDC). In addition, their correlation with the incidence of LN metastasis and the extent were explored.ResultsThe TB and PDC in the invasive front of primary tumors presented significant correlations with the incidence of LN metastasis and the number of LN metastases in CRC (P < 0.001). TB2/3 led to a risk of LN metastasis 6.68-fold higher than TB1, while PDC2/3 resulted in a risk of LN metastasis 8.46-fold higher than PDC1. Additionally, the risk of developing 4 or more LN metastases was 3.08-fold and 2.86-fold higher upon TB2/3 and PDC2/3 than that with TB1 and PDC1, respectively. Moderate positive correlations were found between the invasive front of primary tumors and LN metastases in terms of TB and PDC, respectively.ConclusionsTB and PDC, at the invasive tumor front are important morphological markers to evaluate LN metastasis in CRC, and they can be employed as reference indicators to assess or predict the potential of LN metastasis in CRC in clinical practice.

Pathomorphological parameters of sepsis-associated encephalopathy in deceased septic patients without purulent lesions to the brain

Sepsis-associated encephalopathy (SAE) clinically manifests by delirium and decreased consciousness less than 15 points on Glasgow Coma Scale. SAE pathophysiology includes neuroinflammation, ischemic-hypoxic and dysmetabolic mechanisms. Despite the high frequency and the important role in thanatogenesis, pathomorphological criteria of SAE remain to be defined. The aim of the study was to specify the key pathomorphological parameters of sepsis-associated encephalopathy in deceased septic patients without purulent lesions to the brain by defining the changes of neurogliovascular unit and the level of tissue ammonia. Material and methods. Using pathohistological, histochemical, and immunohistochemical methods we studied cerebral cortex and white matter, hippocampus, thalamus, and cerebellum of 35 deceased septic patients with SAE in comparison with the control group, which included 30 patients who died from acute cardiovascular failure without CNS pathology. Results. In SAE, small foci of encephalolysis due to thrombosis of microvessels, ischemic-hypoxic and apoptotic changes in neurons are associated with the following parameters that are reliably (p &lt; 0.05) different from the control group: higher (up to 199.48 %) level of tissue ammonia and increased number (up to 316.07 %) of caspase-3+ apoptotic neurons in the cortex, hippocampus, thalamus, and cerebellum; in all studied brain regions, an increased expression level of astrocytic glial fibrillary acidic protein (up to 192.69 %), glutamine synthetase (up to 134.41 %) and aquaporin-4 (up to 400.8 %); significant (up to 947.01 %) expansion of perivascular and pericellular “edematous” spaces, increased (up to 479.58 %) immunopositive area of extravascular CD68+ microgliocytes and increased (up to 374.43 %) proportion of CD68+ ameboid microgliocytes, increased (up to 3.66 times) number of Alzheimer type 2 astrocytes in cerebral cortex, thalamus, and cerebellum; increased (up to 2 times) number of amyloid bodies in the thalamus and cerebellum. Conclusions. The obtained data indicate that the delirious state, loss of consciousness and other manifestations of SAE are associated with ischemic-hypoxic and ammonia-induced ischemic and apoptotic changes of the brain neurones; small foci of encephalolysis; adaptive remodeling and dystrophic changes of astrocytes; microglial reactiveness with increased proportion of phagocytic microgliocytes; brain edema and dysfunctional glymphatics.

Clinicopathological features of colon cancer depending on the dMMR status of the tumor

Aim. To conduct a clinical and morphological assessment of the characteristics of colon cancer depending on the dMMR / pMMR status of the tumor.Materials and methods. A retrospective study included 66 patients with operable colorectal cancer (CRC) (T1-4bN0-2bM1), who were treated at Cancer Research Institute of Tomsk National Research Medical Center (NRMC). The average age of the patients was 64.4 ± 12.8 years. All patients underwent hemicolectomy or colon resection, as well as intraoperative resection of distant metastases, if present.Results. We determined that in CRC patients with pMMR tumors, hematogenous metastases were detected in 27.3% of cases, while in patients with dMMR tumors, hematogenous metastases were detected only in 6.1% of cases (p = 0.021). A comparative analysis of dMMR and pMMR tumors also allowed to establish higher frequency of perineural invasion among the pMMR subgroup of carcinomas (p = 0.039). The sign of tumor budding was found both in dMMR carcinomas (36%) and in pMMR tumors (45%). This sign was associated with damage to regional lymph nodes (p = 0.0017). A more detailed analysis of the tumor budding phenomenon showed that in dMMR tumors, Bd1 low-grade budding (83%) predominated. In pMMR tumors, Bd2 intermediate-grade budding (33%) and Bd3 high-grade budding (26.7%) prevailed. Bd2 and Bd3 tumor budding types were associated with hematogenous metastasis (p &lt; 0.001).Conclusion. The obtained data demonstrate the differences in such pathomorphological parameters as perineural invasion and the degree of tumor budding depending on the dMMR / pMMR status of the tumor. These histologic parameters in tumor tissue are also associated with higher incidence of distant metastasis in patients with pMMR carcinomas as opposed to patients with dMMR tumors.

Immediate and postponed results of resection interventions in pulmonary tuberculosis patients with local inflammatory changes in the bronchial tree

The objective: to study the frequency and nature of postoperative complications, immediate and postponed results of resection interventions in pulmonary tuberculosis patients depending on the presence and pathomorphological parameters of local infl ammatory changes in the bronchial tree.Subjects and Methods. 147 pulmonary tuberculosis patients who underwent pulmonary resection were enrolled in the prospective cohort study. Main Group (n=49) included patients with local infl ammatory changes in the bronchi before surgery; Comparison Group (n=98) included patients with no infl ammatory changes in the bronchi.Results. The presence of local infl ammatory changes in the bronchial tree detected by bronchoscopy, did not have a signifi cant impact on the development of complications during surgical treatment - neither on their number nor on structure. The incidence of complications of resection interventions depends on severity of tuberculosis lesions in the lung.

Papillary thyroid carcinoma coexisting with benign thyroid and parathyroid pathology: clinical and pathomorphological features

Background. Papillary thyroid carcinoma (PTC) is the most frequent malignant neoplasm originating from follicular cells of thyroid gland. PTC is often coexisting with other benign thyroid pathology such as chronic lymphocytic thyroiditis, follicular thyroid adenoma, toxic thyroid adenoma, Graves’ disease, non-toxic multinodular goiter. PTC can be diagnosed in patients undergoing surgical treatment for hyperparathyroidism. However, the clinical and pathomorphological features of PTC in the presence of other benign thyroid or parathyroid pathology, as well as possible differences in surgical tactics, remain relevant as evidenced by previously published reports. The purpose of the study is to assess the prevalence and determine the differences in the clinical and pathomorphological parameters of PTC in the presence of benign thyroid and parathyroid pathology. Materials and methods. There were identified 91 patients with PTC, who underwent surgical treatment at the clinical bases of the Department of Surgery of the NSC “Institute of Biology and Medicine” of Taras Shevchenko National University of Kyiv. Results. In the studied PTC cohort, 31 (35 %) patients were without coexisted benign thyroid pathology and 60 (35 %) patients had it (PTC/coexisted). A statistically significantly higher number of mitoses per 10 high power fields in the PTC group were identified in 3 (10 %) patients, as compared to the absence of this pathohistological parameter in the PTC/coexisted (p = 0.037). Further analysis of these 3 cases showed that 4 mitotic figures were found in one PTC, and one mitotic figure in the other two cases per 10 high power fields (400×). Conclusions. Papillary thyroid carcinoma in patients with other benign thyroid pathology is associated with lower biological aggressiveness than PTC without comorbidity as evidenced by a lower frequency of mitotic figures per 10 high power fields. The presence of concomitant benign thyroid pathology can be considered as a favorable prognostic factor for patients with PTC.

Safety and Pharmacokinetics of the Substance of the Anti-Smallpox Drug NIOCH-14 after Oral Administration to Laboratory Animals.

Since most of the modern human population has no anti-smallpox immunity, it is extremely important to develop and implement effective drugs for the treatment of smallpox and other orthopoxvirus infections. The objective of this study is to determine the main characteristics of the chemical substance NIOCH-14 and its safety and bioavailability in the body of laboratory animals. The safety of NIOCH-14 upon single- or multiple-dose intragastric administration was assessed according to its effect on the main hematological and pathomorphological parameters of laboratory mice and rats. In order to evaluate the pharmacokinetic parameters of NIOCH-14 administered orally, a concentration of ST-246, the active metabolite of NIOCH-14, in mouse blood and organs was determined by tandem mass spectrometry and liquid chromatography. The intragastric administration of NIOCH-14 at a dose of 5 g/kg body weight caused neither death nor signs of intoxication in mice. The intragastric administration of NIOCH-14 to mice and rats at doses of 50 and 150 µg/g body weight either as a single dose or once daily during 30 days did not cause animal death or critical changes in hematological parameters and the microstructure of internal organs. The tissue availability of NIOCH-14 administered orally to the mice at a dose of 50 µg/g body weight, which was calculated according to concentrations of its active metabolite ST-246 for the lungs, liver, kidney, brain, and spleen, was 100, 69.6, 63.3, 26.8 and 20.3%, respectively. The absolute bioavailability of the NIOCH-14 administered orally to mice at a dose of 50 µg/g body weight was 22.8%. Along with the previously determined efficacy against orthopoxviruses, including the smallpox virus, the substance NIOCH-14 was shown to be safe and bioavailable in laboratory animal experiments.

Cancer Stem Cell Markers in Rhabdomyosarcoma in Children.

(1) Background: The aim of the present study was to assess the cancer stem cell (CSC) markers CD24, CD44, CD133, and ALDH1A1 in rhabdomyosarcoma (RMS) in children and to define their prognostic role in this group of patients. (2) Methods: The study material was archival tissue specimens collected from 49 patients under 18 years of age and who had been diagnosed with RMS. Immunohistochemistry (IHC) was used to evaluate the expression of the selected CSC markers in the tumor tissue. Expression was evaluated using a semiquantitative IRS scale based on the one developed by Remmele and Stenger and was correlated with the clinical and pathomorphological parameters of prognostic importance in RMS. (3) Results: Expression of the selected CSC markers CD24, CD44, CD133, and ALDH1A1 was demonstrated in 83.7%, 55.1%, 81.6%, and 100% of the RMS patients, respectively. The expression of all of the assessed CSC markers was statistically significantly higher in the study group versus the control group. No significant correlation was found between the expression of the selected CSC markers and clinical and pathological prognostic factors that were analyzed. The expression of the CSC markers did not have a significant influence on RMS survival rates. (4) Conclusions: The results of the conducted study confirm the expression of selected CSC markers in rhabdomyosarcoma tissue in children. The study did not support the prognostic relevance of the expression of any of the assessed CSC markers. However, further studies are needed to fully understand the relevance of the selected CSC markers in RMS carcinogenesis.

Proliferative and apoptotic evaluations of renal preventive effects of coenzyme Q10 in radioiodine-131 induced renal damage

The aim of this study was to investigated anti-proliferative and anti-apoptotic effects of coenzyme Q10 (CoQ10) in the prevention of radioiodine-131 (RAI) (I131) induced kidney damage. A total of 24 Wistar albino rats were separated into equal three groups (n = 8/group): Group 1 (control): untreated group; Group 2 (RAI): 3 mCi/kg RAI oral route; Group 3 (RAI+CoQ10): 3 mCi/kg RAI oral route and intraperitoneally 30 mg/kg/day CoQ10. CoQ10 treatment was started two days before RAI administration and was continued five days once daily after RAI. Pathomorphological parameters of kidneys were measured using hematoxylin–eosin and Masson’s trichrome staining. Immunohistochemically; proliferating cell nuclear antigen (PCNA), caspase 8, caspase 9 and terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick end labeling (TUNEL) were used to determine proliferation and apoptosis. With the exception of the control group, varying degrees of inflammation, degeneration, necrosis, and interstitial/perivascular fibrosis were detected in the kidneys of all rats. This histopathological damage was found to be significantly less in CoQ10 group versus RAI group (P&amp;lt;0.05). The all immunohistochemical examinations demonstrated that administration of CoQ10 had reduced proliferation and apoptosis (P&amp;lt;0.05). The results of kidney histopathology and immunohistochemistry demonstrated that administration of CoQ10 had reduced inflammation, proliferation, and apoptosis. These findings show CoQ10 can play an important role in the radioprotection of kidneys against RAI-induced damage

Relationship of the Levels of microRNA Gene Methylation with the Level of Their Expression and Pathomorphological Characteristics of Breast Cancer.

We studied the relationship of the levels of microRNA group expression and methylation with clinical and pathomorphological parameters of breast cancer and its immunohistochemical status. Quantitative methylation specific PCR analysis showed a significant (p<0.001) increase in the methylation level of 4 microRNA genes (MIR127, MIR129-2, MIR132, and MIR148A) and a significant (p<0.001) decrease for gene MIR375 relative to paired histologically normal tissue. Real-time PCR analysis revealed a significant (p≤0.001) decrease in the expression of 4 microRNAs (miR-127-5p, miR-129-5p, miR-132-3p, and miR-148a-3p) and a significant (p≤0.001) increase in the expression of miR-375-3p. A significant (rs=-0.6--0.7, p≤0.001) relationship between changes in the expression level of miR-129-5p, miR-132-3p, miR-148a-3p, and miR-375-3p and the levels of methylation of the corresponding genes in breast cancer was showed by using Spearman's rank correlation test. Analysis of the samples with consideration of the pathophysiological characteristics of the tumor revealed two significant markers of tumor progression: MIR129-2/miR-129-5p and MIR375/miR-375-3p. Both factors, the increase in the level of MIR129-2 methylation (p<0.001) and a decrease in the expression level of miR-129-5p (p<0.001), are significantly associated (p<0.001) with stage III/IV and the absence of HER2 expression. For MIR375/miR-375-3p, on the contrary, an association of low methylation level and enhanced expression with increased Ki-67 level (>30%, p<0.05) was revealed. These findings are of interest for understanding the mechanisms of breast cancer development and can provide the basis for the diagnosis and prognosis of the course of this disease. Moreover, the revealed features can be useful for adjusting the course of treatment with consideration of the pathophysiological characteristics of the tumor.

Study of the state of laboratory animals after subchronic oral exposure to solid rocket fuels component

The toxic effect of poly[3,3-bis(azidomethyl)oxetane] of high molecular weight in subchronic oral intake of white mongrel rats was investigated. It has been found that in a one month experiment the compound at doses of 90,0 mg/kg, 30,0 mg/kg, and 10,0 mg/kg caused a change in the complex of physiological, behavioral, hematological, biochemical, immunological, and pathomorphological parameters in animals. At the same time, the cumulative properties of the toxicant were not registered.The deviations revealed were dose-dependent. Thus, during the entire period of intragastric administration of the substance, 15 significant changes were noted in the males of the first group, two of which went beyond the 2 sigma deviations in relations to the control values. The same ratio for the second experimental group was 10/1. The oral intake of the substance under investigation at minimum dose was accompanied by 5 violations in the homeostasis of the experimental animals, which did not go beyond the 2 sigma values in relations to the control values.Taking into account the insignificant number of changes detected and based on the current diagnostic criteria, the dose of 10,0 mg/kg has been accepted as a threshold of subacute general toxic effect for poly[3,3-bis(azidomethyl) oxetane] of high molecular weight.The obtained data was used when developing the maximum permissible concentration of the estimated component of solid rocket fuels in the water of water bodies.

ОЦЕНКА ХРОНИЧЕСКОЙ ТОКСИЧНОСТИ КОМПОЗИЦИИ ЛЕЧЕБНЫХ СРЕДСТВ ДЛЯ УСТРАНЕНИЯ ПОСЛЕДСТВИЙ ТОКСИКОЗОВ

The article presents the results of studying the chronic toxicity of a complex of therapeutic agents for eliminating the consequences of animal toxicosis, hepatoprotection and metabolic correc-tion, including choline chloride, succinic acid, xymedon, sorbitol, a suspension of lactic and propion-ic acid microorganisms. The drug was administered to white rats with food at doses of 1/50 and 1/20 of the maximum input (0.04 and 0.1 g / kg of live weight) for 60 days. Clinical, growth-weight, hematological, biochemical and pathomorphological parameters were assessed. It was found that the study drug with prolonged administration does not cause signs of toxicosis, does not have a nega-tive effect on the organism of laboratory animals. The absolute gain in live weight over the experi-ence in the experimental groups was 21.8 and 22.2 % more than the control, respectively, the drug had some growth-stimulating effect. A blood test showed that the values of the studied parameters were slightly higher than the control values, and indicated the presence of a favorable effect of the drug on hematopoiesis and metabolic processes. Macroscopic examination of internal organs showed no pathological changes.

Effect of antibiotics, hormones and anthelmintic on high molecular weight protein fractions in the common carp

We assumed that effect of sulfanilamide, chlortetracycline, nandrolone, and albendazole on the carp fishes depends on substance concentration in the water and associated with changes in the fractional composition of plasma protein. We found that sulfanilamide in concentration of 0.015 mg/dm3 in water practically had no effect, while at concentrations of 0.15 and 0.30 mg/dm3 it changed the protein spectrum of carp blood plasma, reduced the level of proteins with molecular weights of 260 and 140 kDa. Chlortetracycline in the concentration of 1.10 mg/dm3 did not affect the protein content of macromolecular fractions in the blood plasma of fish, and at the doses of 3.15 and 6.30 mg/dm3 it reduced the content of proteins with molecular weights of 450, 340, 260 and 140 kDa. Nandrolone in the concentration of 1.10 mg/dm3 increased the content of individual proteins in carp plasma compared to the control, and in the concentration of 0.10 and 0.50 mg/dm3 it did not affect the fractional composition of proteins with high molecular weight. Albendazole in the concentrations of 0.2, 0.5, and 1.00 mg/dm2 reduced the protein content of macromolecular fractions in carp plasma. Such xenobiotics, like sulfanilamide, chlortetracycline, and albendazole in different concentrations did not affect the total protein content of fish plasma, while the nandrolone increased it. The number of respiratory movements, behavior, body surface, and pathomorphological parameters of the main internal organs in the fish from the experimental groups did not differ from the control. Our results indicated the important role of proteins of high molecular weight fractions in carp blood plasm as these proteins determine the fish adaptation to the water xenobiotics. Keywords: carp, blood plasma, proteins, sulfanilamide, chlortetracycline, nandrolone, albendazole.

Clinical and pathomorphological parameters of brain death: from the origins of the concept to its use in organ transplantation

The criteria for brain death (BD), the parameters of their clinical and pathomorphological determination and use in organ harvesting for transplantation are being clarified in different countries to date.Objective: analysis of the formation and clinical and pathological characteristics of brain death.The review provides retrospective analysis of the formation and improvement of the medical concept of BD: the concepts of “death of the whole brain” (including the brain stem) and “death of the brain stem”. Based on our own data, the main pathomorphological forms of BD are described (total necrosis of the brain, subtotal necrosis of the brain stem and cerebellum), their development mechanisms, and diagnostic pathological parameters. It has been established that the main criterion for the development of human biological death, which determines irreversible cardiac arrest and the impossibility of restoring spontaneous respiration, are irreversible destructive changes in the nuclei of the pons and medulla oblongata, which make up the cardio-respiratory center that regulates heart rate, vascular tone and blood pressure, and generating rhythm and breathing patterns. The modern standards of clinical diagnosis of BD and their real application in different countries during organ transplantation, as well as the prerequisites for the revival of the concept of "circulatory death" in the era of organ transplantation are highlighted.Conclusions. The applied three standards of human death have insufficiently studied medical aspects and unresolved ethical problems.

Inhibitory Effects of Carrageenans on Endotoxin-Induced Inflammation.

The inhibitory effects of carrageenans (CRGs) on lipopolysaccharide (LPS) induced inflammation in a mouse model of endotoxemia and in complex therapy of patients with enteric infections of Salmonella etiology were studied. The atomic force microscopy (AFM) examination of LPS and its mixture with CRGs showed that the LPS morphology is significantly changed under the action of κ- and κ/β-CRGs. CRGs were able to increase the synthesis of anti-inflammatory interleukin 10 (IL-10) in vitro, and, at low concentrations, their activity in the mixture with LPS was higher. The protective effect of CRGs against Escherichia coli LPS was studied in vivo by monitoring the biochemical and pathomorphological parameters. The κ- and κ/β-CRGs and food supplement “Carrageenan-FE” increased the nonspecific resistance of mice to E. coli LPS at the expense of the inhibition of processes of thymus involution, adrenals hypertrophy, thyroid atrophy, hypercorticoidism, glycogenolysis, and lactate acidosis. The estimation of the therapeutic action of food supplement Carrageenan-FE in complex therapy of patients with enteric infections of Salmonella etiology is given. Carrageenan-FE restores the system of hemostasis and corrects some biochemical indicators and parameters in the immune systems of patients. These results allow us to hope for the practical application of CRGs for lowering the endotoxemia level in patients under the development of the infectious process caused by Gram-negative bacteria.

Beneficial effects of vitamin E on radioiodine induced gastrointestinal damage: an experimental and pathomorphological study.

The aim of the present study was to investigate the radioprotective effect of vitamin E in the prevention of radioiodine (RAI) induced gastrointestinal damage. Twenty-four rats were randomly divided into three groups as follows: Group-1 was untreated control group, Group-2 was orally administered single dose of 111 MBq RAI, and Group-3 was orally administered 111 MBq RAI and 1 mL of oral vitamin E. Vitamin E was started two days before RAI administration and was continued for five days once daily after RAI. Pathomorphological parameters of gastrointestinal tissues (stomach, small intestines and bowels) were measured using Hematoxylin-Eosin and Masson's trichrome staining. Varying degrees of inflammation, edema, ulcer, mucosal degeneration, necrosis and fibrosis were seen in the stomach, small intestine and bowel tissues of the rats in both study groups and not in the control group. The differences were statistically significant between these groups for all parameters (p < 0.05). The histopathological damage in the vitamin E treated group was significantly less than the damage in the RAI only group (p < 0.05 for all pathomorphological parameters). The results of this study showed that vitamin E has a radioprotective property with antiinflammatory and antifibrotic effects protecting against gastrointestinal damage caused by radioiodine (Tab. 3, Fig. 3, Ref. 26).

CLINICO-MORPHOLOGICAL PARALLELS OF PLACENTAL DYSFUNCTION AGAINST THE BACKGROUND OF LOW PLACENTATION

Introduction. Complications of pregnancy, which cause high perinatal morbidity and mortality, are accompanied by pathological changes in the placenta, namely, placental dysfunction (PD). 50.7% of PD are diagnosed in pregnant women with a low‐lying placenta (LLP). Aim. Тo study the pathomorphological parameters of placental dysfunction against the background of low placentation. Morphological and histometric features of the placenta from pregnant women with placental dysfunction (PD) against a background of low placental location were studied. The conducted studies show that the formation of placental dysfunction in pregnant women with a low location of the placenta is due to the violation of the physiological mechanisms of the formation of the feto-placental system in the first and second trimesters of gestation, as evidenced by: the predominance of the placenta of oval and anomalous forms (pleated, waist, with additional lobules ); the domination of the eccentric type of attachment of the umbilical cord and the main and intermediate types of branching of vessels. The manifestation of a positive type of compensatory-adaptive reactions at the organ level was a reduction in the thickness of the placenta in combination with an increase in the area of its maternal surface. A negative type of reaction in women with PD on a background of low placentation is a decrease in the volume of the placenta. At the tissue level in placentas from women with PD on a background of low placentation, compensatory-adaptive reactions were diagnosed in 70% of cases: a high percentage of terminal villi (69.4%), terminal villi with SCM (62.3%) and syncytial knots formation (29.5%), increased vascularization of villi (29.5%). In 25% of cases the degree of compensatory-adaptive reactions was significantly lower than in the control. Conclusions. In pregnant women with abnormal placentation, it is advisable to prevent the development of placental dysfunction from early gestation.

Cerebral atherosclerosis: a biomarker profile

To assess the changes in several biomarkers in patients with atherosclerosis of brachiocephalic arteries and shape a biomarker profile of cerebral atherosclerosis as an integrative index. The study included 124 patients with atherosclerotic lesions of internal carotid arteries (82 men and 42 women) aged from 37 to 73 years. The patients were stratified by history of prior stroke into 'asymptomatic' and 'symptomatic'. Along with general clinical and neurological examinations, ultrasound analysis of brachiocephalic arteries, neuroimaging, identification of biomarkers reflecting different stages of atherogenesis and evaluation of pathomorphological parameters of atherosclerotic plaques removed during carotid endarterectomy surgery were performed. Concentrations of NO2, NO3 and NO in blood plasma significantly differed between groups: 58.4, 43.3 and 15 mcmol/l, respectively, in the symptomatic group and 45, 19.2 and 25.8 mcmol/l in the asymptomatic group. The pro-inflammatory character of changes in atherosclerosis was confirmed by the increase in the concentration of lipoprotein-associated phospholipase A2 in patients with stroke (354.72±44.16 ng/ml versus 298.45±54.12 ng/ml). The level of the atheroprotective marker adiponectin decreased significantly in 'symptomatic' patients. Significant changes towards the prothrombotic state of blood were identified via levels of blood markers of fibrinolytic activity: plasminogen tissue activator and plasminogen activator inhibitor-1. Together with other diagnostic methods, identification of biomarkers can increase the accuracy of prognosis and prevention of sudden cardiovascular death. The authors have developed a scale of biomarker 'burdeness' of the patient with cerebral atherosclerosis that may be a first step to individualized prevention of associated ischemic complications.

Correlation of AgNOR count with biological behavior of N-Nitroso-N-Methylurea (NMU)-induced squamous cell carcinoma in Wistar rats

Gastric squamous cell carcinoma is one of the most common malignancies in human beings throughout the world. Assessment of proliferative aggressiveness of squamous cell carcinoma plays an important role in diagnostic, prognostic and therapeutic decisions on them. It is determined by both proliferative fraction and speed of neoplastic cells. AgNOR count is an important easily feasible histochemical technique to assess both proliferative fraction and speed of tumour growth. The present study was aimed at evaluating the ability of AgNOR count to assess proliferative speed of a tumour by correlating with pathomorphological parameters of tumour growths (grading, tumour volume, multinodularity, total number of neoplastic cells and survival period) induced in seven Wistar rats by intraperitoneal administration of N-Nitroso-N-Methylurea (NMU) at the dose rate of 50mg/kg b.wt. once per week for four weeks. Tumours were harvested on necropsy after the natural death of experimental rats. Out of total seven cases of gastric squamous cell carcinoma, four tumours were grade II and other three were of grade III. The t-test showed significantly higher mean values of mAgNOR count, mitotic figure count and different pathomorphological parameters of biological behavior i.e., tumour volume, multinodularity and total cell count in Grade-III compared to Grade-II gastric squamous cell carcinomas, indicating their biologically more aggressive growth. It was observed that mAgNOR count may be helpful in predicting real proliferative nature of a tumour and may help in taking diagnostic, prognostic and therapeutic decisions on gastric squamous cell carcinomas.

Evaluation of clinical, laboratory and morphologic prognostic factors in colon cancer

BackgroundThe long-term prognosis of patients with colon cancer is dependent on many factors. To investigate the influence of a series of clinical, laboratory and morphological variables on prognosis of colon carcinoma we conducted a retrospective analysis of our data.MethodsNinety-two patients with colon cancer, who underwent surgical resection between January 1999 and December 2001, were analyzed. On survival analysis, demographics, clinical, laboratory and pathomorphological parameters were tested for their potential prognostic value. Furthermore, univariate and multivariate analysis of the above mentioned data were performed considering the depth of tumour invasion into the bowel wall as independent variable.ResultsOn survival analysis we found that depth of tumour invasion (P < 0.001; F-ratio 2.11), type of operation (P < 0.001; F-ratio 3.51) and CT scanning (P < 0.001; F-ratio 5.21) were predictors of survival. Considering the degree of mural invasion as independent variable, on univariate analysis, we observed that mucorrhea, anismus, hematocrit, WBC count, fibrinogen value and CT scanning were significantly related to the degree of mural invasion of the cancer. On the multivariate analysis, fibrinogen value was the most statistically significant variable (P < 0.001) with the highest F-ratio (F-ratio 5.86). Finally, in the present study, the tumour site was significantly related neither to the survival nor to the mural invasion of the tumour.ConclusionThe various clinical, laboratory and patho-morphological parameters showed different prognostic value for colon carcinoma. In the future, preoperative prognostic markers will probably gain relevance in order to make a proper choice between surgery, chemotherapy and radiotherapy. Nevertheless, current data do not provide sufficient evidence for preoperative stratification of high and low risk patients. Further assessments in prospective large studies are warranted.