[Interpretation of biopsy material after transuretral and laser en bloc resection of non-muscle-invasive bladder cancer]. / Interpretatsiya biopsiinogo materiala posle transuretral'noi i lazernoi rezektsii edinym blokom nemyshechno-invazivnogo raka mochevogo puzyrya.

Bladder cancer is one of the most common onco-urological diseases, ranked second in frequency among all tumors of the urinary system after prostate cancer. At the time of detection of the primary tumor, approximately 75% of patients have no invasion into the muscularis layer (non-muscle-invasive carcinoma), with tumor growth limited to the basal membrane (stage Ta) or submucosal base (stage T1). Removal of the tumor in a «unified block¼ (laser en-bloc resection or L-ERBT), unlike routine transurethral resection, allows to obtain qualitative biopsy material for precise pathomorphological staging of the tumor process. In order to accurately stratify a patient into one or another risk group, verification of the following morphological parameters is required: degree of tumor differentiation and its malignancy, depth of invasion, foci of carcinoma in situ at resection margins, presence or absence of lymphovascular invasion. Identification of tumor variant histology is also recommended. Information on presence or absence of detrusor elements in the specimen is necessary in the morphological report, as this parameter is considered as a criterion of radically performed tumor removal. According to ICCR recommendations (International Collaboration on cancer reporting), it is recommended to use subclassification of T1 stage using all possible criteria: volume and/or depth of invasion (assessed in mm), and/or width of invasion «spot¼ (assessed in mm), and/or involvement of anatomical structure - muscularis mucosae. Full morphological examination of the material obtained during the primary resection of the tumor is an important step in the diagnosis and treatment of bladder cancer, as it allows to stratify the patient into one or another risk group and, accordingly, allows to develop a personalized postoperative management.

[Ultrastructural characteristics of the mechanisms of varicose transformation of veins of different localization]. / Ul'trastrukturnaya kharakteristika mekhanizmov varikoznoi transformatsii ven razlichnoi lokalizatsii.

The contemporary interpretation of the pathogenesis of varicose vein transformation in young patients indicates the genetically determined pattern of this process. According to the diagnostic criteria proposed by T.I. Kadurina, varicose veins of different localization belong to the so-called minor phenomena of undifferentiated connective tissue dysplasia (UCTD) syndrome. However, its impact on the development of varicose vein transformation is taken into account by not all researchers probably due to the fact that its clinical manifestations remain somewhat unclear. OBJECTIVE: To prove the role of UCTD syndrome in the development of varicose transformation of veins, by examining their wall biopsy specimens at the ultrastructural level. MATERIAL AND METHODS: Vein wall fragments removed from 25 male patients were examined; their mean age was 19 years. All the patients were divided into 3 groups: 1) cases of left-sided varicocele (VC), 2) those of varicose veins in the lower extremities (VVLE), 3) control cases. Electron microscopy examination (EME) and morphometric and statistical analyses were performed. RESULTS AND DISCUSSION: EME showed similar changes in the vein wall biopsy specimens obtained from both pediatric and adult patients with VC and VVLE. Analysis of the qualitative parameters of collagen fiber bundles revealed considerable differences in their thickness compared to those in the control group; the phenomenon of structural chaos; variability of their number in the bundles; uneven bundle thickness; abruptness of individual fibers due to their tortuous course; bundle disorganization areas and an expanded part of interfiber spaces. Morphometric analysis demonstrated a pronounced variability of numerical series when measuring their bundle thickness. The above changes indicate primary incompetence of the connective tissue framework of the varicose vein walls. The measurements of smooth muscle cells showed a decrease in their volume compared to that in the control group; there was an excessive proliferation of connective tissue between them. No substantial difference was found in the arithmetic mean of the measurements in different degrees of VC and VVLE and in the age groups for these diseases. CONCLUSION: The ultrastructural analysis and morphometric results confirm the key role of UCTD syndrome in the pathogenesis of VC and VVLE and make it possible to combine these diseases into one - systemic varicose veins.

[Predictors of perioperative complications in children with obstructive uropathy].

AIM: To identify predictors of perioperative complications in children with obstructive uropathy. MATERIALS AND METHODS: A total of 178 patients with obstructive uropathy were divided into 3 groups. In Group 1 there were 108 children with hydronephrosis, while Group 2 included 47 children with ureterohydronephrosis and Group 3 consisted of 23 children with bladder outlet obstruction according to the results of clinical, laboratory, microbiological, X-ray and pathologic study. The evaluation of the urine level of pro- (IL-8) and anti-inflammatory (IL-10) cytokines was performed at two timepoints, prior to treatment (1 point) and on the 3-5th day after the surgery (2 point) using "Vector - Best" (Russia, Novosibirsk) (IL-8), "Bender Medsystems" (Austria) (IL-10) on the enzyme immunoassay analyzer Stat Fax 2010 (USA). RESULTS: The active phase of chronic pyelonephritis was shown in Groups 1, 2 and 3 in 38%, 36% and 100% of cases, respectively. Microbiological examination of urine allowed to identify a causative agent in 85% and 89% of biopsy specimens from the ureteropelvic and ureterovesical junction, respectively. In all groups, Escherichia coli was a main pathogen (40%). In 25% of patients of Groups 1 and 2, isolated pathogens in biopsy specimen and urine were different. According to the evaluation of cytokines in the urine, during the active phase of chronic pyelonephritis there was an increase in the level of IL8 (p<0.0001) at points 1 and 2 in all patients. In the latent phase of inflammation, there was an increase in the concentration of IL-8 (p<0.04) and IL-10 (p<0.002) at point 2 in Groups 1 and 2. Using the ratio of IL-8 and IL-10, an index of inflammation activity (IIA) was suggested, whose values were increased in all Groups at point 1 and 2. Based on the regression analysis of the changes in IIA level, a model for predicting perioperative complications and an algorithm for personalized patient management were developed. CONCLUSION: Cytokines are indicators of latent inflammation in children with OU and may be predictors of perioperative complications.

[Novel approaches for transurethral en-bloc resection of large bladder tumors].

OBJECTIVE: to develop optimal techniques of en-bloc resection of large non-muscle invasive bladder tumors, determine the proper method of specimen extraction and assess the quality of specimens obtained by different techniques. MATERIALS AND METHODS: A total of 12 patients with primary cT1 bladder cancer underwent transurethral en-bloc resection between January 2018 and March 2019 were enrolled into the study. Tumor size ranged from 3.5 cm to 6.2 cm. For removal and extraction of large bladder tumors using thulium fiber en-bloc laser three different techniques were developed: "swiss cheese technique", "crown and root technique" and "three steps technique" technique". The main pathologic criteria used for assessment of removal technique were tumor grade (G), depth of invasion (T), presence of carcinoma in situ (CIS), variant histology (VH), lymphovascular invasion (LVI), presence of detrusor muscle. Additional criteria were horizontal and vertical resection margin, subclassification of T1-stage and presence of focal necrosis in tumor. RESULTS: Among the techniques developed and tested, the best quality of specimens for morphological evaluation was obtained using the combined "crown and root technique". First step is electroresection of the exophytic part of the tumor into pieces, and the next step is en-bloc laser resection (using thulium fiber or holmium laser) of the tumor base. Overall, the quality of all specimens obtained using three techniques met the current requirements of pathologic study. SUMMARY: En-bloc resection techniques of large bladder tumors allow obtaining specimen suitable for proper morphological evaluation and correct tumor staging. Further studies are required to evaluate the impact of these techniques on long-term results of treatment options.

[Venous wall weackness pathogenesis in varicose vein disease]. / Patogenez nesostoiatel'nosti stenki veny pri varikoznoi bolezni.

Varicose veins of lower extremities, varicocele and varicose dilation of pelvic veins including ovaricovaricocele are the most common non-inflammatory diseases of venous system. The same mechanisms determined varicose dilatation regardless localization of the vein. First of all, these are wall weakness and valvular insufficiency combined with hereditary collagen fiber defectiveness in case of undifferentiated connective tissue syndrome. Imbalance between different types of collagen in vascular wall (especially types I and III) also results wall weakness. Other important mechanisms are smooth muscle cells dysfunction followed by excessive intracellular synthesis and intramuscular fibrosis and imbalance of protease system due to overproduction of metalloproteinases. We consider that different forms of varicose veins (varicose veins of lower extremities, varicocele, ovaricovaricocele) may be unified within one pathology (varicose vein disease).

[Essential cryoglobulinemic vasculitis with the development of mesenteric vascular thrombosis and intestinal gangrene]. / Éssentsial'nyi krioglobulinemicheskii vaskulit s razvitiem tromboza mezenterial'nykh sosudov i gangreny kishki.

The paper describes a case of essential cryoglobulinemia unassociated with hepatitis B and C viruses. The morphological substrate of the disease was exclusively proliferative endothrombovasculitis without destructive changes in the walls of affected vessels. In addition, in the late stage of the disease, there was its unusual manifestation associated with inflammation of the mesentery arteriolar walls and with the formation of occlusive blood clots in their lumens, which led to severe abdominal diseases. The female patient showed a mosaic involvement of the loops of the bowel in the necrotic process as its separate segments, which was associated with damage to a large number of small vessels. The feature of the case is a set of 4 risk factors for a fatal disease outcome, such as age over 65 years, pulmonary, renal, and intestinal lesions.

[Current view on the pathogenesis of varicocele and the problem of its recurrence].

The clinical signs of varicocele typically emerge during the puberty. Varicocele is found in 15% of men in the general population and 25-35% and 50-80% of males presenting with primary and secondary infertility, respectively. Factors contributing to the development and recurrence of varicocele include the abnormalities of the testicular venous drainage and outflow (varicose veins are more common on the left than on the right), the anatomical features of the veins of the testicular and prostatic venous plexus, the patients constitution, predisposition to constipation or diarrhea, physical activity. At present, the genetic defects, including the undifferentiated connective tissue dysplasia (UCTD) with hereditary insufficiency of venous valves and the weakness of the testicular vein walls, are thought to play a key role in the formation of a varicocele. Considering the importance of varicocele in the development of male infertility, the role of the UCTD in varicocele formation warrants a detailed investigation to provide an individual approach to patients and predict the disease recurrence.

[Lower extremity varicose veins in childhood and at a young age: Mechanism of development and specific features]. / Mekhanizmy razvitiia i osobennosti varikoznoi bolezni ven nizhnikh konechnostei v detskom i molodom vozraste.

In Russia more than 125,000 patients with various venous diseases, lower extremity varicose veins (LEVV) being predominant, were annually operated on. In recent years, there has been a trend toward younger patients with signs of LEVV. Screening studies have revealed the signs of the disease in 10-15% of high-school children. The high prevalence of LEVV as a whole and its younger onset in recent decades cause more attention to an investigation of the relationship between the development of varicose veins, in childhood and adolescence in particular, and genomic changes. Patients with varicose veins have been noted to have a genetically reduced capacity for contraction of the smooth muscle cells of the vein walls, their remodeling due to the increased synthesis of matrix Gla protein, overproduction of TGF-ß1, a matrix metalloproteinase inhibitor, hyperhomocysteinemia, and mutations in the genes encoding the synthesis of thrombomodulin. Varicose vein transformation is considered to be a minor phenomenon of undifferentiated connective tissue dysplasia (UCTD) leading to failure of their walls due to abnormalities in the fibrous structures and extracellular matrix. Confirmation of the role of UCTD in the development of varicose veins will be able to provide an individual approach to treating patients and to choosing adequate postoperative therapy aimed at preventing a disease recurrence.

[Ultrastructural assessment of the role of dysangiogenesis in congenital hydronephrosis].

OBJECTIVE: To confirm the key role of vascular malformation by ultrasound examination and to make a more detailed study of the manifestations of dysnephro- and angiogenesis. SUBJECTS AND METHODS: The study enrolled 34 children aged 3 days to 7 years with congenital hydronephrosis, who were divided into 3 groups in accordance with the degree of renal hemodynamic disorders, the criterion for which was a resistive index (RI). RESULTS: The performed electron microscopic study revealed the signs of malformed vessels of all diameters, as well as hypoplastic changes in the renal parenchyma in children of all ages in all the groups. The most significant ultrastructural signs demonstrating a close correlation between dysangio- and dysnephrogenetic processes are the uniformity of structural failure in the glomerular and arteriolar basement membrane, which shows up in the irregularity of its thickness and obliteration of its layers, as well as the immaturity of endothelial cells of both glomerular and arteriolar capillaries (large sizes and a round shape). The important factor confirming their relationship is a direct correlation between the increased RI in all branches of the renal artery as hypoplastic changes progress in the parenchyma of hydronephrotic kidneys. CONCLUSION: The investigation demonstrated the interdependence of dysangio- and dysnephrotic processes in children with congenital hydronephrosis.

[Coupling between the hemodynamic parameters and the morphological changes in the kidney in children with congenital hydronephrosis].

The data of renal ultrasonographic and Doppler studies were comparatively assessed in children with congenital hydronephrosis. The degree of renal B-mode ultrasound hemodynamic parameters was used as the basis for grouping of the children. The resistance index (RI) of all branches of renal arteries receives attention. Morphological studies were carried out on renal biopsy specimens from 29 children from different groups and on 12 removed kidneys; the expression of TGF beta1 and alphaSMA was revealed using the streptavidin-biotin-peroxidase method. Morphological changes as hypoplasia or dysplasia became more pronounced from Group 1 to Group 3, RI increasing to peak in Group 3. Vascular changes were confined to compensatory processes following the pattern of remodeling that was manifested by vascular wall thickening and a gradual increase in RI. Failing compensatory processes resulted in the development of renal functional and hormonal decompensation and in the elevation of RI. There was a coupling between the magnitude of morphological changes and RI increases. A set of the findings emphasizes the undoubtedly important role of renal ultrasound study that makes it possible to judge the state of the vascular bed and to suggest renal structural problems in congenital hydronephrosis.

[Pathological changes in extra- and intracranial vessel in young adults in the aspect of sudden death]. / Patologiia ékstra- i intratserebral'nykh sosudov u lits molodogo vozrasta v aspekte vnezapnoi smerti.

AIM: To determine the main causes and pathomorphological characteristic of extra- and intracranial vessel pathological changes in young adults in the aspect of sudden death (SD). MATERIAL AND METHODS: The authors investigated 10485 SD cases in young adults in the period from 2012 to 2016 (5 years) according to Moscow coroner bureau autopsy data. Morphological, chemical, histological, histochemical methods (staining with hematoxylin and eosin, van Gieson's stain, Masson's trichrome stain) were used. RESULTS: Sudden death events of young adults are up to 11.93% of all non-violent death cases (81.18% of males, 18.81% - females). The mean age of the male group was 24.6, the female group 29.1. Intracranial vessel pathology was found in 549 cases (5%). Inborn aneurysms were identified as follows: arterial (69%), arteriovenous (26%) and arteriovenous malformations not diagnosed during lifetime (5%). In 14% of cases, ruptured aneurysms were combined with small extracranial ones on the convexital brain surface that show no signs of impairment. Histological investigation of aneurysms of any localization demonstrated the absence of multilayered vessel wall structure - elastic compartment with signs of disorganization, twists or total connective tissue replacement. In 93% of deaths caused by intracranial vessels rupture, the following signs of connective tissue dysplasia (CTD) were found: tall height, asthenic constitution, breastbone and cardiovascular pathology, mitral valve prolapse, aorta hypoplasia and so on. During the detailed vessel investigation in CTD group, a complex of pathological characteristics (total hypoplasia, wall thinning, S-form vertebro-basilar system vessels) was found. CONCLUSION: CTD is a pathology that becomes a risk factor for intracranial aneurysms formation and rupture in case of severe physical activity or emotional stress. Hemorrhagic infarct or non-traumatic subarachnoidal hemorrhage development lead to SD in young adults. Prompt CTD markers identification will provide new possibilities to prevent SD of youth.

[Comparative characteristics of morphologic types of mesangiocapillary glomerulonephritis (morphologic correlation analysis)]. / Sravnitel'naia kharakteristika morfologicheskikh tipov mezangiokapilliarnogo glomerulonefrita (morfologicheskii korreliatsionnyi analiz).

39 biopsies from MCGN patients are studied using Avtandilov net. Parameters of the glomeruli and their percentage correlation were determined. Quantitative confirmation of the transformation of the MCGN type I into type IV via the intermediate type is given.

[Morphologic criteria for the assessment of etiology, degree of activity and stage of the process in viral chronic hepatitis B and C]. / Morfologicheskie kriterii otsenki étiologii, stepeni aktivnosti i stadii protsessa pri virusnykh khronicheskikh gepatitakh B i C.

New classification of chronic hepatitis (Los Angeles) and the experts' comments widen the armory of a practical pathologist. A complete system of etiological verification with the use of both direct and indirect markers of various types of chronic viral hepatitis is presented. Original ranking systems of the assessment of the most important parameters in these diseases are also provided: possibility of the evaluation of chronic hepatitis activity depending on the histological activity index and stage of inflammatory process chronicity according to the histological index of the stage of chronicity. This allows to determine the patients' morphological status, this facilitating a precise morphological diagnosis.

[Clinico-morphologic correlations in various types of mesangiocapillary glomerulonephritis]. / Kliniko-morfologicheskie korreliatsii pri razlichnykh tipakh mezangiokapilliarnogo glomerulonefrita.

The possibilities of the transformation of one type of mesangio-capillary glomerulonephritis (MCGN) into another one are studied on the basis of light microscopic and ultrastructural examination of 100 renal biopsies, immunohistochemical reactions and clinical data analysis. Apart from the universally adopted I, II, III and IV types of MCGN, a new type is distinguished which occupies an intermediate position between types I and IV. The degree of clinical manifestations in this type correlated with the progression of morphological changes. Thus, lobular glomerulonephritis (GN) is an evolutive form of MCGN. With the progression of MCGN, the enhancement of severe nephritically-hypertensive forms is noted clinically, domination of the maximally active and active nephritic forms.

[Peptic ulcer and liver pathology (an analysis of 6456 autopsy observations during 1983-1992)]. / Iazvennaia bolezn' i patologiia pecheni (analiz 6456 sektsionnykh nabliudenii za 1983--1992 gg.).

The incidence of various forms of stomach ulcer, their combination with liver diseases and pathogenetic relationships of these two pathological types have been studied on the material of 6456 autopsy cases for 1983-1992. High incidence of nonspecific reactive hepatitis in both gastric and duodenal ulcer and that of liver cirrhosis and cirrhosis-carcinoma in the pyloro-duodenal ulcer is established. A role of gastrin as a promoter in the development of liver cirrhosis and carcinoma in pyloroduodenal ulcer is suggested. The role of nonspecific reactive hepatitis in chronization of the hepatic pathological process is not excluded.

[Subdivision of certain morphological variants of chronic glomerulonephritis]. / O droblenii nekotorykh morfologicheskikh form khronicheskogo glomerulonefrita.

Modern methods allow to detail morphological classification of chronic glomerulonephritis, to adapt it to the clinical classification and to recommend it for practical use. This specification concerns minimal changes and a group of mesangial chronic glomerulonephritis. The term "minimal changes" is a light-microscopic definition and covers rather a heterogeneous group of diseases or their initial manifestations. Differential diagnosis of these diseases is feasible only at the electron microscopic level. A group of chronic glomerulonephritis (mesangioproliferative and mesangiocapillary) includes variants distinguished on the basis of immunohistochemical, light microscopic and electron microscopic methods. Of them, the immunohistochemical method is most valuable for differentiation of mesangioproliferative glomerulonephritis.

[Comparative morphologic characteristics of viral hepatitis B and C]. / Sravnitel'naia morfologicheskaia kharakteristika virusnykh gepatitov B i C.

Using liver biopsies in chronic HBV and HCV infections and their combination, the authors found between them morphological difference represented by nonspecific morphological markers. The combination of fat and hydropic hepatocytes degeneration, their heterogeneity, lymphoid follicles of various location and maturation degree, sinusoidal cell hyperplasia, accumulation of lymphocytes and macrophages in sinusoids, destruction, proliferation and sclerosis of ductules are of a high significance in hepatitis C. Etiological markers of hepatitis B are so-called ground-glass hepatocytes and "sand" nuclei. Various combination of these markers are characteristic for HBV and HCV co-infections with predominance among them of a replicating virus.