[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.

[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).

[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.

[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.

[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.