[A systematic review of radiotherapy for primary renal cell carcinoma].

Renal cell cancer accounts for 2% of all cancers. The gold standard for managing patients with no evidence of distant metastasis renal cell cancer remains is complete surgical resection. The clinical data investigating preoperative radiotherapy failed to reveal benefited from this methods. The role of routine postoperative radiotherapy in the management of renal cell cancer is not established in patients with localized disease after complete surgical resection. Renal cell cancer is radioresistant tumor for conventional radiation therapy. Although renal cell carcinoma is related to radioresistant tumors, in recent years new promising directions in radiation therapy have become apparent. To overcome the radioresistance of renal cell carcinoma, the use of modified radiation therapy regimens with high doses per fraction is justified. new technologies of radiation therapy, which include stereotactic radiation therapy allows to accurately deliver doses of ionizing radiation to a tumor, without the risk of damage to neighboring tissues and organs. Recent data showing that with the use of high-precision methods, such as SBRT, unresectable local renal cell carcinoma can successfully be treated with durable local control and low toxicity. Nonetheless, prospective, randomized trials and omparative effectiveness studies are needed to further evaluate this ablative modality in the treatment of renal cell carcinoma.

[Morphological criteria for progression risk in patients with prostate cancer after radiation therapy].

AIM: To study an importance of new 2016 WHO histologic grading system for prostate cancer in evaluating the risk of progressing after conformal external beam radiation therapy, brachytherapy 125I and androgen deprivation therapy. MATERIALS AND METHODS: A total of 53 patients with prostate acinar adenocarcinoma were undergone to conformal external beam radiation therapy, brachytherapy 125I and androgen deprivation therapy. Age of patients was 54-80 years (68.11+/-4.7 years). T3 and T2 prostate cancer was diagnosed in 42 (79.3%) and 11 (20,7%) patients, respectively. Baseline PSA level ranged from 5.5 ng/ml to 311 ng/ml (39.7+/-7.9 ng/ml). According to the new grading system (the WHO classification, 2016), all patients were divided into five risk groups. RESULTS: Median follow-up was 64.9 months. The biochemical progression was seen in two patients, while three patients had metastatic disease. All patients with progressing prostate cancer were from IV and V prognostic groups. The 5-year progression-free survival rates for patients of IV-V and I-III groups were 44, 4% and 100%, respectively. CONCLUSIONS: According to the results of combination treatment (conformal external beam radiotherapy, brachytherapy 125I and hormonal therapy), progression-free survival rate in patients of IV (Gleason 4+4=8) and V (Gleason 4+5=9 or 5+5=10) groups, according to new WHO grading system were significantly lower, in comparison with patients of I (Gleason 3+3=6), II (Gleason 3+4=7) and III groups (Gleason 4+3=7). Our study showed that new WHO classification allows to predict the progression of prostate cancer not only after prostatectomy, but also after conformal external beam radiation therapy, combined with brachytherapy 125I and androgen deprivation therapy.

[Intrahepatic cholangiocarcinoma].

The paper gives information on current approaches to diagnosing and treating intrahepatic cholangiocarcinoma (IHC), its microscopic and macroscopic varieties. It details the specific features of images of IHC by ultrasonography, X-ray computed tomography, magnetic resonance imaging (MRI), including those by diffusion-weighted MRI. Dynamic intravenous contrast enhancement and analysis of tumor hemodynamic features are emphasized to play a crucial role in different examination (arterial, venous, and delayed) phases. Diffuse heterogeneous enhancement of the whole volume of the tumor in the arterial phase with pronounced peripheral and progressing centripetal enhancement in ensuing phases is considered to be the most common type of an IHC image, which can recognize with confidence this comparatively rare neoplasm.

[Importance of proliferative potential (as the ratio of a proliferative cells number and duration of mitosis) in diagnoses of malignant degree and prognosis of adrenocortical cancer].

The aim of research has been the estimation of a proliferative potential as simultaneous detection of a proliferative cells number (Ki-67 index) and duration of mitosis (nucleolar argyrophilic protein expression--B23/nucleophosmin and C23/nucleolin) at patients with adrenocortical cancer. In according to lifetime of patients after operation 2 groups had been sorted out. The first one included patients surviving 56.12 months, the second one--9.25 months. We've found out that different aspects of tumor diagnosis as well distinction of benignant or malignant tumor growth, a malignant degree of tumors, a prognostic criteria of illness, survival of patients etc. must be characterized by total research both a proliferative cells fraction (Ki-67 index) and a rate of mitosis (expressions of B23/nucleophosmin and C23/nucleolin).

[Embryonic hepatic sarcoma in children: aspects of morphological diagnosis].

13 cases of embryonic undifferentiated sarcoma of the liver were examined. The tumor was detected in children: 50% being between 5-6 years of age and no sex domination was found. The tumors were solitary, large, well demarcated and had cystic areas of gelatinous degeneration. The tumor was composed of atypical round, stellate, spindle and epithelioid-like cells that were loosely arranged in a myxoid stroma. Entrapped bile ducts were commonly present. Electron microscopic and immunohistochemical findings showed no clear-cut differentiation of embryonic sarcoma cells.

[Liver cancer: immunohistochemical and electron microscopic study].

Primary liver tumors, including 7 low-grade hepatocellular carcinomas (HC), 12 average-grade HC (including 2 mixed tumors and 2 cholangiocellular carcinomas (ChC)), obtained from 23 patients, were histologically, immunohistochemically, and electron microscopically. Certain markers were immunohistochemically studied to identify HC and ChC and differentiate liver carcinoma from metastatic tumors of the same organ.

[Identification of the hereditary variants of skin melanoma]. / Identifikatsiia nasledstvennykh variantov melanomy kozhi.

The identification of hereditary variants of cutaneous melanoma and analysis of the role of hereditary factors and syndromes predisposing to cutaneous melanoma were carried out. The involvement of individual nevus phenotypes in the development of this disease was determined. Based on a survey of recent molecular biological data and our studies, the etiological and genetic heterogeneity of cutaneous melanoma is reported. In relatives of patients with cutaneous melanoma and persons with multiple pigmented nevi, the malignant tumors proved to be differentiated in the direction of the neural crist tissues and/or derivatives of cutaneous mesenchyma. Based on the evidence obtained, the approaches have been developed to formation of risk groups for the purpose of early diagnostics of cutaneous melanoma.

[Analysis of mutations in the RET proto-oncogene in patients with medullary thyroid tumor]. / Analiz mutatsii v protoonkogene RET u bol'nykh s medulliarnym rakom shchitovidnoi zhelezy.

The spectrum of mutations of the RET protooncogene was analyzed in Russian patients with inherited or sporadic medullary thyroid carcinoma (MTC). Four RET exons (11, 13, 15, and 16) were subjected to molecular analysis, and mutations were revealed and identified in 47.4% (9/19) patients with sporadic MTC. In total, six mutations (including three new ones) were observed. The most common mutation affected codon 918 to cause substitution of methionine with threonine and accounted for 31.6% alleles. Analysis of exons 11 and 16 revealed four mutations in patients with inherited multiple endocrine neoplasia type 2 (MEN 2). Mutations were found in each patient. Thyroidectomy was performed in four asymptomatic carriers of RET mutations from three MET 2A families (in two families, affected relatives had bilateral pheochromocytoma). In two patients, analysis of the surgery material revealed MTC microfoci in both lobes of the thyroid gland. The results provide the ground for constructing a bank of genetic information on Russian MTC patients with the clinically verified diagnosis.

[Association of polymorphism of genetic markers of CYP19 and CYP17 with sporadic breast cancer]. / Izuchenie assotsiatsii polimorfnykh markerov genov CYP19 i CYP17 so sporadicheskim rakom molochnoi zhelezy.

Polymorphic alleles of CYP17 and CYP19, which are involved in estrogen biosynthesis, were tested for association with breast cancer (BC). Microsatellite (TTTA)n and 3-bp deletion of CYP19 and single-nucleotide polymorphism T27C of CYP17 were analyzed in 123 BC patients and 119 healthy women. Of the six (TTTA)n alleles observed, allele (TTTA)8 proved to be associated with BC (11.8% vs. 6.3%, P = 0.04). Genotype A2/A2 of CYP17 was also associated with BC (32.5% vs. 20.2%, P = 0.04). Risk of BC was especially high in the presence of both factors (7.3% vs. 0%, P < 0.01). Allele (TTTA)8 and genotype A2/A2 were assumed to be risk factors of BC.

Three novel mutations in the RET proto-oncogene.

Medullary thyroid carcinoma (MTC) occurs as a sporadic tumor or in connection with inherited cancer syndromes of multiple endocrine neoplasia type 2 and familial MTC. Missense RET proto-oncogene mutations and small in-frame deletions are found in most of the cases. In a significant amount of sporadic MTC cases somatic mutation at codon 918 (exon 16), or at codons 609, 611, 618, 620 (exon 10), or codons 630, 634 (exon 11) appear. We report here on three new somatic cell missense mutations of the RET proto-oncogene associated with sporadic MTC. In one tumor mutation at codon 922 TCC(Ser)-->TTC(Phe) in exon 16 was found. In another tumor two mutations at codons 639 GCA(Ala)-->GGA(Gly) and 641 GCT(Ala)-->CGT(Arg) in the exon 11 were observed. Allele-specific PCR followed by sequencing demonstrated the presence of both mutations at the same allele.

[Treatment of patients with stage I nonseminomal germ cell testicular tumors]. / Lechenie bol'nykh neseminomnymi germinogennymi opukholiami iachka I stadii.

Three different approaches to treatment of non-seminomal germinogenic testicular tumors (NSGTT) of stage I after orchidofuniculectomy: preventive retroperitoneal lymphadenectomy, preventive chemotherapy, expectant treatment. Recurrences, 5-year recurrence-free and overall survivals reached 17.4, 81.8 and 95.4%; 6.3, 93.8 and 100%; 33.3, 66.4 and 83.5%, respectively. Progression occurred more frequently in patients having invasion of tumor cells in lymphatic and blood vessels in the primary tumor. The authors conclude on preferable use of preventive chemotherapy after removal of the primary tumor.

[Cytomorphological diagnosis of granulosa cell tumor of the ovary]. / Tsitomorfologicheskaia diagnostika granulezokletochnoi opukholi.

The cytology of granulosa cell tumor in children and adults is studied. Cytological smears of ascitic fluid and fresh tissue smears were examined. The tumor was diagnosed in 9 patients aged 11 to 73 years. All patients had symptoms of hyperestrogenia. Adequate treatment of the condition requires the tumor to be differentiated from other tumors (thecoma, low-grade and small-cell carcinomas, carcinoid, yolk-sac tumor, and lymphoma) before or during surgery.

Decrease of ornithine decarboxylase activity in premalignant gastric mucosa and regression of small intestinal metaplasia in patients supplemented with high doses of vitamin E.

The effect of high doses of vitamin E (Vit.E; 400 units/ day) on ornithine decarboxylase (ODC) activity and regression of small intestinal metaplasia (SIM) was studied in a 1-year double-blind intervention trial. Biochemical and morphological parameters were estimated in 14 evaluable SIM patients of 18 in the Vit.E group and in 16 of 18 intestinal metaplasia patients enrolled in control group (placebo). In the control group, there were no statistically significant changes in Vit.E content in blood plasma, ODC activity, and the rate of SIM in multiple biopsies from antrum gastric mucosa. In the Vit.E group, after 6 and 12 months of intervention, the initial content of Vit.E in blood plasma increased from 6.4 +/- 0.9 up to 17.0 +/- 1.8 and 21.2 +/- 2.3 micrograms/ml, respectively, and the initial abnormally high activity of ODC, 62.6 +/- 7.8 units, decreased by 53 and 65%, respectively. Histological analysis of multiple biopsies, taken from the gastric antrum of patients supplemented with Vit.E, revealed that in 8 of 14 patients (57%) after 6 months and in 10 of 14 patients (71%) after 12 months, no signs of SIM were observed; gastroscopic dye procedure confirmed the regression of SIM in these cases and showed the presence of only small isolated stained areas identified as SIM.

Effect of prolonged beta-carotene or DL-alpha-tocopheryl acetate supplementation on ornithine decarboxylase activity in human atrophic stomach mucosa.

The effect of beta-carotene and DL-alpha-tocopheryl acetate (alpha-TAc) on the activity of ornithine decarboxylase (ODC) in human atrophic stomach mucosa and intestinal metaplasia (IM) was studied in a double-blind intervention trial. Persons (227) with upper gastrointestinal symptoms and/or atrophic gastritis (AG) were examined. It was found that ODC activity in the biopsies of antral mucosa increased gradually from normal mucosa (7.2 +/- 1.8 units) to superficial gastritis (22.7 +/- 5.9 units) and to AG (54.2 +/- 6.9 units). Enzyme activity in cases of IM did not differ from atrophic mucosa without IM (56.1 +/- 8.0 versus 51.4 +/- 5.6 units; P > 0.05). For the intervention trial, 3 groups of 20 patients with AG were studied. Patients were supplemented daily for 1 year with beta-C (20 mg; group 1), alpha-TAc (55 mg; group 2), or placebo (group 3). No significant change in ODC activity was observed in placebo-treated subjects during 1-year follow-up. During the first 3 months, beta-C supplementation resulted in about a 50% decrease in ODC activity in atrophic mucosa. A moderate decrease in ODC activity of approximately 18% was observed after 6 months supplementation with alpha-TAc. The possible role of ODC in gastric carcinogenesis is discussed.

[The role of embryoid bodies in the development of germinogenous tumors of complex structure and of the teratoma]. / Rol' émbrioidnykh telets v razvitii germinogennykh opukholei slozhnogo stroeniia i teratomy.

250 germinal gonadal and extragonadal tumors were studied in children and adolescents under 16 years of age. Germinal tumours of complex structure were found in 42 patients and in 36 of them embryoid bodies of various types (full, not-full, amorphous) were distinguished. Certain features were revealed indicating the development of the immature teratoma by means of maturation of preexisting embryoid bodies. The arguments in favour of complex germinal tumour development due to the loss of maturation and differentiation capacity of one or several structural elements of the embryoid bodies are presented. The observation of mature, immature embryonal tissues and proliferating elements of the embryoid bodies in the composition of one and the same tumour may be explained by different biological potency of individual clones of atypical and primordial germinal cells which are the source of the development of these tumours.

[Features of the histogenesis of testicular yolk sac tumors in children]. / Osobennosti gistogeneza opukholi zheltochnogo meshka iaichek u detei.

32 cases of a yolk sac tumour of the testis in children aged up to 5 years underwent retrospective morphological study. Foci of proliferation of activated gonocytes identical to the type A spermatogonia with clear nuclei and the type B spermatogonia characterized by a negative PAS-reaction and reaction to alpha-fetoprotein are observed in the seminiferous tubules surrounding a tumour. Besides this areas of the primordial germinogen cell generation are found among the cells lining the system of labyrinths and channels of the yolk sac tumour. A new hypothesis of the yolk sac tumour histogenesis in the child testis is put forward--namely, through the transformation of the activated gonocytes in the seminiferous tubules into their "somatic" phase, i.e. into the yolk sac elements from which they originate. Likewise, the scheme is suggested reflecting a cyclic character of the germinogenic cells in ontogenesis. This scheme allows visual representation of the process of the parthenogenetic development of germinogenic tumours.

[A comparative study of delayed hypersensitivity due to mycobacteria and their isolated protein fractions]. / Sravnitel'noe izuchenie zamedlennoi giperchuvstvitel'nosti, vyzvannoi mikobakteriiami i vydelennymi iz nikh bel'kovymi fraktsiiami.

The role of intracellular protein fractions, isolated from M. tuberculosis virulent strains in the process of the electrophoretic separation, in the development of delayed hypersensitivity reactions has been studied. Low reactogenicity of protein fractions has been established on the basis of the development of faint immunopathological reactions in sensitized animals. High-molecular fraction 1 may be used as a sensitive preparation for the differentiation of individual mycobacterial species.