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Purpose: Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease with current standard-of-care therapies. Homologous recombination repair (HRR) gene alterations, including BRCA1/2 alterations, can sensitize cancer cells to poly (ADP-ribose) polymerase inhibition, which may improve outcomes in treatment-naïve mCRPC when combined with androgen receptor signaling inhibition., Methods: MAGNITUDE (ClinicalTrials.gov identifier: NCT03748641) is a phase III, randomized, double-blinded study that evaluates niraparib and abiraterone acetate plus prednisone (niraparib + AAP) in patients with (HRR+, n = 423) or without (HRR-, n = 247) HRR-associated gene alterations, as prospectively determined by tissue/plasma-based assays. Patients were assigned 1:1 to receive niraparib + AAP or placebo + AAP. The primary end point, radiographic progression-free survival (rPFS) assessed by central review, was evaluated first in the BRCA1/2 subgroup and then in the full HRR+ cohort, with secondary end points analyzed for the full HRR+ cohort if rPFS was statistically significant. A futility analysis was preplanned in the HRR- cohort., Results: Median rPFS in the BRCA1/2 subgroup was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.6 v 10.9 months; hazard ratio [HR], 0.53; 95% CI, 0.36 to 0.79; P = .001). In the overall HRR+ cohort, rPFS was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.5 v 13.7 months; HR, 0.73; 95% CI, 0.56 to 0.96; P = .022). These findings were supported by improvement in the secondary end points of time to symptomatic progression and time to initiation of cytotoxic chemotherapy. In the HRR- cohort, futility was declared per the prespecified criteria. Treatment with niraparib + AAP was tolerable, with anemia and hypertension as the most reported grade ≥ 3 adverse events., Conclusion: Combination treatment with niraparib + AAP significantly lengthened rPFS in patients with HRR+ mCRPC compared with standard-of-care AAP., [Media: see text].

For the purpose of definition of features immunohistochemical expression of protein Ubiquitin in peritumoral testicular tissue, which can be characterised as precancerous changes, the 40 patients with testicular germ cell tumors are investigated. In peritumoral testicular tissue in patients with disturbance of spermatogenesis. which make 95 %, it is taped: intensifying in seminiferous tubules of ubiquitination processes, testifying about intensive proteolysis of considerable quantity of the damaged intracellular proteins, occurrence of atypical germ cells (TIN), which differ from normal spermatogenesis cells authentically lower of nuclear and cytoplasmatic expression of protein Ubiquitin, and also disturbance of ubiquitination processes in Leydig cells in the form of intensifying of cytoplasmatic expression and total disappearance of nuclear expression of protein Ubiquitin. The received results testify to the important role of structural and functional disturbances of ubiquitin-proteolysis system components at the initial stages of testicular tissue carcinogenesis.

Unlabelled: The androgen-suppressive therapy (AST) in patients with prostate cancer (PC) may dramatically affect the bone mineral density (BMD), which puts patients at risk of severe adverse effects, such as weight-bearing bone fractures., Aim: To study the effect of AST on BMD in patients with non-metastatic hormone-sensitive PC treated with intermittent hormonal therapy, and effect of different total testosterone level on BMD., Materials and Methods: From 2011 to 2013 we treated 56 patients with non-metastatic hormone-naïve PC. Intermittent hormonal treatment with flutamide at a dose of 250 mg 3 times per day with nine monthly injections of luteinizing gonadotropic releasing hormone (LGnRH) ["treatment" period] followed by period of observance ("no treatment") was administered. We evaluated the BMD of lumbar spine and both proximal thighs by means of dual-energy x-ray densitometry at the end of "treatment" period and at the end of "no treatment" period., Results: During the first treatment period, 44 of 56 patients (78.6%) experienced the reduction in BMD in both lumbar spine and thighs. Total testosterone level in all patients dropped to castration level. During the first period of "no treatment" there was an increase in BMD (p < 0.05) in 30 (68.2%) of 44 patients. The median time to recovery of total testosterone level to the level > 50 ng/dl was 91 days (from 30 to 308 days), and > 100 ng/dl was 110 days (from 49 to 343 days). The changes in BMD positively correlated with the changes in total testosterone level (correlation 0.18 [95% CI, 0.04-0.27], p = 0.009). The decline in total testosterone level in serum was followed by the decline in BMD value in the studied areas, and vice versa., Conclusions: The changes in BMD positively correlated with changes in total testosterone level. The BMD decreases during the androgen suppression and increases during the pause in the treatment. This demonstrates the benefit of intermittent AST in preventing osteoporosis, pathological bone fractures and possibly, bone metastases.

For the purpose of definition of characteristic morphological changes of testicular tissue which to be surveyed as precancerous, the peritumoral tissue at 40 patients with testicular germ cell tumors (TGCT) which has been spent orchiectomy is investigated and the diagnosis according to classification TNM is established. In peritumoral tissue in 95% patients with testicular germ cell tumors disturbance of spermatogenesis, characteristic for the secretory form of male infertility, are taped. Occurrence of atypical germ cells (TIN) in semen tubules, which were defined in 60% of cases, and overexpressed hyperplasia of Leydig cells of interstition, defined in 82.5% of cases--the typical changes of peritumoral testicular tissue which can be characterised as precancerous changes. Patients with the secretory form of male infertility whith atypical germ cells (TIN) in semen tubules and the overexpressed hyperplasia of Leydig cells, make hight risk group of development of testicular cancer and demand a dispensary observation.

In an immunohistochemical investigation designed to study a mutated p53 protein in transitional-cell tumours (n = 44) we succeeded in identifying the presence of two types of transitional-cell tumours of human urinary bladder, such as p53 immunopositive and p53 immunonegative transitional-cell tumours. Thus, the results of the immunohistochemical investigation into the protein p53 were found out to directly correlate with the clinical course of transitional-cell tumours, that are held to be of great differential-diagnostic and prognostic significance.

A 31 year old patient with non-seminomatous germ-cell tumour of the testis was treated with Ukrain following operation and gamma-radiotherapy. 20 mg Ukrain ampoules were injected i.v. twice weekly with a total dose of 200 mg for each of three courses of treatment. Within the period of 24 months observation no recurrence or metastases were found. The results testify that Ukrain in complex treatment of patients with non-seminomatous germ-cell tumours of the testis can contribute to optimisation of immune status which improves the prognoses and results of treatment.

We have studied 181 patients with germ-cell tumours of the testis. The first group comprised 80 persons without evidence of metastasizing into retroperitoneal lymph nodes; the second group included 101 patients with germinal testicular tumours metastasizing into regional lymph nodes. Eighty patients were subjected to transperitoneal lymphadenectomy which allowed comparison of the results of lymphoscintigraphy (negative radionuclide diagnosis with colloid agents labelled with gold and technetium positive radionuclide diagnosis with 99mTc-pertechnetate) with the findings of histologic examination. We demonstrated high significance of lymphoscintigraphic methods: sensitivity 83%, specificity 90.9%, significance 86.2%. It was found that information obtained with lymphoscintigraphy can serve as clinical guidelines in determining the site, size and spread of metastasizing, which is very important in choosing fields of irradiation. Lymphoscintigraphy in testicular tumours enables more accurate staging and radicality of lymphadenectomy at different time intervals after surgery.

3-OAK antigen was determined by immunodiffusion in agar by means of immune sera containing antibodies against 3-OAK. In patients with cancer of the urinary bladder the percentage of detecting 3-OAK-Ag in the native serum was 76.9 while in lyophilized it was 41.9. In patients with pretumorous diseases (leukoplakia, chronic cystitis, papillomas) their values were 64.1 and 56.1 respectively. It is concluded that lyophilized blood serum may be used in the clinical practice for immunological and serological examinations.

A comparative evaluation of histologic patterns of non-seminomatous testicular tumors was carried out in 2 groups of patients: those receiving platinum derivative-based preoperative chemotherapy (31) and chemotherapy-free cases (36). Preoperative cytostatic treatment potentiated cell differentiation in retroperitoneal metastases in some patients, the latter effect being considered prognostically favorable.

The effect of combined treatment was studied in 97 patients with nonseminomatous testicular tumors with regional and distant metastases with regard to the blood serum levels of alpha-fetoprotein and chorionic gonadotropin. The disease stage was found closely correlating with the efficacy of the treatment and the level of tumor markers. Complete remission was observed in 84.2 per cent (16 out of 19) patients with normal marker levels and in 26.8 per cent (11 out of 41) of those in whom both markers levels were raised (p less than 0.05). A continuous follow-up revealed that increased marker levels were the evidence of tumor relapse or metastases in clinically silent patients.

Stage I--II disease was identified in 71 out of 219 patients with nonseminomatous germ cell tumors of the testis. After orchifuniculectomy, polychemotherapy was given to 30 patients while the rest underwent transperitoneal lymphadenectomy. Long-term survival in the polychemotherapy group was 83.3%, in the lymphadenectomy one--95.1%. After excision of the retroperitoneal lymph nodes, the patients' follow-up should include regular assays of such tumor markers as alpha-fetoprotein and chorionic gonadotropin as well as X-ray examination of the chest for at least the first 24 months. Polychemotherapy should not be administered unless tumor dissemination or an increase in tumor marker levels are detected.

Out of 335 patients with testicular neoplasms, cryptorchidism was concomitant in 84 cases (25%). 28 patients underwent orchiopexy at the age of 5-52 years. Tumor was detected, on the average, 14,4 years after the operation. Orchiopexy contributes to carcinogenesis in the undescended testicle. The rate of incidence of non-seminomatous tumor is relatively higher in patients after orchiopexy than in untreated cases of cryptorchidism. Patients with undescended testicle should be referred to a group at high risk and be followed up.

A comparative analysis of morphological peculiarities and clinical course of seminoma makes the case for distinguishing three types of the tumor. Prognosis in cases of typical seminoma depends on the level of differentiation of tumor cell elements and stage of tumor. Alkylating drugs and radiotherapy should be a method of choice in treatment of patients with typical seminoma. High orchofuniculectomy may be sufficient at the initial stages of spermatocytic seminoma due to its favorable clinical course determined by a high level of specific differentiation of tumor cells. Electron microscopic analysis of anaplastic seminoma showed cells with signs of differentiation towards trophoblast (chorionepithelioma elements) and embryonal entoderm (yolk sac tumor) characterized by a relatively higher malignancy. These data account for the tendency of anaplastic seminoma to rapidly disseminate and suggest application of adjuvant chemotherapy and lymphadenectomy.

The level of activity in natural killer cells (mononuclears) of peripheral blood relative to 51C-labelled K-562 cells is found to be significantly lower in patients with germinative testicle tumours than in donors. At the same time neither mononuclears of the peripheral blood nor those isolated from the tumour tissue practically lyse tumour tissue cells. The higher activity of natural killer cells relative to K-562 cells corresponds to the higher immunocellular infiltration of the tissue from nonseminomatous tumours.