[Molecular Diagnostics of the Involvement of Visually Normal Mucosa in the Malignancy Process in Urothelial Bladder Cancer].

Immunofluorescent method by flow cytometry was used to quantify the expression of the tumor-associated protein ßIII-tubulin (TUBB3) in the tissue of urothelial bladder cancer and visually normal mucosa (56 samples in total). The expression of the marker was detected in 100% of cases, and heterogeneity of the TUBB3 expression level both in tumor tissue and in "normal" mucosa was revealed. The level of TUBB3 in the "normal" mucosa did not depend on the distance from the tumor (1 cm or more than 3 cm) and, on average, it was lower than in the tumor tissue (21.8 ± 10.8% and 24.9 ± 13.2% vs 35.2 ± 12.4%; p = 0.04 and 0.005, respectively). An increase of the TUBB3 expression in the tumor and in the "normal" mucosa was revealed in muscle invasive bladder cancer compared to non-muscle invasive bladder cancer. Therefore, in urothelial bladder cancer, the tumor-associated protein TUBB3 is a molecular marker of bladder mucosa involvement in the malignancy process and predicts the risk of tumor muscle invasion, which may influence indications for early cystectomy.

[Surgical treatment of lung metastases of kidney cancer].

The medical records of 60 patients who underwent surgery to remove the lung metastases of T1-4N0-2 kidney cancer were retrospectively analyzed. The age of patients ranged from 31 to 70 years. Synchronous lung metastases were diagnosed in 20 (33.3%) cases, metachronous - in 40 (66.7%). 53 (88.3%) patients had lesions in one lung, and 7 (11.7%) patients--in both lungs. Solitary metastases were present in 41 (68.3%) patients, multiple--in 19 (31.7%). In 69.4% of cases, the size of lung metastases was more than 2 cm. Metastasis at other sites at the time of surgery on the lungs were present in 1 patient (supraclavicular lymph nodes). The primary tumor was removed in 56 (93.3%) of 60 patients. All 60 patients underwent removal of lung metastases (radical--53 [88.3%]). One patient underwent a radical supraclavicular lymph node dissection. All tumor lesions were removed in 50 (83.3%) patients. Median followup period was 20 (3-155) months. Perioperative complication rate was 6.6%; no deaths caused by complications of treatment were registered. Histologically, metastases of renal cell carcinoma were verified in all removed lesions from the lungs; 3 (5%) patients had mediastinal lymph node metastases. Five- and 10-year overall, specific and recurrence free survival rates were 36.3 and 19.1%, 38.9% and 27.2, 20.4 and 11.7%, respectively. Univariate analysis demonstrated an adverse effect of pN + category, bilateral pulmonary lesions, the presence of mediastinal lymph nodes metastases and non-radical removal of malignant lesions of the lung on the specific survival. Multivariate analysis confirmed a significant effect of radical surgery on the survival.

[Alteration of VHL gene in patients with metastatic renal cell carcinoma].

Blocks of preparations from 22 patients with metastatic renal cell carcinoma on target therapy were studied. The patients were examined for mutations/methylation of VHL gene. The mutations were detected in 10 (45.5%) of 22 patients, VHL methylation was found in 1 (4.5%) patient. Overall survival was 36.4 and 66.7% in the groups of patients with and without gene VHL alteration, respectively. Progression-free survival was 47.6 and 57.1%, respectively (p = 0.619), relapse-free survival--63.6 and 45.5%, respectively (p = 0.682), progression was registered in 36.4 and 54.5%, respectively (p = 0.682). Gene VHL inactivation had no effect on prognosis of the disease and results of anti-angiogenic therapy.

[Interdisciplinry approach to the treatment of diffuse germinogenic ovarian tumours].

The first stage in the treatment of disseminated germinogenic ovarian tumours (HOT) is induction chemotherapy in accordance with the IGCCCG prognosis group. Dynamic observation is indicated in case of incomplete induction in patients with seminoma excepting those with PET-positive residual tumours bigger than 3 cm to whom second-line chemotherapy or retroperitoneal lymphadenectomy is indicated. Ablation of residual tumour of any localization is indicated to patients with disseminated non-seminoma HOT (NHOT), incomplete induction, and negative level of tumour markers. The necessity of adjuvant chemotherapy in case of a viable malignant HOT in the removed tissues remains debatable. Refractory and recurring HOT are usually treated with a combination of fosfamide and vinblastine. Residual tumours need to be removed after salvation chemotherapy. Surgical treatment is the preferred option for the management of late NHOT relapses.

[Retroperitoneal lymphadenectomy in disseminated non-seminoma germinogenic testicular tumors after chemotherapy in patients with elevated serum tumor markers].

Postchemotherapy retroperitoneal lymph node dissection (RLND) was performed in 70 testicular non-seminoma patients with elevated serum tumor markers (age median 27.0 +/- 8.1 years) from 1983 to 2008. N1, N2, N3, Nx were diagnosed in 4 (5.7%), 10 (14.3%), 35 (50.0%), 21 (30.0%) patients. Distant metastases were present in 23 (32.9%) cases. The level of the initial tumor markers was elevated in all the patients: S1 - 169 (46.0%), S2 - 108 (29.4%), S3 - 51 (13.9%), Sx - 39 (10.6%). According to the IGCCCG prognostic model, 11 (15.7%) patients were classified as good, 19 (27.1%)--as moderate, 16 (22.9%)--as poor prognostic groups. The prognostic group was not identified in 24 (34.3%) cases which started treatment in other hospitals. All the patients received induction cisplatin-based chemotherapy following orchidectomy (first-line--24 (34.3%), second-line--46 (65.7%) which resulted in tumor shrinkage < 50% in 7 (10.0%), 51-90% in 23 (32.9%), > 90%--in 2 (2.9%) cases. The response was not properly assessed in 38 (54.3%) cases. CT scan revealed residual retroperitoneal masses after chemotherapy in all the patients: < 2 cm--5 (7.1%), 2-5 cm--25 (35.7%), > 5 cm--40 (57.1%). The level of the tumor markers remained positive in all the patients. Further chemotherapy was not perspective in all 70 patients who further underwent retroperitoneal lymph node dissection (RLND). Radical RLND was performed in 59 (84.3%) patients. Postoperative chemotherapy was given to 27 (38.6%) cases. Median follow-up was 20.8 (3-137) months. Complications developed in 12.9% (9/70) patients. Mortality was 1.4% (1/70). Histology revealed necrosis in 20 (28.6%), teratoma--in 26 (37.1%), cancer--in 24 (34.3%) specimens. Prognostic factors for cancer in retroperitoneal pathology were the following: S > S1 (p = 0.013), intermediate or poor prognosis group IGCCCG (p = 0.014), absence of embryonal carcinoma (p = 0.003), the presence of choriocarcinoma in the testicular tumor (p = 0.028), second-line chemotherapy (p = 0.001), residual mass > 2 cm (p = 0.006). Five-year overall, specific and progression-free survival of 70 patients was 41.0%, 42.4% and 31.8%, respectively. Univariate analysis revealed an adverse impact on progressive-free survival of category S > S1 (p = 0.015), intermediate or poor prognostic group IGCCCG (p = 0.01), the presence of embryonal carcinoma (p = 0.020) and the absence of choriocarcinoma in the testicular tumor (p = 0.029), tumor shrinkage < 50% (p < 0.0001), incomplete RLND (p = 0.012), an incomplete effect of the combined treatment (p < 0.0001), cancer in the residual mass (p < 0.0001). The multivariate analysis proved predictive value of an incomplete effect of the combined treatment (p < 0.0001). Thus, selected testicular non-seminoma patients with elevated serum tumor markers are curable with surgery. The best candidates for RLND in this group are patients without a tumor markers level increase during chemotherapy, with S1 category, good IGCCCG prognosis, tumor shrinkage > 50% and potentially respectable residual disease.

[Results of surgical and radiotherapy of prostatic cancer T1-4N0-1M0].

To compare the results of radical prostatectomy and conformal radiotherapy in prostatic cancer T1-4N0-1M0, we made a retrospective study of 306 patients with prostatic cancer T1-4N0-1M0 of whom 144 (47.1%) were treated surgically (radical prostatectomy) while 162 (52.9%) were exposed to extracorporeal conformic radiotherapy. Follow-up median was 30.7 +/- 29.8 months. Five and 10-year overall, specific and PSA recurrence free survival in 306 patients was 94.0% and 90.1% (median was not achieved), 96.6% and 94.3% (median was not achieved), 66.1 and 49.2% (median was 84.0 +/- 4.4 months). In multifactorial analysis significant prognostic factors of PSA recurrence free survival were T category (p = 0.021) and Glison's sum (p = 0.002). In the subgroup of patients with local prostatic cancer there was a significant superiority of the operated patients by PSA recurrence free survival over irradiated group in baseline PSA < 10 ng/ ml (p = 0.015), Glison's index < 7 (p = 0.071) and combination of these factors (p = 0.018). A favourable prognosis factor of PSA recurrence free survival in operated patients was operative Glison's index < 7 (p = 0.001), among operated patients--nadir PSA < 1 ng/ ml (p = 0.003). Surgical and radiation treatment of local and locally advanced prostatic cancer provided satisfactory results. In the group of good prognosis (cT1-2N0, PSA < 10 ng/ml, Glison's sum < 7) radical prostatectomy gives advantage of PSA recurrence free survival. In patients with prostatic cancer cT > T2, N+, Glison's index > 7 and PSA > 10 ng/ml surgical treatment and remote radiotherapy are equally effective in respect to survival free of biochemical recurrence.

[Prognostic implications of preoperative diagnosis of clinically local and locally advanced prostatic cancer].

The data of preoperative diagnosis and morphological examination were compared for 144 patients with prostatic carcinoma T1-4N0-XM0 subjected to radical prostatectomy in 1997-2007. In assessment of prostatic capsule invasion, sensitivity of the rectal examination was 21.7%, specificity--89.8%, diagnostic efficacy--68.1%, PPV--50.0%, NPV--70.9%, AUC under ROC curve--0.558 +/- 0.053 (p = 0.348); sensitivity of transrectal ultrasonic investigation--21.7%, specificity--89.8%, diagnostic efficacy--68.8%, PPV--52.6%, NPV--71.2%, AUC under ROC curve--0.563 +/- 0.053 (p = 0.211). Factors of a poor prognosis of prostatic capsule invasion were PSA > 10 ng/ml (p = 0.028) and Gleason score > 7 (p = 0.052). Combined use of these two parameters raises quality of preoperative assessment of category T [sensitivity--80.0%, specificity--55.1%, diagnostic efficacy--56.3%, PPV--80.4%, NPV--44.9%, AUC under ROC curve--0.624 +/- 0.049 (p = 0.017)]. Sensitivity of clinical assessment of N category was 11.1% in 100% specificity, 94.4% diagnostic efficacy, 100% PPV, 94.4% NPV, 0.556 +/- 0.107 (p = 0.577) AUC under ROC curve. A single significant prognostic factor of pN+ category was PSA > 10 ng/ml (p = 0.014). Sensitivity of histological examination of biopsy material in relation to true Gleason's parameter (< 7 or > 7) was 59.4%, specificity 89.3%, diagnostic efficacy 82.6%, PPV 61.3%, NPV 88.5%, AUC under ROC curve 0.743 +/- 0.056 (p < 0.0001). Thus, combined use of a baseline PSA concentration with a borderline value > 10 ng/ml and biopsy Gleason score > 7 raises quality of preoperative evaluation of extraprostatic tumor extension and condition of regional lymph nodes.

[Essays on surgical oncourology].

Based on the personal experience, the authors emphasize the leading role of surgery in the treatment of patients with various malignant neoplasms of the urinary tract and masculine sexual organs. Current standard indications for surgical intervention and its scope are discussed with reference to the methods for the achievement of optimal immediate and delayed postoperative outcomes. Special emphasis is laid on the necessity of combined surgical techniques for the management of local and disseminated tumours of the urinary tract and male sexual organs. The rationale is proposed for extensive and combined operations on such neoplasms. The main avenues of further development of surgical oncosurgery are postulated with a view to improving quality of life of the treated patients.

[The role of preserving therapy of invasive cancer of the urinary bladder].

Cystectomy in the treatment of invasive cancer of the urinary bladder is not the only therapeutic modality in this pathology. In selected patients an alternative exists--transurethral resection of the urinary bladder followed by adjuvant concurrent chemotherapy and radiotherapy. The preserving therapy can be recommended to patients over 60 years of age in the presence of a low-grade solitary tumor of a mobile wall of the urinary bladder respectable with preservation of the organ capacity.

[Regional metastases of penile cancer: optimal treatment policy]. / Regionarnye metastazy raka polovogo chlena - optimal'naia taktika lecheniia.

Emergence of regional penile cancer (PC) metastases reduces late survival of PC patients from 94.4 to 83.9%. PC stage can hardly be diagnosed by clinical data significantly. Bilateral inguinal lymphadenectomy is indicated for all PC patients with enlarged and clinically negative regional lymph nodes in poorly differentiated primary tumor (G3) and stages T2-3. Follow-up can be recommended for patients with stage Tis-T1, low and moderate anaplasia (G1-2) of the primary tumor. Metastases to the iliac lymph nodes are an indication to pelvic lymphadenectomy. Preventive removal of the iliac lymph nodes in intact inguinal ones is not justified. Unremovable fixed regional lymph nodes should be exposed to radiotherapy.

[Organ-saving treatment of penile cancer]. / Organosokhraniaiushchee lechenie raka polovogo chlena.

Conservative penis-salvage treatment provides a complete local effect in 55% cases, preservation of the penis in 51.4% patients without a fall in long-term specific and recurrence-free survival compared to penectomy and can be recommended as an alternative to penis amputation in patients with stages Tis-T2. Removal of a penile tumor raises efficacy of salvage treatment and insignificantly increases survival. Application of surgical treatment only is associated with a high rate of local recurrences. Chemoradiotherapy in penile cancer is significantly more effective vs each method alone. Radiation in a total focal dose more than 60 Gy improves local control over the tumor. Most effective are schemes of chemotherapy based on bleomycin. Polychemotherapy has no advantages over monochemotherapy with bleomycine.

[Paratesticular rhabdomyosarcoma]. / Paratestikuliarnaia rabdomiosarkoma.

Paratesticular rabdomyosarcoma (PR), the most frequently occurring paratesticular tumor, is encountered mostly in young and middle-aged men. PR metastasizes early and is characterized by lymphogenic dissemination of the tumor with affection of the retroperitoneal lymph nodes. Orchofuniculectomy is the first-line treatment in all the patients. If the patient is metastases-free it is followed by preventive retroperitoneal lymphadenectomy with subsequent adjuvant chemoradiotherapy. In disseminated PR, combined treatment is indicated including surgical removal of metastatic foci and adjuvant chemo- or chemoradiotherapy. If surgical removal of all the tumor foci is infeasible, patients with disseminated PR undergo chemotherapy. Radiation of metastatic retroperitoneal lymph nodes is uneffective. Prognosis of PR depends on the age, stage of the disease and treatment.

[Testicular sertolioma]. / Sertolioma iaichka.

Sertolioma accounts for 4.5% of all non-herminogenic testicular tumors. Sertolioma presents clinically with local symptoms (enlarged testis) which may be associated with dyshormonal symptoms. Most sertoliomas are benign, only 16.7% of them are malignant. Metastatic process is primarily lymphogenic and involves first retroperitoneal lymph nodes. Accurate histological criteria of malignancy for sertolioma have not been determined yet. The treatment should be started with orchofuniculectomy. Organ-saving operations may be performed in metastases-free children with bilateral sertoliomas. Surgical treatment is the only treatment effective in malignant sertolioma. Retroperitoneal and (or) solitary distant metastases should be removed surgically. Sertolioma is resistant to chemotherapy and is low sensitive to radiotherapy. Contrary to benign sertolioma, malignant one has poor prognosis.

[Diagnostic difficulties in rare variants of renal angiomyolipoma]. / Diagnostika redkikh variantov pochechnoi angiomiolipomy.

Renal angiomyolipomas (AML) are the most common benign renal tumors. Although AML have a characteristic CT and ultrasound features, a differential diagnosis from other lipomatous tumors and renal cell carcinoma is not always possible. We present four cases of the most unusual radiological appearance of AML. Diagnostic difficulties arise in predominantly myocomponent lesions, in AML with haemorrhagic complications, in aggressive behavior of AML and coexisting renal cell carcinoma. When the diagnosis is equivocal, a fine needle aspiration biopsy is indicated. An accurate preoperative diagnosis of AML allows to avoid undesired nephrectomy and to perform preserving renal surgery in selected patients.

[Water content of the lungs during 7-day anti-orthostatic hypokinesia]. / Soderzhanie vody v legkikh cheloveka vo vremia 7-sutochnoi antiortostaticheskoi gipokinezii.

The time-course variation of the water content of the lungs of seven male volunteers were examined during 7-day head-down tilt (at -15 degrees). As compared to the horizontal subjects, the tilted subjects showed a significant increase in the water content from 557 +/- 19 ml to 612 +/- +/- 63 ml by the 7th hour of the tilt. Later on the parameter gradually declined and on tilt day 7 almost returned to the pretest level, i.e., 567 +/- 46 ml. This increase in the water content during the first hours of the exposure can be attributed to the hydrostatic factors: higher pulmonary artery pressure and higher cardiac output. The increase in the water content on tilt days 3-7 can be associated with changes in the permeability of lung capillaries, drainage function of the lymphatic system of the lungs, and colloidal-osmotic pressure in the perivascular space of the lungs.