[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.

[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.

The influence of tumor immunity suppressors on the effector stage of human and animal lymphokine-activated killer cells.

Spleen cells of tumor-bearing mice suppressed the cytolytic activity of syngeneic LAK cells when added to the mixture of LAK cells and target cells at the beginning of the cytotoxicity test. Spleen cells of MC 14 tumor-bearing mice acquired the suppressor potential as early as 10 days after tumor transplantation; the suppressor activity in the EL 4 and X63-Ag8.653 tumor-bearing animals was first revealed at the 30th day and manifested itself up to the 120th day. The suppressor activity was expressed in a dose-dependent manner, both by unfractionated spleen cells and nylon wool-passed and plastic-adherent sub-populations. Similar results were obtained during the analysis of anti-tumor immunity suppressors in bladder cancer patients. MNC, nylon wool-passed and plastic-adherent cells of patients with stages I-II disease suppressed the cytotoxicity of autologous LAK cells in 2/6 cases; all patients [4] with III-IV stage possessed such suppressor activity. Presumably, the tumor growth induces the activity of suppressor T cells and monocytes/macrophages. The suppressor activity can interfere with the antitumor effect of autologous (syngeneic) LAK cells at the effector stage.

[Germ cell tumors of the testis: current status and future progress]. / Germinogennye opukholi iaichka: sostoianie problemy i nauchnyi progress.

The treatment of testicular cancer has undergone considerable evolution since the introduction of cisplatin and widespread recognition of its curative potentials at any stages of disease. This article provides an overview on statistical and epidemiological information, the latest developments in testicular cancer biology. Also, the results of treating 360 patients with nonseminomatous and 97 patients with seminomatous germ cell tumors are presented. A combined chemotherapy with cisplatin, etoposide and bleomycin demonstrates the highest rate of activity in nonseminomatous germ cell tumor patients. Surgical resection of residual masses after chemotherapy continues to be an important component of combined modality therapy in nonseminomatous testicular tumors. The needs for regular clinical examination during a follow-up have been underlined.

[The prognostic aspects of the morphological signs of bladder cancer]. / Prognosticheskie aspekty morfologicheskikh priznakov raka mochevogo puzyria.

A clinico-morphological study of 150 bladder tumours showed significant dependence of bladder carcinoma prognosis on some morphological indices most important of which were the grade of malignancy, histological type and deepness of growth and spread along the lymphatic and blood vessels. Likewise, nuclear polymorphism and hyperchromasia, mitotic figure number, atypical mitosis have a direct connection with prognosis, but they are an integral part of malignancy grade determination and do not play an independent role. Nucleolar organizer zone may serve as an additional criterium of neoplasm biological activity, in particular, its role is important in differential diagnosis of bladder transitional cell carcinoma I and benign processes or transitional papilloma.

[Effect of retroperitoneal lymphadenectomy on late therapeutic results in testicular tumors]. / O vliianii zabriushinnoi limfadenéktomii na otdalennye rezul'taty lecheniia bol'nykh opukholiami iaichka.

The end results of treatment of patients suffering from testicular tumors without distant metastases were assessed with a due amount of tumor histology and stage. In a study group consisting of 122 patients, orchofuniculectomy was followed by lymphadenectomy and subsequent chemotherapy. In the other group (141 patients), retroperitoneal lymph nodes were not removed and chemotherapy course was started immediately after orchofuniculectomy. Comparison of the end results of therapy in both groups shows that retroperitoneal lymphadenectomy assures a better effect in the treatment of teratoblastoma and embryonal testicular tumor with retroperitoneal metastases.

[Treatment of patients with retroperitoneal metastases of nonseminoma tumors of the testis]. / Lechenie bol'nykh s zabriushinnymi metastazami neseminomnykh opukholei iaichka.

PVB or VAB-6 combination chemotherapy was given to 41 funicular orchiectomized cases of unresectable retroperitoneal metastases of nonseminoma testicular tumors. Seven of them also revealed metastases to the lung. Complete regression of retroperitoneal metastases was observed in 7 and greater than 50% regression--in 20 cases. Six patients showed complete regression of pulmonary lesions. Chemotherapy raised an opportunity for retroperitoneal lymphadenectomy in 31 cases. Lung metastasis was also removed in one patient. Following chemotherapy, histological examination failed to detect metastases in 17 cases, differentiated teratoma elements were found in 6, while tumor cells were identified in the remaining patients. Three-year survival rate for radically treated patients was 55.5% (m = 8.9). Long-term results were shown to depend mainly on the effectiveness of chemotherapy.

[Results of organ-preserving therapy for invasive bladder cancer]. / Rezul'taty organosokhraniaiushchei terapii invazivnogo raka mochevogo puzyria.

87 patients with urinary bladder cancer (UBC) stage T2-3aN0M0 have received an organ-saving treatment which combined neoadjuvant chemotherapy (methotrexate, adriamycin, vinblastin, cysplatinum) followed by transurethral or open resection of the bladder. The patients were followed up for 3 to 60 months. Recurrent tumors arose in 49(56.3%) patients, at the primary site in 94%. Recurrence-free 5-year survival made up 32.8 +/- 14.1 and 24.2 +/- 15.2% after transurethral and open resections of the bladder, respectively. In patients with a complete response to the neoadjuvant chemotherapy 5-year overall and recurrence-free survival reached 89.0 +/- 11.1 and 68.5 +/- 18.9%, respectively. It is thought valid to consider planning organ-saving treatment only in relation to patients with a complete regression of the tumor after neoadjuvant chemotherapy.

[Current approaches to treatment of urinary bladder cancer]. / Sovremennye podkhody k lecheniiu raka mochevogo puzyria.

The study included 30 patients with surface cancer of the urinary bladder stage TA-T1 G1-3. As the first step of the treatment, all the patients were operated with removal of the tumor then the patients were randomized to postoperative intravesicular immunotherapy with ronkoleucine in single doses 500,000 IU (15 patients of group 1) or 1,000,000 IU (15 patients of group 2). It was found that group 2 patients had recurrences much less frequently (26.7 vs 66.7%, respectively). With higher degrees of differentiation of the tumor cells recurrences occurred more frequently in both groups. Group 2 patients developed recurrences significantly less frequently in G1 and G2 (22.2%). In G3 all the patients had recurrences. Intravesicular administration of ronkoleukine raised absolute number of CD3 and CD4 subpopulations during the treatment and after it as well as raised concentration of TNF. The levels of the latter in the urine rose after the end of each immunoprophylaxis course. Intravesicular use of ronkoleukine entailed no specific toxic reactions. Thus, intravesicular prophylactic immunotherapy of recurrent surface cancer of the urinary bladder with ronkoleukine in a single dose 1,000,000 IU is effective prevention in patients with high (G1) and moderate (G2) grade of tumor cell differentiation. The single dose 500,000 IU is uneffective. A rise in subpopulations CD3, CD4 and TNF cytokine in the urine evidences for systemic activation of the immunity.

[A rare case of BCG vaccinal sepsis in a patient with bladder cancer]. / Redkii sluchai BTsZh-vaktsinal'nogo sepsisa u bol'nogo rakom mochevogo puzyria.

Immunotherapy consisting in intravesical injection of BCG vaccine to a 44-year-old patient with surface relapsing cancer of the bladder resulted in development of sepsis. The vaccine in a dose of 120 mg was injected directly after bougienage of the urethra and catheterization of the bladder. As soon as in 2 h the patient developed chill, fever (38.5 degrees C), and felt bad. The condition progressed, but only in 15 days did the patient applied for medical care. Intensive care including antibiotics and antituberculous drugs in massive doses and repeated sessions of hemoperfusion were of no avail. The patient died with signs of progressive hepatorenal failure. Autopsy confirmed vaccinal mycobacterial sepsis. Intravesical immunotherapy after injury to the urethra was an error, promoting generalization of the infection; another cause of lethal outcome was late application for medical care.

[The results of the surgical treatment of bladder cancer patients]. / Rezul'taty operativnogo lecheniia bol'nykh rakom mochevogo puzyria.

101 patients with cancer of the bladder were operated in the Moscow Cancer Research Center from 1990 to 1995. Cystectomy with varying urinary bypass was made in 49 patients. 52 patients were subjected to bladder resection. The former developed recurrences in 28.9%, the latter in 62% of the patients. Recurrences after the resections were primarily local. 5-year survival of transient-cell bladder carcinoma patients after cystectomy made up 68.2%, after the resection 80.7%. The authors hold that both operations are applicable, but they have specific indications.

[Is neoadjuvant chemotherapy valid in invasive cancer of the bladder?]. / Tselesoobrazna li neoad"iuvantnaia khimioterapiia invazivnogo raka mochevogo puzyria?

The role of neoadjuvant chemotherapy for invasive transitional cell carcinoma (TCC) of the bladder is not determined yet. M-VAC and CMV regimens have a complete response rate of 10-47% with an overall response reaching 80%. In 16.7-35% of all the responders and 42.9-92% of the complete responders a functioning bladder can be preserved. The influence of neoadjuvant chemotherapy on long-term survival is questionable. Nevertheless, the authors conclude that neoadjuvant chemotherapy is feasible in patients with invasive TCC as it improves the results of following surgery and in some cases enables an organ sparing operation.

[Current procedure for treating testicular germ-cell tumors]. / Sovremennaia taktika lecheniia germinogennykh opukholei iaichka.

The treatment of testicular cancer has undergone considerable evolution since the introduction of cisplatin and widespread recognition of its curative potentials in any stage of this disease. The authors provide a review of today's therapeutic approaches to testicular cancer with special emphasis on the disease stage and tumor histology.

[Cytotoxic and suppressor activity of human peripheral blood lymphocytes stimulated by interleukin-2 and phytohemagglutinin before and after fractionation in the percoll gradient]. / Tsitotoksicheskaia i supressornaia aktivnost' stimulirovannykh interleikinom-2 i fitogemaggliutininom limfotsitov perifericheskoi krovi cheloveka do i posle razdeleniia v gradiente perkolla.

The cultivation of peripheral blood lymphocytes (PBL) obtained from patients with colorectal or bladder carcinoma and melanoma and from healthy donors in the presence of interleukin-2 (IL-2) and PHA resulted in the induction of cytotoxic activity against autologous and/or allogeneic tumour cells in 12 out of 13 patients and in 10 out of 10 donors. A higher level of cytolytic activity was achieved when PBL were separated by means of Percoll density gradient (1.077; 1.067 and 1.056 g/ml) centrifugation and the cells of fraction II (1.077-1.067 g/ml) were employed in the experiment, the level of cytotoxicity being elevated in all cases (1.7-fold elevation in donors and 2-fold elevation in patients on the average). The addition of fraction I (1.067-1.056 g/ml) to fraction II prevented (PHA + IL-2)-mediated induction of cytotoxic activity in all the patients, but in 4 out of 10 donors, i.e. cells of fraction I expressed a suppressor activity. The immunofluorescent analysis has shown that fraction II was enriched by T cells (92%) and depleted of monocytes (7%), as compared to unseparated PBL (66% and 27%, respectively). On the contrary, fraction I was characterized by a decreased T cell ratio (36%) and an increased monocyte level (up to 69%).

[Combined treatment of malignant kidney tumors]. / Kombinirovannoe lechenie zlokachestvennykh opukholei pochki.

The paper is devoted to the discussion of the results of combined therapy of 79 patients with malignant renal tumors. Eight patients underwent nephrectomy and postoperative irradiation at a mean dose of 28 Gy, a marked radiation reaction was noted in 3 of them, and irradiation had to be discontinued. All 8 patients died within 3 yrs. of a follow-up period. Thirty patients received preoperative irradiation at a single focal dose of 2-2.5 Gy and a summary dose of 30-50 Gy 3-4 weeks before nephrectomy. A dose of 30 Gy did not result in tumor reduction, a dose of 40 Gy led to an insignificant reduction of a tumor size by 1-2 cm, tumor resorption by 30-50% was noted at doses of 50-60 Gy. Thirty-eight patients were given preoperative irradiation at a daily single focal dose of 4 Gy and a summary dose of 20 Gy, followed by nephrectomy in 24-48 h. Radiation reactions in preoperative irradiation were less marked than in postoperative irradiation. The 3-year survival rate in preoperative irradiation and nephrectomy was 72.5%, the 5-year survival rate was 53.2%. A fractionation type did not influence the survival rates.

[The intravesical chemotherapy of surface tumors of the bladder]. / Vnutripuzyrnaia khimioterapiia poverkhnostnykh opukholei mochevogo puzyria.

Intravesical chemotherapy (IVC) for bladder cancer was conducted in 83 patients who had been admitted to the Moscow Cancer Research Center in 1981-1988. Farmorubicin IVC produced a complete response (CR) in 3 (21.4%) and a partial one (PR) in 6 (42.9%) of the 14 patients treated. In mytomicin C administration CR was achieved in 4 (30.8%), PR in 2 (15.4%) of the cases. For adriamycin, spirobromin, thiotef (60 mg), thiotef (20 mg), CR was registered in 4 (30.8%), 5 (17.9%), 1 (11.1%), 2 (18.2%), 2 (25%) patients, PR in 2 (15.4%), 8 (28.6%), 1, 1 (9.1%), 1 (12.5%) patients out of 13, 28, 9, 11, 8 cases, respectively. Complications of the IVC in the form of drug cystitis occurred in 57.1%, 23.1%, 46.4%, 12.5-18.1% of those treated with farmorubicin, mytomicin C, adriamycin, thiotef, respectively. Spirobromin arose no complications.

[Our experience in treating patients with surface cancer of the bladder]. / Nash opyt lecheniia bol'nykh poverkhnostnym rakom mochevogo puzyria.

210 patients with surface cancer of the bladder were divided into three groups. 67 patients of group 1 underwent transurethral resection of the bladder (TRB) followed by preventive intravesical chemotherapy. 91 patients of group 2 received preventive intravesical BCG after TRB. 61 control patients (group 3) had TRB only. Recurrences emerged in 15 (16.5%), 12 (62.7%) and 45 (73.8%) group 2, 1 and 3 patients, respectively. The preventive chemotherapy was effective only in patients with primary tumor (the recurrence rate 42.3%), the relapses being less responsive to it (the recurrence rate 75.6%).

[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.