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Introduction: Out of the 3310 thoracic surgical procedures performed between 1980 and 2000 at the Department of Surgery of the National Institute of Oncology in Budapest, 258 were pulmonary metastasectomies involving 236 patients. Primary tumors were the following in order of decreasing frequency: testicular cancer, colorectal cancer, renal cancer, soft tissue tumor, breast cancer and others., Methods: In the present study the authors report two patients with multiple pulmonary metastases. The primary tumor was non-seminoma testicular cancer in case one and endometrial cancer in case two (previously treated for thyroid cancer). Histological examination of resected specimens revealed unsuspected focal inactive tuberculosis in the first case and medullary thyroid cancer in the second., Conclusions: In the reported two cases the following conditions of metastasectomy were given: 1. satisfactory cardiopulmonary status, 2. possibility of surgical radicality, 3. locoregional disease control, 4. prior chemotherapy in chemosensitive tumor (case one). The generally accepted condition of metastasectomy-lack of clinically manifest disease in other distant organs--was not fulfilled in case two (suspected liver metastases).

Thirty-three [18F]-FDG and ten [11C]-methionine (altogether 43) PET studies were performed in 37 (24 non-seminoma and 13 seminoma) patients. All results were assessed on the basis of histology (or cytology) or clinical follow-up. PET scan identified metastatic disease in 13 cases while 30 investigations resulted in a negative medical report. There were 3 false-positive cases and no false-negative results were obtained. The false-positive results were likely to occur due to FDG accumulation in benign lesions. There were no false-positive findings with the use of [11C]-methionine. Sensitivity, specificity and accuracy were 100%, 91% and 93%, respectively, using both tracers.

To determine whether mdm-2 protein level is aberrant in germ cell testicular tumors (GCTT) and if so, what is the relationship between mdm-2 overexpression and other disease parameter including histologic subtypes, p53 status, metastatic potential, and clinical stage, 81 testicular germ-cell tumors were screened for their mdm-2 expression at the protein levels using immunohistochemistry (IHC) and Western blot (WB) analysis. Overall, in this study 45 (55.6%) tumors showed positive mdm-2 nuclear immunoreactivity. The incidence of mdm-2 immunostaining was significantly higher (p = 0.0007) in non-seminomas (NSGCT) than in seminomas (S). The frequency of positive tumor was higher in tumors from metastatic patients than in tumors of patients free from metastasis (p = 0.011). Mdm-2 expression was detected significantly more frequently in tumors of advanced stages, i.e. II/B, II/C, and III versus tumors of early stages (I and II/A) (p = 0.0098). A significant difference could be established between the three stages of disease and the expression of mdm-2 (chi 2 = 0.0386), namely the incidence of mdm-2 expression increased with an advanced stage. Using Western blotting 22 (68.8%) out of 32 tumors overexpressed the mdm-2 oncoprotein of 90 kd (p90). Mdm-2 expression as detected by immunostaining may provide a reliable prognostic tool to subgroup of patients with more aggressive GCTT.

Bcl-2 expression has been studied extensively in a variety of human tumors. However, there are lack of clinical data in regard to its expression in germ cell testicular tumors (GCTTs). In this study we screened bcl-2 expression in 70 patient with GCTTs using the immunohistochemistry (IHC) and streptavidin biotin alkaline phosphatase method. Furthermore, we correlated this expression with metastatic behaviour and clinical stage. Overall, 41 (58%) carcinomas stained with anti-bcl-2 (DAKO-124) monoclonal antibody, By histologic type, these lesions included 11 (42.3%) of 26 seminomas (S) and 30 (68.18%) of 44 non seminomatous germ cell testicular tumors (NSGCT). The incidence of bcl-2 immunostaining was higher (P = 0.05, two-tailed, Fisher's test) in NSGCT than in seminomas. Bcl-2 expression was higher in tumors from metastatic patients than in tumors from metastatic-free patient (p = 0). There was a significant difference between the three stages of disease as to the expression of bcl-2 (chi 2 = 0). High level of bcl-2 was clearly dominant in tumors of advanced stages. The present finding revealed that bcl-2 expression occurs in GCTTs. Further, they suggested that bcl-2 is associated with a more progressed malignant phenotype in these tumors.

Data concerning the involvement of elevated metallothionein (MT) expression in drug resistance are obviously scattered and contrasting. The presence of the MT gene product protein was screened in 51 untreated human germ cell testicular tumours, furthermore a relationship between MT expression and clinical resistance was investigated. Using monoclonal antibody and immunoenzyme staining elevated MT level could be demonstrated in nuclei and cytoplasm of both seminomas and non seminomatous germ cell testis tumours. Thirty-one tumours (61%) showed extensive, 15 (29%) focal positive staining. In contrast teratomas expressed this antigen negatively or scarcely. The highest level of MT was stated in early stages (I, IIA) compared with progressed stages (IIB, III) (p = 0.0004). Between the high level of MT and clinical resistance a converse correlation could be shown because the resistant tumours expressed no or low, while the sensitive tumours significantly high level of MT protein which can be used as an useful marker to identify patient subgroups sensitive to anticancer therapy, at least in testis tumours.

One of the most common cellular gene which negatively regulates the cell cycle, thus functioning as tumour suppressor gene, is the p-53 gene. The presence of this mutated gene has been correlated with, the aggressiveness of several malignant neoplasmas. Expression of the p-53 gene product protein was screened in 55 untreated human germ cell testicular tumours, furthermore a relationship between p-53 expression and clinical resistance was investigated. Using monoclonal antibody and immunoenzyme staining elevated p-53 level could be demonstrated in nuclei of embryonal carcinoma (84%) and seminoma components (56%). Most of the choriocarcinoma cases showed positive staining. Teratomas expressed this antigen negatively or scarcely. In seminomas the highest level of p-53 was stated in stage I. In contrast the opposite tendency could be demonstrated in embryonal carcinomas where p-53 was ++ positive in stage III. Between the high level of p-53 and clinical resistance a converse correlation could be stated because the resistant tumours expressed no or low, the sensitive tumours high level of p-53 protein (P 0.01). These results suggest that elevated p-53 expression could be a prognostic marker of sensitivity in testis cancer.

The authors investigated the PSA concentration and the preoperative prostate volume of 113 histologically proved BPH and 31 prostate cancer patients. There was no correlation between the age of the patients and the volume of the prostate. Whereas, correlation was proved between the marker concentration and the prostate volume (p < 0.0001). The prostate volume and the PSA concentration ratio correlated between the BPH and tumorous patients (PSA density). The difference was highly significant (p < 0.001). The use of PSAD improves further the diagnostical value of PSA.

The most frequently reported alteration of multidrug-resistant cells is overexpression of a 170 kD glycoprotein (P-glycoprotein or P-170) encoding by the MDR1 gene family. Expression of the multidrug-resistance gene product P-glycoprotein was screened in 55 untreated human germ cell testicular tumors using monoclonal antibody (C219) and immunoenzyme staining. In samples out of 17 seminomatous germ cell testicular tumors (SGCT) 2 seminomas, and out of 38 non-seminomatous tumors (NSGCT) 20 carcinomas (15 teratomas, 4 embryonal carcinomas, 1 with Yolk sac differentiation and 1 embryonal rhabdomyosarcoma) showed high expression of P-glycoprotein. NSGCT-s, which are more refractory than seminomas to anticancer chemotherapy, frequently expressed P-glycoprotein. These immunohistochemically detected elevated P-170 expressions were correlated by the overexpression of MDR1 mRNA gene sequences. A relationship between clinical resistance and P-glycoprotein expression seems thus to exist in 4 teratomas 3 embryonal carcinomas, and 1 seminomas. A significant correlation (p < 0.02) between P-170 expression and clinical drug resistance in stage II-III germ cell testicular tumors could be demonstrated. The results suggest that a multidrug resistant phenotype may also occur and P-glycoprotein might contribute to drug resistance in testicular tumors.

The authors compared the effectivity of doxycyclin or ofloxacin after combined chemotherapy of testicular cancer patients during the leukopenic periods. Between 1988 and 1991 200 patients were randomized and 194 were evaluated. One hundred and fifty two patients had been treated by cytostatic treatment earlier 2.5 or 2.9 times and 17 by irradiation. The average age was 30.1 in the doxycyclin group and 31.5 years in ofloxacin group. The patients characteristics in average age and previous treatments were not significant in the two groups. Doxycyclin was applied at the first day 200 mg and the following days 100 mg for 6.8 days and ofloxacin was given 2 times 100 mg day for 8.0 days. The preventive antibiotic treatment was insufficient in 16 or 6 cases requiring the the new antibiotic therapy. The development of the new infectional lesions was significantly higher in doxycyclin group and it needed the other antibiotic therapy. The condition of the patients did not require systemic antimycotic or antiviral therapy. The toxicity was lower in oflaxacin group. Tarivid is suitable for preventing the infection in neutropenic periods after the cytostatic therapy. The number of infections are decreased the completion with some penicillins. Regarding to previous cytostatic drugs the cephalosporins are suggested for prevention during the neutropenic periods.

Between the period of 1981 and 1991 at the National Institute of Oncology 1300 patients suffering from non-seminoma testicular cancer were treated by chemotherapy. Among them 19 cases of femoral head necrosis, one side or bilateral, were observed. Authors collected and compared the data of 16 patients of osteonecrosis and 28 without it. The aim of the study was the determination of the causes of osteonecrosis and searching for possible relation between antineoplastic therapy and osteoporosis. High alcohol consumption was found in 15 cases in the osteonecrotic group, versus one among the others. Bone mineral content measurement was performed by quantitative computed tomography. Average ages at the time of densitometry: osteonecrotic group 39.17, patients without osteonecrosis 33.91. The relative bone mineral content was found 65.94% in the osteonecrosis (A) group and 77.92% in the group without osteonecrosis. A significant difference was found in the level of serum calcium and the steroid dose applied during chemotherapy.

Chromosomal aberrations were studied in peripheral blood lymphocytes from only surgery treated testicular cancer patients and treated with chemo- and/or radiotherapy. A distinct increase in spontaneous aberration frequency over the level of 27 healthy controls in 27 patients treated with surgery alone was found. Our data suggest the existence of a certain degree of chromosome instability, which may be a factor to the development of testicular tumour. The frequency of aberrant cells was much higher in 102 treated patients than in the controls. The decrease in aberrant cells was only time-dependently gradual in VPB and X-ray treated patients, while the second line combined treatment modalities caused the highest frequency of aberrant cells in the first two years after the end of courses. The possible relationship between the persistence of chromosomal aberrations and the development of malignancies are discussed in this paper.

The antibody-dependent cell mediated cytotoxicity of peripheral blood mononuclear cells from 92 patients with germinal cell tumours and 60 healthy male controls was measured against 0, Rh(D) positive human red blood cells sensitized with anti-D antibody. To determine the maximal K-cell activity the enzym-like kinetic model of citotoxicity was employed in which maximal activity was measured in presence of target-cell excess. To avoid variation due to the individual sensitivity of target erythrocytes red blood cells were obtained from a single donor. It was demonstrated that compared to the control group the K-cell activity of patients with germinal cell tumours was significantly enhanced. Cytotoxic activity of patients with clinically detectable tumours was significantly higher than that of patients with no detectable tumour. The K-cell activity of patients with detectable tumours was significantly increased after chemotherapy.

The data of 1286 testis cancer persons were analyzed by the authors, which were identified in Hungary between 1981 and 1986. The comparison was carried out with international findings in this field. The incidence rate of testis tumor in Hungary reaches a value of 4.16/100,000 men/year, which seems to be quite near to the frequency of cases occurred in Northern-Europe. The patient's age was 32.9 year in the mean at the time of the diagnosis, and the age-specific incidence rate was the highest (11.2) between 25-34 years, according to international experiences. A significant difference was found in the frequency of testis cancer among 19 counties of Hungary. The extremely high testis cancer incidence in the county Vas (West-Hungary) requires further explanations. A seasonal pattern according to the patients birth months was shown, which did not correlate with data of other Hungarian authors concerning seasonal pattern of the undescendent testis.

The 5-year survival of patients with malignant testicular tumors rose during the past 25 years from 10-25% depending on stage to 55-100% after radical castration performed from high inguinal opening, retroperitoneal lymphadenectomy, ultra-tension irradiation and adjuvant chemotherapy. It is stressed that patients diagnosed at stage T1-2, N0-2, M0 may even recover perfectly upon complex therapy. Three to five-year long or even longer survival may be reached with 50% of the patients at the stage T1-3, N1-3, M1. Patients at stage T4, N3-4, M1 die because of the recurrence of the tumor and/or the complication of the adjuvant treatment within 1-3 years and even the interdisciplinary work which is very effective in other stages fails to change this at the present time.