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Introduction: Recent studies have shown an increased risk of lung cancer in patients with bronchial obstructive changes, including patients with COPD. It seems that there are common factors of pathogenesis of both diseases associated with oxidative stress. In the present paper the genes linked to the repair of oxidative damage of DNA, associated with cancer, of iron metabolism and coding proteolytic enzymes were assessed., Material and Methods: The study was conducted in two groups of patients: 53 patients with non-small cell lung cancer and chronic obstructive pulmonary disease, and 54 patients only with chronic obstructive pulmonary disease. The polymorphisms of the single nucleotide were determined in the case of the majority of genes using the PCR-RFLP method. The statistical analysis of quantitative variables was executed using the Mann-Withney U-test and the test of medians; the analysis of genetic variables was executed using the chi² test., Results: Regarding the polymorphisms of genes involved in iron metabolism, statistically significant differences between the two groups have been demonstrated only in the case of haptoglobin gene HP1/2. A higher incidence of form 1/1 was found in patients with COPD and a higher incidence of form 1/2 in patients with lung cancer and COPD. Analysis of gene polymorphisms of proteolytic enzymes and inhibitors of the enzyme gene showed statistically significant differences between the two groups only for the MMP3 gene 6A/5A. In the case of the MMP12 gene polymorphism (A-82G) a tendency toward differences in the occurrence of specific alleles was identified., Conclusions: These results indicate that patients with coincidence of COPD and lung cancer have disorders of the genes involved in iron metabolism, and they have different genetic polymorphisms of proteolytic enzymes comparing to COPD patients.

A 47-year-old, non-smoking woman was admitted to the National Tuberculosis and Lung Diseases Research Institute for diagnosis of progressive exertional dyspnoea and numerous small thin-walled, air-filled cysts equally distributed throughout both lungs revealed in HRCT (high resolution computed tomography) examination. Histological assessment of specimens obtained by open lung biopsy revealed proliferation of immature smooth muscle, showing the expression of the antigen HMB45. On this basis, diagnosis of lymphangioleiomyomatosis was established. The disease caused essential ventilation damage of the lungs (FEV1 1.34 L; 39.71% pred, VC 4.02 L; 94.96% pred, FEV1/ /VC 0.33-4 1.81% pred, DLCO 3.65 mmol/min/Kpa 38.35% pred).During the observation, despite the lack of immunological disorders, the patient developed Pneumocystis jiroveci pneumonia (PCP) that was treated with trimethoprimsulfamethoxazole. Lymphangioleiomyomatosis is a rare disease which results from a defect of TSC genes. The disease is not related to immunological defects or disorders. However, the considerable cystic destruction of the lungs can predispose the patient to opportunistic infections such as the one in the presented case.

Benign metastasizing leiomyoma (BML) is a rare condition in middle-aged women with a history of uterine leiomyomata. It is characterized by the proliferation of, usually multiple, smooth muscle nodules. Approximately 100 cases have been reported in the literature, and the lungs were the most common site of metastases. We report a case of 52-year-old obese woman (BMI 31), hospital worker, smoker, admitted to the hospital with exertional dyspnoea, night sweats, loss of weight, and productive cough. Hysterectomy for a uterine leiomyoma was performed 9 years earlier. In addition, a history of two episodes of superficial vein thrombosis 3 and 2 years before admission was noted. Chest X-ray and subsequently CT chest examinations revealed multiple, non-calcified nodules within the middle and lower parts of both lungs. Specimens obtained by transbronchial biopsy (TBLB) and from open lung biopsy displayed benign muscle cell proliferation compatible with BML. The levels of sex hormones were characteristic for the menopause; therefore, observation was advised. Additionally, Streptococcus pneumoniae was cultured from bronchial washing, and bronchitis was diagnosed. Antibiotics, bronchodilators, and mucolytics were administered, and dyspnoea and cough with expectoration were diminished. Two years later pulmonary lesions have been stable; however, she has put on weight. Subsequently the patient has developed deep vein thrombosis with pulmonary embolism. Anticoagulant treatment was introduced, with some improvement.

Introduction: Individual's risk of developing lung cancer depends not only on exposure to tobacco smoke, but also on the activity of enzymes involved in the activation or deactivation of carcinogens. Arylamine N-acetyltransferase (EC 2.3.1.5) is an enzyme involved in biotransformation of xenobiotics, mainly aromatic and heterocyclic amines and hydrazines. The different acetylation phenotypes within a population are derived from mutations in the NAT 2 gene. These mutations influence the activity (specifically resulting in high or low activity) of the NAT enzyme. Some authors have demonstrated lung cancer predisposing role of slow acetylator phenotype, whereas other reported increased lung cancer risk for fast acetylators or neutral effect of the NAT2 polymorphism. The aim of this preliminary report was to determine the NAT2 gene polymorphism in patients with lung cancer., Material and Methods: 39 patients with inoperable lung cancer (29 - NSCLC and 10 - SCLC), median age 59 years (42- -72) entered the study. Acetylation genotype was determined in the genomic DNA using an allele-specific polymerase chain reaction. We investigated four genetic mutations, C481T, G590A, A803G i G857A, of the gene NAT2., Results: There were 10 different NAT2 genotypes among the 39 patients. Fourteen patients with a NAT2*2 4/4, *4/5, *4/6 and *4/7 were classified as fast acetylators; and 25 patients with a NAT2*5/5, *5/6, *5/7, *6/6, *6/7 or *7/7 genotype were classified as slow acetylators. Among the 10 patients with SCLC - 4 were fast acetylators, and among 29 patients with NSCLC dominated slow acetylation type found in 19 patients (genotypes NAT2 *5/5 and NAT2 *5/6)., Conclusions: Among patients with small cell lung cancer, there was no predominance of genotype of acetylation, whereas among patients with non-small cell lung cancer predominated NAT2*5/5 and NAT2*5/6 genotypes (slow acetylators).

Langerhans cell sarcoma, a neoplastic proliferation of Langerhans cells with malignant cytologic features, is a very rare disease. Only a few cases have been documented in the English-language literature. Special methods, like immunohistochemistry and/or ultrastructural examination, are indispensable for appropriate diagnosis. Correct diagnosis is difficult. In fact, the disease is often misdiagnosed. We present the case of a 47 year-old man with a large mass in the middle lobe of the lung, infiltrating anterior mediastinum, with multiple pulmonary round lesions and enlargement of local lymph nodes, and with bronchoesophageal fistula. Clinical examination indicated the possibility of advanced primary lung cancer. However, the first histological diagnosis was Langerhans cell histiocytosis. In spite of treatment, the progression of pulmonary lesions was observed. Therefore, upper- and middle-lobectomy was performed. The diagnosis of Langerhans histiocytosis was confirmed microscopically again. Nevertheless, the patient's condition deteriorated progressively and he was admitted to the National Tuberculosis and Lung Diseases Research Institute in order to establish a final diagnosis. Revision of earlier resected specimens, as well as an immunohistochemical and ultrastructural examination of samples, taken once again from a bronchial tumor, led to the establishment of a diagnosis of a unique form of Langerhans cell sarcoma with rare pulmonary manifestation.

Organising pneumonia (OP) is a distinct clinicopathological entity resulting from pulmonary reaction to noxious environmental or endogenous factors, but also idiopathic cases have been noted. Frequently, small foci of OP accompany lung cancer infiltrations. Also OP is sometimes a reaction to radio- or chemotherapy, but it is rarely a predominant lesion in the course of lung cancer. We present the case of 65-year-old patient who presented with fever, dry cough, exertional dyspnoea and pneumonic consolidation in the right lower lobe. Bronchoscopy revealed squamous carcinoma obstructing the right lower bronchi. He was surgically treated, and the right lower lobe was resected. Pathological examination of a specimen revealed only small infiltration of carcinoma cells in the wall of the bronchi and large confluent areas of organising pneumonia. Surgery was a sufficient treatment for both diseases. Six months later he was in good condition without any pulmonary infiltrations. To sum up, a case of endobronchial squamous cell carcinoma in stage T1N0M0 with predominant clinical and radiological signs of OP is presented.

The aim of the study was to investigate a relation between p53 and HER2/neu expression in resected lung tumors and the response of those tumors to neoadjuvant chemotherapy. The study population included 67 consecutive patients with non-small cell lung cancer (NSCLC) in stage II or III who were operated on at the Institute of Tuberculosis, Warsaw, Poland, between 20 April 2001 and 10 March 2003. All patients received two cycles of chemotherapy consisting of cisplatin and vinorelbine prior to the operation. The response to therapy was assessed as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD), on the basis of CT scans performed before and after neoadjuvant chemotherapy. p53 and HER2/neu protein expression were evaluated by immunohistochemistry (IHC) using antibodies against p53 (clone PAb 1801, Novocastra) and against HER2/neu (Dako) in paraffin-embedded specimens of tumors. A response to therapy (CR+PR) was observed in 27 patients, while 40 patients (SD+PD) were regarded as resistant to therapy. Resistance was observed significantly more often in tumors above 3 cm in diameter. p53 expression was found in 16 tumors (23.9%) and HER2/neu in 26 tumors (38.8%). We observed a nonsignificant tendency to chemoresistance in tumors with HER-2/neu overexpression and also in tumors with p53 overexpression. If we consider HER-2/neu and p53 together, chemoresistance was observed statistically significantly more often when one or both markers were positive (p<0.05). This significance was independent of tumor size.

The occurence of chylothorax is uncommon and usually is caused by trauma or neoplastic process of the mediastinum. Primary lymphatic lesions of the lungs are extremly rare. One of them is lymphangiomatosis --diffuse lesions characterized primarily by an increased number of complex anastomosing lymphatic channels in which dilatation is secondary phenomenon. These lesions can involve lungs, mediastinum and pleura. The prognosis for the patients with this disease limited to the thorax is guarded and progressive although some patients have realtively indolent course. We present 2 patients : 18-years old boy and 17-years old girl. admitted to hospital because of chylothorax. The diagnostic did could not allow to discover disruption of thoracic duct, even during thoracoscopy. In material taken from the pleura and mediastinum during exploratory thoracotomy - diffuse pulmonary lymphangiomatosis was found. CT examination of the chest revealed osteolysis of the spine. The girl died after 6 weeks from the first symptoms and boy is observed for 18 months with symptoms of progressive restrictive lung disease.

The Aims: 1) comparison of NSCLC stages according to bronchoscopic and radiological findings with pathological outcome (mediastinoscopy), 2) efficacy of the neoadjuvant ChT by means of nodal involvement and primary tumour (downstaging), 3) influence of ChT on the surgical procedures' extension and its morbidity, Material and Methods: 100 consecutive patients with resectable NSCLC in stages IIB (13 pts) or IIIA (57 pts), who were qualified to neoadjuvant ChT, participated in this study (77 men and 23 women, aged 42-73). Tumour and lymph nodes (mediastinal and hilar) were measured in CT scan. Mediastinoscopy was performed in 70 pts (70%). Majority of patients (87%) received two cycles of neoadjuvant ChT (cisplatin 80 mg/m(2) iv on day 1 and vinorelbine 25 mg/m(2) on day 1 and 5) administered every 21 days. After ChT 85 patients were qualified to surgery., The Results: The metastases in mediastinoscopy were excluded in 32 out of 45 patients (71%), whose lymph nodes were enlarged in CT scan (radiological false positive). Metastases were confirmed in 4 out of 25 patients (16%), whose lymph nodes were normal in CT scan (radiological false negative). After ChT the regression of the disease (PR+CR) was noted in 37% of patients. Pneumonectomy was performed in 23 (27%) pts, bilobectomy in 11 (13%) pts, lobectomy in 39 (46%) pts and "extended" (sleeve) lobectomy in 12 (14%) pts. Resected material was examined microscopically very exactly in patients, in whom mediastinoscopy was performed before treatment. Down-staging was confirmed in 6 out of 15 patients (40%)., Conclusions: Neoadjuvant ChT was effective in 37% of patients and allowed us to perform less extensive surgery in these patients. 22 (64,7%) out of 34 patients who responded to ChT underwent lobectomy. Only 17 (36%) out of 51 patients who did not respond to ChT had lobectomy performed. Generally, 85 pts were operated with postroperative complications in 22.3% patients and 2.3% mortality rate. Pneumonol. Alergol. Pol. 2006, 74, 171:178

The aim of this study was to assess the prognosis in LD SCLC pts according to their performance status, local extension of lesions, type of treatment and the completeness of staging. In the period 01.01.1986-31.12.1996 in the Institute of Tuberculosis and Chest Diseases 579 consecutive SCLC pts were treated. LD was diagnosed in 345 pts. In 193 out of them the staging was complete that is in addition to chest x-ray, abdomen USG/CT, brain CT/MRI and bilateral bone marrow trepanobiopsy was done. 152 pts were also regarded as limited but the staging was not complete. LD pts proved by complete staging survived significantly longer (median survival 15.7 months) than others (median survival 10.2 months). The pts in whom complete staging was done were however in better performance status and had smaller local extension of lesions and had more often radiotherapy than others. Status performance, local extension of lesions and radiotherapy but also completeness of staging were independent prognostic factors in multivariate analysis.

The purpose of this study was to evaluate the ability of dynamic contrast-enhanced magnetic resonance to provide differentiation between malignant and benign mediastinal or hilar lymph nodes. The group of 109 patients were examined, with lung carcinoma (63 patients) and sarcoidosis (46 patients). Relative signal intensity increase after administration of Gd-DTPA in standard dose (0.1 mmol/kg) was measured four times (20 s-3 min after injection). There was no significant difference between all groups. In conclusion, differentiation between types of enlarged lymph nodes could not be achieved using the described protocol.

The study was performed to explore the frequency of infections present at death and infection as the main cause of death (fatal infection - FI) in 845 consecutive patients (pts) treated for small cell lung cancer (SCLC) at the Institute of Tuberculosis and Chest Diseases in Warsaw, in the period 1980-1994. Diagnosis of infection was based on clinical signs and symptoms, the presence of new lesions on the chest X-ray, microbiological tests and/or autopsy examination. All cases of fungal infection, Pneumocystis carinii pneumonia (PCP) and tuberculosis were proved by autopsy and microscopic examination (including special staining). FI was diagnosed if no progression of cancer was noted and no other complications occurred. Infection was present at the time of death in 116 patients (13.7%) and FI was the cause of death in 39 of them (4.6%). Nine patients died from fungal infection, eight from bacterial infection, seven from PCP and two from tuberculosis. In 13 cases the aetiology of infection found at autopsy was not determined. All FI patients received chemotherapy and corticosteroids, 16 of them also had radiotherapy on the tumour and mediastinum. Thirty-two out of 35 patients had leucopenia. The risk of death from infection was greater in patients above 60 years of age. Patients in bad performance status died of infection significantly earlier than others (P<0.05).

The authors assessed the diagnostic accuracy of the static telepathology (sTP) for practical consultations in the controversial pulmonary oncology cases. The short characteristics of the diagnostic cases is included. We reported the results of 6 difficult clinico-pathological cases submitted to Dept Quantitative Pathology [DQP] for consultations (5F and 1M, age: 26-68 yrs). Digital images of histological or cytological samples were captured at DQP and transmitted to telepathologist (TPat) in Thoraxklinik, Heidelberg or AFIP, Washington DC. Simultaneously, the same slides (or with a paraffin block) were mailed to TPats for re-evaluation with the conventional microscope (dgn-zwPat). The controversial cases presented 2 types of diagnostic problems: 1/rare entities, 2/common difficulties in the routine work of pathologist, but with indefinitely proved diagnosis. The first group encounters TPat diagnoses as follows: * case A: pulmonary plasma cell granuloma with lymphoidal interstitial infiltrates [LIP]--preleukemia; * case B: microfoci of early metastases of benign uterine leiomyoma; * case D: small cell carcinoma spreading along pleura. The second group included: * case C: invasive epidermoidal carcinoma in bronchus; *case E: probably metastatic adenocarcinoma of colon; *case F: synchronous or metastasising 2 lung tumours sharing NE morphology or NE immunohistochemical features. There was very high concordance between referring pathologist (ref-Pat) diagnoses and TPat diagnoses as well as a consensus in zw-TPat diagnoses. In 2 cases the conceptual problem was solved by TPat. Telepathology offered a support or improved the quality of the final diagnosis. The implementation of sTP remarkably reduced the time of consultations and allowed to present the diagnostic problems to the international group of experts.

The aim of this study was to analyse the frequency of infection as a cause of death in small cell lung cancer (SCLC) patients. Our material consisted of 845 unselected SCLC patients, 246 women and 599 men, aged 29-78 years, treated between 1980-1994 in the Institute of Tuberculosis in Warsaw. 479 patients had limited and 366 extensive disease. 530 were in good (0-2) and 315 in bad (3-4) performance status. 784 patients died. Autopsy was done in 211 patients. Infection was regarded as a main cause of death in 39 patients (4.6%) and as a coexistent cause in 77 (9.1%). At the time of death from and/or with infection in 16 patients complete remission and in 27 partial remission of cancer was confirmed. The risk of death from and/or with infection was not related to the age and sex or to the performance status of patients and to extension of cancer. The risk of death from and/or with infection in the first 3 months of treatment was however greater for patients in bad performance status and with extensive disease and later (after 3rd months) for patients in good performance status and with limited disease.

The aim of this study was to assess the frequency of pulmonary thromboembolism in small cell lung cancer (SCLC) patients (pts) treated in the Institute of Tuberculosis and Chest Diseases in the years 1980-1994. The second aim was to assess whether the occurrence of thromboembolism is connected with the progression of cancer. Pulmonary thromboembolism was recognised in 17 out of 845 pts (2.01%) treated for small cell lung cancer, that is in 2.01% of pts. The frequency of thromboembolism was 8% among patients in which autopsy was done. Pulmonary thromboembolism occurred in 7 pts during progressive disease but also in 9 with partial or complete regression of SCLC. The potential role of chemo- and radiotherapy in the development of thromboembolism in the last group was discussed.

The aim of this study was to review autopsy findings in small cell lung carcinoma (SCLC) patients (pts)--in order to assess the distribution of the disease at the time of death and to analyse the pattern of SCLC in relation with different therapeutic modalities. The pattern of autopsy findings was assessed in 100 pts SCLC: 85 pts after treatment with chemotherapy, with or without chest and cranial irradiation; and 15 pts without any therapy. The primary tumours were present in 59% pts (50 of 85), the residual tumour deposits were diagnosed in 32% (27 of 85) pts. The significant difference in the rate of locoregional disease was found between pts given chemotherapy and pts after combined therapy. The tumours occurred significantly more frequently in pts after chemotherapy, than in pts after chemotherapy with irradiation on the chest (75% and 41% respectively, p = 0.03). The chest irradiation with chemotherapy caused less frequent occurrence of the residual tumours than chemotherapy alone (48% and 20%, respectively, p = 0.026). The rate of brain metastases was significantly higher in pts given chemotherapy than in pts treated with chemotherapy and chest irradiation or chemotherapy and curative brain irradiation (90%, 67% and 36% of 50 cases, respectively). Distant metastases were distributed in the same pattern in both studied groups. The distribution of metastases was not dependent on the disease extent at the time of diagnosis.

Tumor response is used as a main criterion whether or not the treatment yields an anticancer activity. The tumor response criteria are defined by WHO recommendation but little is known about the tests must be used. The aim of this paper was to compare the degree of response to the treatment of 268 patients with limited small cell lung cancer, using independently 3 methods: radiological, bronchoscopic and cytological of bronchial material. Particular categories of response (CR, PR NR and presence or absence of carcinomatous cells) were related to survival time of patients independently to method of assessment. Multivarinte Cox analysis selected 3 parameters related to 3 different methods as independent survival risk factors. We conclude that each of diagnostic method (chest x-ray, bronchoscopy, cytological examination of bronchial material yield independent information correlated with survival risk of particular patient.

Cytokeratin-19, one of the cytoskeletal proteins, is expressed both in bronchial epithelium and in lung cancer cells. The aim of our study was to establish the value of serum cytokeratin-19 soluble fragment (Cyfra 21-1) measurement in lung cancer patients. Cyfra 21-1 levels were estimated in 35 patients (pts) with benign lung diseases and in 116 lung cancer patients: 55 pts with squamous cell lung cancer, 38 pts with small cell lung cancer and 23 pts with adenocarcinoma. The cutoff level was set at 4 ng/ml with a specificity of 94% and a sensitivity of 40%. Elevated Cyfra 21-1 values were found in 44% of squamous cell lung cancer, 39% of adenocarcinoma and 34% of small cell lung cancer pts (the difference was not significant). In squamous cell lung cancer and in adenocarcinoma elevated Cyfra 21-1 values were observed more often in patients with advanced disease than in patients with limited disease. There was no significant correlation between the initial Cyfra 21-1 level and the response to chemotherapy. Cyfra 21-1 was not a prognostic indicator, although in operable squamous cell lung cancer the proportion of survivors in the second year of observation was higher among the patients with normal preoperative Cyfra 21-1 levels.

The aim of the study was to assess how objective is the estimation of the chest lesions regression on RT picture and how extent chest CT can increase the precision of this assessment. The material consisted of 66 SCLC pts observed in the Institute of Tuberculosis and Lung Diseases in Warsaw between 1987 and 1994 in whom RT and CT were performed to estimate the degree of response to treatment. Chest RT were estimated by 4 specialists independently. In 28 cases (42%) opinion concerning the degree of tumor regression was the same. In 23 cases (35%) the opinions were discordant and in 15 cases (13%) (mainly after chest irradiation) all examiners agreed that degree of response is impossible to precise (it ranged between PR and CR). In the second part of this study the degree of cancer regression was assessed in the same patients by 2 specialists independently estimated CT pictures. Opinions were different only in 4 cases. The comparison between these two methods was done. CI examination allowed exact estimation of response degree in 20 out of 24 pts (83%) in whom this assessment was impossible using chest radiography. In 9 cases (21%) the assessment of chest CT changed the previous estimation made using chest radiography (in 5 cases from CR to PR and in 4 cases from PR to CR). In conclusion-estimation of tumor regression using chest RT is very subjective method and many errors are possible. Chest CT estimation is a much better method for estimation of tumor response especially in irradiated patients.

The aim of this study was to assess whether the lowest serum NSE obtained during treatment of small cell lung cancer patients can be helpful in the diagnosis of complete remission (CR). The material consisted of 68 patients with small cell lung cancer, treated in the Institute o Tuberculosis and Lung Diseases from 1.III.1993 to 15.II.1995. In the course of treatment CR was obtained in 13 patients, partial remission (PR) in 37 and no remission (NR) in 18. The distribution and median of the lowest NSE serum levels were the same in CR and RP patients. NSE serum levels remained above normal, that is above 12.5 ng/ml, in two CR patients and in 4 PR patients. 3 patients (2 with CR and I with PR) are still living for 26, 27 and 41 months in spite of NSE serum levels 14.3, 15.6 and 13.6 ng/ml respectively. In those patients in whom NR was obtained the lowest NSE level above 20 ng/l was connected with bad prognosis. We conclude that the estimation of the lowest NSE serum level in the course of treatment can not help to differentiate CR from PR.

The aim of this study was to assess whether thoracic radiotherapy (TRT) is necessary for those patients (pts) with limited small cell lung cancer (SCLC) who obtained CR after induction chemotherapy (ChT). The analysis include retrospective material of 124 consecutive pts with limited SCLC. All pts had induction ChT (3-5 courses): 78 with CAVE (cyclophosphamide, doxorubicine, etoposide) and 46--with other regimens without etoposide. After induction ChT 55 pts were irradiated on tumor and mediastinum and in 69 the same ChT was continued for 6-8 courses or till progression. After induction ChT CR was obtained in 31 pts, PR in 67 and NR in 26. TRT significantly increased the number of CR among those pts who did not achieve satisfactory tumor response after induction ChT. The median survival was 24 months for those patients who obtained CR, 12 months for those who obtained PR and 9 months for those who did not respond. In the group of patients who obtain CR, survival was the same for those treated with ChT alone and for those treated with ChT and TRT. We conclude that in the treatment of individual patient with limited SCLC TRT is indicated for those who did not obtain CR after ChT. Whether patients in whom CR after chemotherapy was obtained can further gain by application of TRT is worth further randomised studies.

HCG-like immunoreactivity has been found in many nontrophoblastic tumors, but the biological behaviour of HCG--producing cells has not been clarified yet. The aim of the study was to estimate the frequency of serum bHCG (sbHCG) elevation in SCLC patients and to assess its possible prognostic role in this type of tumor. 156 SCLC patients entered the study: 93 men, 63 women, median age 58 years. SbHCG activity was measured with immunoenzymassay (Abbott EIA bHCG 15-15) before treatment. ScHCG elevation (5 mIU/ml) was found in 21 of 156 patients (14%). Response to treatment after chemotherapy (CR + PR) was obtained in only 48% of those patients in whom elevated sbHCG was found, in comparison to 73% of response rate observed in the remaining patients. Only 5% of patients with elevated sbHCG survived 2 years, in comparison to 21% of 2-years survivors in the remaining patients. Thus sbHCG elevation in SCLC seems to be a marker of more resistant tumors and of poor prognosis.

NSE was estimated using Pharmacia test and radioimmunologic method in the serum of 41 SCLC patients before treatment, at the time of maximal tumor response and in some patients also during progression. The level of 12,5 ng/l was regarded as the upper limit of normal. Elevated NSE levels before treatment were found in 12 out of 20 patients with limited disease and in 19 out of 21 patients with extensive disease. Complete remission (CR) was observed only in patients with limited disease and in those in whom NSE serum level was below 50 ng/l. Elevated NSE serum levels decreased in all those in whom partial remission (PR) or CR of tumor was obtained. Decrease of elevated NSE levels was however also observed in some patients with no significant regression of tumor. The decrease of serum NSE level seemed to be a good prognostic factor even in this last group. NSE serum level increased in 7 out 10 patients where progressive disease after PR was found. In 3 patients however NSE level persisted in normal values despite progression. The significance of this fact was discussed.

Human chorionic gonadotropin (HCG)-like immunoreactivity has been found in many non-trophoblastic tumours, but the biological behaviour of HCG-producing cells has not been clarified yet. The aim of the study was to estimate the frequency of serum HCG beta subunit (s beta HCG) elevation in patients with small-cell lung cancer (SCLC) and to assess its possible prognostic role in this type of tumour. An attempt was also made to reclassify the histology in selected cases to see whether the elevated (s beta HCG) level is connected with any special subtype of small-cell lung cancer. A total of 156 SCLC patients entered the study: 93 men, 63 women, median age 58 years. s beta HCG activity was measured by immunoenzyme assay (Abbott EIA beta HCG 15-15) before treatment. s beta HCG elevation (above 5 mIU/ml) was found in 21 of 156 patients (14%). Response to treatment after chemotherapy (complete and partial response) was obtained in only 48% of those patients in whom elevated s beta HCG was found, in comparison to the 73% response rate observed in the remaining patients. Only 5% of patients with elevated s beta HCG survived 2 years, in comparison to 21% surviving for 2 years among the remaining patients. The prognostic significance of elevated s beta HCG and extent of disease were independent of each other (Cox's proportional-hazard model). Thus s beta HCG elevation in SCLC seems to be a marker of more resistant tumours and of poor prognosis. We have not found any connection between the subtype of small-cell lung cancer and elevated s beta HCG. Elevated s beta HCG was found in 2 out of 11 patients with oat-cell carcinoma, in 3 out of 10 patients with an intermediate cell type and in 5 out of 13 patients with small-cell lung cancer in which the assessment of the subtype was not possible.

The comparison between results of chemotherapy (ChT) and ChT plus radiotherapy (RT) was performed in the group of 124 patients with limited SCLC. After induction ChT 25% pts obtained CR, 54%-PR and 21% did not respond. In 69 pts ChT was continued and in 55 others RT was added to ChT. The number of patients in whom tumor response was observed increased significantly after addition of RT to ChT. The degree of complete response had important impact on survival time. The pts who obtained CR had significantly longer survival time than those who achieved only PR or NR. Median survival time was very similar in both groups (13 months after ChT alone and 15 months after ChT plus RT). This was also true for the groups of patients who obtained CR after completion of treatment. Achievement of complete response is the most important factor for good prognosis. RT is indicated in those patients who achieved only PR after induction ChT.

Cytokeratins, the intermediate filaments, are expressed by many epithelial cells. Immunohistochemistry revealed the presence of cytokeratin-19 both in bronchial epithelium and in lung cancer cells. The aim of our study was to establish the value of serum cytokeratin-19 estimation by immunoenzymatic assay (Enzymun Cyfra 21-1, Boehringer Mannheim) in the patients (pts) with lung cancer (Ic). 153 pts (104 men, 49 women, median age 50 years) entered this study. The group consisted of 37 pts with benign lung diseases (control group), 56 pts with squamous cell Ic, 37 pts with small cell Ic and 23 with adenocarcinoma. Cut off value was determined at 4 ng/ml, with 96% of specificity. Elevated cytokeratin-19 values were found in 41% of pts with lung cancer (45% of squamous cell Ic, 39% of adenocarcinoma and 35% of small cell Ic). Median cytokeratin-19 values were 2.2 ng/ml in the control group, 3.4 ng/ml in squamous cell Ic, 3.3 ng/ml adenocarcinoma and 2.9 in small cell Ic. Cytokeratin-19 elevation was observed more often in non small cell Ic pts with advanced disease, stage III--46%, stage IV--50% than in early stages (I + II)--34%. In small cell Ic pts the frequency of cytokeratin-19 elevation was 20% in limited disease versus 45% in extensive disease. We conclude that cytokeratin estimation is not valuable in the recognition of histologic type of lung cancer, although elevated levels are seen more often in squamous cell Ic. Cytokeratin-19 estimation may be also helpful in lung cancer staging.

From March 1987 to February 1991, 136 patients with untreated small cell lung cancer (64 patients with limited disease and 72 with extensive disease), were treated as part of a prospective multi-center study, with a combination of cyclophosphamide 1000 mg/m2 i.v. on day 1, epirubicin 70 mg/m2 i.v. on day 1 and etoposide 100 mg/m2 i.v. on days 1, 3 and 5. Courses were repeated every 3 weeks. One-hundred thirty-four patients were evaluable. There were 42 (31%) complete responses and 66 (49%) partial responses for an overall response rate of 80% (95% confidence interval 71-87%). A complete response was seen in 24 patients (38%) with limited disease and in 18 patients (26%) with extensive disease, while a partial response was observed for 31 (48%) and in 35 (50%) patients, respectively. The median duration of response for all patients was 8.9 months (range, 1-60+ months). The median duration of survival for the entire group was 11.4 months (12.5 months for limited disease and 9.8 months for extensive disease). The 2-year survival rate for the whole group was 13%. The main side-effects were myelosuppression, alopecia, nausea and vomiting. Grade 4 toxicity was seen in 8.5% of patients. In conclusion, the studied regimen was found to be active and well tolerated and may be considered as an alternative to standard chemotherapy combinations in SCLC.

16 patients with clinical and radiological symptoms suggesting lung disease were described. Metastatic character of process was documented in 7 of them during life and in 9 after death. The pulmonary symptoms without any signs of primary tumor lasted from few months to 3 years. Two patients revealed primary tumor in ovary, 1-in uterus, 4-in thyroid gland, 2-in prostata, 2-in breast, 2-in pancreas, 1-in bone, one in testicle, and 2-in kidney.

One-hundred forty-six SCLC patients were classified as localised (56) or extensive (90) using chest X-ray, bronchoscopy, brain CT, bone scintigraphy, ultrasonography of the abdomen and bilateral bone marrow trephine biopsy. Bone marrow metastases were found in 28 cases. Patients with bone marrow metastases had significantly shorter time to progression (median 20 weeks) and significantly shorter survival time (median 31 weeks) than other patients with extensive disease (medians 30 and 46 weeks). Patients with bone marrow involvement had significantly more often metastases in three or more organs than others with extensive disease. The negative prognostic significance of bone marrow involvement was however independent of the negative prognostic significance of the number of organs with metastases.

70 SCLC patients (pts): 25 women and 45 men aged 34 to 76 with limited disease were treated with chemotherapy in Institute of Tuberculosis in the period 1.01.1987-31.12.1992. After 3-5 courses of chemotherapy restaging was done using chest X-ray examination, bronchoscopy with cytological examination of bronchial material, abdomen ultrasound examination and other methods according to clinical indications. Complete regression (CR) of the tumor in chest X-ray examination was found in 17 cases, partial regression (PR) in 37 cases and no response (NR)-in 16 pts. The degree of tumor regression on chest X-ray had significant prognostic value. The median survival time in this group was 20 months while median was 13.5 months in PR patients group and 11.5 in NR patients. Bronchoscopy revealed macroscopic or microscopic signs of cancer in 5 of 17 pts with CR on chest X-ray examination, in 23 of 37 cases with PR on X-ray and in 12 of 16 with NR on X-ray. The persistence of tumor signs in bronchoscopic examination seemed to worsen the prognosis in pts with CR on chest X-ray. Complete regression of tumor revealed during bronchoscopy did not have any prognostic significance if CR on the chest X-ray was not obtained. It was concluded that bronchoscopic examinations in early phase of chemotherapy is useful to further treatment planning only in these pts in whom CR of tumor on chest X-ray examination was confirmed.

Bone marrow metastases using Jamshidi needle were found before treatment in 28 of 146 small cell lung cancer patients (19.2%). Bone marrow was a sole site of distant metastases in 3.4% of all cases and in 8.2% of those with no metastases in other organs. Patients with bone marrow involvement had more often metastases in 3 or more organs and had significantly more often liver metastases as well. Bone marrow infiltration was more often observed in patients with poor performance status and with disseminated disease, but was also found in 4 of 47 patients with good performance status and without metastases in other organs. Bone marrow trephine biopsy should be included in staging procedure in small cell lung cancer patients with good performance status, without metastases in other organs and with abnormalities in peripheral blood picture.

In 129 SCLC patients (pts) 250 control fibrobronchoscopic (FOB) procedures were performed during chemotherapy. 71 pts had extensive disease and 58 limited disease. The evident correlation between radiologic and bronchoscopic assessment of tumor regression was confirmed in 60% of examinations. Tumor was visible during 16 bronchoscopic examinations in spite of complete regression on X-ray picture and on 53 chest X-ray examinations despite complete regression in the bronchi. Cancer cells found in 74 out of 250 bronchial washings samples were present significantly more often in these situations in which no regression of tumor in the bronchi was confirmed. Nevertheless tumor cells were also found in 3 out 57 cases in which complete regression on X-ray and in the bronchi was found. It was concluded that complete tumor regression on X-ray picture ought to be confirmed by bronchoscopy with cytologic examination of bronchial washing.

Epirubicin 110 mg/m2 was administered intravenously every 3 weeks to 41 elderly and/or unfit, previously untreated patients with small cell lung cancer (SCLC). There were three complete responses, 16 partial responses and 14 treatment failures, with a response rate of 57% in 33 evaluable patients. The main toxicity was haematological, characterised by leukopenia and, less frequently, thrombocytopenia and anaemia. There were three toxic deaths due to infection occurring during leukopenia. Non-haematological side effects were alopecia, nausea, stomatitis and diarrhoea. WHO grade 2 cardiac toxicity was seen in 3 patients after a cumulative dose of more than 740 mg/m2. In conclusion epirubicin is an active agent in untreated SCLC.

Serum ferritin levels using the radiometric method were determined in 161 lung cancer patients and in 50 patients with non-malignant pulmonary disorders. Elevated serum ferritin levels were seen more often in lung cancer patients (82%) than in those with the non-malignant disorders (52%). The levels of ferritin were also affected by the extension of the disease. In patients with stage III and IV serum ferritin levels were more pronounced (median 577 ng/ml) in comparison with stage I and II (300 ng/ml). Determination of serum ferritin levels may help in evaluating disease progression and staging, but can not be used as a screening test due to a low specificity.

Basing on results of tumor marker levels (CEA, ferritin, orosomucoid) in 271 lung cancer patients and 50 with non-malignant pulmonary diseases the authors found that assessment of different tumor markers is clinically more useful than single marker evaluation. Analysing several markers increases the specificity to almost 100% but decreases the sensitivity. Assessing several markers can help differentiating between malignant and non-malignant pulmonary disorders. It may also help in correctly staging the disease. A 12 month survival rate was seen only in 50% of the patients in whom the levels exceeded the cut-off value of two studied markers, whereas 90% survived 12 months if all marker levels were within normal levels. None of the patients with all markers exceeding the normal values survived one year after surgery. Survival rates of patients treated non-surgically were not influenced by the tumor marker levels.

The aim of the study was to evaluate the + bronchoscopy in monitoring of therapy in SCLC. Sixty patients were included in the study. The number of bronchoscopies ranged from 1 to 4. Evaluation was based on endoscopical analysis and pathomorphological examination of the biopsied material. In 30% of the studied patients bronchoscopy had decisive influence on therapy, irrespective of clinical and radiological criteria. The authors point out, that presence of cancer cells in bronchial aspirates, even in patients with normal endoscopical findings is a decisively poor prognostic factor.

A case is presented of a round coin shadow seen on a routine chest radiogram producing grave diagnostic problems. During hospitalization the patient presented neurological and bone and joint involvement symptoms. Transthoracic needle biopsy of the lesion allowed to diagnose large cell cancer, but autopsy changed this diagnosis to malignant histiocytoma.

Usefulness of a simple microagglutination test for diagnosis of malignant diseases was evaluated in the diagnosis of lung cancer. The test was not specific, being positive in 82% of malignant and 55% of nonmalignant cases. It was shown that poly-L-lysine-induced agglutination of lymphocytes reflects rather changed serum than cell properties and cannot be taken as a method for detection of sensitized cells.

The analysis of clinical determinants of long-term survival in small cell lung cancer was investigated in consecutive series of 469 patients included in prospective multicenter clinical trials from 1981 to 1985. Forty eight patients (19.2%) were alive after 2 years from initiation of therapy and among them 27 (5.8%) were disease free. The most important clinical determinants of long-term survival were: extent of disease, performance status and sex. 38 out of 243 patients with limited disease (15.6%) survived for 2 years or more as well as 10 out of 226 patients with extensive disease (4.4%, p less than 0.001), 33 out of 237 patients with WHO performance status 0 and 1 (13.9%), and 15 out of 232 patients with performance status from 2 to 4 (6.4%, p less than 0.01), 29 out of 229 (12.2%) with absence of weight loss before therapy and 19 out of 240 (7.9%) with weight loss (N.S.), 32 out of 392 males (8.2%) and 16 out of 77 females (20.7%, p less than 0.01). Out of 27 disease-free survivors 21 are alive with no sign of malignancy after 3.5 to 7 years from initiation of therapy. Ten patients out of 229 followed up for a minimum 5 years after inclusion to the studies survived this period with no signs of disease. This study confirms the possible curability of small cell lung cancer, especially in patients with favorable prognostic characteristic.