Cell-free DNA levels in plasma of patients with non-small-cell lung cancer and inflammatory lung disease.

BACKGROUND: The analysis of plasma cell-free DNA (cfDNA) is expected to provide useful biomarkers for early diagnosis of non-small-cell lung cancer (NSCLC). However, it remains unclear whether the intense release of cfDNA into the bloodstream of NSCLC patients results from malignancy or chronic inflammatory response. Consequently, the current diagnostic utility of plasma cfDNA quantification has not been thoroughly validated in subjects with chronic respiratory inflammation. Here we assess the effect of chronic respiratory inflammation on plasma cfDNA levels and evaluate the potential clinical value of this phenomenon as an early lung cancer diagnostic tool. METHODS: We measured plasma cfDNA concentrations in 50 resectable NSCLC patients, 101 patients with chronic respiratory inflammation (chronic obstructive pulmonary disease, sarcoidosis, or asthma) and 40 healthy volunteers using real-time PCR. RESULTS: We found significantly higher plasma cfDNA levels in NSCLC patients than in subjects with chronic respiratory inflammation and healthy individuals (P<0.0001). There were no significant differences in plasma cfDNA levels between patients with chronic respiratory inflammation and healthy volunteers. The cutoff point of >2.8 ng ml(-1) provided 90% sensitivity and 80.5% specificity in discriminating NSCLC from healthy individuals (area under the curve (AUC)=0.90). The receiver-operating characteristics curve distinguishing NSCLC patients from subjects with chronic respiratory inflammation indicated 56% sensitivity and 91% specificity at the >5.25-ng ml(-1) cutoff (AUC=0.76). CONCLUSIONS: We demonstrated that elevated plasma cfDNA levels in NSCLC resulted primarily from tumour development rather than inflammatory response, raising the potential clinical implications for lung cancer screening and early diagnosis. Further research is necessary to better characterise and identify factors and processes regulating cfDNA levels in the blood under normal and pathological conditions.

Diagnostic utility of CYFRA 21-1 and CEA assays in pericardial fluid for the recognition of neoplastic pericarditis.

A positive cytology result in pericardial fluid is the gold standard for recognition of malignant pericardial effusion. Unfortunately, in 30-50% of patients with malignant pericardial effusion cytological examination of the pericardial fluid is negative. Tumor marker assessment in pericardial fluid may help to recognize malignant pericardial effusion. The aim of our study was to estimate the value of CYFRA 21-1 and CEA measurement in pericardial fluid for the recognition of malignant pericardial effusion. To our knowledge this is the first study on CYFRA 21-1 assessment in pericardial effusion. The examined group consisted of 50 patients with malignant pericardial effusion and 34 patients with non-malignant pericardial effusion. Median CEA concentrations in malignant pericardial effusion and non-malignant pericardial effusion were 80 ng/mL (0-317) and 0.5 ng/mL (0-18.4), respectively (p<0.001). Median CYFRA 21-1 concentrations in malignant pericardial effusion and non-malignant pericardial effusion were 260 ng/mL (5.3-10080) and 22.4 ng/mL (1.87-317.6), respectively (p<0.001). The optimal cutoff value for CYFRA 21-1 in pericardial effusion was 100 ng/mL. CYFRA 21-1 >100 ng/mL or CEA >5 ng/mL were found in 14/15 patients with malignant pericardial effusion and negative pericardial fluid cytology. We therefore strongly recommend the use of CYFRA 21-1 and/or CEA in addition to pericardial fluid cytology for the recognition of malignant pericardial effusion.

Inhibition of angiogenesis by sulindac and its sulfone metabolite (FGN-1): a potential mechanism for their antineoplastic properties.

The nonsteroidal antiinflammatory drug sulindac (sulfoxide) is known to cause regression and prevent recurrence of adenomas in patients with familial adenomatous polyposis. The mechanism of action does not appear to require inhibition of prostaglandin synthesis since the sulfone metabolite of sulindac (FGN-1) retains the antineoplastic properties of sulindac but lacks inhibitory effects on cyclooxygenase, types 1 and 2. FGN-1 has been shown to induce apoptosis in a variety of tumor cell lines, and selective apoptosis of neoplastic cells has been proposed to account for its antineoplastic properties. Since angiogenesis is necessary for tumor progression and may be related to apoptosis, it is possible that inhibition of angiogenesis may also contribute to the antineoplastic properties of sulindac or FGN-1. In order to test this possibility, cells derived from several different types of human lung tumors were grafted intradermally in Balb/c mice. Sulindac sulfoxide and its sulfide and sulfone metabolites were administered for 3 days orally, in a daily dose of 0.025-0.5 mg, and angiogenesis was measured after 72 h using a previously described method. The results showed that sulindac sulfoxide and sulfone statistically inhibited angiogenesis.

[Five year survival of patients treated surgically for lung neoplasms]. / Piecioletnie przezycia chorych leczonych chirurgicznie z powodu raka pluc.

The results of surgery for lung cancer performed in 1981 and respectively in 1991 were compared in regards to 5 years survival time. Most centers of thoracic surgery in Poland participated in the study. In 1981 728 patients underwent surgery for LC and in 1991-1141 had some kinds of lung resection for LC. The improvement rate of 17% in regards to 5 years survival time was achieved in the latter period.

[Typical and atypical pulmonary carcinoids--pathologic and clinical analysis of 77 cases]. / Typowe i atypowe rakowiaki pluc--patologiczna i kliniczna analiza 77 przypadków.

Neuroendocrine tumors of the lung represent a group of controversial pulmonary neoplasms regarding their classification, criteria for diagnosis, predictors of future behavior, and therapy. The histologic criteria for their classification rest heavily on the proposed by Arrigoni et al. in 1972, for atypical carcinoid (AC). According to these authors AC has mitoses between 5 and 10 per 10 high power fields (HPF), necrosis, hypercellularity and disorganized architecture. The survival analysis performed by Flieder et al. (1997) for a variety of clinical and histologic features revised the histologic criteria for separating AC from typical carcinoid (TC) and proposed a range of mitotic counts between 2 and 20 per HPF for AC. From 1978 until 1997, 77 resected pulmonary carcinoids were reclassified for TCs and ACs according to Flieder's et al. histologic criteria. The clinical and pathological various features were studied for the group of 62 TCs and 15 ACs. 77 patients (pts) entered the study: 29(38%) males and 48(62%)females; mean age 43 years, range 18-75 years, 46 pts underwent lobectomies, 16 bilobectomies, 12 pneumonectomies and 3 wedge resections. The patients with TC were younger than those with AC (males: 40 vs 50 years and females 42 vs 49 years). TCs were significantly smaller than ACs (mean diameter respectively: 24 mm vs 33 mm). Fifty four (87%) of TCs and all ACs had central localization. The time of patients observation ranged from 2 months to 18 and half years; 2 patients with TC died due to tumours progression; 3 due to other diseases. Regional lymph node metastases occurred in 10% TCs and 33% ACs (p = 0.032). The heterotopic bone formation appeared in 11(18%) TCs and 2(13%) ACs. The mitotic counts for AC range between 2 and 6 per 10 HPF, accompanied by small foci of necrosis in 2 cases. Peripheral carcinoids showed a spindle-cell morphology. The performed study has highlighted the new concept of the carcinoids classification and the importance of the mitotic counts as histologic criteria for AC diagnosis. The data based on the largest in Polish literature lung carcinoids collection.

[Early and late results of surgical treatment for bronchial carcinoids]. / Wczesne i odlegle wyniki leczenia chirurgicznego rakowiaków oskrzeli.

UNLABELLED: The aim of the study was to evaluate the efficacy and safety of surgical treatment of the bronchial carcinoids. Between 1983 and 1996 52 patients (pts) with typical carcinoid were operated. The group consisted of 23 males and 29 females aged from 20 to 68 years (mean 41.3 years). In the chest X-ray and CT scan round shadow were found in 21 (40.4%) cases, lung tissue atelectasis in 23 (44.1%) cases. The bronchial tree was normal in fiberoptic bronchoscopy in 8 cases. We performed 4 pneumonectomies, 3 wedge resection and 45 lobectomies (including 5 "sleeve" lobectomies). We haven't recorded any early post-op deaths. Only two pts (3.8%) developed post-op complications--cardiac arrhythmias. In two cases the surgical treatment was followed by radiotherapy for metastases in regional lymph nodes. The period of follow-up ranged from 3 to 166 months (mean 62.2 months). During that time we noticed the recurrence of tumor in 2 pts (3.8%). One patient died from cardiac reason. The 5-year survival among patients operated in the period 1983-1992 was 91.2%. The 10-year survival in the group of pts operated on between 1983 and 1987 was 90%. CONCLUSION: The surgical treatment of bronchial carcinoid is method of choice, very efficient and safe.

[A rare mediastinal neoplasm in the form of a hemangioma]. / Rzadka forma rozrostu nowotworowego w sródpiersiu pod postacia naczyniaka.

Hemangiomas of the mediastinum are rare tumors. They represent fewer than 0.5% of the mediastinal tumors. Because of their rarity, the diagnosis and treatment of these tumors is difficult. We present a case of venous hemangioma of the mediastinum in a young woman. Despite of routine examination applied in mediastinal tumors the appropriate diagnosis was not done by the accessible methods.

[Five year survival in patients with non small cell carcinoma of the lung treated surgically]. / Piecioletnie przezycia chorych na niedrobnokomórkowego raka pluca leczonych chirurgicznie.

The late results of surgical treatment of non small cell lung cancer in 735 patients treated in the years 1981-1986 are presented. 59.3% of the patients with stage I disease are alive after 5 years; 43% with stage II and 23.6% with stage III. 326 (44.3%) out the initial number of 735 surgically treated patients have survived 5 years. 274 patient died in the course of local recurrencies and distal metastases, while 135 died due to nonmalignant causes.

Diagnostic utility of CYFRA 21-1 and CEA assays in pericardial fluid for the recognition of neoplastic pericarditis.

A positive cytology result in pericardial fluid is the gold standard for recognition of malignant pericardial effusion. Unfortunately, in 30-50% of patients with malignant pericardial effusion cytological examination of the pericardial fluid is negative. Tumor marker assessment in pericardial fluid may help to recognize malignant pericardial effusion. The aim of our study was to estimate the value of CYFRA 21-1 and CEA measurement in pericardial fluid for the recognition of malignant pericardial effusion. To our knowledge this is the first study on CYFRA 21-1 assessment in pericardial effusion. The examined group consisted of 50 patients with malignant pericardial effusion and 34 patients with non-malignant pericardial effusion. Median CEA concentrations in malignant pericardial effusion and non-malignant pericardial effusion were 80 ng/mL (0-317) and 0.5 ng/mL (0-18.4), respectively (p<0.001). Median CYFRA 21-1 concentrations in malignant pericardial effusion and non-malignant pericardial effusion were 260 ng/mL (5.3-10080) and 22.4 ng/mL (1.87-317.6), respectively (p<0.001). The optimal cutoff value for CYFRA 21-1 in pericardial effusion was 100 ng/mL. CYFRA 21-1 >100 ng/mL or CEA >5 ng/mL were found in 14/15 patients with malignant pericardial effusion and negative pericardial fluid cytology. We therefore strongly recommend the use of CYFRA 21-1 and/or CEA in addition to pericardial fluid cytology for the recognition of malignant pericardial effusion. (Int J Biol Markers 2005; 20: 43-49).

Trophoblastic markers and CEA in non-small cell lung cancer: the comparison studies of tumour cells expression and serum concentration.

The study was designed to explore the tumour cell expression of three markers: hCG, SP1 and CEA in lung cancer in relationship with histological type and histological differentiation of tumours as well as serum concentration of antigens. 58 primary resected lung cancers: 28 adenocarcinomas, 27 squamous cell and 3 large cell carcinomas were included. Tumours immunoreactivity of three markers was evaluated by semiquantitative analysis. Simultaneously serum tumour markers were measured in 42 patients by enzyme radioimmunoassays. CEA and SP1 expressions in lung tumours were found in a majority of carcinomas-86% and 79% respectively. Expression of tumour markers was not associated with any certain histological type of carcinoma but was more characteristic for moderately and well differentiated adenocarcinomas. hCG positive tumour staining was less frequent than CEA and SP1 (only 22% tumours) and was much less intensive (5-50% population of carcinomatous cells) in the tumours. The study showed correlation between increased serum CEA concentration and tumour expression of antigen.

Immunohistochemical evaluation of tumour angiogenesis in adenocarcinoma and squamous cell carcinoma of lung.

Experimental studies revealed that growth and expansion of solid tumours depend on angiogenesis. Angiogenesis is very important factor for neoplastic metastasis. The presence of the metastasis is an ominous prognostic factor for many tumours, also for lung cancer. Studies of tumour microvessel density in resected non-small lung cancers have not given convincing data about value of angiogenesis. Only few reports regarded the association with angiogenesis in different histological types in lung carcinoma. Samples of 35 adenocarcinomas and 41 squamous cell resected, primary lung carcinomas were studied. Paraffin sections of tumours were stained immunohistochemically by antibody against endothelial marker CD34. Angiogenesis intensity was measured in the areas of the most active fields of tumour neovascularization. Microvessel density (MD) was higher in adenocarcinoma comparing to squamous cell cancer, but the difference was not statistically significant (p = 0,095). The groups of various stage of extension of disease in each histological type were compared-MD correlated with lymph node metastasis (p = 0,003) in the adenocarcinoma, whilst in squamous cell can cer differences between various groups of nodal involvement were not statistically significant (p = 0,53 and p = 0,22 respectively). Our results suggest that more intensive angiogenesis in adenocarcinoma could be more important factor for metastasis of adenocarcinoma than for squamous tumours. In the latter group angiogenesis may be more important for growth of squamous cell cancers, while the spread of squamous tumours may depend on other mechanisms.

Screening of angiogenesis inhibitors by modified tumor-induced angiogenesis (TIA) test in lung cancer.

Aberrant angiogenesis-the new vessels formation is a mandatory event in the process of tumor growth and expansion. Studies on mechanisms involved in tumor-induced angiogenesis (TIA) and on its possible inhibitors are needed in order to introduce in future new methods of tumor treatment. The aim of our study was to determine the usefulness of the modified cutaneous TIA (mice without immunosuppression) test for screening in vivo of the angiogenesis modifiers. In both models (classical and modified TIA) we demonstrated comparable angiogenesis activity following human lung cells inoculation and similar degree of neovascularization response inhibition caused by theobromine. We reported that in modified TIA model preincubation with theobromine significantly suppressed angiogenic potential of human lung cancer cells as well as the ability of those cells to produce proangiogenic cytokine-bFGF.