Association between the ACE-I/D polymorphism and nicotine dependence amongst patients with lung cancer.

The biologically active peptide angiotensin II is cleaved from angiotensinogen by the renin and the angiotensin-converting enzyme (ACE), an enzymatic cascade known as the renin-angiotensin system (RAS). RAS may be important in the etiology of nicotine dependence by influencing dopaminergic signaling. In the present study, the association between an insertion/deletion (I/D) polymorphism of ACE and nicotine dependence amongst patients with lung cancer was assessed. To date, several studies have shown the relevance of this polymorphic variant in both nicotine dependence and lung cancer. However, the present study is the first to address the potential role of the ACE-I/D polymorphism in nicotine dependence among patients with lung cancer. Genotyping was performed in 305 patients with lung cancer (males/females, 214/91). Significantly more male smokers had the ACE-I allele compared with male non-smokers (44.9 vs. 20.0%; P<0.05). The risk of smoking was ~5-fold higher for males with the ACE-I allele (ACE-II homozygous and ACE-ID heterozygous) vs. ACE-DD homozygous (odds ratio, 5.47; 95% confidence interval, 1.4-21.9; P=0.016). The pack-year smoking history in a subgroup of females with squamous cell carcinoma carrying the ACE-I allele was significantly lower compared with ACE-DD (37.1±14.1 vs. 57.0±29.1; F=4.5; P=0.046). The ACE-I/D polymorphism accounted for 17.6% of the smoking severity in this patient group (ß, -0.42; multiple R2 change, 0.176; P=0.046). These results suggest that the ACE-I/D polymorphism contributes to the risk of nicotine dependence and smoking severity in lung cancer patients in a sex-specific manner.

Diagnostic value of tumour markers in pleural effusions.

INTRODUCTION: We investigated whether tumour markers carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cancer antigen 125 (CA-125), and cytokeratin 19 fragment (CYFRA 21-1) in pleural effusions and serum can be used to distinguish pleural effusion aetiology. MATERIALS AND METHODS: During the first thoracentesis, we measured pleural fluid and serum tumour marker concentrations and calculated the pleural fluid/serum ratio for patients diagnosed with pleural effusion, using electrochemiluminescence immunoassays. Receiver operating characteristic (ROC) analysis was carried out and the Hanley and McNeil method was used to test the significance of the difference between the areas under ROC curves (AUCs). In order to detect which tumour marker best discriminates between malignant and non-malignant pleural effusions and to establish the predictive value of those markers, discriminant function analysis (DFA) and logistic regression analysis were utilized. RESULTS: Serum tumour markers CYFRA 21-1 and NSE as well as pleural NSE were good predictors of pleural effusion malignancy and their combined model was found statistically significant (Chi-square = 28.415, P < 0.001). Respective ROC analysis showed significant discrimination value of the combination of these three markers (AUC = 0.79). CONCLUSIONS: Serum markers showed superiority to pleural fluid markers in determining pleural fluid aetiology. Serum CYFRA 21-1 and NSE concentrations as well as pleural fluid NSE values had the highest clinical value in differentiating between malignant and non-malignant pleural effusions. The combination of these three markers produced a significant model to resolve pleural effusion aetiology.

Association of the FAM46A gene VNTRs and BAG6 rs3117582 SNP with non small cell lung cancer (NSCLC) in Croatian and Norwegian populations.

We analyzed for associations between a variable number of tandem repeat (VNTR) polymorphism in the Family with sequence similarity 46, member A (FAM46A) gene and a single nucleotide polymorphism (rs3117582) in the BCL2-Associated Athanogene 6 (BAG6) with non small cell lung cancer in Croatian and Norwegian subjects. A total of 503 (262 Croatian and 241Norwegian) non small cell lung cancer patients and 897 controls (568 Croatian and 329 Norwegian) were analyzed. We found that the frequency of allele b (three VNTR repeats) of FAM46A gene was significantly increased in the patients compared to the healthy controls in the Croatian and the combined Croatian and Norwegian subjects. Genotype frequencies of cd (four and five VNTR repeats) and cc (four VNTR repeats homozygote) of the FAM46A gene were significantly decreased in the patients compared to the healthy controls in the Croatian and Norwegian subjects, respectively. Logistic regression analyses revealed FAM46A genotype cc to be an independent predictive factor for non small cell lung cancer risk in the Norwegian subjects after adjustment for age, gender and smoking status. This is the first study to suggest an association between the FAM46A gene VNTR polymorphisms and non small cell lung cancer. We found also that BAG6 rs3117582 SNP was associated with non small cell lung cancer in the Norwegian subjects and the combined Croatian-Norwegian subjects corroborating the earlier finding that BAG6 rs3117582 SNP was associated with lung cancer in Europeans. Logistic regression analyses revealed that genotypes and alleles of BAG6 were independent predictive factor for non small cell lung cancer risk in the Norwegian and combined Croatian-Norwegian subjects, after adjustment for age and gender.

Pericardial effusion as the first manifestation of occupational tuberculosis in a health care worker.

Tuberculosis (TB) is an infectious disease and, apart from protecting patients, attention must be given to protecting the persons who come in contact with them, especially nurses and medical practitioners. A 43-year-old immunocompetent male nurse developed occupationally disseminated TB after contact with patients affected by active TB (culture positive) while working in a psychiatric hospital. The first manifestation of the disease was exudative pericarditis with Mycobacterium tuberculosis (MT) confirmed two months after pericardiocentesis and evacuation of 1200 mL of pericardial effusion. Many lymph nodes showed histologic findings of granulomatous inflammation with necrosis. Treatment with antituberculosis drugs caused complications, including transient short-term medication-induced toxic hepatitis, prolonged fever, left pleural nonspecific effusion, and mononeuritis of the right peroneus nerve. The treatment lasted 14 months and led to permanent consequences, including fibrothorax with restrictive ventilation disorders and reduced diffusion of the alveolar-capillary membrane. This case highlights the need to improve the protection of health care workers who are in contact with TB patients, as well as the usefulness of the tuberculin skin test and QuantiFERON-TB test, which can be used to identify early latent TB.

Tumor necrosis factor-alpha gene promoter -308 and -238 polymorphisms in patients with lung cancer as a second primary tumor.

BACKGROUND: Lung cancer is the most common second primary cancer. We investigated whether the TNF-alpha-308 and TNF-alpha-238 polymorphisms were associated with the susceptibility and severity of lung cancer as the second primary cancer (LC2). MATERIAL/METHODS: This study included 104 patients from the group LC2. The control subjects included 2 groups. The first control group (LC1) comprised 201 unrelated patients with lung cancer as a first primary cancer. The second control group (HC) comprised 230 healthy blood donors, matched for sex and age to the study group. RESULTS: The frequencies of the TNF-alpha-238 polymorphism GG genotype and the G allele were higher in the LC2 group than in the LC1 group, but the differences did not reach significance (p=0.054 and p=0.057, respectively). Similar differences were found in the TNF-alpha-238 polymorphism GG genotype and G allele between the LC2 group and the HC group (p=0.054 and p=0.057, respectively). In terms of the different types of lung cancer, patients with a second primary NSCLC (non-small cell lung cancer) more frequently had TNF-alpha-238 polymorphism GG genotypes and G alleles than patients with a first primary NSCLC (the differences approached statistical significance: p=0.060, p=0.064, respectively). All (100%) patients of group LC2 (n=104) had the GG genotype and the G allele. GG genotype was exclusive and no A allele was found in group LC2. CONCLUSIONS: TNF-alpha-238 polymorphism GG genotype and the G allele could have a promotional effect on the development of NSCLC in the group of patients with LC2.

Central type of chondrosarcoma with a fulminant course--a case report.

Primary chondrosarcoma is a rare malignant tumor. The five types of chondrosarcomas are: central, peripheral, mesenchymal, differentiated and clear cell. The classic chondrosarcomas are central (arising within a bone) or peripheral (arising from the surface of a bone). We describe a patient with central chondrosarcoma of the humerus who underwent surgery and only two weeks later presented with multiple metastases of the lung and small pulmonary tumor embolisms mimicking bilateral pneumonic infiltrates. Therefore, such a fulminant course of central chondrosarcoma, which is not described so far, must be taken into consideration during the treatment of patients with primary chondrosarcoma.

Angiotensin-converting enzyme insertion/deletion gene polymorphism in lung cancer patients.

Lung cancer is a complex disease, and many factors, including environmental and occupational exposure, cigarette smoking, and genetics, contribute to its progression. Angiotensin-converting enzyme (ACE) is an important regulator of blood pressure and cardiovascular homeostasis. Plasma levels of ACE depend on an insertion/deletion (I/D) polymorphism in its gene. Current correlation data between lung cancer and the ACE I/D polymorphism are contradictory or insufficient. We investigated whether the ACE I/D polymorphism is associated with a risk for lung cancer development in the Croatian population, representing the first report in a population of Slavic origin. A total of 308 lung cancer patients and 353 control subjects were genotyped for the ACE I/D polymorphism by polymerase chain reaction. The observed distribution of genotypes and alleles showed no significant difference between total patients and controls (p>0.050). However, in a subgroup of nonsmall cell lung cancer patients with squamous cell carcinoma, a significantly higher frequency of the DD genotype (37.7% vs. 27.8%, p=0.030, OR=1.57, 95% CI=1.05-2.36) and D allele was observed compared with the control group (61.3% vs. 52.8%, p=0.015, OR=1.41, 95% CI=1.07-1.87). The DD genotype of ACE may contribute to a higher risk of developing squamous cell carcinoma in the Croatian population.

Primary spontaneous pneumothorax and mitral valve prolapse are not associated.

BACKGROUND: Mitral valve prolapse (MVP) is a common diagnosis in patients with primary spontaneous pneumothorax (PSP). This description assumes that MVP and PSP might be manifestations of a systemic connective tissue abnormality. The purpose of this study was to determine the prevalence of MVP in PSP patients of Croatian origin and evaluate their relationship with connective tissue disorders. We also examined the prevalence of PSP in patients with primary MVP. METHODS: Thirty-two patients with PSP and without underlying pulmonary disease or connective tissue disease underwent two-dimensional transthoracic echocardiography performed by a certified cardiologist. Echocardiography and demographic features were analyzed using descriptive statistics. We also examined the medical records of 60 patients with primary MVP. RESULTS: MVP was found in none of the 32 patients suffering from PSP. The age, sex, smoking status, body mass index, side, rate, and family history were similar to previous investigations. Likewise, none of the 60 patients with primary MVP ever had PSP. CONCLUSION: By applying an updated definition of MVP, we found no MVP case among PSP patients of Croatian origin. We also found no PSP in the primary MVP group. Ethnicity may influence the occurrence of MVP in PSP patients, and PSP in primary MVP patients.

Lower lobe pulmonary tuberculosis in immunocompetent male.

We present a case of 23-year-old student misdiagnosed for two months. Radiological finding showed a pneumonial infiltrate of left lung lower lobe. Antibiotical therapy was not resulting in a radiological regression. Biopsy of the lung infiltrate by transthoracic computed tomography guided histology needle, showed granulomatous inflammation with necrosis. Bronchial aspirate received by bronchoscopy was positive in culture on Mycobacterium tuberculosis. After 6 months of antituberculotic therapy advance the complete regression of lung infiltrate. Tuberculosis of lower lung lobe is difficult to diagnose, particularly in persons who are not immunocompromised or without associated diseases. Lower lobe localization of tuberculosis is between 0.6 to 10.5% in all cases. Early diagnosis and therapy of pulmonary tuberculosis depends on bronchoscopic samples. The biopsy of the lung infiltrate by transthoracic computed tomography guided histology needle in histopathological and bacteriological diagnosis of tuberculosis was also useful.

Primary lung cancer and TNF-alpha gene polymorphisms: a case-control study in a Croatian population.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine involved in the pathogenesis of various inflammatory and malignant diseases. Previous studies investigating the role of the TNF-alpha gene polymorphisms in lung cancer have generated contradictory results. The present study investigated whether the TNF-alpha-308 and TNF-alpha-238 polymorphisms are associated with risk and/or severity of disease in Croatian lung cancer patients. This is the first study in a Caucasian population to analyze the influence of these two polymorphisms on multiple types of lung cancer. MATERIAL/METHODS: In a case-control study, lung cancer patients (n=230) and appropriate age- and sex-matched controls (n=230) were genotyped by the polymerase chain reaction/restriction fragment length polymorphism method. Allele and genotype frequencies were estimated by gene counting. The chi-squared test was used to compare the observed numbers of different TNF-alpha genotypes for the population with those predicted by Hardy-Weinberg equilibrium. Differences in genotype and allele distributions in the patient and control groups were analyzed for statistical significance using the chi-squared test or Fisher's exact test as appropriate. RESULTS: There were no significant differences in the genotype and allele frequencies for the TNF-alpha-308 and TNF-alpha-238 polymorphisms between lung cancer patients and controls. Furthermore, no association between the genotypes and different stages of lung cancer was detected. CONCLUSIONS: This study indicates that the TNF-alpha-308 and TNF-alpha-238 polymorphisms do not influence susceptibility to or severity of lung cancer in a Croatian population.

Multiple recurrence of hydatid disease lasted 19 years.

Hydatid disease (echinococcosis) is a potentially fatal parasitosis caused by tapeworm larvae of the genus Echinococcus which affects primarily the liver and the lungs. However, despite effective medical and surgical treatment, risk of recurrence remains the main problem in the treatment of the disease. We describe here a rare case of multiple recurrence of hydatid disease that lasted more than 19 years. The patient presented with multiple cysts of the liver and dissemination to the lung. The way of dissemination remained unclear and speculative. Despite surgical and intensive medical treatment the disease progressed and the patient died in septic shock.

[Malignant pleural mesothelioma in patients hospitalised at the Clinical Hospital Centre Rijeka between 1989 and 2008]. / Maligni mezoteliom pleure u bolesnika lijecenih u klinickome bolnickom centru Rijeka tijekom 1989-2008. Godine.

Malignant pleural mesothelioma (MPM) is a relatively rare tumour, mainly associated with occupational exposure to asbestos. We retrospectively analysed the records of MPM patients treated at the Pulmonology Department of the Clinic for Internal Diseases, Clinical Hospital Centre Rijeka between 1989 and 2008. to establish the incidence of MPM in that period. Between 1989 and 2008 the hospital received 121 MPM patients, 117 of whom were men and four women. We observed a continued increase in newly diagnosed MPM patients from year to year. Occupational exposure to asbestos was established in 72 patients who worked in shipbuilding. In our region the incidence of MPM has been rising significantly. We believe that this is not related to improved diagnostics, but to the long latency of the disease. This is why we expect this trend to continue for a while. In the U.S.A. and Europe, MPM incidence is expected to peak by 2020, while in countries with poor control over asbestos use this may take longer.

Malignancy risk in patient with neurofibromatosis and autosomal dominant polycystic kidney disease.

Cancer appearance in some inherited diseases depends on the interactions with other genes. Lung cancer is rare in neurofibromatosis and has not been reported in Caucasian population. In this paper, we present the case of lung adenocarcinoma in a patient with neurofibromatosis, pseudoarthrosis of tibia, and autosomal dominant polycystic kidney disease. Cytogenetic analysis of the pleural effusion showed chaotic cleavage and constitutional inversion of chromosome 9, transmitted from the mother. Family investigation revealed two autosomal dominant diseases, neurofibromatosis and polycystic kidney disease in the same family. These findings suggest that the second autosomal dominant disease in the family and inversion of chromosome 9 contributed to the severity of neurofibromatosis and patient's risk to malignancies.