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Background/Aim. Lung cancer (LC) is one of the leading causes of mortality. Disease progression and advanced disease are characterized by the unprotective immune response due to M2 macrophage polarization, myeloid-derived suppressor cells (MDSC) activity, cytokine imbalance, and regulatory T lymphocyte activity. The aim of this study was to investigate the association between Th1/Th2 cytokines and CD14+B7H4+ monocyte (Mo) number in LC patients. Methods. We investigated principal Th1/Th2 cytokines and CD14+B7H4+ Mo number in blood and tumor microcirculation samples of 41 LC patients (III and IV clinical stage) and 30 healthy participants (control group). Results. The serum concentrations of investigated cytokines in all patients vs. heathy controls did not differ significantly. Stratification in groups according to tumor histology, disease extent, and tumor size revealed significant differences. LC patients with different histology types demonstrated significant differences, both in serum and tumor microcirculation samples. The presence of metastasis was associated with increased IFN-γ/IL-4 in blood and increased IL-13 in tumor microcirculation samples. Tumor microcirculation samples of the largest tumors were characterized by the Th2 cytokine profile. Investigation of CD14+B7H4+ Mo in blood samples demonstrated a significant association of extreme value of this cell population with elevated IL-2/IL-13. Patients with the highest CD14+B7H4+ Mo number in tumor microcirculation samples demonstrated significant increments of IL-4, IL-13, IL-10, and TGF-β1. Conclusion. LC patients demonstrated polarization of cytokine response associated with microenvironment origin, tumor histology type, tumor size, and disease extent. The highest number of CD14+ B7H4+ monocytes is significantly associated with the Th2 cytokine profile.

Background/Aim. Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors and a leading cause of cancer-related deaths. The aim of this study was to assess the impact of biological markers on the overall survival rate in surgically treated NSCLC patients who received adjuvant chemotherapy and/or radiation therapy. Methods. This retrospective case series study included patients with NSCLC treated in the period between 2008 and 2017 at the Pulmonology Clinic and the Clinic for Chest Surgery, Military Medical Academy, Belgrade, Serbia. The survival analysis performed was based on immunohistological findings, histology type, and tumor, node, metastasis (TNM) stages. Results. The mortality rate was higher in the adenocarcinoma patient group compared to the squamous cell carcinoma group, albeit without statistical significance (58.3% vs. 31.2%, respectively; p = 0.175). Overall survival was shorter in the adenocarcinoma patient group compared to the squamous cell carcinoma group by approximately 750 days. Likewise, overall survival was shorter in the adenocarcinoma patient group compared to the squamous cell carcinoma group for CD31 positive (p = 0.029), p-63 positive (p = 0.049), MMP-9 positive (p = 0.032), and matrix metalloproteinase (MMP)-2 positive patients (p = 0.016). Conclusion. Adenocarcinoma is a more aggressive cancer type compared to squamous cell carcinoma with shorter overall survival. Our research showed a poorer overall survival in the adeno-carcinoma group of patients compared to the squamous cell carcinoma group in CD31, p-63, MMP-9, and MMP-2 positive patients.

Introduction. The anomalies of the size and shape of the foramen magnum (FM), followed by its stenosis, take a special place in clinical and forensic practice. The clinical picture of FM stenosis is variable, but it is not specific, which is why these anomalies are sometimes not recognized in time and are only detected by autopsy. Case report. This paper analyzes the case of a sudden death caused by the unusual shape of the FM stenosis. On autopsy, we found exostoses on the front and rear edges of the FM with their prominence into the FM. The exostoses reduced the sagittal diameter of the FM and practically divided it into two asymmetric semicircles, which is why we called this stenosis the "keyhole" stenosis of the FM. This form of the FM stenosis pushes the medulla oblongata aside, resulting in its incarceration into one of the FM semicircles. Conclusion. A stenosis of the FM can represent a threat to life, especially when combined with its unusual shape, as in our case. In this way, the critical stenosis of the FM becomes clinically clearly manifested, and there is a loss of consciousness that can also end with a sudden death, as in our case.

Background/Aim. Myeloid-derived suppressor cells (MDSCs) suppress immune responses via a series of inhibitory mechanisms, which ultimately could lead to tumor growth. B7-H4 expression is significantly associated with poor outcome and promotion of tumor cell proliferation, invasion and migration in patients with various cancers. Data concerning B7-H4 expression in lung cancers (LC), either on tumor or immunological cells, are still sporadic. The aim was to estimate and correlate the number of CD14+B7-H4+MDSCs in blood and lung tumor microcirculation with clinical stage, histology type of tumor, tumor node metastasis (TNM) stadium, nodal status and disease outspread. Methods. The study included 44 lung cancer patients (III and IV clinical stage) and 30 healthy controls. CD14+B7-H4+ MDSC number was estimated by flow cytometry in blood and tumor microcirculation samples of each patient. Results. CD14+B7-H4+ MDSCs number was significantly higher in patients’ samples compared to controls. CD14+B7-H4+ MDSC number was significantly increased in tumor compared to blood sample of the same patient. Clinical stage III patients had the increased number of the CD14+B7-H4+ MDSC compared to stage IV, in both types of samples. According to histology, small cell lung cancer (SCLC) patients had the highest average CD14+B7-H4+ MDSCs number, significantly increased compared to patients with squamous and large cell LC histology type. Tumor size was directly associated with the number of the CD14+B7-H4+ MDSC, both in blood and tumor samples. Furthermore, nodal involvement was associated with the gradual increase of the CD14+B7-H4+ MDSC number, being the highest in the N3 group, again both in blood and tumor samples. Finally, we detected higher CD14+B7-H4+ MDSCs number in the samples of patients without metastases. Conclusion. CD14+B7-H4+ MDSCs n umber in L C patients is significantly associated with tumor histology type, lymph node involvement, disease extent degree and tumor size. Concerning their large number in LC tumor microenvironment together with immunosuppressive capacities, CD14+B7-H4+ MDSCs could represent important tumor promoting factor in LC pathophysiology.

Background/Aim. Serbia belongs to the group of countries with a high lung cancer incidence and mortality rate. p63 gene plays an important role in development of lung cancer and immunohistochemical expression of p63 is considered to be a reliable marker for squamous histology. The results of some in vitro studies show a significant association of p63 expression and cisplatin chemoresistance. The aim of this study was to estimate the significance of p63 expression as predictive and prognostic factor in advanced non-small-cell lung cancer (NSCLC). Methods. Expression of p63 in 85 NSCLC (stages III, and IV) was investigated by the use of immunohistochemistry. Four weeks after the completion of 2 cycles of platinum-based doublet chemotherapy all the patients were evaluated based on the treatment response. Kaplan-Meier analysis with log-rank tests were used for overall survival (OS) and progression free survival (PFS) calcultations. Results. The expression of p63 was present in 49.4% of the patients out of whom 38.8% were with positive expression (p63+) and 10.6% of the patients were with weak expression (p63+-). Positive expression of p63 was seen in 93.9% of squamous cell carcinomas (SQCC), 5% of adenocarcinomas (AC), and in no patient with not otherwise specified (NOS) NSCLC. Weak expression of p63 was found in 12.5% of AC, 25% of NOS and only in 3% of SQCC. Analysis of the impact of the presence of p63 expression on the initial response to chemotherapy showed no statistical significance. The patients with weak p63 expression had a significantly shorter OS than the patients with no p63 expression (p = 0.049), and the tendency of shorter OS than the patients with p63 expression (p = 0.068). Conclusion. This study shows that p63 expression has no predictive significance for tumor response to initial chemotherapy regimen gemcitabine/ cisplatin or paclitaxel/cisplatin observed in advanced NSCLC. Weak expression of p63 have a negative prognostic effect in stage III and IV NSCLC.

Background/Aim. Lung cancer is one of the most common malignant tumors. About 80% of all lung cancers are non-small cell lung cancer (NSCLC). According to histopathological characteristics, the most common types of NSCLC are squamous cell carcinoma and adenocarcinoma. The aim of this study was to evaluate the overall survival rate in the NSCLC patients initially received surgery according to its histopathological type and T – primary tumor, N –regional lymph nodes, M – distant metastasis (TNM) stages which were treated with surgical treatment, and after that, according to the TNM stage, chemotherapy protocols and/or radiation therapy. Methods. This retrospective case series study included all patients with NSCLC admitted to the Military Medical Academy in Belgrade in the period 2010–2015. A total number of selected patients was 85 (27 females and 58 males). Results. Out of 41 patients with squamous cell carcinoma, 19.5% deceased. On the other hand, in the group of patients with adenocarcinoma, 43.2% out of 44 patients deceased. The average cumulative survival was statistically significantly lower in the adenocarcinoma patients in comparison to the patients with squamous cell carcinoma (1,605.2 vs.1,304.8 days; p = 0.005). On the other hand, the average cumulative survival was statistically significantly lower in our patients in the recurrence group with adenocarcinoma in comparison to the recurrence group with squamous cell carcinoma (1,212.8 vs. 1,835.5 days; p = 0.032). Conclusion. Adenocarcinoma is more aggressive cancer in comparing to squamous cell carcinoma with lower overall survival in comparing to squamous cell carcinoma. Additional studies are needed to identify risk factors for recurrence after surgery, and to additionally explain role of tumor markers and molecular biological techniques in the progression of this kind of cancer.

Background/Aim. Bronchial asthma is a disease that is characterized by the variability of the clinical picture, physical and functional status and the existence of bronchial hypersensitivity and hyperreactivity with varying degrees. Bronchial responsiveness and sensitivity are tested in patients with clinically suspected existence of asthma and normal spirometry test. The aim of the study was to analyze the patients with atopic asthma and study test results of skin sensitization to inhaled allergens, nonspecific bronchial hyperreactivity and specific hyperreactivity estimated by bronchial provocation tests with inhalant allergens. Methods. The prospective study at the Pulmonology Clinic of the Military Medical Academy in Belgrade Serbia, during 2014, included 70 male subjects aged 18–30 years, who had perennial asthma symptoms. All subjects were nonsmokers, with normal spirometry findings, with normal radiological chest findings and with no symptoms of respiratory infection over the past two months. All respondents were tested with skin prick tests with inhalant allergens and nonspecific bronchial provocation test with histamine. On the basis of histamine test, subjects were divided into two groups: the group I, in which there was a slight degree of hypersensitivity [provocation concentration of histamine causing a 20% fall in forced expiratory volume – PC20 = 6.09 ± 1.1 mg/mL], and the group II with negative histamine test (PC20 = 14.58 ± 6.34 mg/mL). Specific bronchial provocation test was performed in all patients, and the selection of the allergens was carried out based on the results of testing of skin hypersensitivity. Results. Results of skin sensitization show the highest incidence of mites Dermatophagoides pterronissinus (83.3% group I and 85.0% group II) followed by grass pollen (53.3% group I and 52.0% group II), and house dust (33.3% group I and 50.0% group II). There were no statistically significant differences in allergens between groups (p > 0.05). In both groups, spirometry findings were within normal values [forced vital capacity – FVC and forced expiratory volume 1 – FEV1 > 80% predictive value], but statistically significant difference was found in FEV1 between groups (p < 0.05). Specific bronchial provocation tests with solutions of inhaled allergens in both groups caused a significant decline in FEV1 (≥ 20%) in all patients individually. No statistically significant differences were found neither between groups, nor between individual allergens (average decline in FEV1: Group I 32.9 ± 2.4% and group II 31.5 ± 2.2%). Conclusion. There is no relationship between the degree of specific and non-specific bronchial hyperreactivity in patients with allergic asthma.

Introduction. Pseudomesotheliomatous lung carcinoma is a special, rare entity characterized by large pleural growth and minor invasion of lung tissue. Clinically, radiologically, macroscopically and even histologically this tumor can be misdiagnosed as malignant pleural carcinoma. Case report. We represent a 64-year-old male patient, former smoker. Due to difficulties in the form of dry cough, feeling of dis-comfort and pain in the right hemithorax, fatigue, heavy breathing, sweating, fever up to 39.6°C the patient was treated as with combined antibiotic therapy (macrolides, cephalosporins and penicillin), but without improving of his condition. Chest radiography showed a shadow of pleural effusion by the height of the front end of the third right rib. Chest MSCT showed the extremely thickened pleura apically and to the posterior along the upper right lobe in addition to existence of massive pleural effusion. Subpleural condensation of parenchyma ranging about 30 mm was described in the upper right lobe. Cytological analysis of the pleural effusion showed the presence of malignant cells impossible to differentiate whether they were metastasis of adenocarcinoma or malignant pleural mesothelioma. By histochemical and immunohistohemical analyses of a pleural sample, pseudomesotheliomataus lung adenocarcinoma was diagnosed. Conclusion. Pseudomesotheliomataus carcinoma of the lungs can be a diagnostic problem. Its diagnosis is based on recognition of histopathological characteristics which enable its discernment from the epithelial variant of malignant pleural mesothelioma.

Introduction. Hereditary hemorrhagic telangiectasia (HHT) also known as Osler-Weber-Rendu syndrome is an autosomal dominant disease that occurs due to vascular dysplasia associated with the disorder in the signaling pathway of transforming growth factor β (TGF-β). The clinical consequence is a disorder of blood vessels in multiple organ systems with the existence of telangiectasia which causes dilation of capillaries and veins, are present from birth and are localized on the skin and mucosa of the mouth, respiratory, gastrointestinal and urinary tract. They can make a rupture with consequent serious bleeding that can end up with fatal outcome. Since there is a disruption of blood vessels of more than one organic system, the diagnosis is very complex and requires a multidisciplinary approach. Case report. We reported a 40-year-old female patient with a long-time evolution of problems, who was diagnosed and treated at the Clinic for Lung Diseases of the Military Medical Academy in Belgrade, Serbia, because of bilaterally pulmonary arteriovenous malformations associated with HHT. Embolization was performed in two acts, followed with normalization of clinical, radiological and functional findings with the cessation of hemoptysis, effort intolerance with a significant improvement of the quality of life. Conclusion. HHT is a rare dominant inherited multisystem disease that requires multidisciplinary approach to diagnosis and treatment. Embolization is the method of choice in the treatment of arteriovenous malformations with minor adverse effects and very satisfying therapeutic effect.

Introduction. Bronchial carcinoids belong to a rare type of lung tumors. If they do not expose outstanding neuroendocrine activity, they develop without clearly visible symptoms. They are often detected during a routine examination. According to their clinical pathological features, they are divided into typical and atypical tumors. Typical bronchial carcinoids metastasize to distant organs very rarely. Localized forms are effectively treated by surgery. The methods of conservative treatment should be applied in other cases. Case report. We presented a 65-year-old patient with carcinoid lung tumor detected by a routine examination. Additional analysis (chest X-ray, computed tomography of the chest, ultrasound of the abdomen, skeletal scintigraphy, bronhoscopy, histopathological analysis of the bioptate of bronchial tumor, as well as bronchial brushing cytology and immunohistochemical staining performed with markers specific for neuroendocrine tumor) proved a morphologically typical lung carcinoid with dissemination to the liver and skeletal system, which is very rarely found in typical carcinoids. Conclusion. The presented case with carcinoid used to be showed morphological and pathohistological characteristics of typical bronchial carcinoid. With its metastasis to the liver and skeletal system it demonstrated unusual clinical course that used to be considered as rare phenomenon. Due to its frequent asymptomatic course and varied manifestation, bronchial carcinoid could be considered as a diagnostic challenge requiring a multidisciplinary approach.

Background/Aim. The diagnosis of bronchial asthma, a chronic inflammatory disease of the respiratory tract, is made on the basis of anamnesis, pathologic auscultatory findings of the lungs, lung function disturbances, skin tests, as well as the basic indices of immunologic condition in bronchial trunk. The aim of the study was to find out correlation of objective indices of the disease and than relation with the symptoms in the patients with bronchial asthma. Methods. The study included 60 young male non smokers with long lasting symptoms of bronchial asthma including shortness of breath, wheezing, hard breathing, nonproductive or productive cough, weakness and night hard breathing. There were no symptoms of respiratory infection over the past two months and lung radiography and spirometry were normal. Based on the results of nonspecific bronchoprovocative test two groups of the patients were formed, group I (n = 30) with positive histamine test (average value of the inhaled histamine concentration with FEV1 drop by 20% in regard with the initial value (PC20) = 2.99 ± 0.51 mg/ml of histamine) and group II (n = 30) with negative histamine test (PC20(a) = 14.58 ± 6.34 mg/ml of histamine). Results. The obtained spirometry results revealed a statistically significant difference in values of FEV1 between groups: I group - FEV1 = 93.2%; II group - FEV1 = 101.8%; (p < 0.05, Wilcoxon test), although all the FEV1 values were normal. Regarding the presence of the most common symptoms there was not statistically significant difference between the groups (p > 0. 05, chisquare test). Pathologic auscultatory lung findings were found in 73.4% of the patients in the group I and 27.5% of the patients in the group II. There was statistically significant difference (p < 0.05, chi-squared test). A positive correlation between the degree of hypersensitivity and lung physical findings was confirmed (p < 0.05 Spearman's rho), but there was no correlation with FEV1 values. Conclusion. There is a correlation with lung pathologic physical findings, lower values of FEV1 (in a range of normal values) and the degree of nonspecific bronchial sensitivity as objective indices of activity of bronchial asthma. There is no correlation of these parameters with patient's symptoms as subjective indices of bronchial asthma.

Background. Dysphagia can be a serious problem in patients with inflammatory myopathies. It may be associated with nutritional deficit, aspiration pneumonia, and poor prognosis. Case report. We presented a 60-year-old male, suffering from difficulty in swallowing, pain and weaknes in the proximal parts of his extremities, and skin manifestation. Laboratory findings showed increased creatine kinase and aldolase. Antinuclear antibodies to HEP-2 subtrate revealed titer of 1:40. Electromyoneurography demonstrated evidence of a proximal myopathy. A muscle biopsy revealed myositis. The baruim swallow test was remarkable for regurgitation, and nasal emerging of barium. Nuclear magnetic resonance images of cranium was normal. Tumor markers CEA, and Ca 19-9 were increased. A dose of 1 mg daily prednisolone was administered and percutaneous enteral feeding was performed. Two months later, the patient developed febrile state, aspiration pneumonia, and died due to respiratory failure. Conclusion. In cases of dermatomyositis with the serious dysphagia, percutaneous endoscopic gastrostomy should be performed as soon as possible. Owerall survival rate is low, even with an adequate therapy administration. Inflammatory myopathies should be considered in any patient with oropharyngeal dysphagia.