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Desetogodišnjica potpisivanja Istanbulske konvencije ukazuje na promenu stava država koje su u vreme njenog nastanka bile njene najvatrenije zagovornice. Promena diskursa je rezultirala istupanjem Turske iz Konvencije, i javljanjem novih glasova u državama ukazujući na nespremnost na preduzimanje društvenih promena, pozivanjem na tradicionalne porodične i međupolne vrednosti. Šta je najveća prepreka daljem usvajanju Konvencije, i pored negativnih statistika prepreka ističe novo shvatanje roda, kao društveno definisane kategorije, što ipak u velikoj meri utiče na opšteprihvaćene tradicionalne društvene vrednosti. Polazeći od kratkog prikaza Istanbulske konvencije i u pogledu rodno zasnovanog nasilja i porodičnog nasilja? U radu se, kao najveća načina regulisanja rodno zasnovanog nasilja u istoj, centralni segment rad odnosi na analizu pojma roda u Konvenciji. Ističući novo shvatanje roda kao društvene kategorije, a u vezi sa statističkim podacima iznetim u uvodnom delu, u radu je upravo taj segment Konvenije opredeljen kao problematičan sa aspekta šire implementacije. Cilj ovog rada jeste osvetljavanje mogućnosti za ostvarivanja ciljeva Konvencije u svetlu (ne)spremnosti za promenu društvenog tradicionalnog diskursa.

Background/Aim. Thymoma is the most common mediastinal tumor. The treatment procedures are based on the results from the research of retrospective studies because they are not frequent tumors. The aim of this work was to define common clinical features, therapeutic aspects, survival and recurrence free survival. Methods. This study was performed in the Clinic for Pulmonology, Clinical Centre of Serbia, Belgrade from January 1993 to December 2013. We analyzed 62 patients with histopathologically proven thymoma. The results were obtaind from medical history, physical exam, chest X-ray and/or computed tomography and operational findings or diagnostic procedure reports. Thymomas were clasiffied according to the World Health Organization classifying system, based on histopathological findings, and staged according to the Masaoka-Koga staging system. Results. There were more female (54.8%) patients. Patients were mostly in the seventh decade of life. One third (29%) of the patients were asymptomatic. Cough was the dominant symptom. Myasthenia gravis was the most common paraneoplastic syndrome (12.9%). Solitary tumor was the most common in our patients (61.3%), as well as the tumors larger than 5 cm (52.5%), and noninvasive thymomas (52.5%). The majority of patients (40%) were in the stage I of the disease. The operative approach was conducted in most of the patients (88.7%). A statistically significant difference in survival was in women, patients with solitary tumor, non-invasive thymomas, patients in the stage I of the disease, and those who were operated. The dimension of the tumor mass approached the conventional level of significance. Conclusion. In patients with thymomas, statistically significant survival rate predictors are gender, presence of solitary tumor mass, tumor invasiveness, clinical stage and surgical treatment of the disease.

Introduction. Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm. This disease, of unknown etiology, runs an unpredictable course. Its definitive diagnosis calls for a detailed histopathological analysis including immunohistochemistry. Microscopically, IMT is composed of myofibroblastic spindle and inflammatory cells in different proportions. It presents infrequently in adults with nonspecific symptomatology. The presence of IMT is described in every anatomical region but the tracheal one is especially uncommon. Case report. A 41- year-old female patient checked into our institution due to exacerbation of asthma-like symptoms such as shortness of breath, cough and exertion intolerance. She was originally treated as the asthmatic patient with the bronchodilator therapy with no success. Chest x-ray done during one of the outpatient follow-up appointments pointed to a suspected change in the tracheal distal part. After her admission to our institution, the following diagnostic procedures were performed: spirometry, chest computed tomography (CT) scan, chest magnetic resonance imaging (MRI) and bronchoscopy and the change in tracheal distal third was confirmed. Right-sided thoracotomy with mobilization of lung, tracheal resection and termino-terminal (T-T) anastomosis was undertaken. Subsequent histopathological analysis of surgically removed afflicted tracheal part of them trachea including immunohistochemistry enabled us to definitively of diagnose IMT. Four years after surgical resection, the patient showed no recidivism of illness. Conclusion. Definitive IMT diagnosis requires the detailed diagnostic tests, most importantly, an adequate histopathological analysis including immunohistochemistry. Complete surgical resection is the treatment of choice in case of IMT. Further monitoring of patients is necessary due to a risk of recurrence.

Lymphangioleiomyomatosis (LAM) is a rare disease that most commonly affects women of reproductive age. The disease is manifested by diffuse destruction of the pulmonary parenchyma with the formation of cysts on a characteristic finding of multidetector computerized tomography (MD-CT) of the chest. It is thought that the presence of cells with estrogen and progesterone receptors among proliferating smooth muscle cells lead to the spread of cystic structures lined by endothelial cells. Towards the end of pregnancy and after childbirth, collapse of the lung parenchyma or rupture of the cyst wall occurs causing a dramatic clinical picture in the form of pneumothorax. Sirolimus is the only drug of choice that should improve and stabilize the patient’s pulmonary function and quality of life. Unfortunately, this drug is not always effective enough, so only option for treatment is bilateral lung transplantation. The authors present the patient in the last trimester of pregnancy who was admitted to the hospital with clinical picture of bilateral spontaneous pneumothorax. Dramatic picture of pneumothorax could not be solved solely by drainage in which atypical segmental resection of the lung was performed within a few days so on these samples lymphangioleiomyomatosis were diagnosed.

Recent studies suggest that rare variants exhibit stronger effect sizes and might play a crucial role in the etiology of lung cancers (LC). Whole exome plus targeted sequencing of germline DNA was performed on 1045 LC cases and 885 controls in the discovery set. To unveil the inherited causal variants, we focused on rare and predicted deleterious variants and small indels enriched in cases or controls. Promising candidates were further validated in a series of 26,803 LCs and 555,107 controls. During discovery, we identified 25 rare deleterious variants associated with LC susceptibility, including 13 reported in ClinVar. Of the five validated candidates, we discovered two pathogenic variants in known LC susceptibility loci, ATM p.V2716A (Odds Ratio [OR] 19.55, 95%CI 5.04–75.6) and MPZL2 p.I24M frameshift deletion (OR 3.88, 95%CI 1.71–8.8); and three in novel LC susceptibility genes, POMC c.*28delT at 3′ UTR (OR 4.33, 95%CI 2.03–9.24), STAU2 p.N364M frameshift deletion (OR 4.48, 95%CI 1.73–11.55), and MLNR p.Q334V frameshift deletion (OR 2.69, 95%CI 1.33–5.43). The potential cancer-promoting role of selected candidate genes and variants was further supported by endogenous DNA damage assays. Our analyses led to the identification of new rare deleterious variants with LC susceptibility. However, in-depth mechanistic studies are still needed to evaluate the pathogenic effects of these specific alleles.

Benign epithelial tumors of the lung are uncommon and can represent a diagnostic challenge. Herein, we describe one such emblematic case. A 59-year-old former smoker male was admitted to the hospital complaining of cough for a long time. A radiological examination showed a centrally excavated mass strictly connected to the visceral pleura. The patient underwent tumorectomy. At gross examination, the tumor was composed of solid and cystic areas containing clear liquid. Histological examination highlighted a sub-pleural encapsulated tumor, with foci of capsular invasion, characterized by a single layer of columnar and cuboidal epithelial cells lining moderately cellular fibro-vascular cores. A wide spectrum of immunohistochemical markers was performed. The final diagnosis was suggestive of a peripheral pulmonary papillary tumor of undetermined malignant potential. At the last follow-up, six years after surgery, no recurrence or metastases were described. Reporting this case, we would like to point out the existence of these rare entities that should be taken into account in the diagnostic process, thus avoiding potential misdiagnosis. Moreover, the presence of capsular invasion should be better investigated in order to reconsider the exact terminology of the tumor and the classification of its malignant potential.

IntroductionThymomas and thymic carcinoma (TC) are the most common neoplasms localised in the thymus. These diseases are poorly understood, but progress made in next-generation sequencing (NGS) technology has provided novel data on their molecular pathology.Material and methodsGenomic DNA was isolated from formalin-fixed paraffin-embedded tumour tissue. We investigated somatic variants in 35 thymoma patients using amplicon-based TruSeq Amplicon Cancer Panel (TSACP) that covers 48 cancer related genes. We also analysed three samples from healthy individuals by TSACP platform and 32 healthy controls using exome sequencing.ResultsThe total number of detected variants was 4447, out of which 2906 were in the coding region (median per patient 83, range: 2-300) and 1541 were in the non-coding area (median per patient 44, range: 0-172). We identified four genes, APC, ATM, ERBB4, and SMAD4, having more than 100 protein-changing variants. Additionally, more than 70% of the analysed cases harboured protein-changing variants in SMAD4, APC, ATM, PTEN, KDR, and TP53. Moreover, this study revealed 168 recurrent variants, out of which 15 were shown to be pathogenic. Comparison to controls revealed that the variants we reported in this study were somatic thymoma-specific variants. Additionally, we found that the presence of variants in SMAD4 gene predicted shorter overall survival in thymoma patients.ConclusionsThe most frequently mutated genes in thymoma samples analysed in this study belong to the EGFR, ATM, and TP53 signalling pathways, regulating cell cycle check points, gene expression, and apoptosis. The results of our study complement the knowledge of thymoma molecular pathogenesis.

Background In spite of the progress made in neoadjuvant therapy for operable non small-cell lung cancer (NSCLC), many issues remain unsolved, especially in locally advanced stage IIIA. Methods Retrospective data of 163 patients diagnosed with stage IIIA NSCLC after surgery was analyzed. The patients were divided into two groups: a preoperative chemotherapy group including 59 patients who received platinum-etoposide doublet treatment before surgery, and an upfront surgery group including 104 patients for whom surgical resection was the first treatment step. Adjuvant chemotherapy or/and radiotherapy was administered to 139 patients (85.3%), while 24 patients (14.7%) were followed-up only. Results The rate of N2 disease was significantly higher in the upfront surgery group ( P 0.05). Conclusion There was significant difference in preoperative chemotherapy group regarding relapse rate and treatment outcomes related to the lymph node status comparing to the upfront surgery group. Neoadjuvant/adjuvant chemo-therapy is a part of treatment for patients with stage IIIA NSCLC, but further investigation is required to determine optimal treatment.

Neuroendocrine lung tumors (NET) include typical carcinoids (TC), atypical carcinoids (AC), large cell NE carcinoma (LCNEC) and small-cell carcinoma (SCLC), with different clinicopathological profiles and relative grades of malignancy. Although differences between carcinoids and high grade carcinomas are recognized, precise differences and behavior of TC and AC have not been clearly defined. The aim of this study was to better define the differences in the clinical behavior of TC and AC, and to establish new prognostic factors of overall survival (OS), by determining the levels of genetic expression of IGF1R, ERCC1, Bax, p53, Bcl2 and Bcl2/Bax ratio.The histopathological diagnosis of 52 surgically resected pulmonary carcinoid tumors was made according to the WHO classification. Gene expressions were evaluated by quantitative real-time PCR.The confirmed prognostic factors for overall survival (OS) were pTNM T (p0.01), pTNM N (p0.05), clinical stage (p0.05), type of surgery (p0.01) and histopathological (HP) tumor type (p0.05). Bcl2 mRNA level and Bcl2/Bax ratio were found to have a potential for discrimination of the HP type of tumor (AC vs TC, Receiver Operating Characteristics (ROC) cut-off values 0.1451 and 0.3015, respectively), but without statistically significant impact on OS.In patients with NETs, smaller primary tumor, absence of positive lymph nodes, and TC type of tumor predicted longer OS. Type of resection has influence on OS. Bcl2 expression and Bcl2/Bax ratio might be valuable as independent diagnostic parametars in lung carcinoids. Therapeutic approaches using attenuation of Bcl2 or upregulation of Bax might prove useful in lung NETs.

Prognostic significance of immune microenvironment has been emphasized using the most advanced analysis, with consecutive attempts to reveal prognostic impact of this findings. The aim of this study was to compare and define prognostic significance of clinical parameters, microvessel density (MVD) in tumour tissue and expression of CD44s as adhesive molecule on tumour cells in diffuse large B cell lymphoma-DLBCL, primary central nervous system DLBCL-CNS DLBCL and follicular lymphoma-FL. A total of 202 histopathological samples (115 DLBCL/65 FL/22 CNS DLBCL) were evaluated. Overall response (complete/partial remission) was achieved in 81.3 % DLBCL patients, 81.8 % primary CNS DLBCL and 92.3 % FL. Absolute lymphocyte count-ALC/Absolute monocyte count-AMC2.6 in DLBCL and ALC/AMC ≥ 4.7 in FL were associated with better event-free survival (EFS) and overall survival (OS) (p 0.05). In DLBCL, MVD 42 blood vessels/0.36 mm(2) correlated with primary resistant disease (p 0.0001), poorer EFS and OS (p = 0.014). High CD44s expression in FL correlated with inferior EFS and OS (p 0.01). In DLBCL, multivariate Cox regression analysis showed that ALC/AMC was independent parameter that affected OS (HR 3.27, 95 % CI 1.51-7.09, p = 0.003) along with the NCCN-IPI (HR 1.39, 95 % CI 1.08-1.79, p = 0.01). Furthermore, in FL, ALC/AMC mostly influenced OS (HR 5.21, 95 % CI 1.17-23.21, p = 0.03), followed with the FLIPI (HR 3.98, 95 % CI 1.06-14.95, p = 0.041). In DLBCL and FL, ALC/AMC is simple and robust tool that is, with current prognostic scores, able to define long-term survival and identify patients with inferior outcome. The introduction of immunochemotherapy might altered the prognostic significance of microenvionmental biomarkers (MVD and CD44s).

Background Idiopathic Pulmonary Fibrosis (IPF) is a lethal lung disease of unknown etiology. A major limitation in transcriptomic profiling of lung tissue in IPF has been a dependence on snap-frozen fresh tissues (FF). In this project we sought to determine whether genome scale transcript profiling using RNA Sequencing (RNA-Seq) could be applied to archived Formalin-Fixed Paraffin-Embedded (FFPE) IPF tissues. Results We isolated total RNA from 7 IPF and 5 control FFPE lung tissues and performed 50 base pair paired-end sequencing on Illumina 2000 HiSeq. TopHat2 was used to map sequencing reads to the human genome. On average ~62 million reads (53.4% of ~116 million reads) were mapped per sample. 4,131 genes were differentially expressed between IPF and controls (1,920 increased and 2,211 decreased (FDR

Background In spite of the progress made in neoadjuvant therapy for operable non small‐cell lung cancer (NSCLC), many issues remain unsolved, especially in locally advanced stage IIIA. Methods Retrospective data of 163 patients diagnosed with stage IIIA NSCLC after surgery was analyzed. The patients were divided into two groups: a preoperative chemotherapy group including 59 patients who received platinum‐etoposide doublet treatment before surgery, and an upfront surgery group including 104 patients for whom surgical resection was the first treatment step. Adjuvant chemotherapy or/and radiotherapy was administered to 139 patients (85.3%), while 24 patients (14.7%) were followed‐up only. Results The rate of N2 disease was significantly higher in the upfront surgery group (P < 0.001). The one‐year relapse rate was 49.5% in the preoperative chemotherapy group compared to 65.4% in the upfront surgery group. There was a significant difference in relapse rate in relation to adjuvant chemotheraphy treatment (P = 0.007). The probability of relapse was equal whether radiotherapy was applied or not (P = 0.142). There was no statistically significant difference in two‐year mortality (P = 0.577). The median survival duration after two years of follow‐up was 19.6 months in the preoperative chemotherapy group versus 18.8 months in the upfront surgery group (P = 0.608 > 0.05). Conclusion There was significant difference in preoperative chemotherapy group regarding relapse rate and treatment outcomes related to the lymph node status comparing to the upfront surgery group. Neoadjuvant/adjuvant chemo‐therapy is a part of treatment for patients with stage IIIA NSCLC, but further investigation is required to determine optimal treatment.

Introduction. Langerhans cell histiocytosis encompasses a group of disorders of unknown origin with different clinical presentations and outcomes. It is characterized by infiltration of the involved tissues by large numbers of Langerhans cells, often organized into granulomas. The accumulation of these cells causes the classic lytic bone lesions, skin rashes, lymphadenopathy, splenomegaly, and dysfunction of organ such as the pituitary gland, lungs, liver, and bone marrow. Pulmonary histiocytosis. Adult pulmonary Langerhans cell histiocytosis is a rare disorder of unknown etiology. It occurs predominantly in male smokers, with an incidence peak between 20 and 40 years of age. High-resolution computed tomography of the chest can show nodules, cavitated nodules, and thickand thin-walled cysts. The definite diagnosis of pulmonary Langerhans cell histiocytosis requires identification of Langerhans? cell granulomas infiltrating and destroying distal bronchioles, which is usually achieved by lung biopsy at a site selected by chest high-resolution computed tomography. Treatment. Treatment options for adults have never been clarified by a clinical trial. The published literature provides minimal data on the comparative efficacy of various treatment options which include surgery/curettage, steroids, radiation, and various chemotherapy regimens. The improved understanding of the mechanisms involved in the pathogenesis of pulmonary Langerhans cell histiocytosis should help in the development of specific therapeutic strategies and effective treatment.

Background: in carcinoid tumours, the need for refinement of pathological classification, influence of the carcinoid syndrome in N1 disease and the role of adjuvant treatment are still controversial. Methods: retrospective study including patients who underwent a lung resection for bronchial carcinoid tumours in a recent 10-years period. Results: a total of 52 patients (typical - group 1 and atypical - group 2) with 26 patients each, underwent a lung resection for lung carcinoid tumours, representing around 2.5% of patients operated for malignant lung tumours. The M:F for typical and atypical subtypes was 1.14 and 1.16: 1, respectively. The patient distribution within age intervals of 50 years for typical carcinoids was 19.3, 30.7 and 50%, respectively; for atypical carcinoids, it was 7.7, 34.6 and 57.7%, respectively (P Conclusion: there are some differences between typical and atypical carcinoids whose prognostic significance needs to be assessed on bigger patient populations.

Nonspecific interstitial pneumonia (NSIP) is often associated with connective tissue diseases (CTD). The diagnosis of NSIP was confirmed in a 63-year-old man by high-resolution computed tomography and an open lung biopsy. Anti-Golgi complex autoantibodies (AGA) and anti-Ro52 antibodies were simultaneously detected at high concentrations. Autoantibodies to aminoacyl-tRNA synthetases (ARS) were negative. The patient was treated with corticosteroids for six months. During the seven-year follow-up, NSIP had a slow progression and patient had not developed the clinical features of CTD. The present study potentially demonstrates that the autoimmune process elicited by AGA and/or Ro/SSA may play a role in promoting idiopathic NSIP independently of the typical ARS routes, which has not been reported thus far.

Although international organizations as subjects of international law are obliged to respect fundamental human rights in their acting, a very small number of them are contracting parties to international instruments for human rights protection, unlike their member states, which are contracting parties to many of them. As international organizations take more and more activities that can and often result in violation of human rights there is an obvious problem to what forum victims of those violations can turn to for determining responsibility of the international organization. The European Court of Human Rights and the European Court of Justice have developed through their practices modalities for indirect control of acts of international organizations by controlling the acts of their member states, which result from their duties as members of those organizations. The paper assumes that such control is efficient and that it fills the void in the international system of determining responsibility for violation of human rights through acts of international organizations according to which, the states basically keep on being responsible for violation of human rights.

Background For patients with two or more primary cancers a correct diagnosis is critically important because prognosis and treatment vary considerably between multiple primary cancers and metastatic disease. Case report Two bilateral synchronous primary lung malignancies of different histological types were diagnosed and immunohistochemically confirmed in a 60-year-old woman. In biopsy specimens of the right lung pure squamous cell carcinoma was detected (stage IIIa). The tumor expressed AE1/AE3, cytokeratin 5 and 34βE12. In biopsy specimens of the left lung small cell carcinoma was detected (stage IIIa). The small cells expressed synaptophysin, chromogranin A and CD56. DNA was extracted from paraffin-embedded tissue of both tumors. Exons 5–9 of the TP53 gene were examined for genetic mutations by polymerase chain reaction and DNA sequencing analysis. Direct sequencing of DNA isolated from the small cell carcinoma revealed a TGC to TTC mutation at codon 404 of TP53 exon 5. In DNA isolated from the squamous cell carcinoma no TP53 mutation was found. The tumors' different response to chemotherapy also suggested that they belonged to different histological types. The patient lived 24 months after the diagnosis, which is more typical for stage III than for stage IV lung carcinoma. Conclusion Discrimination of synchronous primary lung cancers from intrapulmonary metastases based only on clinical findings can be very difficult. Multidisciplinary diagnostic evaluation is therefore very helpful in cases like this, because a correct diagnosis will determine the best treatment for the patient and consequently a better prognosis.

The inactivation of p53 and PTEN tumor suppressor genes is a common genetic event in lung cancer. However, data on the effect of the joint inactivation of tumor-suppressor genes in non-small cell lung carcinoma (NSCLC) are lacking. The purpose of this study was to investigate the alterations in PTEN and p53 genes, as well as to evaluate their mutual role in NSCLC pathogenesis and their impact on survival rate. To that end, polymerase chain reaction single-strand conformational polymorphism (PCR-SSCP), sequencing, methylation-specific PCR, and fragment analysis were used. The results obtained were correlated with clinicopathologic parameters, the level of genomic instability, and patient survival. Overall, 13% of specimens had aberrant p53 only, 13% had inactive PTEN only, and 50% of samples had both genes altered. Correlation analyses showed that the mutual inactivation of p53 and PTEN was a frequent event that was associated significantly with the increased level of genomic instability and lymph node invasion implying their synergistic effect in promoting metastatic phenotype of this kind of cancer. In addition, our results revealed a significant association of joint alterations of these genes with dramatically shortened survival indicating that aberrant p53 and PTEN could be used as an adverse prognostic factor for NSCLC patients' outcome. Our findings established the relevance of the combinatorial inactivation of p53 and PTEN in NSCLC progression and identified a subgroup of patients with a particularly aggressive disease.

Introduction. Sarcoidosis is a multisystem, granulomatous disease of unknown etiology. Sarcoid granulomas appear as immunological response to a particular but still unknown agent of the human body. Objective. The main purpose of this study was to point out the important fact that the exact diagnosis of sarcoidosis must be estimated by clinical and pathological correlation, and team cooperation between the clinician and the pathologist. Methods. Of 751 patients referred with the suspected diagnosis of sarcoidosis, from 1995 to1999, 663 (431 female and 232 male) were analyzed and confirmed as having sarcoidosis stage I-III based on biopsy findings obtained by bronchoscopy, open lung biopsy, skin biopsy, liver biopsy or splenectomy. Results. Diagnosis of sarcoidosis was made in 663 patients, 431 females and 232 males (ratio 1.9:1). The average age of patients varied from 16 to 67 years, with those below age 50 years being predominant (78.4%). The highest number of patients was diagnosed in stage I of lung sarcoidosis (81.7%). Sarcoidosis was the most common cause of hilar and mediastinal lymphadenopathy (72.2%). Conclusion. Biopsy is a necessary diagnostic procedure for pathological diagnosis of sarcoid granu- loma before treatment even in patients where clinical, radiological, biochemical and immunological tests imply the diagnosis of sarcoidosis.

Lung cancer is the most common cause of neoplasia-related death worldwide. One of the crucial early events in carcinogenesis is the induction of genomic instability and mutator phenotype. We investigated genomic instability in 30 patients with non-small-cell lung cancer (NSCLC) by comparing DNA fingerprints of paired tumor and normal tissues using arbitrarily primed polymerase chain reaction (AP-PCR). Selected 21 DNA bands with altered mobility were isolated from polyacrylamide gels, cloned and sequenced. Obtained sequences were submitted to homology search in GenBank database which revealed the following genes: TSPAN14, CDH12, RDH10, CYP4Z1, KIR, E2F4, PHACTR3, PHF20, PRAME family member and SLC2A13. Following the identification of these genes we examined their relation to the clinicopathological parameters and survival of the patients. Our study revealed that genetic alterations of TSPAN14, SLC2A13 and PHF20 appeared prevalently in tumors of grade 1, stage I suggesting that structural changes of these genes could play a role in NSCLC promotion. Contrary to this CYP4Z1, KIR and RDH10 were prevalently mutated in tumors of grade 3, stage III suggesting that they could play a role in NSCLC progression. E2F4, PHACTR3, PRAME family member and CDH12 most probably play important role in NSCLC geneses. In conclusion, our study revealed altered genes previously not described in regard to this type of cancer.

We reported the first case of inoperative thymic adenocarcinoma successfully palliative treated by the double-stent procedure. In a patient who expressed stridor, computed tomography was done and necrotic mediastinal mass, which protrudes into a trachea, was demonstrated. Fiberoptic bronchoscopy showed tracheal infiltration and 70% stenosis; therefore, surgical resection was inapplicable. Recanalization with repeated argon plasma coagulation and debridement of necrotic mass was performed, followed by placement of the endotracheal stent, radiotherapy, and chemotherapy. After 1 year, the patient developed gastric aspiration and tracheoesophageal fistula; therefore, the esophageal stent was placed. The outcome was lethal, but the placement of endotracheal stent significantly increased a length of survival for the patient with invasive thymic adenocarcinoma.

UNLABELLED Patients with advanced non-small cell lung cancer (NSCLC) usually undergo toxic treatment (chemotherapy and/or radiotherapy). They can experience devastating effects of illness and therapies on their psychological and emotional well-being. On the other hand, untreated psychological distress is associated with reduced quality of life and inadequate palliation of physical symptoms. In order to estimate frequency of anxiety and depressive symptoms and influence of demographic, socioeconomic and clinical factors on psychological well-being, we performed this cross-sectional study in group of 100 patients with advanced stage of disease. Symptoms of anxiety and depression were assessed using the Hamilton Anxiety Rating Scale (HARS) and Hamilton Depression Rating scale (HDRS). Health-related quality of life data are obtained by EORTC QLC C30 and SF 36. Patients with poor performance status (PS) experienced significantly more anxiety and depressive symptoms (p=0.001) and worse emotional (p=0.001) and mental functioning (p=0.001). Treated patients had significantly better mental (p=0.011) and emotional (p=0.001) functioning in compared to newly diagnosed ones. Somewhat unusual, unemployed participants reported significantly less anxiety (p=0.029) and depressive (p=0.002) symptoms, better mental (p=0.030) and emotional functioning (p=0.007). Additionally, nausea and vomiting adversely affected mental health and emotional functioning and correlated significantly positively with HARS and HDRS scores. Our findings suggest significant impact of some disease-related factors (PS, active treatment) and treatment-related factors (chemotherapy -induced nausea and vomiting) on psychological well-being of patients with advanced NSCLC. This should be taking an account when appropriate interventions are planned. KEYWORDS lung cancer, anxiety, depression, quality of life, chemotherapy, chemotherapy-induced nausea and vomiting.

Acquired pure red-cell aplasia (PRCA) is an uncommon disorder of erythrocytopoiesis that can develop in association with thymic tumors. We present the very rare case of a severely anemic 62-year-old man with PRCA and a concurrent neuroendocrine carcinoid tumor of the thymus. The anterior mediastinal thymus tumor was completely excised, and following histological and immunohistochemical analyses (showing positive staining for cytokeratin, chromogranin A, synaptophysin, and neuron-specific enolase) the diagnosis of a (grade I; T(1)N(0)M(0)) typical carcinoid tumor of the thymus was made. Postoperatively the anemia persisted despite no signs of residual tumor on CT chest. A hematological work up found: normocellularity with

The Prothrombin Factor II G20210A Mutation with Pulmonary Thromboembolism and a Normal Level of Fibrin Degradation ProductsDiagnosis of pulmonary thromboembolism (PTE) usually includes clinical pretest probability assessment, testing for specific degradation products of cross-linked fibrin (D-dimer) and imaging studies. Patients with radiological findings attributable to pulmonary infarction and normal D-dimer level, may present a diagnostic and therapeutic challenge. A 37-year-old Caucasian female had episodes of hemoptysis, and bilateral pulmonary nodular infiltrates on chest radiograph and computerized tomography. The plasma D-dimer level was normal, perfusion lung scan was not conclusive and histological examination of an open lung biopsy revealed recent thrombotic pulmonary infarction. She deteriorated and more perfusion defects were detected on perfusion lung scan. Genetic analysis revealed her to be a carrier of the prothrombin factor II (FII) G20210A mutation.

The patient suffered loss of consciousness, dysarthria and right sided hemiparesis. The CT scan and MRI scans were negative. These findings are more in keeping with a diagnosis of Transient Ischemic Attack (TIA) or mild CVA. Hypoglycemia per se does not usually cause hemiparesis. The blood glucose level was low but I am not sure if one can conclude that hypoglycemia caused the above noted neurological signs and symptoms. The authors do not present any data to prove that this patient had "hypoglycemic coma".

In the present study, we used DNA profiling to measure genomic instability in 22 patients with non-small cell lung cancer (NSCLC). Genomic instability was correlated with gender, the age of the patients at the time of diagnosis, the NSCLC subtype, histological grade and stage of the tumor, necrosis presence in the tumor and lymph node invasion. Genomic instability was significantly higher in patients older than 50 and those with adenocarcinoma compared to squamous-cell carcinoma. Most importantly, genomic instability significantly decreased as the tumor grade increased. Extensive genomic instability in the early carcinogenesis could be the prerequisite for NSCLC progression.

INTRODUCTION Castleman disease was for the first time described in 1956 as a mediastinal tumour mass. Etiology of this disease is still unknown. The disease can be solitary and multicentric or rarely of a mixed type. The former is often of hyaline vascular type, while the latter is of plasma cell type. CASE REPORT Castleman disease was diagnosed in a 26-year old male patient when a well defined shadow was incidentally detected in the middle lobe of the right lung. A year before, he was diagnosed with allergic rhinitis to Ambrosia. Two years after surgery the patient was feeling well, and was without any recurrence, however, allergic rhinitis still persisted. CONCLUSION Castleman disease can occur in any organ containing lymph tissues. Most frequently the disease is described as mediastinal, rarely as an intrapulmonary tumorous mass, and it is most frequently seen in younger persons. The solitary type of Castleman disease is surgical treatable with a prospect of good prognosis, while the multicentric and mixed types recur despite treatment with cortisone, irradiation and cytostatics. As the association between Castleman disease and allergic diseases has not been confirmed up-tonow, it could be concluded that this patient suffered from two separated diseases.

Objective: To demonstrate the diagnostic challenge of tracheal hamartoma in a patient with chronic obstructive pulmonary disease (COPD). Clinical Presentation and Intervention: A 65-year-old man with COPD was admitted with sudden onset of asphyxia attacks related to the position of his body. Computerized tomography (CT) of the neck showed a soft tissue mass with calcification, which occluded more than two-thirds of the proximal part of the trachea. The tumor was completely removed, and histopathology confirmed hamartoma. Conclusion: This case report showed the detection of a primary tracheal tumor on CT. This finding enabled the correct diagnosis and led to appropriate treatment in the form of surgery.

The aim of the study was to assess the expression and significance of HER2 and HER3, and Ile/Val single nucleotide polymorphism (SNP) of HER2 in lung cancer patients. Thirty seven cases of lung cancer were investigated immunohistochemically for HER2 and HER3 expression. PCR followed by restriction fragment length polymorphism (RFLP) was used to analyze the presence of HER-2 SNP at codon 655 in 20 samples. The results were compared with clinical and pathological parameters of investigated patients. We found that 100 % of the cases were negative for HER2, 29.7 % were with moderate or strong HER3 expression and 70.3 % of the tumors—without or with low expression for HER3. Lymph node metastasis were found in 40 % of HER3 positive cases (χ2 = 4.752; p = 0.029). Moderately-differentiated tumors do not express neither of investigated markers (χ2 = 6.719; p = 0.035). HER2 RFLP—PCR analysis showed genotype AG in five patients (25 %) and the rest of 15 cases (75 %) had АА (Ile/Ile) genotype. Patients with metastasis had genotype АА (Ile/Ile) in 80 % and genotype AG (Ile/Val) in 20 % (χ2 = 2.857; p = 0.091). Our results indicate that SNP in HER2 codon 655 and investigation of HER2 and HER3 expression could be helpful to outline the prognosis for patients with lung adenocarcinoma.

Primary lung enteric adenocarcinoma is a rare type of invasive lung carcinoma. Its morphology and immunohistochemistry are those of colorectal carcinoma, but there is no associated primary colorectal carcinoma. The present study describes the case of a 53-year-old female who presented with an irritating cough and a mass around the right sternoclavicular joint. Comprehensive evaluation revealed involvement of the mediastinum, lungs, right sternoclavicular joint and right kidney. Biopsies from the mediastinal and right sternoclavicular joint tumors showed features of adenocarcinoma. Immunohistochemistry was positive for cytokeratin (CK)20 and caudal type homeobox transcription factor 2, and negative for CK7, thyroid transcription factor-1 and napsin A. Genotypic analysis identified the expression of wild-type epidermal growth factor receptor, Kirsten rat sarcoma viral oncogene homolog, serine/threonine-protein kinase B-Raf and UDP-glucuronosyltransferase 1-1. There was no expression of echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase and a moderate expression of excision repair cross-complementation group 1, ribonucleoside-diphosphate reductase large subunit and tubulin β-3 chain. A strong expression of thymidylate synthase and 677TC genotype expression of methylenetetrahydrofolate reductase was observed. Gastroscopy, enteroscopy, colorectal colonoscopy and positron emission tomography-computed tomography failed to find evidence of a gastrointestinal malignancy and primary lung enteric adenocarcinoma was diagnosed. The presence of multiple metastases did not permit curative surgery. The patient was treated with 3 monthly cycles of the XELOX chemotherapy regimen; the response was poor with progression of supraclavicular lesions. Treatment was switched to the TP regimen for 4 monthly cycles, which resulted in a significant reduction in the size of the lung lesions; however, the supraclavicular lesion responded poorly to the treatment. The patient then received 2 cycles of the FOLFIRI regimen; however, the lung and right supraclavicular lesions progressed, causing increased right upper limb pain. The pain was alleviated by palliative surgery. Following surgery, the DP regimen was employed. Follow-up of the patient remains ongoing. The present findings suggest that the early diagnosis and treatment of primary lung enteric adenocarcinoma is likely to improve patient outcome.

Introduction Clinical studies indicate involvement of the liver and spleen in approximately 20-30% of patients affected with sarcoidosis and their detection should be based on a standardized diagnostic procedure. Diagnostic procedures Ultrasonography is a reliable and safe method to assess changes related to size and structure of the affected organs that are pathognomonic for sarcoidosis. Further evaluation may include computerized tomography or magnetic resonance, while percutaneous needle aspiration biopsy or laparoscopy may also be applied when indicated. The most important criterion used for final diagnosis is pathohistological evidence of epithelioid noncaseating granuloma in bioptic material along with already established sarcoidosis of the lungs or some other organ. Material and methods The study on the incidence of liver and spleen sarcoidosis included a group of 130 patients affected with sarcoidosis hospitalized at the Institute of Pulmonary Diseases and Tuberculosis, Clinical Center of Serbia, over the period 2002-2003. Results The analysis evidenced that 31.5% of sarcoidosis patients had pathognomonic echographic findings of abdominal organs: splenomegaly (13%), hepatomegaly (10.8%) and hepatosplenomegaly (7.7%). Three patients underwent surgical treatment of liver and spleen sarcoidosis. Conclusion Pathognomonic findings of liver and spleen sarcoidosis were evidenced in approximately one third of sarcoidosis cases and they represented a significant parameter for further therapy, particularly in chronic patients.

Lung cancer is the most common cause of neoplasia-related death worldwide. Accounting for approximately 80\% of all lung carcinomas, the non-small cell lung carcinoma (NSCLC) is the most common clinical form with its two predominant histological types, adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Although surgical resection is the most favorable treatment for patients with NSCLC, relapse is still high, so neoadjuvant chemotherapy (NAC) is an accepted treatment modality. In this study we examined whether some of the key molecules associated with the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signaling pathways could have predictive and prognostic value for the NAC application. To that end we examined the expression status of PTEN, pAKT, pERK and loss of heterozygosity (LOH) of PTEN in two groups of NSCLC patients, those who received and those who did not receive NAG LOH PTEN and low pERK expression is shown to be correlated with the longest survival of patients with SCC and ADC, respectively, who received NAC. These results point that the application of NAC is beneficial in the NSCLC patients with specific molecular alterations which could further help to improve constant search for the druggable molecular targets used in personalized therapy. (C) 2014 Elsevier Inc. All rights reserved. Ministry of Education, Science and Technological Development of the Republic of Serbia {[}III41031]

Introduction: Differentiation between adenocarcinoma of the lung (LADC) from the other non-small cell lung carcinoma (NSCLC) is possible by immunohistochemistry. When diagnosis of LADC is established, the rest of lung cancer tissue could be used for molecular testings, particularly EGFR analysis Aim: To evaluate 4 antibodies TTF-1, Napsin-A, Cytokeratin7 and Surfactant B in diagnosis of LADC. Materialsand Methods: Fifty small-sized samples, obtained upon bronchoscopy or transthoracic fine-needle lung biopsy, were included in this study. Diagnosis of LADC was performed after routine hematoxylin-eosin examination and TTF-1, Napsin-A, Surfactant B and Cytokeratin7 immunohistochemistry. Descriptive statistical method (%) was used in the study. Results: Cytokeratin7 was expressed in 90% (45/50), than TTF-1-86% (43/50) and Napsin-A - 82% (41/50) and Surfactant B in 6% (28/50) in LADCs. Conclusion: TTF-1 is the most useful for diagnosis of LADC and Napsin-A in cases where TTF-1 is not expressed. Cytokeratin7 is useful in differentiation from digestive adenocarcinoma and Surfactant B in cases where TTF-1 and Napsin-A, individually or both are not expressed.

An association between sarcoidosis and lymphoproliferative diseases (LD), the sarcoidosis-lymphoma syndrome, has been previously described, and may be attributed to the underlying immunological abnormalities that occur during the sarcoidosis disease process. We report two patients who developed Hodgkin's disease and diffuse large B-cell non-Hodgkin's lymphoma (NHL) subsequent to their diagnosis of sarcoidosis after latency periods of 6 years and 18 years respectively. Both patients developed histologically-proven sarcoidosis late in life, at 46 years and 58 years, and had differing clinical courses. The first had radiographically staged II chronic progressive respiratory sarcoidosis (RS) and required long-term methotrexate to control the disease, while the second achieved a spontaneous remission of her stage I intrathoracic RS. After treatment, the patient with Hodgkin's disease remains in remission 2.5 years following six cycles of ABVD protocol chemotherapy and involved-field radiotherapy, while the NHL patient remains in remission at 3 years following six cycles of R-COP protocol chemotherapy. Clinicians should be aware of the potential risks of malignancy, and especially of LD in sarcoidosis patients. They should be alerted to the possibility of additional pathology by any atypical clinical features, and should biopsy new lesions and adenopathy to exclude any coexistent neoplasm.

Introduction The aim of this study was to assess the effects of preoperative pulmonary rehabilitation (PPR) on preoperative clinical status changes in patients with chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC), and net effects of PPR and cancer resection on residual pulmonary function and functional capacity. Material and methods This prospective single group study included 83 COPD patients (62 ±8 years, 85% males, FEV1 = 1844 ±618 ml, Tiffeneau index = 54 ±9%) with NSCLC, on 2–4-week PPR, before resection. Pulmonary function, and functional and symptom status were evaluated by spirometry, 6-minute walking distance (6MWD) and Borg scale, on admission, after PPR and after surgery. Results Following PPR significant improvement was registered in the majority of spirometry parameters (FEV1 by 374 ml, p < 0.001; VLC by 407 ml, p < 0.001; FEF50 by 3%, p = 0.003), 6MWD (for 56 m, p < 0.001) and dyspnoeal symptoms (by 1.0 Borg unit, p < 0.001). A positive correlation was identified between preoperative increments of FEV1 and 6MWD (r s = 0.503, p = 0.001). Negative correlations were found between basal FEV1 and its percentage increment (r s = –0.479, p = 0.001) and between basal 6MWD and its percentage change (r s = –0.603, p < 0.001) during PPR. Compared to basal values, after resection a significant reduction of most spirometry parameters and 6MWD were recorded, while Tiffeneau index, FEF25 and dyspnoea severity remained stable (p = NS). Conclusions Preoperative pulmonary rehabilitation significantly enhances clinical status of COPD patients before NSCLC resection. Preoperative increase of exercise tolerance was the result of pulmonary function improvement during PPR. The beneficial effects of PPR were most emphasized in patients with initially the worst pulmonary function and the weakest functional capacity.

p16 and PTEN are tumor suppressors that are commonly inactivated in human cancers. Loss of each of these molecules is widely studied in lung cancer, including non-small cell lung carcinoma (NSCLC), its most common clinical form. However, the importance of their mutual alterations for NSCLC pathogenesis has been barely examined so far. In this study we tested hypothesis that aberrant p16 might cooperate with inactive PTEN during pathogenesis of NSCLC, particularly in promoting tumor aggressiveness and invasiveness. Initially, we screened NSCLC tumor samples from patients for the presence of the most common genetic and epigenetic alterations of p16 and further correlated them with previously detected aberrations in PTEN gene. Statistical analyses showed that aberrant p16 directly correlated with altered PTEN. Such significant correlation was also observed in groups of patients with high genomic instability, with squamocellular histological subtype, with disease grade 2 and with lymph node invasion. Finally, survival analyses revealed dramatic decrease in survival rate of patients with mutual alterations of p16 and PTEN, but without prognostic significance. Overall results implicate cooperation between aberrant p16 and PTEN in pathogenesis of NSCLC and suggest that their combination might be considered as potential molecular marker for specific subgroups of NSCLC patients.

The actual nature of spindle cell carcinoma has been debated extensively because of its rarity. It carries a poor prognosis, even when early-stage disease is diagnosed and resected. In view of the rarity and the significance of the histological diagnosis, we report a patient with rapidly progressing spindle cell lung carcinoma with soft tissue metastasis. Diagnosis was confirmed by immunohistochemistry finding. Analysis of the TP53 gene mutations by polymerase chain reaction and DNA sequencing revealed insertion of single thymine resulting in frameshift mutation in the exon 8. Prognosis of spindle cell lung carcinoma might be determined by the sarcoma component of the tumor and, based on that, we wonder if this type of lung carcinoma could be followed-up and treated by strategies for soft tissue sarcomas, because of its rapid, sarcomatous type of growth, beside the properly lung carcinoma oncological treatment.

Non–small-cell lung carcinoma (NSCLC) (n = 65) were analyzed for promoter methylation of RASSF1A, CDH13, MGMT, ESR1, and DAPK genes in matching lung tumors, normal lung tissue, and blood samples. Aberrant methylation in CDH13 and MGMT was associated with clinicopathologic features of NSCLC. Hypermethylation detected in primary tumors was not observed in corresponding blood samples, which rendered this an unsuitable blood-based test for NSCLC detection.Systemic methylation changes may be a diagnostic marker for tumor development or prognosis. Here, we investigate the relationship between gene methylation in lung tumors relative to normal lung tissue and whether DNA methylation changes can be detected in paired blood samples.Sixty-five patients were enrolled in a surgical case series of non-small-cell lung carcinoma at a single institution. By using bisulfite pyrosequencing, CpG methylation was quantified at 5 genes (RASSF1A, CDH13, MGMT, ESR1, and DAPK) in lung tumor, pathologically normal lung tissue, and circulating blood from enrolled cases.The analyses of methylation in tumors compared with normal lung tissue identified higher methylation of CDH13, RASSF1A, and DAPK genes, whereas ESR1 and MGMT methylation did not differ significantly between these tissue types. We then examined whether the 3 aberrantly methylated genes could be detected in blood. The difference in methylation observed in tumors was not reflected in methylation status of matching blood samples, which indicated a low feasibility of detecting lung cancer by analyzing these genes in a blood-based test. Lastly, we probed whether tumor methylation was associated with clinical and demographic characteristics. Histology and sex were associated with methylation at the CDH13 gene, whereas, stage was associated with methylation at MGMT.Our results showed higher methylation of RASSF1A, CDH13, and DAPK genes in lung tumors compared with normal lung. The lack of reflection of these methylation changes in blood samples from patients with non-small-cell lung carcinoma indicates their poor suitability for a screening test.

Angiomatosis is an extremely rare disease characterized by benign thin-walled blood vessel proliferation with asymptomatic bone destruction. This type of blood vessels proliferation with bone destruction is well known as massive osteolysis or Gorham’s disease [1, 2]. It is progressive osteolysis affecting mostly the mandible, humerus or femur. Osteolysis is usually a monostotic process. The skull is less frequently involved. Gorham’s disease becomes symptomatic in childhood or adolescence. About 200 patients with this proliferation had been described by the end of 2008 [3–5]. We describe a case of asymptomatic, incidentally detected angiomatosis affecting the thoracic wall. The patient and his parents gave consent to publish the following data. Case report

We present a case of large cell lung carcinoma in sixty-one year old male with typical lung cancer symptoms but unusual radiological presentation and immunophenotype. Tumor morphological finding related to its radiological finding was suggestive for large cell lymphoma or carcinoma, but its immunophenotype made confusion for pathological diagnosis. No p53 mutations were detected in genetic investigation. Multidisciplinary diagnostic approach to some tumors is useful for their final diagnosis.

Tuberculosis (TB) is declared global emergency. Miliary TB is a treatable, potentially lethal form of TB resulting from massive lympho-hematogenous dissemination of Mycobacterium tuberculosis. Impaired cell-mediated immunity underlies the disease's development. We present a case of specific synovitis in a 21-year-old Caucasian HIV-seronegative woman. She presented with high fever and swelling of the right knee. Chest radiograph revealed bilateral nodular opacities in upper pulmonary lobes and signs of pleural effusions. Sputum samples were negative for Acid Fast Bacilli (AFB) and Löwenstein-Jensen (L-J) culture negative. Diagnosis was confirmed histologically by pleural biopsy and positive L-J cultures of knee puncture, also documented by MRI. Treatment outcome was successful with anti-tuberculous drugs following standardized treatment regimen.

The aim of the study was to analyse changes in histological type and age of presentation in female lung cancer patients during a period of 20 years. The obtained results are compared with those available from the literature published in various parts of the world.

Introduction Sclerosing haemangioma is a benign tumor, also known under the term "pneumocytoma". It is mostly notified in older females and is usually solitary. According to the histological appearance, sclerosing haemangioma could be: papillary, sclerotic, solid and haemorrhagic. Case outline A 68-year old female patient was radiologically diagnosed with coin lesion in the lower right lobe. Lower right lobectomy was performed after clinical investigations. In pulmonary parenchyma, there was found a well circumscribed node of up to 35 mm in maximal diameter. The tumor was histologically established as sclerosing haemangioma, containing two types of cells with the same immunophenotype. A multiple type of tumor was excluded by postoperative radiological examinations. Two years after surgery, the patient is without disease recurrence. Conclusion Sclerosing haemangioma should be considered in patients with radiologically diagnosed "coin-like" lesions of a solid as well as multiple type.

We report a case of mucous gland adenoma arising in the left main bronchus which was initially misdiagnosed as asthma and review the previous reported cases of this rare tumor published in the available literature.

Background It is still not clear whether an intrapericardial pneumonectomy indicates a more advanced stage of the disease compared to a standard pneumonectomy. Methods This was a retrospective study of 164 patients who underwent a pneumonectomy for lung cancer. The first group consisted of 82 patients who had a standard pneumonectomy and the second group was 38 patients who had a intrapericardial pneumonectomy, for both groups in the latest 5-year period. The third group was 44 patients with had a sleeve pneumonectomy in the latest 10-year period. The groups were compared in relation to the overall and stage-related survival, influence of T and N factors, operative morbidity and mortality. The statistics used were Kaplan–Meier, U-test, t-test, χ2 test. Results There was no statistically significant difference in stage distribution between standard and intrapericardial pneumonectomies; stages I, II, IIIA and IIIB occurred for 10.9% vs 2.6%, 30.5% vs 26.3%, 46.4% vs 65.8% and 12.2% vs 5.3% of patients, respectively. For patients who had a sleeve pneumonectomy, stage IIIA was significantly more frequent. Although the overall survival (63.5% vs 57.6%) and stage-related 5-year survival were better in the first compared to the second group, especially for stage IIIA (58.6% vs 42.6%), these differences were not statistically significant. There were no significant differences in operative morbidity and mortality between groups 1 and 2, but both were significantly higher in the third group (35.7% and 15.9%). Conclusions An intrapericardial pneumonectomy does not always indicate a more advanced stage of the disease. The need for an intrapericardial pneumonectomy, either established preoperatively or during the operation, as a single factor, even for marginal surgical candidates, is not strong enough to reject these patients for surgery.