Pseudomesotheliomatous carcinoma of the lung.

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.

Nitrofurantoin-induced immune-mediated lung and liver disease.

INTRODUCTION: Nitrofurantoin, a furan derivative, introduced in the fifties has widely been used as an effective agent for the treatment and prevention of urinary tract infections (UTI). Spectrum of adverse reactions to nitrofurantoin is wide, ranging from eosinophilic interstitial lung disease, acute hepatitis and granulomatous reaction, to the chronic active hepatitis, a very rare adverse effect, that can lead to cirrhosis and death. CASE REPORT: We presented a 55-year- old female patient with eosinophilic interstitial lung disease, severe chronic active hepatitis and several other immune- mediated multisystemic manifestations of prolonged exposure to nitrofurantoin because of the recurrent UTI caused by Escherichia coli. We estimated typical radiographic and laboratory disturbances, also restrictive ventilatory changes, severe reduction of carbon monoxide diffusion capacity and abnormal liver function tests. Lymphocytic-eosinophylic alveolitis was consistent with drug-induced reaction. Hepatitis was confirmed by liver biopsy. After withdrawal of nitrofurantoin and application of high dose of glicocorticosteroids, prompt clinical and laboratory recovery was achieved. CONCLUSION: Adverse drug reactions should be considered in patients with concomitant lung and liver disease. The mainstay of treatment is drug withdrawal and the use of immunosuppressive drugs in severe cases. Consideration should be given to monitor lung and liver function tests during long term nitrofurantoin therapy.

Primary pulmonary alveolar proteinosis.

INTRODUCTION: Pulmonary alveolar proteinosis is an uncommon disease characterized by the accumulation of surfactant proteins and phospholipids within the alveolar spaces. Acquired disease can be idiopathic (primary) and secondary. The prevalence of acquired pulmonary alveolar proteinosis is about 0.37 per 100,000 persons. Common symptoms are dyspnea and cough. Chest X-ray shows bilateral perihilar infiltrates. Open-lung biopsy is the gold standard for the diagnosis. Treatment includes whole-lung lavage, application of granulocyte-macrophage colony-stimulating factor and lung transplantation. CASE REPORT: We reported a 51 year-old man with primary form of the disease. It was the second case of this extremely rare disease in the past 30 years in our clinic. The symptoms were long-lasting dry cough, fever and physical deterioration. Chest Xray revealed bilateral pulmonary infiltrates; computed tomography showed patchy ground-glass opacification with interlobular thickening. The diagnosis was established by open lung biopsy. Additional tests were performed to exclude secondary form of the disease. CONCLUSION: We presented a rare clinical entity with typical clinical features and clinical and radiological course of the disease, in order to improve differential diagnostic approach to patients with bilateral lung infiltrations. In patients with pulmonary alveolar proteinosis timely diagnosis and adequate treatment can improve a prognosis.

[The Mounier-Kuhn syndrome].

BACKGROUND: The Mounier-Kuhn syndrome (MKS) or tracheobronchomegaly (TBM) is a rare condition of unknown frequency, up to now about 100 cases have been reported. It presents by marked dilatation of the trachea and major bronchi, recurrent respiratory infections and consecutive bronchiectasis and scars in lung parenchyme. Sometimes enlargement of transversal colon may be present. Diagnosis is usually made radiologically. CASES REPORT: We rewieved two patients 77 and 72 years old with typical clinical presentation and enlarged upper airways, in whom diagnosis of MKS was established by chest multislice computed tomography (MSCT). Transversal diameter of trachea was 30 mm in the first patient and 33 mm in the other one. Complications of syndrome (tracheal diverticulosis in the first patient, and pulmonary fibrosis, bulous emphysema and bronchiectasis in both patients) also were seen. Lung function tests showed mixed ventilation disorder, and disturbance of respiratory gases values in arterial blood samples. CONCLUSION: The Mounier-Kuhn syndrome is rare disorder, although diagnosis is often missed. Clinical presentation is similar to chronic obstructive pulmonary disease or bronchiectasis. Computed tomography is gold standard for diagnosis. Therapy is presumely supportive.

[K-ras mutation predictive significance in platinum based chemotherapeutic protocols in patients with advanced non-small cell lung cancer].

BACKGROUND/AIM: K-ras oncogene is mutated in about 20% of lung cancer. The purpose of this study was to investigate the predictive significance for therapeutic response of K-ras mutations in advanced non-small cell lung cancer (NSCLC) patients. METHODS: Bronchial aspirate samples were assessed prior to platinum-based chemotherapy start in 39 patients with stage IIIb or IV NSCLC. K-ras mutations at codons 12 and 13 were analyzed by single strand conformation polymorphisam (SSCP) and allele specific oligonucleozide hybridisation of polymerase chain reaction (PCR) of the patient's DNA present in bronchial aspirate. After two cycles of chemotherapy the patients were subjected to response evaluation. RESULTS: Of 39 patients 10 (25.5%) demonstrated K-ras mutations, while 29 (74.4%) patients had not. There were no significant differences between these two groups of patients with respect to baseline patient caracteristics. Partial response to the therapy had 16 (41%), no changes 14 (36%), and progressive disease 9 (23%) patients. There was a tendency to higher response rate for patients without K-ras mutations versus those with mutations, but not statistically significant (p = 0.14). CONCLUSION: There was no significant predictive value for therapeutic response of K-ras mutations for advanced non-small cell lung cancer.

[Symptoms, physical findings and bronchial hypersensitivity in patients with bronchial asthma and normal spirometry].

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 3.2%; II group--EV1 = 101.8%; (p .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, chi-square 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.

[Lung involvement in systemic connective tissue diseases].

BACKGROUND/AIM: Systemic connective tissue diseases (SCTD) are chronic inflammatory autoimmune disorders of unknown cause that can involve different organs and systems. Their course and prognosis are different. All of them can, more or less, involve the respiratory sistem. The aim of this study was to find out the frequency of respiratory simptoms, lung function disorders, radiography and high-resolution computerized tomography (HRCT) abnormalities, and their correlation with the duration of the disease and the applied treatment. METHODS: In 47 non-randomised consecutive patients standard chest radiography, HRCT, and lung function tests were done. RESULTS: Hypoxemia was present in nine of the patients with respiratory simptoms (20%). In all of them chest radiography was normal. In five of these patients lung fibrosis was established using HRCT. Half of all the patients with SCTD had simptoms of lung involment. Lung function tests disorders of various degrees were found in 40% of the patients. The outcome and the degree of lung functin disorders were neither in correlation with the duration of SCTD nor with therapy used (p > 0.05 Spearmans Ro). CONCLUSION: Pulmonary fibrosis occures in about 10% of the patients with SCTD, and possibly not due to the applied treatment regimens. Hypoxemia could be a sing of existing pulmonary fibrosis in the absence of disorders on standard chest radiography.

[Influence of chemiotherapeutic protocol and neuroendocrine differentiation on metastatic non-small cell lung cancer treatment results].

BACKGROUND/AIM: In 40-50% of patients with non-small cell lung cancer (NSCLC) at the time of making a diagnosis, the disease is yet at IIIb and IV stage. Standard in the treatment of these patient is the application of systemic chemiotherapy based on CIS/Carboplatin preparations. The aim of this study was to determine the influence of two different chemiotherapeutic protocols and neuroendocrine differentiation on treatment response and survival in patients with metastatic NSCLC. METHODS: We examined 85 patients with metastatic NSCLC, of which 51 with stage IIIb, and 34 with stage IV of the disease. The histologic diagnosis of NSCLC was determined by tissue assays using hematoxylin eosin method. Neuroendocrine differentiation was determined by immunohistochemical analysis of neuron-specific enolase (NSE), chromogranin A, and synapthophysin expression using monoclonal mouse anti-human bodies (DAKO, Denmark). According to chemiotherapeutic protocol, the patients were randomly assigned into combined Taxol + Cisplatin group (Tax + Cis, n = 35), and Cyclophosphamide + Etoposide + Carboplatin group (CEP, n = 50). The treatment was conducted within 4-6 chemiotherapeutic cycles. The efficacy was assessed after the therapy regimen and median survival time was assessed after the randomization. RESULTS: A total of 31 (36.47%) patients had a favourable therapeutic response, both partial and complete response (54.2% in the Tax + Cis group and 24% in CEP group of patients, respectively, p < 0.001). The median survival time in both groups was 13.1 months (15.3 months in the Tax + Cis group and 10.6 months in the CEP group, respectively, p < 0.001). A one-year follow-up survival period was confirmed in 40% of patients (60% only in the Tax + Cis group). A total of 23 (27.05%) patients with metastatic NSCLC had neuroendocrine differentiation. The disease progression or stable disease was noted only in patient with NSCLC without neuroendocrine differentiation (n = 42, 67.7%, p < 0.001). The median survival time in patients with NSCLC and neuroendocrine differentiation was 14.8 months, without neuroendocrine differentiation 10.7 months (p < 0.001). The patients with NSCLC and neuroendocrine differentiation in the CEP group had a longer one-year follow-up survival period than patients in Tax + Cis group (p < 0.001). In Tax-Cis group of patients, there was no significant difference in one-year follow-up survival period with neuroendocrine differentiation. CONCLUSION: Better therapeutic response and longer median survival time in metastatic NSCLC was obtained using Tax + Cis as compared to CEP protocol. Similar effect was noted using CEP protocol in patients with NSCLC and neuroendocrine differentiation.

[Transitional type of Castleman's disease manifested as the POEMS syndrome]. / Kastlemanova bolest prelaznog tipa ispoljena kao POEMS sindrom.

BACKGROUND: Castleman's disease is an atypical lymphoproliferative disorder characterized by angiofollicular hyperplasia of lymph nodes. Histologically, it can be classified into a hyaline-vascular type, plasma-cell type, and transitional (mixed-cell) type, while clinically localized type has been classified as unicentric, or generalized (multicentric) form of the disease. CASE REPORT: This paper presents a 21 year old male patient with multicentric Castleman's disease, a transitional (mixed-cell) type. The disease was manifested by fever, generalized enlargement of peripheral lymph nodes, breast glands enlargement, hyperemia of the face, and weakness of the lower extremities. We found mediastinal lymphadenopathy, pleural and pericardial effusions, sensorimotor peripheral neuropathy and polyclonal hypergammaglobulinemia. The simultaneous presence of these manifestations of the disease (sensomotor peripheral neuropathy, lymphadenopathy, effusions, endocrinopathy, polyclonal gammaglobulinemia and skin changes) is indentified as POEMS syndrome. The diagnosis of Castleman's disease was based on the results of histopathologic analysis of mediastinal lymph node biopsies after thoracotomy. The patient was treated with corticosteroids (prednisone 80 mg daily for 2 weeks followed by 60 mg daily). A partial response was achieved after 4 months of treatment. CONCLUSION: A transitional type of multicentric Castleman's disease may be present itself as POEMS syndrome. The effect of corticosteroid therapy in this form of the disease is unpredictable.

[Allergic granulomatous angiitis]. / Alergijski angiitis i granulomatoza.

Allergic granulomatous angiitis (AGA)--Churg-Strauss syndrome, is a rare autoimmune disease characterized by three distinct clinical phases: prodromal, eosinophilic, and vasculitic, and most of respiratory symptoms and signs begin in the first two phases of the disease. Two female patients of different age, who fulfilled the diagnostic criteria for AGA, and were in different phases and with the different duration of the disease are presented. The first patient (24 years of age) was admitted to the hospital due to aggravation of asthma, heart failure, and polyneuropathy. The second one (45 years of age) was also hospitalized due to the worsening of asthma, polyneuropathy, and fever. Both were treated continuously with glucocorticoids. The older patient also received a total of six pulse doses of cyclophosphamide. Satisfactory response to such a treatment was achieved in both cases.

[Diagnosis of multiple myeloma based on the material obtained by fine needle aspiration biopsy of the lungs]. / Dijagnoza multiplog mijeloma na osnovu materijala dobijenog perkutanom iglenom biopsijom pluca.

The patient presented in this paper was admitted to the hospital for the evaluation of radiologically revealed shadow in both lungs. In the course of diagnostic procedures, fine needle aspiration biopsy of the intrathoracic mass was performed. Cytologic analysis of the smear was performed because of clinical suspicion of plasma cell proliferative disease that was confirmed by bone marrow aspiration. Thus, the cytologic finding of intrathoracic lesion preceded the diagnosis of multiple myeloma.

[Primary ciliary dyskinesia]. / Primarna cilijarna diskinezija.

In patients with chronic respiratory diseases that last since the early childhood, primary ciliary dyskinesia (PCD) needs to be considered. Four patients reviewed in this paper were with typical disease history and clinical picture, as well as clear ciliary axonema damage. Complete examination was performed in all the patients, including bronchoscopy with bronchography, and the examination of the biopsy samples of respiratory airways' mucous membrane, obtained by transmission electron microscope (TEM). In two of the patients spermatozoa were also examined by TEM. Large anatomic defects of airways were found in all the patients, but pulmonary function was normal (except in one case), representing one of PCD's significant characteristics. First two cases fulfilled the criteria for Kartagener's syndrome, which was initially sufficient for the diagnosis of PCD.

[Potential role of cholesterol in distinguishing malignant from benign pleural effusion]. / Moguci znacaj holesterola u razlikovanju malignog od nemalignog pleurnog izliva.

Cholesterol and carcinoembryonic antigen (CEA) levels in pleural effusion and sera, were measured in 199 patients with pleural effusions of various origins. Malignant cause was found in 93, and nonmalignant in 106 patients. Mean cholesterol level in sera of patient with malignant disease was 5.0 +/- 0.93 mmol/L, and in nonmalignant group 4.34 +/- 1.32 mmol/L. The difference was not statistically significant. Mean cholesterol level in nonmalignant pleural effusions was higher thAn those in malignant (2.51 +/- 1.23 mmol/L; and 2.28 +/- 1.06 mmol/L), but the difference was also not significant. Average pleural fluid/serum cholesterol ratio (Holl/S) in nonmalignant group was 0.61 +/- 0.32 and in malignant group 0.46 +/- 0.22. The difference between those mean values was significant. Higher ratio, at the cut off value of 0.5 was found in 79/106 and in 25/93 malignant patients. Calculated sensitivity was 75%, specificity 73%, positive predictive value 76%, negative predictive value 65% and accuracy 69%. Significant negative correlation between Holi/S and pleural fluid CEA was found (p < 0.05). It was assumed that pleural fluid/serum cholesterol ratio lower than 0.5 could be of great benefit, as an additional test in the differentiation of malignant from benign pleural effusion.

[Chylous effusions]. / Hilozni izlivi.

This paper presents 4 patients with chylothorax, and one patient with bilateral chylothorax and chyloperitoneum. The chylous effusions were of benign etiology, developed as a complication of miliary tuberculosis (1 patient), after L-2 vertebral body fracture (1 patient), and idiopathic (2 patients). The diagnosis was confirmed by the presence of chylomicrons and high content of triglycerides in the effusion, ranged 11.9-29.1 mmol/l. Lymphangiography showed multiple abnormalities of lymphatic system, the obstruction of ductus thoracicus, dilatation and convulsion of lymphatic channels, but the site of lymphatic leak was not detected. The treatment included an extended period of pleural and peritoneal drainage with total parenteral nutrition (1 patient), pleurodesis using Corynebacterium parvum (2 patients), and surgical partial parietal pleurectomy with continuous drainage (1 patient). The treatment was successful in all patients.

[Diagnostic thoracoscopy]. / Dijagnosticka torakoskopija.

Diagnostic thoracoscopy in patients with pleural effusion of unclear origin mostly provides the correct diagnosis. Results from published reports of previous researches are not uniform. In 47 male and 20 female patients with pleural effusion of unknown etiology, after receiving negative results obtained from cytological finding of pleural effusion and percutaneous needle biopsy, thoracoscopy with biopsy of one or both pleurae was performed. Procedure was done in local anesthesia using Stortz rigid thoracoscope. In 37 patients with malignant disease (primary or metastatic) diagnosis was confirmed histopathologically in 31 patient (81.12%). In 27 patients with inflammatory pleural disease diagnosis was confirmed histopathologically in 22 patients (81.4%). Among 11 patients with specific pleural effusions, tuberculosis was confirmed in 10 (90.91%). Normal finding in cases of spontaneous pneumothorax and pulmonary embolism was taken as a positive result. Total number of positive findings was 55 (82.10%). In one patient, the third spontaneous pneumothorax was the indication for thoracoscopy, and after numerous bullae were seen during the procedure, talcum powder pleurodesis was done. In four patients low intensity subcutaneous emphysema occurred one day after thoracoscopy. It can be concluded that thoracoscopy in local anesthesia out of the operating room is good and practical method for solving the unclear pleural effusions, with neglectable rate of complications.

[Tumor markers in pleural effusions in bronchogenic carcinoma and tuberculosis]. / Tumorski obelezivaci u pleuralnom izlivu zbog bronhogenog karcinoma i tuberkuloze.

Concentrations of carcinoembryonic antigen (CEA) and carborhydrate antigen (CA) 50 were measured in pleural effusion and sera of 57 patients with bronchogenic carcinoma and in 73 patients in whom the effusion was the sequela of tuberculous pleurisy. In the group with bronchogenic carcinomas, planocellular was confirmed in 19, microcellular in 17, macrocellular in 2, and adenocarcinoma in 18, while in 1 patient it was not possible to determine the histopathologic structure. The diagnosis of pleural disease was established upon the cytologic examination of the effusion and histopathologic examination of the pleural sample obtained by blind percutaneous needle biopsy or following pleuroscopy. CEA concentration in the sera of patients with bronchogenic carcinoma was significantly higher than in the patients with tuberculosis (p < 0.001), with sensitivity of 44% and ideal specificity and positive predictive value of 100%. In the same group highly significant difference of mean values of CEA concentrations in pleural effusion (p < 0.001), was also found with sensitivity of 60%, significant specificity of 99% and positive predictive value of 97%. CA 50 concentrations in the sera of patients with lung carcinoma were significantly higher than those in the sera of patients with tuberculous pleurisy (p < 0.05), and the sensitivity was 50%, while the specificity was 94% and positive predictive value was 75%. Significantly higher was also the value in the pleural effusion (p < 0.05), but the sensitivity was slightly lower--40%, but specificity was favorable as well as the positive predictive value (94 and 86%, respectively). The results indicate the significance of the determination of CEA and CA 50 in the sera and pleural effusion in the differentiation of malignant from tuberculous pleural effusion.