Ilija Tomic

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.

[Neuroendocrine differentiation as a survival prognostic factor in advanced non-small cell lung cancer].

BACKGROUND/AIM Neuroendrocine lung tumors are histologically heterogenous group of cancers with different clinical progression. In non-small cell lung cancer (NSCLC) neuroendocrine differentiation exists in 10-30% of patients. The aim of this study was to determine the frequency and influence of neuroendocrine differentiation on survival of treated patients with advanced non-small cell lung cancer (NSCLC). METHODS A clinical trial included 158 patients (74% males and 26% females), with the diagnosis of NSCLC, determined by histological verification. The patients were treated by combined chemo - and X-ray therapy in stage III (without pleural effusion) or chemotherapy only in stage III (with pleural effusion) and stage IV. Chemotherapy was conducted until progression of the disease, but no more than six cycles. When the progression had been noted in stage III (without pleural effusion), the treatment was continued with X-ray therapy. Neuron specific enolase, chromogranin A, as well as synapthophysin expression in tissue examples were determined by immunohistochemical analysis with monoclonal mouse anti-human-bodies. Survival was assessed within a year and two years follow-up examination. RESULTS A total of 53 patients (34%) had NSCLC with neuroendocrine differentiation, confirmed rather in large cell lung cancer and lung adenocarcinoma (66.7% and 40%, respectively). Neuron specific enolase, chromogranin A and synapthophysin expression was noted in 45 (28.50/0), 34 (21.5%) and 33 (20.1%) patients, respectively. The one year and two years follow-up survival periods were confirmed in 39% and 17% of patients respectively. The median survival time in the patients with the neuroendocrine expression as compared to those without the expression was 15.6 vs 10.8 months; one year survival time with the expression compared to those without the expression achieved in 62% vs 27% of the patients, (< 0.001); a two-year survival time noted in 30% of the patients (p = 0.000). One year follow-up survival time was longer in the patients with neuron specific enolase and chromogranin A expression lung cancer (p < 0.001). Synapthophysin expression was not statisticaly significant for survival (p > 0.05). CONCLUSION The results of this study suggest that almost the third of the advanced NSCLC has neuroendocrine differentiation. The median survival time of the treated patients is longer when the tumor is associated with neuron specific enolase and chromogranin A expression.

[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 patients 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.

[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.

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 Spearmans 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 patients symptoms as subjective indices of bronchial asthma.

Allergic granulomatous angiitis

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.