Demet Karnak

Endobronchial Fungal Disease: An Under-Recognized Entity

Most fungi enter the human body via inhalation; however, endobronchial fungal infection (EBFI) seems to be a rare manifestation compared to pulmonary or systemic disease. This presentation seems to be related to environmental factors as well as to the host status. With the increasing popularity of flexible bronchoscopy, it is being recognized with a higher frequency. Bronchoscopic findings in EBFI vary from mild mucosal inflammation to central airway obstruction. We searched English literature related to the topic and found 228 total cases of EBFI: Aspergillus species (121), Coccidioides immitis (38), Zygomycetes (31), Candida species (14) Cryptococcus neoformans (13), and Histoplasma capsulatum (11). We have also included a single case of endobronchial Pseudallescheria boydii infection in a lung transplant recipient that has not been reported previously. Most patients were immunocompromised, exhibited systemic manifestations of the primary infection, and responded to appropriate therapy. EBFI should be included in the differential diagnosis of any form of airway lesions in immunocompromised patients, especially among residents from the endemic areas.

Impact of TNF-alpha and IL-6 levels on development of cachexia in newly diagnosed NSCLC patients.

Objectives:We investigated the role of cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in cachexia development in newly diagnosed nonsmall cell lung cancer (NSCLC) patients. Methods:We evaluated 44 (M/F:41/3) NSCLC patients and 12 (M/F:10/2) age matched healthy smokers. NSCLC cases with a weight loss of ≥10% consisted the cachectic group (n:23, M/F:21/2) and the ones with <10% weight loss consisted the noncachectic group (n:21, M/F:19/2). Results:Body mass index (BMI) of cachectics was significantly lower than that of noncachectics (21.0 ± 2.9 versus 24.5 ± 3.6, P = 0.02) and controls (21.0 ± 2.9 versus 25.5 ± 2.6, P = 0.01). Serum TNF-α level did not differ between cachectic and noncachectics (37.3 ± 39.1 and 51.6 ± 84.2 pg/mL, respectively). However, it was significantly higher in NSCLC patients compared with controls (44.1 ± 64.3 and 15.1 ± 14.3 pg/mL, P = 0.03). Serum IL-6 level was not different between 3 groups (6.4 ± 4.1, 8.9 ± 16.3, and 4.1 ± 3.5 pg/mL, respectively) but it correlated significantly with TNF-α (r = 0.4, P = 0.006) and BMI (r = −0.3, P = 0.03). Erythrocyte sedimentation rate (ESR) correlated significantly with TNF-α (r = 0.4, P = 0.003) and BMI (r = −0.3, P = 0.03). Among 44 cases, survival of 12 and 17 patients was recorded in cachectics and noncachectics, with no statistical difference (12.2 ± 3.7 and 11.2 ± 1.0 months, respectively). Conclusions:TNF-α and IL-6 levels did not differ significantly between cachectics and noncachectics. However, significant correlations between IL-6, BMI, and TNF-α suggested that these cytokines acted as cofactors in weight loss. Survival was neither influenced by BMI, nor the cytokine levels in the present study. The significant correlation of ESR with TNF-α suggested that ESR could provide valuable clue for considerable weight loss in the follow-up of NSCLC patients.

Reactivation of pulmonary tuberculosis in malignancy.

Aims and Background Deterioration of immunity due to local or systemic effects of the tumor itself and/or administered chemotherapeutics or radiotherapy may play roles in the reactivation of tuberculosis, increasing the mortality in patients with various malignancies. In a country with a high prevalence of tuberculosis such as Turkey, most people have inactive tuberculous lesions and tuberculin test positivity. Therefore, a prospective study was carried out to investigate the frequency of tuberculosis reactivation in patients with a malignancy. Methods Seventy-three patients with a malignancy and undergoing diagnostic fiberoptic bronchoscopy were enrolled in the study during a 2-year period (1993-1995). Bronchoscopic biopsies and cytologic materials were obtained. Bronchoalveolar lavage fluids, bronchial washings, and pre- and post-bronchoscopic sputum specimens were also evaluated for acid-fast bacilli. A diagnosis of tuberculosis was based on smear and/or culture positivity for acid-fast bacilli. Results The mean age of the patients was 56.2 ± 13.6 years, with a male/female ratio of 69/4. The biopsy proven malignancies were as follows: primary lung carcinoma (n = 66, 90.4%), lymphoma (n = 5, 6.8%), metastatic breast adenocarcinoma (n = 1, 1.4%), and acute myelocytic leukemia (n = 1, 1.4%). Thirty-one of all patients had findings compatible with tuberculosis on radiology. The sputa and bronchial washing specimens were smear negative in all patients. Acid-fast bacilli were grown on culture in 6 patients (8%) (primary lung cancer, n = 5; non-Hodgkin lymphoma, n = 1). Four of these 6 patients had positive radiology for tuberculosis. These subjects were treated with a three- or four-drug anti-tuberculosis regimen. Two months later, smears remained acid-fast bacilli negative, or no bacilli were grown on culture. Conclusions The possibility of coexisting tuberculosis should be kept in mind in patients with a malignancy, especially those with lung carcinoma in countries with a high prevalence of tuberculosis. Pulmonary infections encountered in such patients should raise the suspicion of tuberculosis reactivation, and in addition to direct microscopic evaluation, sputum specimens and materials obtained by fiberoptic bronchoscopy should be cultivated for tuberculosis. Three-four-drug anti-tuberculosis regimens should be given, especially in countries with high drug-resistance rates for eradicating tuberculosis.

Diagnostic Accuracy of Cytokine Levels (TNF-α, IL-2 and IFN-γ) in Bronchoalveolar Lavage Fluid of Smear-Negative Pulmonary Tuberculosis Patients

Background: The determination of cytokine concentrations in serum and bronchoalveolar lavage fluid (BALF) may contribute to the diagnosis of tuberculosis (TB) since cytokines have been ascribed an important role in TB pathogenesis. Objective: To assess the diagnostic accuracy of TNF-α, IFN-γ and IL-2 levels in serum and BALF of smear-negative pulmonary TB patients. Method: BALF was obtained from the affected lobe in patients with smear-negative TB or other pulmonary diseases (OPD), and from the right middle lobe in healthy controls. ELISA and a nephelometric method were used to detect cytokine and albumin levels. Results: TNF-α levels in BALF were significantly elevated in the TB group (n = 15) compared with the OPD patients (n = 40) and controls (n = 17; p < 0.001). Although these three cytokines correlated well with each other in BALF (p < 0.0001, and r ≧ 0.7, respectively), BALF IL-2 and IFN-γ levels were not significantly different among the groups (p > 0.05). BALF TNF-α or IFN-γ levels were significantly higher in patients with cavitary disease (n = 11) versus those without (n = 61; p < 0.05). However, no significant difference was found between cavitary (n = 7) and non-cavitary TB in cytokine levels (p > 0.05). Neither gender nor smoking status showed any statistical differences in cytokines in the groups (p > 0.05). Sensitivity and specificity of BALF TNF-α were found to be 73 and 76%, respectively. The positive and negative predictive values for BALF TNF-α were 44 and 91%, respectively. Conclusion: In cases of smear-negative TB, BALF TNF-α can be a useful tool to identify healthy subjects rather than smear-negative TB patients.

Rapid on-site evaluation and low registration error enhance the success of electromagnetic navigation bronchoscopy.

BACKGROUND: Electromagnetic navigation bronchoscopy (EMN) is a novel technology which allows localizing peripheral lung lesions and mediastinal lymph nodes for sampling and thus increasing diagnostic yield of Flexible Bronchoscopy. OBJECTIVES: A prospective study was conducted to investigate the diagnostic yield of EMN with lower average fiducial target registration error (AFTRE) and rapid on-site evaluation (ROSE). METHODS: Consecutive patients with peripheral lung lesion (PL) or enlarged mediastinal lymph node (MLN) which could not be diagnosed by conventional techniques and/or if the patients were not suitable for such interventions were included. The navigation procedure was continued once registration error was reached below/equal to the absolute value of 5 mm. ROSE was performed by an expert cytopathologist. RESULTS: A total of 76 patients; 22 having only PLs, 41 having only MLNs, and 13 having both PLs and MLNs together were enrolled. Thirty-two of 35 PLs (91.4%) and 85 of 102 MLNs (83.3%) were successfully sampled. Overall diagnostic yield was 89.5%. PLs and MLNs were further grouped according to their size (PLs: <20 mm vs ≥20 mm, MLNs: <15 mm vs ≥15 mm). The sampling yield was independent of size for both PL and MLN (P = 1.00, P = 0.38). In diagnostic EMN cases, mean AFTRE was 4.33 ± 0.71 mm, whereas it was 5.16 ± 0.05 mm (P = 0.008) in nondiagnostics. The total duration of procedure was 36.17 ± 9.13 min. Pneumothorax was observed in three patients (3.9%). CONCLUSION: EMN with low AFTRE in combination with ROSE is a reliable method with high sampling and/or diagnostic rate in PLs and MLNs.

Tracheobronchial variations in Turkish population.

The tracheobronchial tree exhibits highly individualistic features and many variations. As the anatomic variations among Turkish population have not been studied previously, we aimed to evaluate the type and frequency of tracheobronchial variations (TBVs) in our bronchoscopy population. In a 3‐year period, 1,114 patients underwent flexible bronchoscopy (FB). Among these, 780 (70%) were male. The mean age of the patients was 51.3 ± 15.1 (range: 17–84) years. In 639 cases, no TBV were detected. A total of 999 TBV were observed in 475 patients. Of all, 71.3% (713) of the total TBV were detected in males. Forty‐nine and six‐tenths percent (49.6%) of the TBV were observed on the right bronchial system, 49.2% on the left, and 1.2% in the trachea. The five most frequently observed TBV were right lower lobe basal orifice with two subsegments, left lower lobe basal orifice with two subsegments, left upper lobe with three segments, right upper lobe with two segments, and right lower lobe with a subapical segment. In the same lobe bronchus, single variation and two different TBV were seen in 85% and 15% of patients, respectively. Number of TBV increased linearly with the number of lobes involved. The availability and popularity of FB in recent years has led to the increase in identification and reporting of TBV. TBV should be correctly identified and documented. This information is invaluable during follow‐up bronchoscopies as well as lung resection. Clin. Anat. 21:531–538, 2008.

Neuron-specific enolase and lung cancer.

Objective:Serum and bronchoalveolar lavage fluid (BALF) neuron-specific enolase (NSE) levels in lung cancer have been investigated widely; however, their diagnostic values have not yet been clarified. The authors investigated the diagnostic validity of NSE in BALF and serum in lung cancer. Materials and Methods:In this prospective case-control study, NSE levels in BALF (B-NSE) and serum (S-NSE) of 3 groups of subjects were analyzed: control subjects (group 1, n = 15), patients with chronic obstructive pulmonary disease (COPD; group 2, n = 15), and lung cancer (group 3, n = 35). Results:The differences in S-NSE and B-NSE levels between the groups were not significant (P > 0.05). S-NSE and B-NSE levels did not show any difference between smokers and nonsmokers, small cell lung cancer and nonsmall cell lung cancer patients, and stage I–II and stage III–IV patients in group 3 (P > 0.05). B-NSE or B-NSE/urea did not show any significance in comparison with S-NSE in the diagnosis and/or staging of malignancy (P > 0.05). S-NSE and B-NSE were well correlated with each other (r = 0.84, P = 0.000). The sensitivity of the S-NSE was 60% and the specificity was 40%. Conclusion:The authors conclude that, although elevation of B-NSE is a well-known parameter in small cell lung cancer, it can also be elevated considerably in nonsmall cell lung cancer and COPD. Because of the significant correlation between S-NSE and B-NSE, it may be sufficient to measure S-NSE activity because it is easier and less invasive. However, NSE has no role in the exact diagnosis of lung cancer; it can only be investigated in a scientific setting.

Evaluation of Cyfra 21-1: A Potential Tumor Marker for Non-Small Cell Lung Carcinomas

Abstract. Cyfra 21-1 is a tumor marker based on the determination of water-soluble cytokeratin 19 which is secreted by normal or malignantly transformed epithelial cells. It is suggested to be a valuable marker in patients with non-small cell lung carcinoma (NSCLC). A prospective clinical study was conducted to investigate the value of Cyfra 21-1 for diagnosis, determination of subtypes, staging, and evaluation of therapy response in patients with lung carcinoma (Ca). Sixty-nine patients (mean age: 60.9 ± 9.2 years, M/F:12.8) treated between 1994 and 1998 inclusive, and 13 healthy smokers (mean age:50.9 ± 4.8 years, M/F:1.6) constituted the study group and control group, respectively. Venous blood samples (10 ml) were obtained from all subjects. Posttreatment blood samples were also obtained from 14 NSCLC patients. Cyfra 21-1 levels (cutoff value 3.3 ng/ml) were determined by ELSA-Cyfra 21-1 kit (CIS bio international, France) through immunoradiometric assay (IRMA). Cyfra 21-1 levels did not differ between smoking and non-smoking subjects within each group (p > 0.05). Cyfra 21-1 was significantly elevated in lung Ca cases irrespective of the cell type (p < 0.05). It was significantly elevated in squamous cell and adenocarcinoma varieties with the most prominent elevation in squamous cell type (p < 0.05). In lung Ca, the specificity and sensitivity of Cyfra 21-1 was 92.3% and 52.2%, respectively. Sensitivity was 65.5% for NSCLC, 70.5% for squamous cell, and 45.5% for adenocarcinoma varieties, with highest sensitivity rates in Stage IIIA + IIIB (87.5%) and Stage IV (75%) of squamous cell lung Ca. Cyfra 21-1 level was significantly decreased after treatment in NSCLC patients (n 14) (p < 0.01). Cyfra 21-1 is a tumor marker that helps to establish the diagnosis and differentiation of cell type and evaluation of response to therapy in patients with NSCLC.

Concurrent measurement of adenosine deaminase and dipeptidyl peptidase IV activity in the diagnosis of tuberculous pleural effusion.

Measurement of pleural fluid adenosine deaminase (ADA) levels aids diagnosing tuberculous pleural effusion (TPE). Dipeptidyl peptidase IV (DPP) enzyme is closely related to ADA. Our aim was to determine the value of concurrent measurement of these T-cell-associated enzymes, ADA and DPP levels in the diagnosis of TPE. Patients with pleural effusion were grouped as TPE, parapneumonic, malignant, congestive heart failure related, and miscellaneous pleural effusions. Pleural and serum ADA and DPP levels were measured. Pleural and serum levels of ADA and pleural DPP were higher in TPE group than the rest. In 7 patients, pleural biopsy revealed granulomatous pleuritis. All of these patients had TPE and had elevated serum and pleural ADA levels. Serum and pleural ADA or DPP levels and pleural ADA and DPP levels correlated with each other. Selecting cutoff values of 40 and 27 IU/L for pleural ADA and DPP, respectively, the sensitivity of concurrent measurement of both enzymes was 77%, specificity 94%, and diagnostic efficiency 91%. ADA and DPP play an important role in tuberculous immunopathogenesis. The utility of DPP in the diagnosis of TPE has never been determined before. Concurrent measurement of ADA-DPP can aid in diagnosing TPE with higher specificity, sensitivity, and efficiency.

Electromagnetic navigation‐guided TBNA vs conventional TBNA in the diagnosis of mediastinal lymphadenopathy

Conventional transbronchial needle aspiration (C‐TBNA) is a safe method for the diagnosis of hilar and mediastinal lymphadenopathy (MLN). However, diagnostic yield of this technique varies considerably. Electromagnetic navigation bronchoscopy (ENB) is a new technology to increase the diagnostic yield of flexible bronchoscopy for the peripheral lung lesions and MLN. The aim of this prospective study was to compare the diagnostic and sampling success of ENB‐guided TBNA (ENB‐TBNA) in comparison with C‐TBNA while dealing with MLN.