Analyses of P16INK4a gene promoter methylation relative to molecular, demographic and clinical parameters characteristics in non-small cell lung cancer patients: A pilot study.

BACKGROUND: The aim of this study was to examine the methylation status of p16INK4a promoter region in non small cell lung cancer (NSCLC) patients and their associations with single nucleotide polymorphisms (SNPs) of the epidermal growth factor receptor (EGFR) gene, as well as with demographic or clinical characteristics. METHODS: Formalin-fixed and paraffin-embedded (FFPE) DNA samples extracted from 22 NSCLC patients were analyzed with methylation-specific polymerase chain reaction (PCR) method to obtain promoter methylation profile. The same cohort was genotyped for - 216G > T, -191 C > A, and 181,946 C > T EGFR SNPs. RESULTS: There was a significant association between methylated p16INK4a in patients prior therapy (p = 0.017) since a significantly higher frequency of methylated p16INK4a was detected in these patients (40.9%) in comparison to frequency in patients after therapy (31.8%). Also, a higher frequency of methylated p16INK4a was detected among patients with leucopenia (p = 0.056). No associations were observed between the methylation status of the p16INK4a promoter region and EGFR SNPs or other clinical and demographic data in this cohort. CONCLUSION: High frequency of methylation of the p16INK4a gene promoter was observed in NSCLC patients prior therapy and with leucopenia that can indicate their significance related to advanced clinical stage.

Frequencies of EGFR single nucleotide polymorphisms in non-small cell lung cancer patients and healthy individuals in the Republic of Serbia: a preliminary study.

The purpose of this study was to determine the frequencies of EGFR -216G>T, -191C>A, and 181946C>T in Serbian non-small cell lung cancer (NSCLC) patients, as well as to compare it with healthy individuals, in order to assess their potential importance for lung cancer in Serbia. The study involved 56 NSCLC patients and 53 unrelated healthy volunteers, and genotyping was performed on DNA samples obtained from formalin-fixed paraffin-embedded lung tumor tissue and blood, respectively. This was the first time to show genotype frequencies of those single nucleotide polymorphisms for this study group from the territory of the Republic of Serbia. There was very strong evidence of association between age and death due to lung cancer (Pearson chi-square = 43.439, df = 2, p < 0,001), as well as between ever smoking and death due to lung cancer (Pearson chi-square = 31.727, df = 1, p < 0.001). When dominant genetic model (GG vs. GT+TT) was used for -216G>T, we have found significant association (p = 0.012) between -216GG genotype and NSCLC patients within smokers' subgroup. So, carriers of -216GG genotype had higher risk (OR = 4.33, 95 % CI = 1.324-14.179) than noncarriers (GT and TT) for developing non-small cell lung cancer in our patients.

Optimization of PCR conditions for amplification of GC-Rich EGFR promoter sequence.

BACKGROUND: Polymerase chain reaction (PCR) is an extremely sensitive method that often demands optimization, especially when difficult templates need to be amplified. The aim of the present study was to optimize the PCR conditions for amplification of the epidermal growth factor receptor (EGFR) promoter sequence featuring an extremely high guanine-cytosine (GC) content in order to detect single nucleotide polymorphisms -216G>T and -191C>A. METHODS: Genomic DNA used for amplification was extracted from formalin-fixed paraffin-embedded lung tumor tissue and PCR products were detected by agarose gel electrophoresis. RESULTS: Results showed that addition of 5% dimethyl sulfoxide (DMSO), as well as DNA concentration in PCR reaction of at least 2 µg/ml, were necessary for successful amplification. Due to high GC content, optimal annealing temperature was 7°C higher than calculated, while adequate MgCl2 concentration ranged from 1.5 to 2.0 mM. CONCLUSION: In conclusion, EGFR promoter region is a difficult PCR target, but it could be amplified after optimization of MgCl2 concentration and annealing temperature in the presence of DMSO and the DNA template of acceptable concentration.

Autofluorescence imaging videobronchoscopy improves assessment of tumor margins and affects therapeutic strategy in central lung cancer.

OBJECTIVE: Autofluorescence imaging (AFI) videobronchoscopy is a new endoscopic tool that improves visualization of neoplastic changes in the bronchial mucosa. The major aim of our study was to determine sensitivity and specificity of the technique in the assessment of tumor extent (margins). The secondary objective was to evaluate the possible effect of AFI on the change in therapeutic decisions of lung cancer treatment. METHODS: In this prospective trial, we enrolled 104 patients in whom we performed 624 targeted biopsies, 3 from the pathologically altered mucosa (red-brownish or magenta colored) and 3 from randomly picked normal areas. We were using the Olympus BF-F260 videobronchoscope and EVIS LUCERA system. White light videobronchoscopy (WLB) preceded AFI examination and biopsy collection. All biopsy specimens were examined by a pathologist blinded to bronchoscopy findings, and where applicable surgically resected specimens were examined. RESULTS: In 14.4% of the patients, AFI revealed a greater extent of the tumor than WLB, and in 11.5% that finding led to change in therapeutic decision (lesser or greater resection or avoidance of surgery). We found a significant correlation between tumor extent determined by AFI and changes in therapeutic decisions (P < 0.01). Sensitivity, specificity, positive predictive value and negative predictive value for AFI in the assessment of tumor extension were 93%, 92%, 92% and 93%, respectively. Corresponding results for WLB were 84%, 79%, 77% and 85%, respectively. Relative sensitivity of AFI is 1.11. CONCLUSIONS: Our results confirm that AFI videobronchoscopy significantly improves the assessment of central lung cancer extension and influences the therapeutic strategy. This technique has greater sensitivity and specificity, in assessment of tumor margins, than WLB alone.

Radiation therapy for early stage (I/II) non-small cell lung cancer.

For patients with early (stage I/II) non-small cell lung cancer (NSCLC) surgery is considered as the standard treatment of choice, although recent data on additional chemotherapy (CHT) showed that it may be beneficial in this setting. There is, however, a subset of patients that never undergo surgery. These patients are considered technically operable, but medically inoperable, due to existing comorbidities. In addition, frequently elderly patients with early NSCLC are denied surgery due to expected peri- and/or postoperative complications. Finally, in recent years there has been an increase in the incidence of patients refusing surgery. For all these patients, radiation therapy (RT) was traditionally considered as the standard treatment option. Data accumulated over the last 5 decades showed that RT alone can produce median survival times of up to > 30 months and 5-year survival of up to 30%. When cancer-unrelated deaths were taken into account, cause-specific survival rates were usually higher for some 10-15%. Accumulated experience seems to suggest that doses of at least 65 Gy with standard fractionation or its equivalent when altered fractionation is used are necessary for control of the disease. Smaller tumors seem to have favorable prognosis, while the issue of elective nodal RT continues to be controversial. Patterns of failure have clearly identified local failure as the predominant one. Although a number of potential pretreatment patient- and tumor-related prognostic factors have been examined, none has been shown to clearly influenced survival. Toxicity was usually low.

Radiochemotherapy in extensive disease small cell lung cancer ED-SCLC.

Patients with extensive disease small cell lung cancer (ED-SCLC) represent approximately one-third of all SCLC patients. For these patients, chemotherapy (CHT) is the standard treatment of choice. With CHT given alone, however, there is not a high risk of distant progression, but also progression within the thorax and brain frequently occurs, even in patients achieving a response to CHT. To improve poor figures obtained with CHT alone and address important issue of intrathoracic tumor control and it relationship to overall survival, thoracic radiation therapy (TRT) was introduced with a curative intent in a prospective randomized trial by Jeremic et al (1988-1993). In that trial CHT alone was compared with CHT followed by TRT, and in both groups by a prophylactic cranial irradiation. This trial showed that TRT can offer an improvement on local control that leads to an improvement in overall survival. Toxicity was acceptable, while multivariate analysis identified number of metastasis as an independent prognosticator of outcome. Based on the data of this trial, researchers in the USA and Europe will undergo two prospective trials addressing the issue of TRT in ED-SCLC.

Acute pneumothorax due to immunotherapy administration in non-small cell lung cancer.

Nowadays we have novel therapies for advanced stage non-small cell lung cancer. Immunotherapy has been introduced in the market for several years and until now its administration is mostly based on the programmed death-ligand 1. First line treatment with immunotherapy can be administered alone if programmed death-ligand 1 expression is ≥ 50%. All therapies for advanced stage disease have advantages and disadvantages, immunotherapy until now has presented mild adverse effects when compared to chemotherapy. However; it is known to induce inflammatory response to different tissues within the body. In our case acute pneumothorax was induced after immunotherapy administration.

Lung cancer biopsies: Comparison between simple 22G, 22G upgraded and 21G needle for EBUS-TBNA.

Introduction: Novel technologies are currently used for lung cancer diagnosis. EBUS-TBNA 22G is considered one of the most important tools. However; there are still issues with the sample size.Patients and Methods: 223 patients underwent EBUS-TBNA with a 21G Olympus needle, 22GUS Mediglobe and 22GUB Mediglobe. In order to evaluate the efficiency of 22GUB novel needle design. In order to evaluate the sample size of each needle, we constructed cell blocks and measured the different number of slices from each biopsy site. Results: The 22GUB novel needle had similar and larger number of slices from each biopsy site compared to 21G needle. Discussion: Firstly as a novel methodology we used the number of slices from the constructed cell blocks in order to evaluate the sample size. Secondly, we should seek novel needle designs and not only concentrate on the volume of the sample size.

Sex Differences and Adverse Effects between Chemotherapy and Immunotherapy for Non-Small Cell Lung Cancer.

Introduction: Lung cancer remains the leading cause of cancer mortality in men and women and around the world. Approximately 90% of cases of lung cancer are caused by smoking and the use of tobacco products. However, other factors such as asbestos, air pollution and chronic infections can contribute to pulmonary carcinogenesis. Lung cancer is divided into two broad histological categories, which develop and spread different small cell lung carcinomas and non-small cell lung carcinomas. The treatment options for lung cancer include surgery, radiotherapy, chemotherapy and targeted treatments. Tumor induced immune suppression is vital for malignant progression. Immunotherapies act by strengthening the patient's innate tendency for an immune response and give positive promise to patients with non-small cell lung cancer and small cell lung cancer. Immune checkpoint inhibitors are a new approach to cancer therapies. Just as immune therapies include a new approach to cancer biology, the toxicities associated with these factors have created new challenges in clinical practice. Materials & Methods: Patients (218) aged 40-80 years were treated with either chemotherapy or immunotherapy. Their response to treatment and any subsequent adverse drug reactions were studied. Results: 69% of patients were treated with chemotherapy and 31% were treated with immunotherapy. The type of treatment had a statistically significant effect on the undesirable effects of the treatment. Conclusions: The type of treatment was statistically significant in responding to the treatment and treatment side effects but not in the rate of death.

Narrow band imaging videobronchoscopy improves assessment of lung cancer extension and influences therapeutic strategy.

OBJECTIVE: Narrow band imaging (NBI) videobronchoscopy is a new technique aimed at lung cancer detection. This study investigated its sensitivity and specificity for evaluation of lung cancer extension and its possible influence on therapeutic decision, compared with white light videobronchoscopy. METHODS: In this prospective study, we evaluated 106 patients with suspected lung cancer. All patients were examined using EVIS LUCERA videoendoscopy system. In every patient, at least three biopsies were taken from places visualized as pathologic, surrounding primary tumor, and three biopsies from places that appeared normal. The overall number of biopsies performed in 106 patients was 636. RESULTS: The specificity and sensitivity of NBI in revealing greater lung cancer extension were 85.6% and 95%, respectively; positive and negative predictive values were 84% and 95.6%, respectively. Specificity and sensitivity were significantly better when compared with white light bronchoscopy alone (P < 0.01). NBI led to the change in therapeutic decision in 14 patients. There was statistically significant correlation between NBI assessment of tumor extension and change in therapeutic decision (P < 0.000). CONCLUSIONS: NBI showed significantly better specificity and sensitivity in the assessment of lung cancer extension. NBI proved that it might have potential influence on therapeutic decision, making it more accurate. The procedure is safe and easily deployed in everyday practice.

PD-1 and PD-L1 Protein Expression Predict Survival in Completely Resected Lung Adenocarcinoma.

BACKGROUND: We assessed the prognostic value of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in patients with completely resected lung adenocarcinoma. PATIENTS AND METHODS: PD-1 and PD-L1 expression was determined using immunohistochemistry in formalin-fixed paraffin-embedded surgical specimens and correlated with the clinicopathologic features and survival of 161 patients with lung adenocarcinoma. RESULTS: PD-1 expression on immune cells was observed in 71 of 159 evaluable tumor samples (45%) and was not significantly associated with the clinicopathologic features. Multivariate analyses identified PD-1 expression as an independent prognostic factor for recurrence (adjusted hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.36-0.95; P = .03) and death (adjusted HR, 0.48; 95% CI, 0.27-0.86; P = 0.01). PD-L1 expression on tumor cells was seen in 59 of 161 cases (37%) and correlated with KRAS mutation status (P = .02) and type of surgery (P = .01). PD-L1 expression was not associated with recurrence-free survival in the patients (adjusted HR, 0.90; 95% CI, 0.55-1.48; P = .68) but correlated with longer overall survival (adjusted HR, 0.54; 95% CI, 0.30-0.97; P = .04). CONCLUSION: PD-1 and PD-L1 expression was associated with favorable overall survival in patients with completely resected adenocarcinoma of the lung.

The cost of hospital treatment of advanced stage lung cancer patients in a developing South East European country.

Assessing the lung cancer treatment costs is necessary in order to estimate the budget impact of new interventions and therapeutic innovations. However, there are few studies regarding the use of resources and costs associated with treatment of lung cancer patients, not only in Serbia, but internationally. The aim of this paper was to assess the hospital costs of diagnosing and treating patients with stage IIIB and IV non-small cell lung cancer. Analysis of costs of care, services, medications and medical supplies, as well as of total hospital costs, was performed. Patients diagnosed with stage IIIB or IV NSCLC in the Institute during the year 2013 were enrolled in the study. A total of 187 patients with stage IIIB or IV NSCLC were analyzed. Total hospital costs were 506.970€, of which nearly two thirds was accounted to costs of services and medications. The mean cost per patient with adenocarcinoma was 3.075€, and for squamous cell lung carcinoma patient 1.943€. Statistically significant difference was shown when comparing mean hospital costs between patients in stage IIIB and stage IV adenocarcinoma, where this cost is higher in patients with stage IIIB. Mean hospital cost per female patient was nearly double as high that of the male patients, although without statistically significant difference. The mean cost for all adenocarcinoma patients was 1.317€, and for only four patients treated with TKI therapy 21.233€. This cost analysis could provide useful information in terms of budget impact of different lung cancer treatments and innovations in Serbia and corresponding developing countries.

Clinicopathological features and relation between anaplastic lymphoma kinase (ALK) mutation and histological subtype of lung adenocarcinoma in Eastern European Caucasian population.

Introduction: The incidence of echinoderm microtubule-associated protein-like4-anaplastic lymphoma kinase (EML4-ALK) mutation among surgically treated patients with adenocarcinoma of the lung of the Eastern European ethnicity is underreported. The aim of this trial was the determination of EML4-ALK mutation frequency in investigated population, and the evaluation of correlations between lung adenocarcinoma subtype and clinical characteristics with mutation status. Patients and methods: This was a prospective trial which included 195 patients with adenocarcinoma of the lung who underwent surgical treatment. ALK mutation screening was performed by immunohistochemistry (IHC). IHC scores of 2+ and 3+ were regarded as positive. Confirmatory FISH was performed in all IHC positive and in 2:1 ratio in negative patients. Results: Overall ALK mutation rate established by IHC was 6.2%, while FISH confirmed rate of 5.1%. The FISH confirmed ALK positivity in 7.6% Hungarians, 5.5% Serbians, and 6.6% Slovakians. Acinar subtype of adenocarcinoma of the lung was significantly (p=0.02) related to EML4-ALK positive mutation status. Most of the patients were males (56.9%), smokers (50.8%), or former smokers (28.7%) with acinar (55.4%) or solid (35.9%) adenocarcinoma of the lung. Sensitivity and specificity of IHC were 100% and 98.9% respectively. Conclusions: ALK mutation rate in surgically treated patients with adenocarcinoma of the lung was found to be 6.2% by IHC and 5.1% by FISH. Acinar subtype of the adenocarcinoma of the lung was significantly related to ALK positive mutation.

Radial Endobronchial Ultrasound (EBUS) Guided Suction Catheter-Biopsy in Histological Diagnosis of Peripheral Pulmonary Lesions.

BACKGROUND: EBUS guided trans-bronchial biopsy became routine in diagnosis of peripheral pulmonary lesions (PPL). Suction catheter-biopsy is a technique for obtaining a tissue sample from peripheral lung parenchyma. Aim of this study was to evaluate diagnostic efficiency, feasibility and safety of EBUS guided suction catheter-biopsy (SCB) in comparison to trans-bronchial biopsy (TBB) in diagnosis of PPL. The main intention was to demonstrate non-inferiority of the technique over trans-bronchial biopsy, especially when used under navigation of the EBUS. METHODS: Radial EBUS probe (UM-3R, Olympus Co, Japan.) without guiding sheath was used to navigate suction catheter and TBB forceps to the PPL. The catheter was connected to the collection canister via vacuum pump. The SCB specimens were fixed with 10% buffered formalin. RESULTS: There were 168 patients enrolled in this study; 69.9% males and 30.1% females. Main lesion diameter was 4.1±1.9 cm. Majority of patients, 131(77.9%) were diagnosed with lung cancer. Per-biopsy calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for EBUS-SCB were 92.4%, 100%, 100% and 67.7%, respectively. Corresponding values for EBUS-TBB were 92.3%, 100%, 100% and 69.7%. Only the size of the lesion significantly influenced (p=0.005) diagnostic performance. Complications occurred in 2 patients; one pneumothorax and one excessive bleeding. CONCLUSION: EBUS guided SCB is efficient, feasible and safe in diagnosis of peripheral lung cancer. The technique is complementary to trans-bronchial biopsy.

EGFR-TKIs in adjuvant treatment of lung cancer: to give or not to give?

Epidermal growth factor receptor-tyrosine-kinase inhibitors (EGFR-TKIs) brought a significant revolution in the treatment of non-small-cell lung cancer (NSCLC). In a short period of time, EGFR-TKIs became the standard of treatment for mutation-positive, advanced stage non-squamous NSCLC. In recent years, second- and third-generation EGFR-TKIs are emerging, further widening the clinical use. However, the question of EGFR-TKIs efficiency in the treatment of early stage NSCLC still remains open. Early clinical trials failed to approve the use of EGFR-TKIs in adjuvant setting. The majority of these early trials were performed in unselected NSCLC populations and without standardized biomarker identification. One should certainly not rely solely on these results and dismiss the use of EGFR-TKIs as adjuvant therapy. Many important questions are still unanswered. Most important issues such as stage heterogeneity (IA-IIIA), timing (after or concomitantly with chemotherapy), and type of administration (monotherapy or combination) need to be answered in near future. Adjuvant TKIs in the treatment of lung cancer might offer significant number of advancements. Having in mind the significant duration of response observed in advance disease setting, there could be place for prolongation of response in adjuvant setting potentially, leading to improvement in survival. TKIs could offer less-toxic adjuvant treatment with better efficiency than chemotherapy. However, there is a chronic lack of randomized controlled trials in this field, leading to inability to draw any scientifically sound conclusion with regard to the adjuvant treatment. For now, the use of EGFR-TKIs outside clinical trial setting is not recommended. The purpose of this review is to evaluate current and available data.

Clinical characteristics, tumor, node, metastasis status, and mutation rate in domain of epidermal growth factor receptor gene in serbian patients with lung adenocarcinoma.

OBJECTIVE: Mutation rate in domain of EGFR gene varies between populations of lung cancer patients. Primary aim of this study was to analyze clinical and pathological characteristics, and tumor, node, metastasis status and stage of diseases, in relation to mutation status. METHODS: After histological confirmation of lung adenocarcinoma tissue obtained during bronchoscopy was consecutively sent for EGFR testing. Genomic DNA extraction was performed with the QIAamp DNA FFPE Tissue kit. Clinical data for multivariate analysis were extracted from hospital based-lung cancer registry. RESULTS: Among 360 tested patients, there was 67.8% males and 32.2% females, aged 61 ± 9.8 years. Majority of patients were smokers (57.0%) with Eastern Cooperative Oncology Group 1 performance status (92.2%). Mutation in EGFR gene was detected in 42 (11.7%) patients. Deletion in exon 19 was detected in 24 (6.7%) patients, mutation in exon 21 in 17 (4.7%), and mutation in exon 18 in one patient (0.3%). Patients were mostly diagnosed in stage IV adenocarcinoma (74.4%). Statistically significant differences were determined in relation to smoking (p < 0.001), T descriptor (size; p = 0.019) and gender (p = 0.002). CONCLUSIONS: Mutation rate in domain of EGFR gene in investigated lung cancer population is in range with reported data in Caucasian race. Smoking, T descriptor and gender were found to be related to the EGFR status.

Diagnostic value of autofluorescence bronchoscopy in lung cancer.

The role of autofluorescence bronchoscopy (AFB) was primarily investigated in regard to the detection of precancerous lesions of bronchial mucosa. Most of the results confirmed higher sensitivity for the detection of precancerous bronchial lesions, when compared to white light bronchoscopy (WLB) alone. However, it is commonly known that the specificity of AFB remains low. Our findings agree in terms of the detection of premalignant bronchial lesions and early lung cancer, but regarding the detection of synchronous lesions or in the evaluation of lung cancer extension, the specificity of AFB is significantly higher. There is still an ongoing debate in the scientific community whether or not autofluorescence should be used as a screening tool for lung cancer. Results of the majority of published series did not support the general use of AFB as a screening tool for lung cancer; however, these results suggest its use in groups of patients with a high risk of lung cancer. Despite this, some authors still do not recommend its use even in high-risk cases. In recent years, the indications for AFB have been widening and this tool may find its place in routine bronchoscopy. With new indications for AFB, such as the evaluation of tumor extension or follow up after surgical resection, bronchoscopists may make use of this tool more often. A sharp learning curve and a clear distinction between healthy and pathologically altered mucosa make this technology acceptable for inexperienced bronchoscopists. We also investigate new hardware and software improvements in AFB. The addition of backscattered light analysis, ultraviolet spectra, fluorescence-reflectance or dual digital systems could improve the diagnostic yield of this technology.

Linear and radial endobronchial ultrasound in diagnosis and staging of lung cancer.

Endobronchial ultrasound (EBUS) in recent years has become a routine diagnostic procedure in bronchology. Linear EBUS shows high diagnostic yield in evaluation of mediastinal lymph nodes. It is mainly used for nodal evaluation in lung cancer, but has also proven to be efficient in diagnostic evaluation of mediastinal masses. This technique has been shown to be complementary to mediastinoscopy. In combination with PET and rapid on site cytology (ROSE), the diagnostic yield of EBUS is significantly higher. Radial EBUS is used for diagnosis of peripheral lung lesions. This technique facilitates evaluation of bronchial wall in central lung cancer lesions, enabling differentiation between early and invasive lung cancer. The diagnostic yield of radial EBUS in the diagnostics of peripheral lung lesions is high, reducing the number of diagnostic thoracotomies. The application of miniature radial EBUS probes, together with guiding sheaths and other guiding accessories, allow the access to smaller and more peripheral lung lesions. In addition, EBUS bronchoscopy can be utilized for the placement of brachytherapy catheters, or evaluation of the distal bronchi in order to chose between different therapeutic bronchoscopic techniques for desobstruction. An experienced bronchoscopist, availability of ROSE and additional guiding devices might be necessary to accomplish the best possible results of EBUS bronchoscopy.

Detection of premalignant bronchial lesions can be significantly improved by combination of advanced bronchoscopic imaging techniques.

BACKGROUND: The search for the most efficient bronchoscopic imaging tool in detection of early lung cancer is still active. The major aim of this study was to determine sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each bronchoscopic technique and their combination in detection of premalignant bronchial lesions. METHODS: This was a prospective trial that enrolled 96 patients with indication for bronchoscopy. Lesions were classified as visually positive if pathological fluorescence was observed under autofluorescence imaging (AFI) videobronchoscopy or dotted, tortuous, and abrupt-ending blood vessels were identified under narrow band imaging (NBI) videobronchoscopy. Squamous metaplasia, mild, moderate, or severe dysplasia, and carcinoma in situ (CIS) were regarded as histologically positive lesions. RESULTS: Sensitivity, specificity, PPV, and NPV of white light videobronchoscopy (WLB) in detection of premalignant lesions were 26.5%, 63.9%, 34.4%, and 54.9%, respectively; the corresponding values for AFI were 52%, 79.6%, 64.6%, and 69.9% respectively, for NBI were 66%, 84.6%, 75.4%, 77.7%, respectively, while the values for combination of NBI and AFI were 86.1%, 86.6%, 84.6%, and 88%, respectively. Combination of NBI and AFI significantly improves sensitivity when compared to each individual technique (P < 0.001). When specificity is of concern, combination of techniques improves specificity of WLB (P < 0.001) and specificity of AFI (P = 0.03), but it does not have significant influence on specificity of NBI (P = 0.53). CONCLUSION: Combination of NBI and AFI in detection of premalignant bronchial lesions increases both sensitivity and specificity of each technique. However, it seems that NBI is most sufficient and effective in detection of these lesions.

Relation between vascular patterns visualized by Narrow Band Imaging (NBI) videobronchoscopy and histological type of lung cancer.

Narrow Band Imaging (NBI) videobronchoscopy is a new technique for visualization of microvascular changes in bronchial mucosa. The primary aim of this study was to evaluate relation between vascular patterns visualized by NBI and histology of lung cancer. We prospectively evaluated 65 patients with suspected lung cancer scheduled for bronchoscopy. NBI followed conventional WL videobronchoscopy. After identification of endoscopically visible tumor, NBI was used to determine predominant type of pathological vascular pattern (dotted, tortuous, abrupt-ending blood vessels-Shibuya descriptors). All the lesions were biopsied and histologically confirmed. There were 81.5 % male and 18.5 % female patients evaluated in the study. Lung cancer was confirmed in all patients; 63.1 % were diagnosed with squamous cell lung cancer (SCC), 24.6 % had adenocarcinoma, 9.2 % had small-cell (SCLC) and 3.1 % large-cell lung cancer (LC). Dotted blood vessels were significantly (p < 0.000) associated with adenocarcinoma, identified in 68.4 % adenocarcinoma and 31.6 % SCC. Tortuous blood vessels were identified in 72 % SCC, 8 % adenocarcinoma, 12 % SCLC and 8 % of LC. Tortuous blood vessels were significantly (p < 0.000) associated with SCC. Abrupt-ending vessels were identified in 81 % SCC, 14.3 % SCLC and 4.8 % adenocarcinoma and were significantly associated (p < 0.000) with SCC. Dotted visual pattern of blood vessels identified during NBI videobronchoscopy is highly suggesting adenocarcinoma histology of lung cancer. Tortuous and abrupt-ending blood vessels visualized under NBI videobronchoscopy significantly suggest squamous cell histology of lung cancer. Large-scale studies should be designed in order to determine true relation between visual appearance and histology in lung cancer.