A case report of high-grade intraepithelial neoplasia of the bronchial mucosa.

BACKGROUND: Lung cancer is the most common cause of cancer death worldwide and poses an immediate health threat. Despite decades of basic and clinical research, the 5-year survival rate for lung cancer patients is less than 10%.The most important drawbacks in efficient treatment of lung cancer are delayed diagnosis and absence of effective screening. Detection and study of precancerous lesions of the bronchial mucosa might be one of the turning points in understanding of neoplastic transformation. Therefore, it would be the most effective prevention and early treatment modality. We report a case of high-grade intraepithelial neoplasia of the bronchial mucosa in which a neoplastic growth in the lumen of intrinsic segment in the upper lobe of the left lung was detected on electronic bronchoscopy, and biopsy confirmed squamous papillary hyperplasia with high-grade intraepithelial neoplasia. CASE PRESENTATION: A 74-year-old male was admitted to the hospital due to a mass lesion in his left lung. After admission, computed tomography scan of the chest showed an intraluminal mass in the intrinsic segment of the upper lobe of the left lung and an enlarged left hilum. CONCLUSIONS: High-grade intraepithelial neoplasia of the bronchial mucosa is rare in the respiratory system. We report a case that can provide useful information for early diagnosis and treatment of the disease.

Trends in Imaging Patterns of Bronchogenic Carcinoma: Reality or a Statistical Variation? A Single-Center Cross-Sectional Analysis of Outcomes.

INTRODUCTION: Bronchogenic carcinoma accounts for more cancer-related deaths than any other malignancy and is the most frequently diagnosed cancer in the world. Bronchogenic carcinoma is by far the leading cause of cancer death among both men and women, making up almost 25% of all cancer deaths. The objective of this study was to identify the changing trends, if any, in radiological patterns of bronchogenic carcinoma to document the various computed tomography (CT) appearances of bronchogenic carcinoma with histopathologic correlation. METHODS: This was a single-center cross-sectional study on 162 patients with clinical or radiological suspicion of bronchogenic carcinoma with histopathological confirmation of diagnosis. RESULTS: There was a male preponderance with bronchogenic carcinoma and smoking being the most common risk factor. Squamous cell carcinoma followed by adenocarcinoma and small cell carcinoma is the most common histologic subtype. Squamous cell carcinoma was noted to be present predominantly in the peripheral location (55.5%), and adenocarcinoma was noted to be present predominantly in the central location (68.4%). CONCLUSION: CT is the imaging modality of choice for evaluating bronchogenic carcinoma and provides for precise characterization of the size, extent, and staging of the carcinoma. Among 162 bronchogenic carcinoma cases evaluated in the current study, a definite changing trend in the radiological pattern of squamous cell carcinoma and adenocarcinoma was observed. Squamous cell carcinoma was predominantly noted to be a peripheral tumor, and adenocarcinoma is predominantly noted to be a central tumor. Surveillance or restaging scans are recommended, considering the high mortality rate in patients with bronchogenic carcinoma.

Diagnosis and Treatment of Three Cases of Bronchial Carcinoma In Situ.

As part of a retrospective study on bronchoscopies performed at the Clinic of Pneumonology and Phthisiatry of the University Hospital - Pleven by autofluorescence bronchoscopy we found 3 cases diagnosed with carcinoma in situ. They were treated in different ways - endobronchial electrocoagulation, extraction by forceps biopsy and open surgery, but the result was the same - clinical healing. The paper presents the three clinical cases and the analysis of the treatment.

Expansion of myeloid-derived suppressor cells in chronic obstructive pulmonary disease and lung cancer: potential link between inflammation and cancer.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a risk factor for lung cancer (LC). Myeloid-derived suppressor cells (MDSCs) down-regulate the T cell receptor ζ chain (TCR ζ) through L-arginine deprivation and lead to T cell dysfunction and deficient antitumor immunity. We hypothesized that abnormally high levels of MDSCs in COPD patients may alter tumor immunosurveillance. METHODS: We compared the proportion of circulating MDSCs (Lin-HLA-DR-/CD33+/CD11b+) (by flow cytometry), arginase I (ARG I) serum levels (by ELISA), and expression levels of TCR ζ on circulating lymphocytes (by flow cytometry) in 28 patients with LC, 62 subjects with COPD, 41 patients with both LC and COPD, 40 smokers with normal spirometry and 33 non-smoking controls. T cell proliferation assays were performed in a subgroup of participants (CFSE dilution protocol). RESULTS: We found that: (1) circulating MDSCs were up-regulated in COPD and LC patients (with and without COPD); (2) MDSCs expansion was associated with TCR ζ down-regulation in the three groups; (3) in LC patients, these findings were independent of COPD and tobacco smoking exposure; (4) TCR ζ down-regulation correlates with T cell hyporesponsiveness in COPD and LC patients. CONCLUSIONS: These results suggest that tumor immunosurveillance might be impaired in COPD and may contribute to the increased risk of LC reported in these patients.

Telomere Length of Human Adult Bronchial Epithelium and Bronchogenic Squamous Cell Carcinoma Measured Using Tissue Quantitative Fluorescence in situ Hybridization.

BACKGROUND: Telomeres are repetitive DNA sequences located at the ends of chromosomes. Chromosomal and genomic instability due to telomere dysfunction has been known to play an important role in the carcinogenesis of some organs. OBJECTIVES: The aim of this study was to examine the correlation between smoking and the telomere length of human bronchial epithelial cells in individuals with and without lung cancer. PATIENTS AND METHODS: We examined 68 non-lung cancer adult autopsy cases and 24 surgically resected cases of lung squamous cell carcinoma. Telomere lengths of the basal cells of bronchial epithelium were measured using the tissue quantitative fluorescence in situ hybridization method and were expressed in normalized telomere-to-centromere ratios (NTCRs). RESULTS: The autopsied individuals included 27 current smokers (CuS), 33 never-smokers (NeS), and 8 ex-smokers (ExS). The NTCRs in the central bronchi of CuS, NeS, and ExS were 1.515, 1.372, and 1.204, respectively. The bronchial epithelial telomeres of CuS were significantly longer than those of non-CuS (NeS + ExS). When the analysis was conducted separately for females and males, a significant difference between CuS and NeS + ExS was recognized only for males. The NTCRs of the bronchial epithelium of lung cancer cases and lung cancer tissue are 1.514 and 1.385, respectively. CONCLUSIONS: Our findings suggest that smoking causes telomeric elongation in the bronchial epithelium. Therefore, it appears that the mechanism of carcinogenesis in smoking-related carcinomas may differ from that of many other carcinomas in which genetic instability due to aging-related telomeric shortening is assumed to play a role.

Clinico-pathological Profile of Bronchogenic Carcinoma Among Females in North India.

OBJECTIVE: The present study was undertaken to explore the clinico-pathological profile of bronchogenic carcinoma among females. METHODS: One hundred and twenty-four female patients with histopathologically proven bronchogenic carcinoma who were hospitalised in the Department of Pulmonary Medicine, King George's Medical University, Lucknow from July 1985 to February 2007 were retrospectively studied. RESULTS: Their mean age was 61 years; 12.9% of these were less than 40 years of age. Of these, 79% of female patients of lung cancer were first regarded as pulmonary tuberculosis; 76% belonged to rural area. Use of biomass fuel and kerosene oil exposure was the predominant risk factors evident among the 116 non-smoker women. Adenocarcinoma was observed in 43.5%, followed by squamous cell carcinoma in 33.1% and the remaining 23.4% cases were small cell carcinoma. The majority (77.4%) of non-small cell lung cancer (NSCLC) patients had advanced stage disease (I]Ib and IV) and 58% of small cell lung cancer (SCLC) patients had limited disease and 42% of SCLC patients had extensive disease at the time of diagnosis. CONCLUSION: Adenocarcinoma was found to be the most common histopathological type of bronchogenic carcinoma among these females.

[Robot-assisted minimally invasive lobectomy with systematic lymphadenectomy for lung cancer]. / Roboterassistierte minimalinvasive Lobektomie mit systematischer Lymphadenektomie zur Behandlung des Bronchialkarzinoms.

BACKGROUND AND INTRODUCTION: Lobectomy for lung cancer is the standard therapy for lung cancer in limited stages. The adoption of minimally invasive lobectomy (video-assisted thoracic surgery or VATS lobectomy) has increased worldwide since its first description more than 15 years ago. However, the VATS technique has a long learning curve and sometimes limitations in terms of precise preparation and presentability of the central structures of the lung hilus due to the limited mobility of the standard thoracoscopic instruments. By using a four-arm robotic platform (DaVinci®), not only the preparation of the hilus structures but also the central lymphadenectomy can be performed in a comfortable and safe way under a clear and precise view. INDICATION: Surgical treatment of locally limited lung cancer in the right lower lobe (squamous cell carcinoma). PROCEDURE: Robot-assisted, minimally invasive right lower lobectomy with systematic lymphadenectomy. CONCLUSION: Robot-assisted minimal invasive lobectomy is feasible with special regard to oncological and technical aspects. Especially the intrathoracic precise dissection of the tissue under a perfect view allow a comfortable and safe operation technique.

Bronchial carcinoid tumors: A rare malignant tumor.

Bronchial carcinoid tumors (BCTs) are an uncommon group of lung tumors. They commonly affect the young adults and the middle aged, the same age group affected by other more common chronic lung conditions such as pulmonary tuberculosis. Diagnosis is commonly missed or delayed due to a low index of suspicion. Surgery is the mainstay of treatment with an excellent outcome. There are many reports of this rare group of tumors in the Western and Asian regions. The only report around our sub-region is a post mortem report of an atypical variant. We wish to report a case of the typical variant and increase our index of suspicion. A 25-year-old male presented with a 4 years history of cough and haemoptysis. He was repeatedly treated for bronchial asthma and pulmonary tuberculosis with no improvement of symptoms. Chest X-ray and chest computed tomography scan revealed a left upper lobe tumor. Histology reported a typical variant of BCT which was confirmed by immunohistochemistry. He had a left upper lobectomy and has done excellently well thereafter. A high index of suspicion is needed to reduce the risk of missing or delaying the diagnosis.

[Resected non-small cell bronchogenic carcinoma stage pIIIA-N2. Which patients will benefit most from adjuvant therapy?]. / Carcinoma broncogénico no microcítico resecado, estadio pIIIA-N2. ¿En qué pacientes la adyuvancia ofrece mayor beneficio?

BACKGROUND: Controversy persists as regards the indications and results of surgery in the treatment of patients with stage pIIIA-N2 non-small cell lung cancer (NSCLC). The objective of this study was to analyze the overall survival of a multicentre series of these patients and the role of adjuvant treatment, looking for factors that may define subgroups of patients with an increased benefit from this treatment. METHODS: A retrospective study was conducted on 287 patients, with stage pIIIA-N2 NSCLC subjected to complete resection, taken from a multi-institutional database of 2.994 prospectively collected consecutive patients who underwent surgery for lung cancer. Adjuvant treatment was administered in 238 cases (82.9%). Analyses were made of the age, gender, histological type, administration of induction and adjuvant chemotherapy and/or radiation therapy treatments. RESULTS: The 5-year survival was 24%, with a median survival of 22 months. Survival was 26.5% among patients receiving with adjuvant treatment, versus 10.7% for those without it (P=.069). Age modified the effect of adjuvant treatment on survival (interaction P=.049). In patients under 70 years of age with squamous cell carcinoma, adjuvant treatment reduced the mortality rate by 37% (hazard ratio: 0,63; 95% CI; 0,42-0,95; P=.036). CONCLUSIONS: Completely resected patients with stage pIIIA-N2 NSCLC receiving adjuvant treatment reached higher survival rates than those who did not. Maximum benefit was achieved by the subgroup of patients under 70 years of age with squamous cell carcinoma.

External auditory canal mass as the first manifestation of a bronchogenic carcinoma: report of a rare case.

OBJECTIVES: Metastatic tumors in the external auditory canal (EAC) are exceptionally rare. These metastases almost always occur in the latter stages of the disease process. Ten cases of metastatic tumors of the EAC have been reported in the literature. We report the first case of a metastatic bronchogenic adenocarcinoma that presented initially as an EAC mass. METHODS: We present a case report and a literature review. RESULTS: Although bronchogenic adenocarcinoma not uncommonly metastasizes to the temporal bone, metastasis to the EAC is extremely rare. We report the case of a 62-year-old woman who presented with a 6-week history of swelling in her right EAC and sudden onset of hearing loss. Physical examination revealed a small, polypoid, friable mass originating from the superior-posterior wall of the right EAC. Incision biopsy was performed, and the histopathologic examination of specimens revealed a moderately to poorly differentiated adenocarcinoma compatible with a bronchogenic origin. CONCLUSIONS: A patient with an aural mass presents a diagnostic dilemma. Metastatic tumors in the EAC are extremely rare, but they should be included in the differential diagnosis of a mass in this location.

Importance of systemic mediastinal lymphadenectomy in exact staging of bronchogenic carcinoma.

BACKGROUND: Constituent part of radical lung resection for lung cancer is a dissection of mediastinal lymph nodes. Lymphadenectomy is a standard procedure in an assessment of clinical stage of the disease. The aim of the study was to map metastasizing of bronchogenic non-small cell lung carcinoma into homolateral mediastinal lymph nodes and to assess the importance of mediastinal lymphadenectomy for exact staging and survival. METHODS: Study of 31patients with lung resection and systematic mediastinal lymphadenectomy operated from August 2004 to January 2007, with pre-operative stage Ia to IIb (TNM classification) - according to CT without mediastinal lymph nodes invasion and with positive histological finding after systematic mediastinal lymphadenectomy. RESULTS: Tumors in right upper lobe metastasized in 45.5 % into group 1 nodes (stages N1-N4) and group 3 nodes (stages N7) and in 9 % into group 4 nodes (stages N8-N9). Tumors of the right middle lobe metastasized in 100 % into group 3 nodes (stage N7).Tumors of the right lower lobe metastasized in 87.5 % into group 3 nodes (N7) and in 12.5 % into group 4 nodes (stages N8-N9). Tumors of the left upper lobe metastasized in 9.0 % in group 1 nodes (stages N1-N4), in 82 % into group 2 nodes (stages N5-N6) and in 9.0 % were found skip metastases into group 4 nodes (stages N8-N9). Tumors of the left lower lobe metastasized in 26.7 % in group 4 nodes, 46.6 % into group 3 nodes, in 20,0 % into group 2 nodes and in 6,7 % into group 1 nodes. CONCLUSION: Systematic mediastinal lymphadenectomy is crucial for determining the stage of the disease according to the TNM classification. Systematic lymphadenectomy is essential for the diagnosis of stage IIIa disease and setting of additional therapy that prolongs survival (Ref. 17).

[The clinical value of autofluorescence bronchoscopy for precancerous lesions in operable primary lung cancer patients]. / Primer akciger karsinomu nedeniyle opere edilecek hastalarda otofloresan bronkoskopi ile prekanseröz lezyonlarin arastirilmasi.

INTRODUCTION: The aim of the present study is to show the role of autofluorescence bronchoscopy (AFB) compare with white light bronchoscopy (WLB) in detecting synchronous cancer and precancerous lesions in cases with operable primary lung cancer. MATERIALS AND METHODS: Fourty-nine patients were included in the study. WLB findings were grouped as group 1 normal, group 2 erithema or edema, group 3 nodular lesions or mucosal abnormality. AFB findings were grouped as group 1 normal, group 2 light brownish abnormal areas, group 3 brownish abnormal areas. Biopsies were obtained from group 2 and 3 patients. In 12 (24.5%) of the patients no areas were suspected and no biopsies were taken. RESULTS: Twenty-six (53%) of 49 patients did not show abnormal biopsy results in any of the specimens. One (2%) patient had metaplasia, 1 (2%) patient had dysplasia, 1 (2%) patient had in situ carcinoma. The diagnostic accuracy rates for the detection of synchronous cancer and precancerous lesions using WLB and AFB were as follows respectively: sensitivity 77.8% vs. 100%; specificity 37.5% vs. 3%; positive predictive value 21.9% vs. 24.3%; negative predictive value 88.2% vs. 100%. The relative sensitivity of AFB to WLB is 1.28. CONCLUSION: This study demonstrated that, AFB is an effective method in detecting synchronous cancer and precancerous lesions because of its low specificity it is more likely to be complementary to WLB.

Synergistic effects of erlotinib and everolimus on bronchial carcinoids and large-cell neuroendocrine carcinomas with activated EGFR/AKT/mTOR pathway.

BACKGROUND: Epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (mTOR) are crucial targets in cancer therapy. Combined inhibition of both targets yielded synergistic effects in vitro and in vivo in several cancer entities. However, the impact of EGFR and mTOR expression and combined inhibition in neuroendocrine lung tumors other than small-cell lung cancer remains unclear. MATERIAL AND METHODS: Expression and activation of EGFR/AKT/mTOR pathway constituents were investigated in typical and atypical bronchial carcinoid (AC) tumors and large-cell neuroendocrine lung carcinomas (LCNEC) by immunohistochemistry in 110 tumor samples, and correlated with clinicopathological parameters and patient survival. Cytotoxicity of mTOR inhibitor everolimus and EGFR inhibitor erlotinib alone and in combination was assessed using growth inhibition assay in NCI-H720 AC and SHP-77 LCNEC cells. Cell cycle phase distribution was determined by FACS. Apoptosis-associated activation of caspase-3/7 was measured by Caspase-Glo® assay. Activity status of EGFR and mTOR pathway components was analyzed by immunoblotting. RESULTS: Activation of the EGFR/AKT/mTOR axis could be demonstrated in all entities and was significantly increased in higher grade tumors. Neoadjuvant chemotherapy correlated significantly with p-AKT expression and p-ERK loss. Erlotinib combined with everolimus exerted synergistic combination effects in AC and LCNEC cells by induction of apoptosis, while cell cycle phase distribution remained unaffected. These effects could be explained by synergistic downregulation of phospho-mTOR, phospho-p70S6 kinase and phospho-AKT expression by everolimus and erlotinib. CONCLUSIONS: Our study indicates that EGFR and mTOR are clinically important targets in bronchial neuroendocrine tumors, and further in vivo and clinical exploration of combined inhibition is warranted.

Mediastinal lymph node staging: from noninvasive to surgical.

OBJECTIVE: The purpose of this review is to describe the current lymph node stations and lymph node staging of non-small cell lung carcinoma. Minimally invasive and invasive methods of mediastinal lymph node staging are emphasized, and the relative accuracy and limitations of each modality are described. CONCLUSION: Lung carcinoma remains the most common cause of cancer death in the United States. Accurate staging of lung cancer is imperative for implementing the correct therapy and assessing patient prognosis.

[Role of imaging techniques in the TNM classification of non-small cell bronchogenic carcinoma]. / Papel de las técnicas de imagen en la nueva clasificación TNM del carcinoma broncogénico no microcítico.

The Seventh Edition of the TNM Classification for non-small cell bronchogenic carcinomas include a series of changes in the T and M descriptor, in particular a re-classification of malignant pleural and pericardial effusions and of separated tumour nodes, new tumour size cut-off values and sub-divisions of the T1-T2 and M1 categories. We review these corrections that led to the changes in the staging system that affects stages II-III. Furthermore, we describe and illustrate the role of the different imaging techniques in tumour staging (CT, PET, PET-CT and MRI), highlighting their respective indications, advantages and disadvantages, as well their complementary function.

A Case Report of an Unusual Cause of Dysphagia from Enlarged Subcarinal Lymph Node.

Cough, hemoptysis, chest pain, and weight loss are classic symptoms of bronchial carcinoma. Small cell lung cancer presents late with obviously abnormal chest radiographs and with bulky, usually mediastinal lymph node involvement. Dysphagia rarely occurs in patients with bronchial carcinoma. There are many causes of dysphagia in bronchial carcinoma such as mediastinal lymphadenopathy, direct tumor invasion of the mediastinum, radiotherapy, secondary achalasia. This report presents a case of progressive dysphagia to solid foods and weight loss of a 28-year-old male, non-smoker due to subcarinal lymph node enlargement from metastatic bronchial adenocarcinoma.

Anal-transitional and bronchial metaplasia within the ileostomy of a small bowel allograft: a case report.

Epithelial metaplasia is a phenomenon where a native mucosal cell type is replaced by another due to altered stem cell differentiation, usually as the result of long-standing injury or inflammation. It is common in ileostomies performed with native small bowels for both neoplastic and inflammatory conditions. We present a case of anal-transitional and bronchial epithelial metaplasia that occurred near the ileostomy of a small bowel allograft in a seven-month-old male transplanted for short bowel syndrome related to gastroschisis. The anal-transitional metaplastic mucosa had an immunophenotype (CK7- and p63-positive) similar to that of normal mucosa at the anal transition zone and a DNA STR profile consistent with the donor. To our knowledge, this represents the first report of this type of metaplasia occurring in ileostomies in the English literature. It is important for clinicians and pathologists to recognize these benign mucosal alterations to avoid diagnostic confusion.

The diagnostic yield and safety of ultrasound-assisted transthoracic fine-needle aspiration of drowned lung.

BACKGROUND: Proximal lung tumors, though not discernable by means of transthoracic ultrasound (US), may cause varying degrees of pulmonary collapse and postobstructive pneumonitis which may give rise to a 'drowned lung' appearance on chest computed tomography (CT) and US. The diagnostic yield for malignancy of US-assisted transthoracic fine-needle aspiration (FNA) of these areas of drowned lung is unknown. OBJECTIVES: We aimed to explore the feasibility of US-assisted FNA in this setting by prospectively investigating its diagnostic yield and safety. METHODS: We enrolled 31 patients (aged 59.4 ± 9.7 years, 17 males) with central tumors and secondary drowned lung on CT scan. A respiratory physician performed transthoracic US to identify the target drowned lung tissue. Three US-assisted superficial FNA passes (≤20 mm from the pleura) were followed by 3 deeper FNA passes (>20 mm) aimed in the direction of a visible or approximated central mass. Rapid on-site evaluation of specimens was used. RESULTS: Superficial FNA was diagnostic in 11 patients (35.5%), whereas deeper FNA was diagnostic in 23 patients (74.2%, p = 0.002). Deeper FNA confirmed malignancy in all cases with diagnostic superficial FNA. We observed no pneumothoraces or major hemorrhage. All patients were ultimately diagnosed with malignancy (bronchogenic carcinoma, n = 30; lymphoma, n = 1). CONCLUSIONS: US-assisted FNA of drowned lung has an acceptable diagnostic yield and is safe.