Autofluorescence bronchoscopy in the detection of squamous metaplasia and dysplasia in current and former smokers

BACKGROUND: New methods are needed to detect precancerous lesions in lung tissue. We conducted a study to determine the utility of LIFE (laser-induced fluorescence emission) autofluorescence bronchoscopy for the detection of squamous metaplasia and dysplasia in current and former smokers. METHODS: In this prospective, single-center study, 53 participants underwent standard white-light bronchoscopy and 39 underwent both white-light and LIFE bronchoscopy. Bronchial biopsy specimens were obtained from all participants at six pre-determined sites using white-light bronchoscopy and from all other sites that appeared to be abnormal in participants who underwent LIFE bronchoscopy. Relationships between LIFE imaging and histologic findings were examined for 245 biopsy specimens obtained from those participants who had undergone LIFE bronchoscopy. RESULTS: LIFE imaging revealed abnormalities designated as either class II or class III in 89 (36.3%) and 16 (6.5%) of the 245 sites examined, respectively, and histopathologic examination showed dysplasia and metaplasia in eight (3.3%) and in 52 (21.2%) of the 245 specimens, respectively. Among the 105 biopsy specimens obtained from sites with abnormal LIFE imaging, only 26 (24.8%) exhibited squamous metaplasia and/or dysplasia, similar to the findings for sites with normal LIFE imaging (34 [24.3%] of 140). Comparison of individuals examined by LIFE imaging with those who underwent white-light bronchoscopy alone revealed no increase in the detection of dysplasia or metaplasia with LIFE bronchoscopy. CONCLUSION: In this population of current and former smokers, abnormalities detected by LIFE bronchoscopy did not improve the detection of squamous metaplasia or dysplasia.     

Scanning electron microscopy of the bronchial mucosa in some lung diseases using bronchoscopy specimens. A pilot study including cases of bronchial carcinoma, sarcoidosis, silicosis and tuberculosis

In order to study the lung defence mechanisms and the mucociliary transport system scanning electron microscopy was performed on biopsy specimens obtained at bronchoscopy under local anaesthesia. There were great variations in the appearance of the cilitated epithelium from the large bronchi in 40 patients with bronchial carcinoma, sarcoidosis, silicosis, tuberculosis and other lung diseases. Areas with a low frequency of cilia were observed mainly in granulomatous disorders, and in silicosis, atypical cilia occurred abundantly. Squamous metaplasia with a complete loss of cilia was found in chronic bronchitis, bronchial carcinoma, after radiotherapy and in two of seven cases of sarcoidosis. Scanning electron microscopy seems to be an excellent method for studying the surface of the bronchial epithelium in many lung diseases, and may prove to be helpful in occupational medicine.     

Performance of various X-ray film/screen systems in demonstrating small simulated low-density lung nodules

A high-quality, conventional chest radiograph should be obtained in lung cancer screening programs to efficiently detect the faint, small nodular shadows due to early lung cancer in the lung fields, although, it is difficult to image the entire lung field within the linear part of the characteristic curve of the screen/film system owing to the wide variation in tissue density in the thorax, which ranges from the well aerated lung superimposed on the intercostal spaces to the lung area superimposed on the heart or diaphragm. In the detection of early cancer in the lung fields, it is important to consider the very low density (CT values of nearly -600 HU to -300 HU) commonly exhibited by early adenocarcinomas in the lung. The detectability of such nodules would be greatly influenced by the contrast and noise characteristics of the photographic system, the complexity of anatomical structures around the nodule, the characteristics of the observation system for x-ray films, the interpreter, and so on. The choice of x-ray film/screen system basically determines the efficacy of screening; specifically, the contrast characteristics of x-ray films together with noise level, which varies at different optical densities, affect the detectability of nodular shadows. The present study was carried out to determine the most suitable sensitometric characteristics and to assess the effects of the noise level of the x-ray film/screen system on the detectability of nodular shadows within the lung fields, particularly in low-density areas.     

Overexpression and activation of hepatocyte growth factor/scatter factor in human non-small-cell lung carcinomas

Hepatocyte growth factor/scatter factor (HGF/SF) stimulates the invasive growth of epithelial cells via the c-MET oncogene-encoded receptor. In normal lung, both the receptor and the ligand are detected, and the latter is known to be a mitogenic and a motogenic factor for both cultured bronchial epithelial cells and non-small-cell carcinoma lines. Here, ligand and receptor expression was examined in 42 samples of primary human non-small-cell lung carcinoma of different histotype. Each carcinoma sample was compared with adjacent normal lung tissue. The Met/HGF receptor was found to be 2 to 10-fold increased in 25% of carcinoma samples (P = 0.0113). The ligand, HGF/SF, was found to be 10 to 100-fold overexpressed in carcinoma samples (P < 0.0001). Notably, while HGF/SF was occasionally detectable and found exclusively as a single-chain inactive precursor in normal tissues, it was constantly in the biologically-active heterodimeric form in carcinomas. Immunohistochemical staining showed homogeneous expression of both the receptor and the ligand in carcinoma samples, whereas staining was barely detectable in their normal counterparts. These data show that HGF/SF is overexpressed and consistently activated in non-small-cell lung carcinomas and may contribute to the invasive growth of lung cancer.     

Systemic embolism in a renal transplant patient. Echocardiographic demonstration of bronchial carcinoma with intracardiac invasion

A 45 year old female renal transplant patient was admitted for subacute ischaemia of a lower limb. Echocardiography was performed and showed the presence of bronchial carcinoma with intracardiac invasion. The tumour was confirmed by thoracic computerised tomography and by bronchoscopy. Histological investigation of bronchial biopsies and of the arterial embolism extracted at surgery showed large cell malignant disease. The tumour partially responded to chemotherapy and the patient survived for 5 months. Extension of a bronchial carcinoma to the left atrium is a classical complication in autopsy reports but rarely a source of systemic embolism. Echocardiographic diagnosis of this condition is very rare. The incidence of malignant diseases is higher in renal transplant patients than in the general population but this has not been verified for bronchial carcinoma. Echocardiography played an essential role in this case, detecting the tumour and its extension, indicating a poor prognosis and guiding treatment.     

Mediastinoscopy, thoracoscopy, and video-assisted thoracic surgery in the diagnosis and staging of lung cancer

The surgical approach to the diagnosis and staging of lung cancer requires the assessment of the lung parenchyma, hilum, pleura, chest wall, and intrathoracic lymph nodes. Chest computerized tomography is sensitive in defining the location of the primary tumor, but is relatively insensitive to invasion. Similarly, radiographic imaging can identify lymph node enlargement, but lymph node enlargement alone is insufficient for accurate staging. To facilitate the tissue biopsies of both the primary tumor and potential sites of metastatic disease, video thoracoscopy has provided a useful complement to traditional bronchoscopy and mediastinoscopy. These instruments provide minimally invasive access to the lung, pleura, and ipsilateral lymph nodes. The combined application of thoracoscopy, bronchoscopy, and mediastinoscopy can provide intrathoracic staging information while minimizing surgical morbidity.     

Investigation of specimen mislabelling in paraffin-embedded tissue using a rapid, allele-specific, PCR-based HLA class II typing method

Topical application of 5-aminolevulinic acid (5-ALA), with subsequent synthesis of protoporphyrin IX (PPIX), is a novel outstanding procedure for photodynamic treatment. So far, clinical experience has been reported with creams containing 5-ALA for the therapy of skin cancer, oral application for the treatment of gastrointestinal disease and intravesical instillation of 5-ALA solutions for fluorescence detection of superficial bladder cancer. Inhalation of 5-ALA for the staining of bronchial malignancies is a preferred method in clinical pulmonology. Since no adverse reaction was observed in lung function in a canine following inhalation of 5-ALA in increasing concentrations, clinical applications were performed. Seven patients with positive or suspicious sputum cytology, but negative white light bronchoscopy, received 5-10 wt.% 5-ALA in NaCl solution by means of a medical nebulizer. No side effects were observed during and after 5-ALA inhalation. After a period of 3 h, patients underwent fluorescence bronchoscopy using violet light for fluorescence excitation and an optical multichannel analyzer for fluorescence detection in situ. The results showed fluorescence spectra which could be related to PPIX induced by 5-ALA in the bronchial mucosa. The fluorescence intensity was sufficiently high for video imaging using a target integrating color CCD camera adapted to the flexible bronchoscope. Carcinoma in situ, as well as dysplasias, showed a clear positive fluorescence. A correlation of fluorescence contrast with histology on 30 biopsies revealed a high sensitivity, but a specificity below 50%. Improvements in light and drug dosimetry will form the basis for further clinical trials.     

Disruption of the middle bronchus

Disruption of the middle lobe broncus as a result of blunt chest trauma is described. Patient underwent emergency reconstructive operation. Follow-up examination revealed normal postoperative chest radiogram but bronchoscopy showed decreased patency of bronchial anastomosis. Perfusion lung scintigraphy showed severely decreased perfusion of the entire right lung. Concomitant fracture of right clavicle resulted in false joint which required surgical intervention 4 weeks after the chest trauma.     

Cytology of bronchial biopsy rinse fluid to improve the diagnostic yield for lung cancer

Sampling techniques are combined during bronchoscopy to increase the diagnostic yield for endobronchial malignant tumours. Bronchial biopsy provides the definitive histological diagnosis in most cases, but accompanying cytological procedures such as washing, brushing, needle aspiration or imprint cytology can increase diagnostic yield. In this prospective study, a different cytological technique, that could enhance the diagnostic yield of bronchoscopy without increasing its time or cost, was tested. Flexible bronchoscopy was performed in 93 patients suspected of having pulmonary neoplasms. Bronchial biopsies were initially placed in a balanced salt solution. When bronchoscopy was finished, all visible tissue fragments were removed and placed in formalin to undergo histopathological examination and the rinse fluid was sent for cytological examination. Washing was performed routinely but no cytological brushing was employed. Eighty-two patients had final diagnoses of malignant neoplasm. In four (4.8%) of these patients, the only positive result came from the cytological examination of the bronchial biopsy rinse fluid. No false-positive results were found. The agreement with the histological results was 81.8%. The addition of bronchial biopsy rinse-fluid examination increased the sensitivity of bronchoscopy from 65.8% to 70.7% (McNemar's p=0.009). The cytological study of bronchial biopsy rinse fluid offers reliable positive results in an additional 4.8% of cases, thus enhancing bronchoscopic diagnostic yield for malignant endobronchial tumours while neither prolonging the procedure nor increasing costs.     

The value of diagnostic methods used to assess the response to treatment in patients with limited small cell lung carcinoma

Tumor response is used as a main criterion whether or not the treatment yields an anticancer activity. The tumor response criteria are defined by WHO recommendation but little is known about the tests must be used. The aim of this paper was to compare the degree of response to the treatment of 268 patients with limited small cell lung cancer, using independently 3 methods: radiological, bronchoscopic and cytological of bronchial material. Particular categories of response (CR, PR NR and presence or absence of carcinomatous cells) were related to survival time of patients independently to method of assessment. Multivarinte Cox analysis selected 3 parameters related to 3 different methods as independent survival risk factors. We conclude that each of diagnostic method (chest x-ray, bronchoscopy, cytological examination of bronchial material yield independent information correlated with survival risk of particular patient.     

Interbronchoscopist variability in the diagnosis of lung cancer by flexible bronchoscopy

STUDY OBJECTIVE: We evaluated the interbronchoscopist variability in the diagnosis of lung cancer by flexible bronchoscopy. DESIGN AND SETTING: A retrospective review of the bronchoscopic records and clinical charts of patients at a university-affiliated hospital. PATIENTS AND MEASUREMENTS: All records of flexible bronchoscopic procedures performed for the diagnosis of lung cancer were retrospectively reviewed, and procedures that obtained histologic or cytologic evidence of malignancy were considered positive. Rates of positivity were compared according to the following factors: operator, operator experience, bronchoscopic findings, tumor location, and tumor laterality. Factors that affected the positivity rate were evaluated using logistic regression analysis. RESULTS: Of 384 bronchoscopic procedures performed in 353 patients, 275 (72 percent) were positive. The positivity rate differed significantly depending on the operator (p = 0.003) and the bronchoscopic findings (p < 0.001). A difference between operators was noted in technically difficult cases without epithelial or subepithelial findings and when tumors were located in the upper lobe or the superior segment of the lower lobe. The bronchoscopic findings and the operator also emerged as factors significantly affecting the positivity rate in the logistic analysis. CONCLUSIONS: The diagnostic yield of bronchoscopy for lung cancer is dependent on both the type of bronchial lesion present and the bronchoscopist.     

Onset of the neuromuscular block simulated in an anatomical model

Radioiodine scintigraphy is the gold standard exploration for imaging metastases of differentiated thyroid cancer and enables the decision of therapy with 131 radioactive iodine to be made. However, other approaches may be of use for diagnosis when there is no visible uptake after the administration of 131I, while elevated thyroblobulin levels suggest the presence of metastatic tissue in one third of metastatic patients. In order to detect recurrences or metastases, in conjunction with conventional imaging techniques (cervical and hepatic ultrasonography, lung CT scan..), other scintigraphic explorations with various radiopharmaceutics may be used, although none of them has any specificity towards thyroid cancer. Tl201 and MIBI which are used as perfusion tracers for myocardial explorations, are also used for detection of various tumors and for metastatic thyroid cancer. The performances of both radiopharmaceutics in imaging metastases are differently evaluated between investigators with a sensitivity ranging from 45 to 94% while the specificity varies less (82-97%). 18-Fluoro-deoxyglucose is retained in malignant tissue depending on the grade of malignancy. It has been shown to accumulate in thyroid cancer and metastases. Its detection by whole body PETscan represents a limitation for use which will be modified by new techniques. 111In-octreotide which binds to somatostatin receptors located on tumor cell membranes is able to show thyroid cancer metastases in some instances. We report on the very preliminary results of these combined scintigraphic approaches, performed in a limited number of patients who had no radioiodine uptake and elevated Tg levels, in order to determine the most appropriate exploration in terms of performance and cost.     

Preliminary results of fine needle aspiration biopsy histology in upper gastrointestinal submucosal tumors

To elucidate the characteristics of lung cancer complicated by pneumoconiosis, we compared the clinical features of complicated and uncomplicated lung cancer cases. The average age at onset was higher for patients with pneumoconiosis than for those without. Because pneumoconiosis presents various respiratory symptoms, subjective symptoms were less important than objective symptoms in detecting lung cancer complicated by pneumoconiosis. Although fiberoptic bronchoscopy was the predominant diagnostic method, it could not be used with the pneumoconiosis patients. Diagnoses of lung cancer complicated by pneumoconiosis were made more after by percutaneous needle aspiration cytology. Squamous cell carcinoma is the most frequent form of cancer in patients with pneumoconiosis, which suggests that the inhalation of carcinogens may play a role in the pathogenesis of lung cancer. With respect to the smoking index (SI), histological specimens indicated that the incidence of squamous cell carcinoma in patients with pneumoconiosis was significantly higher in heavy smokers (SI > or = 600) than in light smokers (SI < 600) or nonsmokers. It is suspected that smoking affects carcinogenesis of pneumoconiosis. No differences in the distribution of lung cancer (right-left, hilar-peripheral) distinguished the 2 groups. Many of the patients with peripheral-type lung cancer and pneumoconiosis had tumors in the lower lung lobes. These findings underline the importance of encouraging pneumoconiosis patients to avoid lung cancer by not smoking, and to have lung cancer detected in its early stages by undergoing regular medical exams.     

Effect of aging on detrusor function in males

Some of the most dramatic advances in the treatment of cancer have used the immune system in combination with conventional or transplantation chemotherapy. Adoptive immunotherapy has been used for relapses after allogeneic bone marrow transplantation, and it has been particularly effective for chronic myeloid leukemia. Adoptive immunotherapy also has been used for Epstein-Barr virus-related lymphomas developing after allogeneic marrow transplantations. Cellular therapy, including the infusion of tumor-reactive immune cells, has been used to mediate response of established solid tumors. This has been used for therapeutic benefit for renal cell carcinoma, melanoma, lung cancer, and breast cancer. Current research is focusing on reducing the toxicity of these approaches as well as further defining the appropriate target tissue.     

Assessment of complications in patients with lung transplantation with high resolution computerized tomography

INTRODUCTION: High Resolution Computed Tomography (HRCT) has been used by many authors to study the early complications of lung transplantation. Bronchoscopy, transbronchial biopsy and the clinical parameters are the tools of choice to diagnose such complications; HRCT showed excellent sensitivity (100%) and good specificity (93%) especially in detecting bronchial stenoses. We report the preliminary results of HRCT in detecting early/late complications in lung transplant recipients. MATERIAL AND METHODS: Sixteen lung transplant recipients (5 single and 11 double transplants) were examined with HRCT at the Servizio Speciale Diagnostica V of "La Sapienza" University (Rome, Italy). The CT findings were compared with the results of bronchoscopy and respiratory function tests. The patients (8 men and 8 women; age range: 18-57 years, mean: 37.5) had cystic fibrosis (9), emphysema (3), alpha-1-antitrypsin deficiency (1), idiopathic pulmonary fibrosis (2), and bronchiectasis (1). RESULTS AND DISCUSSION: During the follow-up, one patient died of pulmonary edema. CT findings were normal in 3 patients and mild pleural effusion was seen in 2. The other HRCT findings were: bronchial stenosis in 5 cases (which was bilateral in 1) and bronchial dehiscence in 1 patient; four cases of infection (1 CMV, 1 aspecific bacterial pneumonia, 1 Chlamydia psittacea and 1 Aspergillosis) and one of brochiolitis obliterans. A patient was treated for acute and one for chronic rejection. A CMV infection involved only the native lung in a patient. CT is easy to perform and a repeatable and well-tolerated tool with high sensitivity (100%) and good specificity (93%) in the early diagnosis of complications, particularly bronchial stenoses, which complications are often missed at bronchoscopy or clinically silent. CT should be always performed before bronchoscopy because it can provide valuable information for bronchoscopy targeting. CONCLUSIONS: In agreement with other authors we consider HRCT a very useful tool in the early diagnosis of the complications following lung transplantation.     

Bronchus associated lymphoid tissue (BALT) in human lung: its distribution in smokers and non-smokers

BACKGROUND: Bronchus associated lymphoid tissue (BALT) is a normal component of the lung's immune system in many animals and may be analogous to gut associated lymphoid tissue (GALT). This study aimed at assessing the nature and extent of BALT in human lung and determining whether its expression is induced within the human airway in response to smoking. METHODS: Paraffin embedded, formalin fixed full thickness bronchial wall sections were examined from 31 whole lung specimens derived from both smokers and non-smokers. Samples were taken from throughout the bronchial tree to include main stem bronchi, lobar bronchi and segmental bronchi, as well as first to third generation carinae. Standard 4 microns step sections were stained by haematoxylin and eosin and immunocytochemical methods to show foci of BALT. RESULTS: Examination of 256 airway sites detected 46 foci of BALT. These differed from those described in other mammals in being distributed throughout the bronchial tree, in being found in relation to bronchial glandular epithelium as well as luminal bronchial epithelium, and in lacking any accompanying M cells. Analysis by smoking status showed that the expression of BALT was significantly more common in smokers than non-smokers (82% (14/17) v 14% (2/14) respectively). CONCLUSIONS: The findings support the view that BALT in humans is an integral feature in a comparatively small proportion of lungs from non-smokers while being significantly more prominent in lungs from smokers. The tissue shows several important differences from that described in other mammals.     

Inhibition of antibody-dependent cell-mediated cytotoxicity (ADCC) as a means of detection of immune complexes in the sera of patients with thyroid disorders and bronchogenic carcinoma

Circulating immune complexes in the sera of patients with thyroid disorders or bronchogenic carcinoma were investigated using an assay system based on the inhibition of the ADCC activity of rat spleen cells. Increased inhibition, as compared with that of the sera of age and sex matched controls, was found in patients with thashimoto thyroiditis, primary hypothyroidism and bronchogenic carcinoma. The degree of inhibition in the first two groups was markedly increased compared with control sera of the same IgG content. However, the results in the lung cancer group were slightly but not significantly greater than in controls with the same level of IgG. Increased IgG levels were found in patients with thashimoto thyroiditis and thyrotoxicosis, and also in patients with bronchogenic carcinoma who had mediastinal gland involvement. The lower level of sensitivity of the assay system was approximately 600 ng added aggregated IgG, corresponding to a concentration of 6mu g/ml in the sample assayed. It is possible that circulating immune complexes may exist in lung cancer, but at a level below that of the present assay system.     

Tumour markers in the diagnosis of bronchial carcinoma: new options using fuzzy logic-based tumour marker profiles

The diagnosis of lung cancer and early knowledge of its histological type are very important; however, this is still a difficult subject for the physician. The aim of this study was to improve the diagnostic efficiency of tumour markers in the diagnosis of bronchial carcinoma by mathematical evaluation of a tumour marker profile employing fuzzy logic modeling. A panel of five tumour markers, including CYFRA 21-1, CEA, NSE, and five additional parameters was determined in 281 patients with confirmed primary diagnosis of bronchial carcinoma of different histology and stage. A further 131 persons, who had acute and chronic benign lung diseases, served as a control group. A classificator was developed using a fuzzy-logic rule-based system. The diagnostic value of the combined tumour markers was significantly better than that of the individual markers and of a combination of CYFRA 21-1, CEA, and NSE. The discrimination of malignant vs benign diseases was realized with a sensitivity of 87.5% and specificity of 85.5%. The rate of correct classification of small-cell vs non-small-cell lung carcinoma was 90.6% and 91.1%, respectively; for squamous cell carcinoma vs adenocarcinoma it was 76.8% and 78.8%, respectively. Our detailed analysis has shown that the fuzzy logic system improves diagnostic accuracy up to a rate of 20%, especially in early stages and in patients with all marker levels in the grey area. Our concept proved to be more powerful than measurement of single markers or the combination of CEA, CYFRA 21-1, and NSE. Its use may help in distinguishing between malignant and benign disease and make it possible to define different subgroups of patients earlier in the course of their disease.     

Antibiotic resistance in Helicobacter pylori: implications for therapy

In most previous reports telomerase activity in lung cancer patients has been detected using tissue extracts. We have developed a semiquantitative fluorescence-based TRAP assay using fluorescence-end-labeling primers. Moreover, we also developed an in situ TRAP assay that detects telomerase activity at the cellular level. Thus, using these TRAP assays, we can detect telomerase activity in lung cancer cells obtained from bronchial washings. A high incidence of lung cancer patients with class I-III cytology had detectable telomerase activity, thus, a combination of a cell extract based. TRAP assay and an in situ TRAP assay may provide additive information to cytology for the diagnosis of lung cancer.