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1.  Detection of Pre-invasive Endobronchial Tumors with D-light/Autofluorescence System 
Journal of Korean Medical Science  2006;21(2):242-246.
Autofluorescence bronchoscopy (AFB) is one of the newly developed diagnostic tools to detect the pre-cancerous lesions in the bronchial tissue. The utility of D-Light/AFB in the detection of pre-cancerous lesions was compared to the standard white light bronchoscopy (WLB). In 113 patients (male 106, female 7), who visited hospital for evaluation of lung cancer, WLB and AFB were done and 364 biopsy specimens were obtained from November 2001 to August 2002. The bronchoscopic findings on WLB and AFB were compared to the pathological findings. The pathologic diagnoses of the specimens were as follows: normal in 96; hyperplasia in 69; metaplasia in 32; mild dysplasia in 13, moderate dysplasia in 6, severe dysplasia in 4; carcinoma in situ in 6; invasive carcinoma in 57. The relative sensitivity of adjunctive AFB to WLB vs. WLB alone was 1.5 in moderate dysplasia or worse lesions, and 3.2 in intraepithelial neoplasia. The specificity of adjunctive AFB and WLB alone were 0.91 and 0.5, respectively. The adjunctive AFB to the standard WLB increased the detection rate of the localized pre-invasive lesions. However, there was high rate of false positive in AFB.
PMCID: PMC2733998  PMID: 16614508
Bronchoscopes, Fluorescence; Bronchoscopy; Lung Neoplasms
2.  Autofluorescence bronchoscopy with white light bronchoscopy compared with white light bronchoscopy alone for the detection of precancerous lesions: a European randomised controlled multicentre trial 
Thorax  2005;60(6):496-503.
Background: The potential of autofluorescence bronchoscopy (AFB) to detect precancerous lesions in the central airways and its role in lung cancer screening is uncertain. A study was undertaken to evaluate the prevalence of moderate/severe dysplasia (dysplasia II–III) and carcinoma in situ (CIS) using a newly developed AFB system in comparison with conventional white light bronchoscopy (WLB) alone.
Methods: In a prospective randomised multicentre trial, smokers ⩾40 years of age (⩾20 pack-years) were stratified into four different risk groups and investigated with either WLB+AFB (arm A) or WLB alone (arm B).
Results: 1173 patients (916 men) of mean age 58.7 years were included. Overall (arms A and B), preinvasive lesions (dysplasia II–III and CIS) were detected in 3.9% of the patients. The prevalence of patients with preinvasive lesions in the WLB arm was 2.7% compared with 5.1% in the WLB+AFB arm (p = 0.037). For patients with dysplasia II–III, WLB+AFB increased the detection rate by a factor of 2.1 (p = 0.03), while for CIS the factor was only 1.24 (p = 0.75). The biopsy based sensitivity of WLB alone and WLB+AFB for detecting dysplasia II–III and CIS was 57.9% compared with 82.3% (1.42-fold increase). The corresponding specificity was 62.1% compared with 58.4% (0.94-fold decrease).
Conclusions: This first randomised study of AFB showed that the combination of WLB+AFB was significantly superior to WLB alone in detecting preneoplastic lesions. Our findings do not support the general use of AFB as a screening tool for lung cancer, but suggest that it may be of use in certain groups. The precise indications await further study.
PMCID: PMC1747416  PMID: 15923251
3.  Autofluorescence bronchoscopy for lung cancer surveillance based on risk assessment 
Thorax  2006;62(4):335-340.
This is a preliminary report of an ongoing prospective bimodality lung cancer surveillance trial for high‐risk patients. Bimodality surveillance incorporates autofluorescence bronchoscopy (AFB) and spiral CT (SCT) scanning in high‐risk patients as a primary lung cancer surveillance strategy, based entirely on risk factors. AFB was used for surveillance and findings were compared with conventional sputum cytology for the detection of malignancy and pre‐malignant central airway lesions.
402 patients registering at Roswell Park Cancer Institute were evaluated with spirometric testing, chest radiography, history and physical examination, of which 207 were deemed eligible for the study. For eligibility, patients were required to have at least two of the following risk factors: (1) ⩾20 pack year history of tobacco use, (2) asbestos‐related lung disease on the chest radiograph, (3) chronic obstructive pulmonary disease with a forced expiratory volume in 1 s (FEV1) <70% of predicted, and (4) prior aerodigestive cancer treated with curative intent, with no evidence of disease for >2 years. All eligible patients underwent AFB, a low‐dose SCT scan of the chest without contrast, and a sputum sample was collected for cytological examination. Bronchoscopic biopsy findings were correlated with sputum cytology results, SCT‐detected pulmonary nodules and surveillance‐detected cancers. To date, 186 have been enrolled with 169 completing the surveillance procedures.
Thirteen lung cancers (7%) were detected in the 169 subjects who have completed all three surveillance studies to date. Pre‐malignant changes were common and 66% of patients had squamous metaplasia or worse. Conventional sputum cytology missed 100% of the dysplasias and 68% of the metaplasias detected by AFB, and failed to detect any cases of carcinoma or carcinoma‐in‐situ in this patient cohort. Sputum cytology exhibited 33% sensitivity and 64% specificity for the presence of metaplasia. Seven of 13 lung cancers (58%) were stage Ia or less, including three patients with squamous cell carcinoma. Patients with peripheral pulmonary nodules identified by SCT scanning of the chest were 3.16 times more likely to exhibit pre‐malignant changes on AFB (p<0.001).
Bimodality surveillance will detect central lung cancer and pre‐malignancy in patients with multiple lung cancer risk factors, even when conventional sputum cytology is negative. AFB should be considered in high‐risk patients, regardless of sputum cytology findings.
PMCID: PMC2092474  PMID: 17101735
4.  Fiberoptic bronchoscopy, as a valuable diagnostic option in sputum negative pulmonary tuberculosis: A prospective study 
World Health Organization recommends bacteriological confirmation of pulmonary tuberculosis (PTB) by the detection of acid-fast bacilli (AFB) in respiratory specimens. However about 40-60% of patients with PTB suspected clinically or radiologically may fail to produce sputum, or when it is available, AFB may be negative on repeated smear examination. These sputum smear negative patients and those who fail to produce any sputum can be diagnosed by flexible fiberoptic bronchoscopy.
Our study was an attempt to analyze the role of fiberoptic bronchoscopy in sputum smear negative PTB patients with respect to their association with clinical and radiological profile.
Materials and Methods:
In this prospective, open label, observational study, 40 cases of sputum smear negative PTB were subjected to bronchoscopic examination after taking informed consent and samples like bronchial aspirate, bronchoalveolar lavage and post bronchoscopy sputum were collected. The data was analysed and the results were given in percentage.
Out of the total 40 patients, overall diagnosis was confirmed in 24 (60%) patients. Of these 24 patients, 17 patients were confirmed for PTB whereas 7 had other diagnoses.
The study concludes that fiberoptic bronchoscopy is a useful tool in diagnosing sputum smear negative PTB patients with respect to their association with clinical and radiological profile, and also identifies individuals at a higher risk for progression of disease, at an early stage despite not meeting routine bacteriological criteria for confirmation of PTB.
PMCID: PMC3678692  PMID: 23776825
AFB-negative; pulmonary tuberculosis; AFB-negative sputum; fiberoptic bronchoscopy; pulmonary tuberculosis
5.  Early Localization of Bronchogenic Carcinoma 
The performance of a fluorescence imaging device was compared with conventional white-light bronchoscopy in 100 patients with lung cancer, 46 patients with resected stage I non-small cell lung cancer, 10 patients with head and neck cancer, and 67 volunteers who had smoked at least 1 pack of cigarettes per day for 25 years or more. Using differences in tissue autofluorescence between premalignant, malignant, and normal tissues, fluorescence bronchoscopy was found to detect significantly more areas with moderate/severe dysplasia or carcinoma in situ than conventional white-light bronchoscopy with a similar specificity. Multiple foci of dysplasia or cancer were found in 13–24% of these individuals. Fluorescence bronchoscopy may be an important adjunct to conventional bronchoscopic examination to improve our ability to detect and localize premalignant and early lung cancer lesions.
PMCID: PMC2362470  PMID: 18493345
6.  Autofluorescence Detection of Bronchial Tumors With the D-Light/AF 
We present a newly developed diagnostic system combining a conventional light source (white light mode and two different fluorescence excitation modes), a bronchoscope and optionally a highly sensitive camera (Baumgartner et al., Photochem. Photobiol. 1987; 46(5): 759–763). Routine diagnostics can be performed with the autofluorescence bronchoscopy (AFB) and the white light bronchoscopy (WLB) in one diagnostic procedure. The image is visible directly with the naked eye. The system was evaluated in a pilot study including 60 patients. Two hundred and sixty-four biopsies were taken to detect premalignant and malignant findings (Stanzel et al., Contribution to 10th World Congress for Bronchology, June 1998). The sensitivity of the combination of WLB and AFB was 2.8 times higher than that of the conventional WLB. The specificity decreased from 94% (WLB) to 89% (WLB + AFB). The results of this preliminary pilot study are being confirmed in a multicenter study, which will begin at seven European centers.
PMCID: PMC2362621  PMID: 18493489
7.  Early Detection of Bronchial Lesions Using Lung Imaging Fluorescence Endoscope 
The performance of the Lung Imaging Fluorescence Endoscope (LIFE) system was compared with conventional bronchoscopy in 158 patients: 68 patients with invasive cancer, 42 patients with abnormal sputum cytology findings (12 early cancer and 26 dysplasia), 17 cases with resected lung cancer and 31 smokers with symptoms. The respective results of conventional bronchoscopy and LIFE for detection of dysplasia were; sensitivity 52% and 90% (biopsy basis), 62% and 92% (patient basis). Fluorescence bronchoscopy may be an important adjunct to conventional bronchoscopy to improve the localization of subtle lesions of bronchus.
PMCID: PMC2362618  PMID: 18493486
8.  Genome-Wide and Differential Proteomic Analysis of Hepatitis B Virus and Aflatoxin B1 Related Hepatocellular Carcinoma in Guangxi, China 
PLoS ONE  2013;8(12):e83465.
Both hepatitis B virus (HBV) and aflatoxin B1 (AFB1) exposure can cause liver damage as well as increase the probability of hepatocellular carcinoma (HCC). To investigate the underlying genetic changes that may influence development of HCC associated with HBV infection and AFB1 exposure, HCC patients were subdivided into 4 groups depending upon HBV and AFB1 exposure status: (HBV(+)/AFB1(+), HBV(+)/AFB1(-), HBV(-)/AFB1(+), HBV(-)/AFB1(-)). Genetic abnormalities and protein expression profiles were analyzed by array-based comparative genomic hybridization and isobaric tagging for quantitation. A total of 573 chromosomal aberrations (CNAs) including 184 increased and 389 decreased were detected in our study population. Twenty-five recurrently altered regions (RARs; chromosomal alterations observed in ≥10 patients) in chromosomes were identified. Loss of 4q13.3-q35.2, 13q12.1-q21.2 and gain of 7q11.2-q35 were observed with a higher frequency in the HBV(+)/AFB1(+), HBV(+)/AFB1(-) and HBV(-)/AFB1(+) groups compared to the HBV(-)/AFB(-) group. Loss of 8p12-p23.2 was associated with high TNM stage tumors (P = 0.038) and was an unfavorable prognostic factor for tumor-free survival (P =0.045). A total of 133 differentially expressed proteins were identified in iTRAQ proteomics analysis, 69 (51.8%) of which mapped within identified RARs. The most common biological processes affected by HBV and AFB1 status in HCC tumorigenesis were detoxification and drug metabolism pathways, antigen processing and anti-apoptosis pathways. Expression of AKR1B10 was increased significantly in the HBV(+)/AFB1(+) and HBV(-)/AFB1(+) groups. A significant correlation between the expression of AKR1B10 mRNA and protein levels as well as AKR1B10 copy number was observered, which suggest that AKR1B10 may play a role in AFB1-related hepatocarcinogenesis. In summary, a number of genetic and gene expression alterations were found to be associated with HBV and AFB1- related HCC. The possible synergistic effects of HBV and AFB1 in hepatocarcinogenesis warrant further investigations.
PMCID: PMC3877066  PMID: 24391771
9.  Detection of premalignant bronchial lesions can be significantly improved by combination of advanced bronchoscopic imaging techniques 
Annals of Thoracic Medicine  2013;8(2):93-98.
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.
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.
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).
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.
PMCID: PMC3667452  PMID: 23741271
Autofluorescence bronchoscopy; bronchoscopy; interventional pulmonology; lung cancer; narrow band imaging; premalignant lesions
10.  Results of Two Years Expenience with Fluorescence Bronchoscopy in Detection of Preinvasive Bronchial Neoplasia 
The aim of the study was to determine whether use of fluorescence bronchoscopy improves the detection of preinvasive neoplastic bronchial lesions. The data of all patients who underwent fluorescence bronchoscopy and in whom bronchial biopsies were taken, were analyzed. Most patients were at risk for preinvasive lesions. A total of 174 bronchoscopies were performed in 95 patients. Of the 681 representative biopsies, 31 were found to be moderate dysplastic, 39 were found to be severe dysplastic and 9 exhibited carcinoma in situ. These 79 preinvasive lesions were found in 34 patients. The respective results of fluorescence bronchoscopy in addition to conventional bronchoscopy and of conventional bronchoscopy alone for detection of preinvasive lesions were: sensitivity 85% (67/79) and 59% (47/79); specificity 60% (351/581) and 85% (493/581); positive predictive values of 23% (67/297) and 35% (47/135); negative predictive values of 97% (351/363) and 94% (493/525). A separate analysis of only the first bronchoscopy of each patient showed similar results. Results of fluoresence bronchoscopy were better in the second part of the patient group. We conclude that after a learning period fluorescence bronchoscopy can increase the yield of finding preinvasive neoplastic lesions when used in addition to conventional bronchoscopy.
PMCID: PMC2362614  PMID: 18493485
11.  Detection of 8,9-dihydro-(7'-guanyl)-9-hydroxyaflatoxin B1 in human urine. 
A possible role of aflatoxin B1 (AFB) in the etiology of human liver cancer has been suggested from several epidemiological studies. This has been based upon the association between consumption of AFB-contaminated food and the liver cancer incidence in different parts of the world. To further establish the role of AFB as a major factor, we initiated a pilot study in three different districts of Kenya to determine the number of individuals exposed to significant amounts of AFB as measured by the urinary excretion of 8,9-dihydro-8-(7-guanyl)-9-hydroxyaflatoxin B1 (AFB-Gua), an adduct formed between the ultimate carcinogenic form of AFB and nucleic acids. This product has previously been detected in urine from rats treated with AFB. Urine collected at the outpatient clinics at the district hospitals were concentrated on C18 Sep-Pak columns and analyzed by high-pressure liquid chromatography under two different chromatographic conditions. The chemical identity of the samples showing a positive response in both chromatographic systems was verified by synchronous scanning fluorescence spectrophotometry. The highest number of individuals with detectable urinary AFB-Gua lived in either Murang'a district or the neighboring Meru and Embu districts. In Murang'a district a rate of 12% was observed in the January-March period, while only 1 of 32 patients (3%) had a detectable exposure in July-August.(ABSTRACT TRUNCATED AT 250 WORDS)
PMCID: PMC1568656  PMID: 3936705
12.  Atypical presentations of pulmonary tuberculosis diagnosed by fibreoptic bronchoscopy. 
Postgraduate Medical Journal  1993;69(814):621-623.
A total of 356 patients were subjected to fibreoptic bronchoscopy from September 1989 to June 1991 to exclude bronchial carcinoma. Bronchial biopsy, bronchial brush smears and bronchial wash were obtained. Bronchial wash was examined for acid fast bacilli (AFB) compatible with Mycobacterium tuberculosis. The total number diagnosed as pulmonary tuberculosis by fibreoptic bronchoscopy was 21(5.8%). The sputum smears were negative for AFB in all these patients. Previous studies have shown the importance of fibreoptic bronchoscopy in suspected cases of tuberculosis where the sputum smear is negative. This study is further evidence of the importance of routine examination of bronchial wash for AFB in all cases undergoing fibreoptic bronchoscopy to detect atypical cases of pulmonary tuberculosis.
PMCID: PMC2399695  PMID: 8234105
13.  Electromagnetic Navigation Diagnostic Bronchoscopy 
Rationale: Electromagnetic navigation bronchoscopy using superDimension/Bronchus System is a novel method to increase diagnostic yield of peripheral and mediastinal lung lesions.
Objectives: A prospective, open label, single-center, pilot study was conducted to determine the ability of electromagnetic navigation bronchoscopy to sample peripheral lung lesions and mediastinal lymph nodes with standard bronchoscopic instruments and demonstrate safety.
Methods: Electromagnetic navigation bronchoscopy was performed using the superDimension/Bronchus system consisting of electromagnetic board, position sensor encapsulated in the tip of a steerable probe, extended working channel, and real-time reconstruction of previously acquired multiplanar computed tomography images. The final distance of the steerable probe to lesion, expected error based on the actual and virtual markers, and procedure yield was gathered.
Measurements: 60 subjects were enrolled between December 2004 and September 2005. Mean navigation times were 7 ± 6 min and 2 ± 2 min for peripheral lesions and lymph nodes, respectively. The steerable probe tip was navigated to the target lung area in all cases. The mean peripheral lesions and lymph nodes size was 22.8 ± 12.6 mm and 28.1 ± 12.8 mm. Yield was determined by results obtained during the bronchoscopy per patient.
Results: The yield/procedure was 74% and 100% for peripheral lesions and lymph nodes, respectively. A diagnosis was obtained in 80.3% of bronchoscopic procedures. A definitive diagnosis of lung malignancy was made in 74.4% of subjects. Pneumothorax occurred in two subjects.
Conclusion: Electromagnetic navigation bronchoscopy is a safe method for sampling peripheral and mediastinal lesions with high diagnostic yield independent of lesion size and location.
PMCID: PMC2648102  PMID: 16873767
diagnostic bronchoscopy; electromagnetic navigation; mediastinal lymph node; solitary pulmonary nodule; transbronchial biopsy
14.  Synchronous double primary lung cancers via p53 pathway induced by heavy smoking 
Annals of Saudi Medicine  2010;30(3):236-238.
Differences in the histological manifestation of synchronous lung cancers are rare. Synchronous multiple primary lung cancers (SMPLC) are associated with long-term tobacco use, which could independently lead to mutations in the p53 and K-ras genes. We present the case of an 82-year-old man who smoked 30 cigarettes daily for the past 60 years. CT of the chest showed a right upper lobe mass. Bronchoscopy revealed an intra-lumen nodular lesion in the right lower lobe bronchus. The diagnoses of small cell lung carcinoma (SCLC) of the right upper lobe and non-small cell lung carcinoma (NSCLC) of the right lower lobe were confirmed by the morphologic features and the detected immunoreactivity. Immunohistochemical analyses showed a strong positive reaction for p53 in samples of the SCLC and NSCLC. The cancers had a different phenotype, but similar genetic abnormalities may have developed due to the carcinogens in the cigarettes.
PMCID: PMC2886876  PMID: 20427942
15.  Role of sputum examination for acid fast bacilli in tuberculous pleural effusion 
Sputum for acid fast bacilli (AFB) is seldom looked for in the etiological diagnosis of tuberculous pleural effusion usually due to the absence of any parenchymal lesion radiologically, but presence of tubercle bacilli in sputum may have important epidemiological and therapeutic implication.
This study aims to evaluate the role of sputum examination for AFB in the patients of tuberculous pleural effusion with no apparent lung parenchymal lesion radiologically.
Settings and Design:
Forty-five consecutive indoor patients of suspected tuberculous pleural effusion having no apparent lung parenchymal lesion on chest radiography were selected for our study. It was a prospective and observational study conducted over a period of 1 year.
Materials and Methods:
After confirming the etiology of pleural effusion as tuberculous by biochemical, cytological, histopahtological, and microbiological tests, emphasis was given on sputum examination for AFB by smear examination and culture for Mycobacterium tuberculosis.
Sputum was bacteriologically (smear and /or culture) positive for tuberculosis in 10 out of 30 cases (33.33%) in which tuberculous etiology was confirmed by histology and /or bacteriology (definite tuberculosis). No sputum AFB (smear and culture) was found in 15 cases of probable tuberculosis where tuberculous etiology was established by indirect methods like Adenosine de aminase level more than 40 unit/l and other relevant investigations. Over all, sputum was bacteriologically smear and/or culture positive in 10 out of 45 cases (22.22%).
Careful and thorough sputum examination in cases of tuberculous pleural effusion may help as a diagnostic tool and it has therapeutic and epidemiological implications.
PMCID: PMC3099505  PMID: 21654981
Mycobacterium tuberculosis; pleural biopsy; pleural effusion; sputum examination
16.  Photodynamic therapy (PDT) in early central lung cancer: a treatment option for patients ineligible for surgical resection 
Thorax  2006;62(5):391-395.
To review the Yorkshire Laser Centre experience with bronchoscopic photodynamic therapy (PDT) in early central lung cancer in subjects not eligible for surgery and to discuss diagnostic problems and the indications for PDT in such cases.
Of 200 patients undergoing bronchoscopic PDT, 21 had early central lung cancer and were entered into a prospective study. Patients underwent standard investigations including white light bronchoscopy in all and autofluorescence bronchoscopy in 12 of the most recent cases. Indications for bronchoscopic PDT were recurrence/metachronous endobronchial lesions following previous treatment with curative intent in 10 patients (11 lesions), ineligibility for surgery because of poor cardiorespiratory function in 8 patients (9 lesions) and declined consent to operation in 3 patients. PDT consisted of intravenous administration of Photofrin 2 mg/kg followed by bronchoscopic illumination 24–48 h later.
29 treatments were performed in 21 patients (23 lesions). There was no procedure‐related or 30 day mortality. One patient developed mild skin photosensitivity. All patients expressed satisfaction with the treatment and had a complete response of variable duration. Six patients died at 3–103 months (mean 39.3), three of which were not as a result of cancer. Fifteen patients were alive at 12–82 months.
Bronchoscopic PDT in early central lung cancer can achieve long disease‐free survival and should be considered as a treatment option in those ineligible for resection. Autofluorescence bronchoscopy is a valuable complementary investigation for identification of synchronous lesions and accurate illumination in bronchoscopic PDT.
PMCID: PMC2117198  PMID: 17090572
17.  Endobronchial Aspergilloma: Report of 10 Cases and Literature Review 
Yonsei Medical Journal  2011;52(5):787-792.
A retrospective investigation of the clinical and radiologic features as well as the bronchoscopic appearance was carried out in patients with endobronchial aspergilloma.
Materials and Methods
Ten patients with endobronchial aspergilloma diagnosed by bronchoscopy and histological examination were identified at the Gyeongsang University Hospital of Korea, from May 2003 to May 2009.
The patients included 9 men and 1 woman, and the age of the patients ranged from 36 to 76 (median, 58 years). The associated diseases or conditions were: previous pulmonary tuberculosis in 7 patients, lung cancer in 2 patients, pulmonary resection in 1 patient, and foreign body of the bronchus in 1 patient. The chest radiologic finding showed fibrotic changes as a consequence of previous tuberculosis infection in 6 patients and a mass-like lesion in 2 patients. Two patients had a co-existing fungus ball, and an endobronchial lesion was suspected in only 2 patients on the CT scan. The bronchoscopic appearance was a whitish to yellow necrotic mass causing bronchial obstruction in 7 patients, foreign body with adjacent granulation tissue and whitish necrotic tissue in 1 patient, whitish necrotic tissue at an anastomosis site in 1 patient, and a protruding mass with whitish necrotic tissue in 1 patient.
An endobronchial aspergilloma is a rare presentation of pulmonary aspergilosis and is usually incidentally found in immunocompetent patients with underlying lung disease. It usually appears as a necrotic mass causing bronchial obstruction on bronchoscopy and can be confirmed by biopsy.
PMCID: PMC3159936  PMID: 21786444
Endobronchial aspergilloma
18.  Evaluation of clinico-radiological, bacteriological, serological, molecular and histological diagnosis of osteoarticular tuberculosis 
Indian Journal of Orthopaedics  2008;42(2):173-177.
The diagnosis of osteoarticular tuberculosis is clinico-radiological in endemic areas. However every patient does not have the classical picture. Osteoarticular tuberculosis is a paucibacillary disease hence bacteriological diagnosis is possible in 10-30% of the cases. The present study is undertaken to correlate clinico-radiological, bacteriological, serological, molecular and histological diagnosis.
Materials and Methods:
Fifty clinico-radiologically diagnosed patients of osteoarticular tuberculosis with involvement of dorsal spine (n = 35), knee (n = 8), shoulder (n = 1), elbow (n = 2) and lumbar spine lesion (n = 4), were analyzed. Tissue was obtained after decompression in 35 cases of dorsal spine and fine needle aspiration in the remaining 15 cases. Tissue obtained was subjected to AFB staining, AFB culture sensitivity, aerobic/anaerobic culture sensitivity histopathological examination and polymerase chain reaction (PCR) using 16srRNA as primer. Serology was performed by ELISA in 27 cases of dorsal spine at admission and one and three months postoperatively.
AFB staining (direct) and AFB culture sensitivity was positive in six (12%) cases. Aerobic/anaerobic culture sensitivity was negative in all cases. Histology was positive for TB in all the cases. The PCR was positive in 49 (98%) cases. All dorsal spine tuberculosis cases showed fall of IgM titer and rise of IgG titer at three months as compared to values at admission.
Histopathology and PCR was diagnostic in all cases of osteoarticular tuberculosis. The serology alone is not diagnostic.
PMCID: PMC2759633  PMID: 19826523
AFB culture sensitivity; AFB staining; ELISA for tuberculosis; osteoarticular tuberculosis; polymerase chain reaction
19.  Increases in Diagnostic Yield of Fiberoptic Bronchoscopy by Fluoroscopy 
Fiberoptic bronchoscopy was performed in 46 patients in the evaluation of pulmonary lesions. Twenty-five of the patients had lung cancer; the remainder had benign lesions. Definitive diagnosis was established in all patients by a combination of forceps biopsy, brush biopsy, bronchial aspiration, and post-bronchoscopy sputum studies. All endoscopically visible lesions were diagnosed by forceps biopsy. Fluoroscopic localization of biopsy forceps and brush made the yield in peripheral, nonvisualized lesions almost equal to that of more central lesions. Fluoroscopic control markedly increases the diagnostic yield in fiberoptic bronchoscopy.
PMCID: PMC2552857  PMID: 7120459
20.  Methylene Blue-Aided In Vivo Staining of Central Airways during Flexible Bronchoscopy 
The Scientific World Journal  2012;2012:625867.
Background. The early diagnosis of malignant and premalignant changes of the bronchial mucosa remains a major challenge during bronchoscopy. Intravital staining techniques are not new. Previous small case series suggested that analysis of the bronchial mucosal surface using chromoendoscopy allows a prediction between neoplastic and nonneoplastic lesions. Objectives. The aim of the present study was to evaluate chromobronchoscopy as a method to identify malignant and premalignant lesions in the central airways in a prospective manner. Methods. In 26 patients we performed chromoendoscopy with 0.1% methylene blue during ongoing flexible white light bronchoscopy. Circumscribed lesions in central airways were further analyzed by biopsies and histopathologic examination. Results. In the majority of cases neither flat nor polypoid lesions in the central airways were stained by methylene blue. In particular, exophytic growth of lung cancer did not show any specific pattern in chromobronchoscopy. However, a specific dye staining was detected in one case where exophytic growth of metastatic colorectal cancer was present in the right upper lobe. In two other cases, a circumscribed staining was noted in unsuspicious mucosa. But histology revealed inflammation only. Conclusions. In contrast to previous studies, the present findings clearly indicate that chromobronchoscopy is not useful for early detection of malignant or premalignant lesions of the central airways.
PMCID: PMC3415176  PMID: 22919343
21.  Characteristics of chromate workers' cancers, chromium lung deposition and precancerous bronchial lesions: an autopsy study. 
British Journal of Cancer  1994;70(1):160-166.
The characteristics of lung cancers induced by inhaled chromate were studied in 13 consecutive autopsies on male ex-chromate workers. In addition to histopathology, we examined: (1) the relationship between the occurrence of lung cancer and the amount of chromium (Cr) deposited in the lung as determined by atomic absorptiometry and (2) the chronological changes in five precancerous lung lesions followed by bronchoscopy till death. Twenty-one cancers were identified, including 16 lung tumours observed either during follow-up or at autopsy. Of these 16 tumours, 13 were found in six subjects, implying a high frequency of multiple cancers. Eleven (69%) out of the 16 tumours were of squamous cell type (including carcinoma in situ), this being twice as frequent as in age-matched controls. A further characteristic was predominance in the central part of lung (69%). The lung Cr burden was very much higher [40-15,800 micrograms g-1 (dry)] in patients with lung tumours than in those without (8-28 micrograms g-1). Five of the precancerous lesions followed by bronchoscopy originated at bronchial bifurcations. Four of these cases showed a return to normal histology at autopsy even without therapy, and the other did not progress.
PMCID: PMC2033298  PMID: 8018529
22.  Late age at first full term birth is strongly associated with lobular breast cancer 
Cancer  2010;117(9):1946-1956.
Late age at first full-term birth (AFB) and nulliparity are known to increase breast cancer risk. The frequency of these risk factors has increased in recent decades.
We conducted a population-based case-control study to examine associations between parity, AFB, and specific histological subtypes of breast cancer. Women with breast cancer (N=21,266) were identified from cancer registries in Wisconsin, Massachusetts, and New Hampshire. Control women (N=26,677) were randomly selected from population lists. Interviews collected information on reproductive histories and other risk factors. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) of ductal, lobular, and mixed ductal-lobular breast cancer diagnosis in association with AFB and nulliparity.
AFB ≥ 30 years of age was associated with a 2.4-fold increase in risk of lobular breast cancer compared to AFB < 20 years (OR 2.4; 95%CI 1.9–2.9). The association was less pronounced for ductal breast cancer (OR 1.3; 95% CI, 1.2–1.4). Nulliparity was associated with increased risk for all breast cancer subtypes, compared to women with AFB <20 years, but the association was stronger for lobular (OR 1.72, 95% CI 1.34–2.20) than for ductal (OR 1.19, 95% CI 1.08–1.31) subtypes (P=0.004). The adverse effects of later AFB was stronger with obesity (P=0.03) in lobular, but not ductal, breast cancer.
Stronger associations observed for late AFB and nulliparity suggests that these preferentially stimulate growth of lobular breast carcinomas. Recent temporal changes in reproductive patterns and rates of obesity may impact the histological presentation of breast cancer.
PMCID: PMC3117094  PMID: 21509772
Epidemiology; reproduction; lobular breast cancer; ductal breast cancer; risk factors
23.  Color Fluorescence Ratio for Detection of Bronchial Dysplasia and Carcinoma In situ 
Autofluorescence bronchoscopy is more sensitive than conventional bronchoscopy for detecting early airway mucosal lesions. Decreased specificity can lead to excessive biopsy and increased procedural time. Onco-LIFE, a device that combines fluorescence and reflectance imaging, allows numeric representation by expressing red-to-green ratio (R/G ratio) within the region of interest. The aim of the study was to determine if color fluorescence ratio (R/G ratio) added to autofluorescence bronchoscopy could provide an objective means to guide biopsy.
Subjects at risk for lung cancer were recruited at two centers: VU University Medical Centre (Amsterdam) and BC Cancer Agency (Canada). R/G ratio for each site appearing normal or abnormal was measured before biopsy. R/G ratios were correlated with pathology, and a receiver operating characteristic curve of R/G ratio for high-grade and moderate dysplasia was done. Following analysis of the training data set obtained from two centers, a prospective validation study was done.
Three thousand three hundred sixty-two adequate biopsies from 738 subjects with their corresponding R/G ratios were analyzed. R/G ratio 0.54 conferred 85% sensitivity and 80% specificity for the detection of high-grade and moderate dysplasia, area under the curve was 0.90, and 95% confidence interval was 0.88 to 0.92. In another 70 different sites that were assessed, κ measurements of agreement of R/G ratios with visual scores and pathology were 0.66 (P < 0.0001) and 0.61 (P < 0.0001), respectively. R/G ratio combined with visual score improved specificity to 88% (95% confidence interval, 0.73–0.96) for high-grade and moderate dysplasia.
Color fluorescence ratio can objectively guide the bronchoscopist in selecting sites for biopsy with good pathologic correlation.
PMCID: PMC2762942  PMID: 19584169
24.  A system for transformation of rat liver cells in vitro by acute treatment with aflatoxin. 
British Journal of Cancer  1987;55(6):595-598.
Aflatoxin B1 (AFB1) induced rat liver cancer is a well studied system of hepatocarcinogenesis. AFB1 has also been used to transform cultured rat liver derived cells in vitro. Cells in culture often have a reduced capacity to metabolise the AFB1 to its active metabolite, and often prolonged periods of exposure to the toxin have to be employed, with a long latency in the appearance of transformed cells in culture. We report here the transformation of a rat liver derived cell line by acute treatment with AFB1. An extrinsic metabolising system of quail microsomes, which convert AFB1 to its epoxide form with high efficiency, was used to activate the AFB1. A dose dependent cytotoxicity was obtained and neoplastic transformation was seen in the higher doses used. The enzyme GGT which has strong association with liver cell transformation both in vivo and in vitro was also elevated in the treated cells.
PMCID: PMC2002029  PMID: 2887193
25.  Comparison of fluorescent BACTEC 9000 MB system, Septi-Chek AFB system, and Lowenstein-Jensen medium for detection of mycobacteria. 
Journal of Clinical Microbiology  1996;34(10):2391-2394.
The newly developed fluorescent BACTEC 9000 MB system for automated culture of mycobacteria was compared with the Septi-Chek AFB system and Lowenstein-Jensen medium (LJ). A total of 2,005 clinical specimens were included in the study. Mycobacteria were isolated from 202 (10.1%) specimens, including 155 Mycobacterium tuberculosis complex isolates and 47 Mycobacteria other than M. tuberculosis isolates. Of 131 isolates detected by the BACTEC system, the Septi-Chek AFB system, or both, 120 (91.6%) were detected by the BACTEC system and 105 (80.2%) were detected by the Septi-Chek AFB system (P < 0.02). The recovery rate in the BACTEC system compared with that in the Septi-Chek AFB system was significantly higher for M. tuberculosis complex isolates (P < 0.005) and for isolates from acid-fast smear-negative specimens (P < 0.01). Of 148 isolates detected by the BACTEC system, LJ, or both, 142 (95.9%) were detected by the BACTEC system and 118 (79.9%) were detected by LJ (P < 0.001). The recovery rate in the BACTEC system compared with that on LJ was significantly higher for M. tuberculosis complex isolates (P < 0.001). The BACTEC system detected more mycobacteria from both smear-positive and smear-negative specimens than LJ. The mean times to detection of mycobacteria were 17.6 days for the BACTEC system, 26.0 days for the Septi-Chek AFB system, and 29.4 days for LJ. The BACTEC fluorescent 9000 MB system is a rapid, sensitive, and efficient method for the isolation of mycobacteria.
PMCID: PMC229277  PMID: 8880486

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