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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.
doi:10.3346/jkms.2006.21.2.242
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.
doi:10.1136/thx.2005.041475
PMCID: PMC1747416  PMID: 15923251
3.  Autofluorescence bronchoscopy for lung cancer surveillance based on risk assessment 
Thorax  2006;62(4):335-340.
Background
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.
Methods
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.
Results
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).
Conclusion
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.
doi:10.1136/thx.2006.068999
PMCID: PMC2092474  PMID: 17101735
4.  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.
doi:10.1155/DTE.1.75
PMCID: PMC2362470  PMID: 18493345
5.  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.
doi:10.1155/DTE.5.105
PMCID: PMC2362621  PMID: 18493489
6.  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.
doi:10.1155/DTE.5.85
PMCID: PMC2362618  PMID: 18493486
7.  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.
doi:10.1155/DTE.5.77
PMCID: PMC2362614  PMID: 18493485
8.  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.
doi:10.4103/0256-4947.62837
PMCID: PMC2886876  PMID: 20427942
9.  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.
doi:10.1164/rccm.200603-344OC
PMCID: PMC2648102  PMID: 16873767
diagnostic bronchoscopy; electromagnetic navigation; mediastinal lymph node; solitary pulmonary nodule; transbronchial biopsy
10.  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
11.  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.
Images
PMCID: PMC2002029  PMID: 2887193
12.  Photodynamic therapy (PDT) in early central lung cancer: a treatment option for patients ineligible for surgical resection 
Thorax  2006;62(5):391-395.
Objectives
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.
Methods
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.
Results
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.
Conclusion
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.
doi:10.1136/thx.2006.061143
PMCID: PMC2117198  PMID: 17090572
13.  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.
Images
PMCID: PMC2399695  PMID: 8234105
14.  Role of sputum examination for acid fast bacilli in tuberculous pleural effusion 
Background:
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.
Aims:
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.
Results:
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%).
Conclusion:
Careful and thorough sputum examination in cases of tuberculous pleural effusion may help as a diagnostic tool and it has therapeutic and epidemiological implications.
doi:10.4103/0970-2113.76296
PMCID: PMC3099505  PMID: 21654981
Mycobacterium tuberculosis; pleural biopsy; pleural effusion; sputum examination
15.  Endobronchial Aspergilloma: Report of 10 Cases and Literature Review 
Yonsei Medical Journal  2011;52(5):787-792.
Purpose
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.
Results
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.
Conclusion
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.
doi:10.3349/ymj.2011.52.5.787
PMCID: PMC3159936  PMID: 21786444
Endobronchial aspergilloma
16.  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
17.  Comparison of Direct and Concentrated Acid-Fast Smears To Identify Specimens Culture Positive for Mycobacterium spp. 
Journal of Clinical Microbiology  1999;37(11):3564-3568.
Microscopic examination of respiratory specimens for acid-fast bacilli (AFB) plays a key role in the initial diagnosis of tuberculosis, monitoring of treatment, and determination of eligibility for release from isolation. The objective of this study was to compare the sensitivity obtained with smears for detection of AFB (AFB smears) made directly from respiratory specimens (direct AFB smears) to that obtained with parallel smears made from concentrates of the specimens (concentrated AFB smears). A total of 2,693 specimens were evaluated; 1,806 were from the University of California Irvine Medical Center Medical Microbiology Laboratory (UCIMC), which serves a tertiary-care hospital with outpatient clinics, and 887 were from the Microbial Disease Laboratory at the California Department of Public Health (MDL), which receives specimens from outpatient facilities and clinics on Pacific islands. Of the 353 AFB culture-positive specimens at UCIMC, there was a statistically significant difference in the sensitivity of the direct AFB smear (34%) and that of the smear made from the concentrated specimen (58%) (P < 0.05). This was also true for the 208 specimens positive for Mycobacterium tuberculosis, for which the sensitivity of the direct smear was 42% (87 of 208) and that for the smear made from the concentrated specimen was 74% (154 of 208). At MDL, where all but 1 of the 45 culture-positive specimens grew M. tuberculosis, the sensitivity of the smear made from the concentrated specimen was 93% (42 of 45) and was not significantly higher than the sensitivity of the direct smear, which was 82% (37 of 45). By combining the results from both laboratories, 42 patients from whom at least three specimens were received were culture positive for M. tuberculosis. The cumulative results for the initial three specimens from these patients showed that the direct smear detected M. tuberculosis in 81% of these patients, whereas the smear made from the concentrate detected M. tuberculosis in 91% of these patients. In summary, when all culture-positive specimens are considered, the sensitivity of the direct smear compared to that of a smear made from the concentrated specimen was significantly different overall in the two different laboratory settings. However, this difference was reduced only if the cumulative results for the initial three specimens received from patients who were culture positive for M. tuberculosis were evaluated.
PMCID: PMC85691  PMID: 10523552
18.  Evaluation of clinico-radiological, bacteriological, serological, molecular and histological diagnosis of osteoarticular tuberculosis 
Indian Journal of Orthopaedics  2008;42(2):173-177.
Background:
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.
Results:
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.
Conclusion:
Histopathology and PCR was diagnostic in all cases of osteoarticular tuberculosis. The serology alone is not diagnostic.
doi:10.4103/0019-5413.40253
PMCID: PMC2759633  PMID: 19826523
AFB culture sensitivity; AFB staining; ELISA for tuberculosis; osteoarticular tuberculosis; polymerase chain reaction
19.  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.
doi:10.1100/2012/625867
PMCID: PMC3415176  PMID: 22919343
20.  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.
Images
PMCID: PMC2033298  PMID: 8018529
21.  Color Fluorescence Ratio for Detection of Bronchial Dysplasia and Carcinoma In situ 
Background
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.
Methods
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.
Results
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.
Conclusion
Color fluorescence ratio can objectively guide the bronchoscopist in selecting sites for biopsy with good pathologic correlation.
doi:10.1158/1078-0432.CCR-08-1644
PMCID: PMC2762942  PMID: 19584169
22.  Physiological effect of endobronchial radiotherapy in patients with major airway occlusion by carcinoma. 
Thorax  1993;48(2):110-114.
BACKGROUND: Endobronchial radiotherapy by a high dose rate remote after-loading technique (high dose rate brachytherapy) has become an established treatment for major airway occlusion by inoperable carcinoma of the bronchus. Only limited objective data on its effect on pulmonary physiology and on radiographic and bronchoscopic appearances are available. The aim of this study was to make a detailed assessment of patients before and after high dose rate brachytherapy to determine which investigations were useful and to generate data for comparing this with other methods of treatment. METHODS: Twenty patients with major airway obstruction by inoperable lung cancer underwent a detailed assessment before receiving endobronchial radiotherapy (15 Gy at 1 cm in a single fraction) and six weeks after treatment. This included chest radiography, computed tomography of the thorax, bronchoscopy including an obstruction index, five minute walking tests, isotope ventilation and perfusion lung scanning, and full lung function tests with maximum inspiratory and expiratory flow-volume loops. RESULTS: Nineteen patients (mean age 69 years) completed the study. Symptomatic improvement occurred in 17 patients. A collapsed lobe or lung, seen on the chest radiograph in 13, reexpanded in nine. Bronchoscopic appearances improved in 18, the mean obstruction index decreasing from 6.2 to 2.8. The isotope scans showed significant increases in the percentage of total lung ventilation (V) and perfusion (Q) measured over the abnormal lung (V 17.7% to 27.7%, Q 15.1 to 21.9%). Five minute walking distance (305 to 329 m), forced expiratory volume in one second (FEV1 1.45 to 1.61 l), forced vital capacity (FVC 2.17 to 2.48 l) and ratio of forced expiratory to forced inspiratory flow rate at 50% vital capacity (FEF50/FIF50 0.58 to 0.88) all increased significantly. CONCLUSIONS: Endobronchial radiotherapy led to subjective benefit in most cases in terms of symptoms and bronchoscopic and radiological appearances. There was objective improvement in spirometric indices and in exercise tolerance with increased pulmonary ventilation and perfusion and evidence of decreased intrathoracic airway obstruction.
PMCID: PMC464283  PMID: 8388128
23.  Bronchial sleeve resection for early-stage squamous cell carcinoma 
A 75-year-old man complained of sputum and was referred to our department. His sputum cytology was class III. Chest X-ray and computed tomography showed no abnormalities, but bronchoscopy revealed an elevated lesion in the membranous portion of the left main bronchus, which was pathologically diagnosed as squamous cell carcinoma in situ. Since bronchoscopy revealed no other lesions in the visible parts of the airway, it was considered to be a solitary, early lung cancer, and sleeve resection of the left main bronchus was performed. The postoperative pathological diagnosis was squamous cell carcinoma in situ, pTisN0M0, stage 0. In recent years, an increasing number of studies have reported photodynamic therapy and brachytherapy for the treatment of early lung cancer. However, aggressive bronchoplastic surgery with emphasis on curability should be considered for lesions that are deemed resectable based on their number and extent of invasion.
doi:10.1186/1749-8090-7-33
PMCID: PMC3466150  PMID: 22510543
Early-stage lung cancer; Bronchial sleeve resection; Surgery
24.  Late age at first full term birth is strongly associated with lobular breast cancer 
Cancer  2010;117(9):1946-1956.
Background
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.
Methods
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.
Results
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.
Conclusion
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.
doi:10.1002/cncr.25728
PMCID: PMC3117094  PMID: 21509772
Epidemiology; reproduction; lobular breast cancer; ductal breast cancer; risk factors
25.  Comparison of the modified fluorescent method and conventional Ziehl–Neelsen method in the detection of acidfast bacilli in lymphnode aspirates 
Cytojournal  2009;6:13.
Objectives:
The objectives were to correlate the modified fluorescent method with the conventional Ziehl–Neelsen (ZN) method for the detection of acid-fast bacilli (AFB) and, also to study the efficacy and advantages of using the auramine–rhodamine stain on lymph node aspirates under fluorescent microscopy.
Methods:
In 108 consecutive patients with a clinical suspicion of tuberculosis (TB) presenting with lymphadenopathy, fine needle aspirations were performed. Smears from the aspirates were processed for routine cytology, the conventional ZN method, and the modified fluorescent method. The significance of the modified fluorescent method over the conventional ZN method was analyzed using the chi-square test.
Results:
Out of 108 aspirates, 102 were studied and remaining 6 were excluded from the study due to diagnosis of malignancy in 4.04% (4/6) and inadequate aspiration in 2.02% (2/6). Among the 102 aspirates, 44.11% (45/102) were positive for AFB on the conventional ZN method, 58.9% (60/102) were indicative of TB on cytology, while the smear positive increased to 81.37% (83/102) on the modified fluorescent method.
Conclusions:
Fluorescent microscopy has the advantage of speed and ease of screening, and reduces observer fatigue. The modified fluorescent method was found to be more advantageous than routine cytology and conventional ZN method, particularly in paucibacillary cases. The bacillary positivity rates were higher in the modified fluorescent method than in the ZN method. Hence, the modified fluorescent method can be an adjuvant when used with routine cytology for the identification of AFB.
doi:10.4103/1742-6413.53887
PMCID: PMC2716690  PMID: 19680441
Cytology; fluorescent method; tuberculosis; Ziehl–Neelsen stain

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