Colleen A. Wright

Utility of Rapid On-Site Evaluation of Transbronchial Needle Aspirates

Background: Rapid on-site evaluation has been proposed as a method to improve the yield of transbronchial needle aspiration. Objectives: This study investigated whether on-site analysis facilitates routine diagnostic bronchoscopy in terms of sampling, yield and cost. Methods: Patients with lesions accessible for transbronchial needle aspiration on computed tomography were investigated. A cytopathologist screened the needle aspirates on site for the presence of diagnostic material. The bronchoscopic sampling process was adjusted according to the results. In 90 consecutive patients with neoplastic disease (n = 70; 78%), non-neoplastic disease (n = 16; 18%) or undiagnosed lesions (n = 4; 4%) we aspirated 162 lung lesions (paratracheal tumours or lymph nodes: 7%; tracheobronchial lymph nodes: 68%; other: 25%). Results: The diagnostic yield of needle aspiration was 77 and 25% in patients with neoplastic and non-neoplastic lesions, respectively. Sampling could be terminated in 64% of patients after needle aspiration had been performed as the only diagnostic modality, and on-site analysis identified diagnostic material from the first site aspirated in 50% of patients. Only in 2 patients (2%) diagnostic aspirates were not recognized on site. On-site analysis was cost effective due to savings for disposable diagnostic tools, which exceeded the extra expense for the on-site cytology service provided. Conclusions: Rapid on-site analysis of transbronchial aspirates is a highly useful, accurate and cost-effective addition to routine diagnostic bronchoscopy.

Safety and yield of ultrasound-assisted transthoracic biopsy performed by pulmonologists

Background: Transthoracic ultrasound (US) has gained popularity as a tool for visualizing pleural effusions and assisting thoracentesis or chest drain placement. In the absence of effusion, US just as well demonstrates solid masses involving or abutting the pleura, yet biopsy of such lesions is not widely performed by chest physicians. Objective: To assess the feasibility and the safety of US-assisted cutting needle biopsy performed by chest physicians in routine practice. Methods: Lesions involving or abutting the pleura ≧20 mm in diameter on US were sampled with a 14-gauge cutting needle under local anesthesia. Biopsy site, needle direction and depth of penetration were determined with US. The procedure was performed without direct US guidance in ‘free-hand’ technique. Results: Ninety-one patients underwent 96 cutting-needle biopsies for suspected peripheral lung tumors (n = 44, 46%), pleural-based (n = 39, 41%), mediastinal (n = 10, 10%), or chest wall lesions (n = 3, 3%), which were single in 71%, multiple in 6% and diffuse in 23%. Sensitivity for malignant neoplasms (n = 65) was 85.5% and 100% for mesothelioma (n = 10). Pneumothorax occurred in 4%. Conclusions: US-assisted cutting-needle biopsy of lesions ≧20 mm in diameter is safe in the hands of pulmonologists. The yield for neoplastic disease including mesothelioma is high.

Tuberculous lymphadenitis as a cause of persistent cervical lymphadenopathy in children from a tuberculosis-endemic area

Background: Cervical lymphadenitis is the most common form of extrapulmonary tuberculosis in children, although its relative contribution as a cause of persistent cervical adenopathy is not well-documented. The aim of this study was to determine the relative contribution of tuberculous lymphadenitis as a cause of persistent cervical adenopathy in a tuberculosis-endemic setting and to document its clinical presentation at the primary health care level. Methods: A prospective descriptive study was conducted from February 2003 through October 200 at 5 primary health care clinics in Cape Town, South Africa. The study included all children younger than 13 years presenting with persistent cervical adenopathy to the local primary health care clinic. Results: A total of 158 children were evaluated of whom 35 (22.2%) were diagnosed with tuberculous lymphadenitis. Bacteriologic confirmation was achieved in 27 of 35 (77.1%) children; all 35 responded to standard antituberculosis treatment. The majority of those without tuberculous lymphadenitis (105 of 123, 85.4%) had a visible superficial lesion in the area drained by the affected nodes. In children with persistent lymphadenopathy ≥2 × 2 cm, tuberculosis lymphadenitis was diagnosed in 31 of 33 (93.9%); specificity was 98.4%, sensitivity was 88.6% and the positive predictive value was 93.4%. Conclusion: Children commonly present with persistent cervical adenopathy to the primary health care clinic. The use of a simple clinical algorithm provided an accurate diagnosis of tuberculous lymphadenitis in the study setting. Fine needle aspirations provided a rapid and definitive diagnosis in the majority of children and will have added diagnostic value in settings where alternative diagnoses are more likely.

Direct comparison of the diagnostic yield of ultrasound-assisted Abrams and Tru-Cut needle biopsies for pleural tuberculosis

Background Tuberculous pleuritis remains the commonest cause of exudative effusions in areas with a high prevalence of tuberculosis and histological and/or microbiological confirmation on pleural tissue is the gold standard for its diagnosis. Uncertainty remains regarding the choice of closed pleural biopsy needles. Objectives This prospective study compared ultrasound-assisted Abrams and Tru-Cut needle biopsies with regard to their diagnostic yield for pleural tuberculosis. Methods 89 patients (54 men) of mean±SD age 38.7±16.7 years with pleural effusions and a clinical suspicion of tuberculosis were enrolled in the study. Transthoracic ultrasound was performed on all patients, who were then randomly assigned to undergo ≥4 Abrams needle biopsies followed by ≥4 Tru-Cut needle biopsies or vice versa. Medical thoracoscopy was performed on cases with non-diagnostic closed biopsies. Histological and/or microbiological proof of tuberculosis on any pleural specimen was considered the gold standard for pleural tuberculosis. Results Pleural tuberculosis was diagnosed in 66 patients, alternative diagnoses were established in 20 patients and 3 remained undiagnosed. Pleural biopsy specimens obtained with Abrams needles contained pleural tissue in 81 patients (91.0%) and were diagnostic for tuberculosis in 54 patients (sensitivity 81.8%), whereas Tru-Cut needle biopsy specimens only contained pleural tissue in 70 patients (78.7%, p=0.015) and were diagnostic in 43 patients (sensitivity 65.2%, p=0.022). Conclusions Ultrasound-assisted pleural biopsies performed with an Abrams needle are more likely to contain pleura and have a significantly higher diagnostic sensitivity for pleural tuberculosis.

Transbronchial needle aspirates: how many passes per target site?

Transbronchial needle aspiration is a bronchoscopic sampling method for a variety of bronchial and pulmonary lesions. The present study investigated whether and how serial needle passes contribute to the yield of transbronchial needle aspiration at specific target sites. A total of 1,562 needle passes, performed at 374 target sites in 245 patients with neoplastic disease (82%), non-neoplastic disease (15%) or undiagnosed lesions (3%), were prospectively recorded and rated for anatomical location, size, bronchoscopic appearance and underlying disease. Positive aspirates were obtained in 75% of patients and at 68% of target sites. A diagnosis was established with the first, second, third and fourth needle pass at 64, 87, 95 and 98% of targets, respectively. The absolute yield varied strongly with target site features, but the stepwise increment to the maximum yield provided by serial passes was similar across target sites. In conclusion, three transbronchial needle passes per site are appropriate when only a tissue diagnosis is sought and when alternative sites or sampling modalities are available. At least four or five passes should be carried out at lymph node stations critical for the staging of lung cancer.

Xpert MTB/RIF for Rapid Diagnosis of Tuberculous Lymphadenitis from Fine-Needle-Aspiration Biopsy Specimens

ABSTRACT This study demonstrates the excellent diagnostic accuracy of the Xpert MTB/RIF test in patients with tuberculous lymphadenitis. The test sensitivity and specificity were 96.7% (95% confidence interval [CI], 86.6 to 100%) and 88.9% (95% CI, 69.6 to 100%), respectively, and it correctly identified 6/6 (100%) of the cytology smear-negative/culture-positive cases and 1 of 2 (50%) rifampin-resistant cases.

Diagnosing mycobacterial lymphadenitis in children using fine needle aspiration biopsy: Cytomorphology, ZN staining and autofluorescence-making more of less

Although the incidence of TB has stabilized or declined in most world regions, it is increasing in Africa, Southeast Asia, and the Eastern Mediterranean, fuelled by the HIV pandemic. More than 4,000 people died daily from TB‐related illnesses in 2005. TB is a major cause of childhood morbidity and mortality in these developing countries, and there is an urgent need for rapid and definitive modalities for mycobacterial diagnosis in children. This prospective study in Tygerberg Hospital, Cape Town, South Africa, evaluates the ability of fine needle aspiration biopsy (FNAB) to diagnose mycobacterial lymphadenitis in children, using cytomorphology, autofluorescence on Papanicolaou stained smears, Ziehl‐Nielsen (ZN) staining and/or culture. FNABs were performed on 200 children, and 25 (12.5%) aspirates were inadequate. Cultures were positive in 79/175 (45%); Mycobacterium tuberculosis was identified in 61 and Mycobacterium bovis BCG in 18 cases. Using culture as the gold standard, the concordance of the different techniques was as follows: cytomorphology 70%, ZN staining 73%, and autofluorescence 68%. Using an alternative gold standard (culture positive and/or suggestive cytomorphology plus positive autofluorescence or ZN smear), the “true” diagnostic performance of the various techniques was as follows: cytomorphology—sensitivity 78%, specificity 91%, positive predictive value (PPV) 93%, ZN staining ‐ sensitivity 62%%, specificity 97%, PPV 97%; autofluorescence—sensitivity 67%, specificity 97%, PPV 97%; and culture—sensitivity 75%, specificity 100%, and PPV 100%. FNAB was shown to provide a rapid and definitive diagnosis in the majority of cases of suspected tuberculous lymphadenitis in children, based on cytomorphology and identification of the organism. Diagn. Cytopathol. 2008;36:245–251.

Ultrasound-assisted transthoracic biopsy: fine-needle aspiration or cutting-needle biopsy?

The present study compared the diagnostic yield of ultrasound-assisted cutting-needle biopsy (CNB) and fine-needle aspiration biopsy (FNAB) in chest lesions. A physician performed ultrasound and FNAB with a 22-G spinal needle in all patients, directly followed by a 14-G CNB in patients without contraindication. A total of 155 consecutive lesions arising from the lung (74%), pleura (12%), mediastinum (11%) or chest wall (3%) in patients with a final diagnosis of lung carcinoma (74%), other malignant tumours (12%), non-neoplastic disease (9%) or unknown (5%) were prospectively included. The overall diagnostic yield was 87%. Combined specimens were obtained in 123 lesions (79%). In these, yields of FNAB, CNB and both methods combined were 82, 76 and 89%, respectively. FNAB was significantly better than CNB in lung carcinoma (95 versus 81%) but CNB was superior in noncarcinomatous tumours and in benign lesions. On-site cytology was 90% sensitive and 100% specific for predicting a positive FNAB. One patient required drainage for pneumothorax (0.6%). Ultrasound-assisted fine-needle aspiration biopsy performed by chest physicians is an accurate and safe initial diagnostic procedure in patients with a high clinical probability of lung carcinoma. All other patients should undergo concurrent fine-needle aspiration biopsy and cutting-needle biopsy.

Adjunctive tests for diagnosis of tuberculosis: Serology, ELISPOT for site-specific lymphocytes, urinary lipoarabinomannan, string test, and fine needle aspiration

The diagnostic gold standard for active tuberculosis (TB) is the detection of Mycobacterium tuberculosis (MTB) by culture or molecular methods. However, despite its limited sensitivity, sputum smear microscopy is still the mainstay of TB diagnosis in resource-limited settings. Consequently, diagnosis of smear-negative pulmonary and extrapulmonary TB remains challenging in such settings. A number of novel or alternative techniques could provide adjunctive diagnostic use in the context of difficult-to-diagnose TB. These may be especially useful in certain patient groups such as persons infected with human immunodeficiency virus (HIV) and children, who are disproportionably affected by smear-negative and extrapulmonary disease and who are also most adversely affected by delays in TB diagnosis and treatment. We review a selection of these methods that are independent of nucleic acid amplification techniques and could largely be implemented in resource-limited settings in current or adapted versions. Specifically, we discuss the diagnostic use and potential of serologic tests based on detection of antibodies to MTB antigens; interferon gamma release assays using site-specific lymphocytes; detection of lipoarabinomannan, a glycolipid of MTB, in urine; the string test, a novel technique to retrieve lower respiratory tract samples; and fine needle aspiration biopsy of lymph nodes.

The Safe Passage Study: Design, Methods, Recruitment, and Follow-Up Approach

BACKGROUND The Safe Passage Study is a large, prospective, multidisciplinary study designed to (1) investigate the association between prenatal alcohol exposure, sudden infant death syndrome (SIDS), and stillbirth, and (2) determine the biological basis of the spectrum of phenotypic outcomes from exposure, as modified by environmental and genetic factors that increase the risk of stillbirth, SIDS, and in surviving children, fetal alcohol spectrum disorders. METHODS The results provided are based on an interim assessment of 6004 women enrolled, out of the 12,000 projected, from the Northern Plains, US, and Cape Town, South Africa, areas known to be of high risk for maternal drinking during pregnancy. Research objectives, study design, and descriptive statistics, including consent, recruitment, and retention information, are provided. RESULTS Overall visit compliance is 87%, and includes prenatal, delivery/newborn, and postnatal contacts through 1 year post-delivery. Pregnancy outcome ascertainment is 98% prior to medical chart review; less than 2% of women withdraw. Consent for the use of DNA and placental tissue exceed 94%, and consent to participate in the autopsy portion of the study is 71%. CONCLUSIONS The Safe Passage Study is the first multi-site study of SIDS and stillbirth to integrate prospectively collected exposure information with multidisciplinary biological information in the same maternal and fetal/infant dyad using a common protocol. Essential components of the study design and its success are close ties to the community and rigorous systems and processes to ensure compliance with the study protocol and procedures.