Processing and Analysis of Tissue Samples from Esophageal Cancer Patients in an African Setting.

Although infectious diseases continue to present a major health care problem in Africa, the incidence of cancer is increasing rapidly on the African continent and this merits an increased investment in cancer research in low to medium resource settings. Esophageal squamous cell carcinoma (ESCC) has a high incidence in Eastern and Southern Africa, with late clinical presentation and a very poor prognosis. There is limited research on the molecular pathology of this cancer in Africa, partly as a result of a lack of infrastructure for biobanking and sample processing in many African countries. The aim of this study was to establish a practical and robust workflow to collect, store, and process esophageal cancer samples such that both the tissue architecture and quality of the samples would be preserved and suitable for future genomic research. We developed a workflow that allows storage of fresh biopsy tissue in sterile Eppendorf tubes containing RNAlater, an efficient RNAse inhibitor. We collected 142 ESCC biopsy samples and showed that storage in RNAlater for up to 18 months did not alter tissue morphology, thus allowing histologic assessment by experienced pathologists and determination of tumor content in each biopsied sample. DNA and RNA extracted from tissue samples was assessed for purity, molecular size, and yield. The quantity and quality of nucleic acids obtained were suitable for genomic applications, and whole-exome sequencing of DNA from tumor tissues produced sequence data with a high proportion of both usable reads and correct base calling. We conclude that this workflow may be applicable to a wide range of malignancies for future genomic research in low-resource settings.

Xpert MTB/RIF Ultra Is Highly Sensitive for the Diagnosis of Tuberculosis Lymphadenitis in a High-HIV Setting.

Tuberculosis lymphadenitis (TBL) is the most common extrapulmonary tuberculosis (EPTB) manifestation. Xpert MTB/RIF Ultra (Ultra) is a World Health Organization-endorsed diagnostic test, but performance data for TBL, including on noninvasive specimens, are limited. Fine-needle aspiration biopsy specimens (FNABs) from outpatients (≥18 years) with presumptive TBL (n = 135) underwent (i) routine Xpert MTB/RIF testing (later with Ultra once programmatically available), (ii) MGIT 960 culture (if Xpert or Ultra negative or rifampicin resistant), and (iii) study Ultra testing. Concentrated paired urine specimens underwent Ultra testing. Primary analyses used a microbiological reference standard (MRS). In a head-to-head comparison (n = 92) of an FNAB study Ultra and Xpert, Ultra had increased sensitivity (91% [95% confidence interval: 79, 98] versus 72% [57, 84]; P = 0.016) and decreased specificity (76% [61, 87] versus 93% [82, 99]; P = 0.020) and diagnosed patients not on treatment. Neither HIV nor alternative reference standards affected sensitivity and specificity. In patients with both routine and study Ultra tests, the latter detected more cases (+20% [0, 42]; P = 0.034), and false-negative study Ultra results were more inhibited than true-positive results. Study Ultra false positives had less mycobacterial DNA than true positives (trace-positive proportions, 59% [13/22] versus 12% [5/51]; P < 0.001). "Trace" exclusion or recategorization removed potential benefits offered over Xpert. Urine Ultra tests had low sensitivity (18% [7, 35]). Ultra testing on FNABs is highly sensitive and detects more TBL than Xpert (Ultra still missed some cases due in part to inhibition). Patients with FNAB Ultra-positive "trace" results, most of whom will be culture negative, may require additional clinical investigation. Urine Ultra testing could reduce the number of patients needing invasive sampling.

Nicotinic Receptors in the Brainstem Ascending Arousal System in SIDS With Analysis of Pre-natal Exposures to Maternal Smoking and Alcohol in High-Risk Populations of the Safe Passage Study.

Pre-natal exposures to nicotine and alcohol are known risk factors for sudden infant death syndrome (SIDS), the leading cause of post-neonatal infant mortality. Here, we present data on nicotinic receptor binding, as determined by 125I-epibatidine receptor autoradiography, in the brainstems of infants dying of SIDS and of other known causes of death collected from the Safe Passage Study, a prospective, multicenter study with clinical sites in Cape Town, South Africa and 5 United States sites, including 2 American Indian Reservations. We examined 15 pons and medulla regions related to cardiovascular control and arousal in infants dying of SIDS (n = 12) and infants dying from known causes (n = 20, 10 pre-discharge from time of birth, 10 post-discharge). Overall, there was a developmental decrease in 125I-epibatidine binding with increasing postconceptional age in 5 medullary sites [raphe obscurus, gigantocellularis, paragigantocellularis, centralis, and dorsal accessory olive (p = 0.0002-0.03)], three of which are nuclei containing serotonin cells. Comparing SIDS with post-discharge known cause of death (post-KCOD) controls, we found significant decreased binding in SIDS in the nucleus pontis oralis (p = 0.02), a critical component of the cholinergic ascending arousal system of the rostral pons (post-KCOD, 12.1 ± 0.9 fmol/mg and SIDS, 9.1 ± 0.78 fmol/mg). In addition, we found an effect of maternal smoking in SIDS (n = 11) combined with post-KCOD controls (n = 8) on the raphe obscurus (p = 0.01), gigantocellularis (p = 0.02), and the paragigantocellularis (p = 0.002), three medullary sites found in this study to have decreased binding with age and found in previous studies to have abnormal indices of serotonin neurotransmission in SIDS infants. At these sites, 125I-epibatidine binding increased with increasing cigarettes per week. We found no effect of maternal drinking on 125I-epibatidine binding at any site measured. Taken together, these data support changes in nicotinic receptor binding related to development, cause of death, and exposure to maternal cigarette smoking. These data present new evidence in a prospective study supporting the roles of developmental factors, as well as adverse exposure on nicotinic receptors, in serotonergic nuclei of the rostral medulla-a finding that highlights the interwoven and complex relationship between acetylcholine (via nicotinic receptors) and serotonergic neurotransmission in the medulla.

The Stillbirth Classification System for the Safe Passage Study.

Objective Describe the classification system for assigning the cause of stillbirth in the Safe Passage Study, an international, multi-institutional, prospective analysis conducted by the NIAAA/NICHD-funded Prenatal Alcohol in SIDS and Stillbirth (PASS) Research Network. The study mission is to determine the role of prenatal alcohol and/or cigarette smoke exposure in adverse pregnancy outcomes, including stillbirth, in a high-risk cohort of 12,000 maternal/fetal dyads. Methods The PASS Network classification system is based upon 5 "sites of origin" for cause of stillbirth, further subdivided into mechanism subcategories; both are employed to assign an ultimate cause of death. Each PASS stillbirth was assigned a cause of death and status of sporadic versus recurrent. Adjudication involved review of maternal and obstetrical records; fetal autopsy and placental findings; and required complete consensus in each case. Two published classification systems, ie, INCODE and ReCoDe, were used for comparison. Results Causes of stillbirth classified were fetal (26%), placental (53%), external (5%), and undetermined (16%). Nine cases (47%) had placental causes of death due to maternal disorders that carry recurrence risks. There was full agreement for cause of death across the 3 classification systems in 26% of cases and partial agreement among them in 42% of cases. Conclusions The proposed PASS schema employs a user-friendly classification that provides comparable information to previously published systems. Advantages include its simplicity, mechanistic formulations, tight clinicopathologic integration, provision for an undetermined category, and its wide applicability to perinatal mortality review boards with access to information routinely collected during clinicopathologic evaluations.

Successful Introduction of Fine Needle Aspiration Biopsy for Diagnosis of Pediatric Lymphadenopathy.

Accurate and rapid diagnosis of extrapulmonary nodal tuberculosis in children is of paramount importance. This retrospective study performed at Tygerberg Hospital using data from the laboratory records between January 1, 2004 and June 30, 2014 demonstrates how since the introduction laboratory-run FNAB service; fine needle aspiration biopsy has become an acceptable and routine diagnostic procedure for triage of pediatric lymphadenopathy.

Ultrathin bronchoscopy for solitary pulmonary lesions in a region endemic for tuberculosis: a randomised pilot trial.

BACKGROUND: The evaluation of solitary pulmonary lesions (SPL) requires a balance between procedure-related morbidity and diagnostic yield, particularly in areas where tuberculosis (TB) is endemic. Data on ultrathin bronchoscopy (UB) for this purpose is limited. To evaluate feasibility and safety of UB compared to SB for diagnosis of SPL in a TB endemic region. METHODS: In this prospective randomised trial we compared diagnostic yield and adverse events of UB with standard-size bronchoscopy (SB), both combined with fluoroscopy, in a cohort of patients with SPL located beyond the visible range of SB. RESULTS: We included 40 patients (mean age 55.2 years, 45 % male) with malignant SPL (n = 16; 40 %), tuberculous SPL (n = 11; 27.5 %) and other benign SPL (n = 13; 32.5 %). Mean procedure time in UB and SB was 30.6 and 26.0 min, respectively (p = 0.15). By trend, adverse events were recorded more often with UB than with SB (30.0 vs. 5.0 %, p = 0.091), including extensive coughing (n = 2), blocked working channel (n = 2), and arterial hypertension requiring therapeutic intervention (n = 1), all with UB. The overall diagnostic yield of UB compared to SB was 55.0 % vs. 80.0 %, respectively (p = 0.18). Sensitivity for the diagnosis of malignancy of UB and SB was 50.0 % and 62.5 %, respectively (p = 0.95). CONCLUSION: UB is not superior to SB for the evaluation of SPL in a region endemic with tuberculosis, when combined with fluoroscopic guidance only. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT02490059 ).

Mediastinal granulomatous lymphadenitis in a population at risk for HIV and tuberculosis.

BACKGROUND: Granulomatous inflammation on transbronchial needle aspirates from mediastinal lymph nodes is an infrequent yet important finding. We determined associations between cytomorphological features and underlying aetiology in an area of high prevalence of HIV-infection and tuberculosis. METHODS: We identified cases with granulomatous inflammation on mediastinal aspirates from January 2003 to July 2010. Cytomorphological features were evaluated and graded according to a simple and reproducible system including the presence, quality (discrete or vague), and number (≤5 or more) of granulomas as well as the presence of necrosis, lymphocytes, multinucleated giant cells, and neutrophils. RESULTS: In 81 patients (36 male, 9 HIV-positive) the final diagnosis was tuberculosis in 37 (46%), sarcoidosis in 40 (49%), fibrosing mediastinitis in 1 (1%), and unknown in 3 (4%). The presence of necrosis (P < 0.001) and neutrophils (P = 0.05) was associated with tuberculosis and numerous discrete granulomas were associated with sarcoidosis (P = 0.03). All HIV-positive patients were diagnosed with tuberculosis. CONCLUSION: Granulomatous disease identified on TBNA from mediastinal lymph nodes is mostly associated with sarcoidosis and tuberculosis. Ancillary investigations for sarcoidosis are appropriate if numerous discrete granulomas are found. Tuberculosis must be excluded if necrosis and neutrophils are present and in HIV-positive individuals, particularly in high-burden areas of tuberculosis.

Incorporating microarray assessment of HER2 status in clinical practice supports individualised therapy in early-stage breast cancer.

Accurate determination of human epidermal growth factor receptor-2 (HER2) status is essential for optimal selection of breast cancer patients for gene targeted therapy. The analytical performance of microarray analysis using TargetPrint for assessment of HER2 status was evaluated in 138 breast tumours, including 41 fresh and 97 formalin-fixed paraffin embedded (FFPE) specimens. Reflex testing using immunohistochemistry/in situ hybridization (IHC/ISH) in four discordant cases confirmed the TargetPrint results, achieving 100% agreement regardless of whether fresh tissue or FFPE specimens were used. One equivocal IHC/ISH case was classified as HER2-positive based on the microarray result. The proven clinical utility in resolving equivocal and borderline cases justifies modification of the testing algorithm under these circumstances, to obtain a definitive positive or negative test result with the use of microarrays. Determination of HER2 status across three assay platforms facilitated improved quality assurance and led to a higher level of confidence on which to base treatment decisions.

Rapid diagnosis of pediatric mycobacterial lymphadenitis using fine needle aspiration biopsy.

BACKGROUND: Diagnosis of tuberculosis in children is challenging and fine needle aspiration biopsy (FNAB) is used worldwide in the diagnosis of palpable masses including peripheral lymphadenopathy. Recent studies of the use of nucleic acid amplification such as the Xpert MTB/RIF test on FNAB in adult patients have shown considerable promise. Xpert MTB/RIF allows for the rapid diagnosis of Mycobacterium tuberculosis and identification of rifampicin susceptibility. Studies to date have been predominantly performed in adults. This study aims to determine the accuracy of Xpert MTB/RIF for the detection of M. tuberculosis complex in FNAB from children with clinically suspected mycobacterial lymphadenitis. METHODS: Prospective hospital-based study of children <13 years referred for FNAB at Tygerberg hospital and Dora Nginza hospital, South Africa, for suspected mycobacterial lymphadenitis. Aspirates were performed and the results of the Xpert MTB/RIF test were compared with liquid (mycobacterial growth indicator tube) culture and cytology. RESULTS: FNABs were collected from 110 children and 38 (35%) cases were excluded. Of the 72 cases included in the study, 32 were positive for M. tuberculosis complex on Xpert MTB/RIF, 36 on cytology and 25 were culture positive for M. tuberculosis complex. Compared with the combined reference standard (cytomorphology suggestive of mycobacterial disease with direct visualization of the organism and/or bacteriological culture), Xpert MTB/RIF identified 32 of 40 cases as positive with a sensitivity and a specificity of 80% and 93.8%, respectively. CONCLUSIONS: FNAB and Xpert MTB/RIF enable a rapid diagnosis in pediatric mycobacterial lymphadenitis, expediting appropriate treatment and potentially preventing morbidity and mortality.

MammaPrint Pre-screen Algorithm (MPA) reduces chemotherapy in patients with early-stage breast cancer.

BACKGROUND: Clinical and pathological parameters may overestimate the need for chemotherapy in patients with early-stage breast cancer. More accurate determination of the risk of distant recurrence is now possible with use of genetic tests, such as the 70-gene MammaPrint profile. OBJECTIVES: A health technology assessment performed by a medical insurer in 2009 introduced a set of test eligibility criteria - the MammaPrint Pre-screen Algorithm (MPA) - applied in this study to determine the clinical usefulness of a pathology-supported genetic testing strategy, aimed at the reduction of healthcare costs.Methods. An implementation study was designed to take advantage of the fact that the 70-gene profile excludes analysis of hormone receptor and human epidermal growth factor receptor 2 (HER2) status, which form part of the MPA based partly on immunohistochemistry routinely performed in all breast cancer patients. The study population consisted of 104 South African women with early-stage breast carcinoma referred for MammaPrint. For the MammaPrint test, RNA was extracted from 60 fresh tumours (in 58 patients) and 46 formalin-fixed, paraffin-embedded (FFPE) tissue samples. RESULTS: When applying the MPA for selection of patients eligible for MammaPrint testing, 95 of the 104 patients qualified. In this subgroup 62% (59/95) were classified as low risk. Similar distribution patterns for risk classification were obtained for RNA extracted from fresh tumours v. FFPE tissue samples. CONCLUSIONS: The 70-gene profile classifies approximately 40% of early-stage breast cancer patients as low-risk compared with 15% using conventional criteria. In comparison, more than 60% were shown to be low risk with use of the MPA validated in this study as an appropriate strategy to prevent chemotherapy overtreatment in patients with early-stage breast cancer.

An interinstitutional review of the value of FNAB in pediatric oncology in resource-limited countries.

Fine-needle aspiration biopsy (FNAB) has been widely accepted as a reliable diagnostic modality in the general pediatric population, but its role in pediatric oncology still remains elusive. With new treatment protocols subscribing to preoperative chemotherapy, the need for a quick, minimally invasive, and accurate diagnostic procedure has arisen. This study assesses the feasibility of FNAB in childhood malignancies to render a specific diagnosis on which treatment can be initiated. An 11-year retrospective study was done on FNABs in patients 19 years and under referred for clinically malignant mass lesions. Cases were confirmed with histology, immunocytochemistry, flow cytometry, or clinical follow-up. Of the 357 patients referred for FNABs, 36 patients were lost to follow-up and 31 FNABS were inadequate. A total of 290 cases were included in the study, of which 68 (23%) cases were benign and 222 (77%) were malignant. The most frequently occurring tumors were nephroblastoma (68), non-Hodgkin's lymphoma (39), rhabdomyosarcoma (22), Hodgkin's lymphoma (22), and neuroblastoma (22). The sensitivity of the procedure for neoplasia was 96.6%, the specificity 97.0%, positive predictive value 99.0%, and negative predictive value 90.1%, with a diagnostic accuracy of 96.7%. The ability of FNAB to enable a specific diagnosis to be made, that is correct and accurate subtyping of the tumor on which chemotherapy or radiotherapy could be commenced was 75.7%. This study shows that FNAB can be used with confidence to confirm malignancy in children. With clinicoradiological correlation and the aid of ancillary techniques, FNAB allows a rapid and accurate preoperative diagnosis for definitive therapy commencement in most cases.

Necrotizing enterocolitis in HIV-exposed and nonexposed infants: clinical presentation and histopathological features.

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in neonates and is associated with significant morbidity and mortality. An association between HIV-positive maternal status and increased risk of NEC in preterm infants has been described, and antiretroviral therapy has been proposed as an independent risk factor. Our aim was to compare the clinical presentation and histopathological features of necrotizing enterocolitis in HIV-exposed and unexposed infants. A retrospective study of archival material from the National Health Laboratory Services Histopathology Laboratory in Tygerberg Hospital/Stellenbosch University from 1992 to 2008 was conducted. All surgical specimens from infants who presented to pediatric surgery for a laparotomy and bowel resection for NEC and in whom the HIV status was known were included in the study. In the 37 cases that fulfilled these criteria, male gender was overrepresented in the study population (67%). Nonsteroidal anti-inflammatory drugs appeared to play a significant role in the development of surgical NEC in infants who were not exposed to HIV, but HIV-exposed infants had a significantly poorer survival rate. There was no significant difference in the histopathology between HIV-exposed and nonexposed infants, and Cytomegalovirus infection was not identified in any of the cases studied.

A comparison of specimen adequacy in fine needle aspiration biopsies performed by pathologists, trained nursing staff and clinicians.

Fine needle aspiration biopsies (FNAB) performed by trained professional nurses and pathology registrars in an FNAB clinic were compared with aspirates by clinicians from regional clinics and hospitals. Of the 7709 reports retrieved from the archives, the highest number of unsatisfactory aspirates came from clinicians (42%), followed by registrars (20.09%) while the nurses had the lowest overall unsatisfactory rate (14.32%). We conclude that, in countries experiencing a shortage of adequately qualified and experienced medical personnel, it is essential to train nurses to perform and manage FNAB clinics.

Comparison of the quality of smears in transbronchial fine-needle aspirates using two staining methods for rapid on-site evaluation.

Transbronchial needle aspiration (TBNA) via flexible bronchoscopy is a well-established sampling modality for lung masses. The procedure is useful in the diagnosis of neoplastic and non-neoplastic lesions as well as for staging of bronchogenic carcinoma. Rapid on-site evaluation (ROSE) adds value as it has the advantage of triaging material during the procedure so avoiding a battery of investigations. Frequently used rapid stains are the modified Wright-Giemsa water-based stain (WG-ROSE) and the alcohol-based modified Papanicolaou stain (Pap-ROSE). Final review of laboratory-based Giemsa and Pap stains supplemented by ancillary investigations is essential for quality assurance. To investigate whether and how ROSE influenced the quantity and quality of the material submitted to the laboratory we randomized 126 patients to WG-ROSE, requiring only one pathologist on-site, or combined WG- and Pap-ROSE, requiring an additional person on-site to assist with staining. In those patients with positive TBNA we graded the laboratory-based slides of the first pass containing diagnostic material into insufficient, suspicious, adequate and excellent. The first diagnostic pass was found after 3.06 ± 1.94 (SD) passes and 3.13 ± 2.16 passes with WG-ROSE and combined ROSE (P = 0.87), respectively. Following WG-ROSE and combined ROSE 69% and 71.1% (P = 0.509) of slides were diagnostic (adequate or excellent) on laboratory-based Giemsa stains, and 93.3% and 100% (P = 0.134) were scored adequate or excellent on laboratory-based Pap stains. We concluded that the less costly and labour intensive WG-ROSE procedure is adequate for TBNA. This has cost implications especially in resource poor settings.

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.

Xpert MTB/RIF for rapid diagnosis of tuberculous lymphadenitis from fine-needle-aspiration biopsy specimens.

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.

Cytomorphological patterns of M. bovis BCG and M. tuberculosis on fine needle aspiration biopsies: does HIV make a difference?

To determine if fine needle aspiration (FNAB) of mycobacterial lymphadenopathy can differentiate infection with M. bovis BCG (BCG) from M. tuberculosis (TB) and whether HIV status affects discriminatory cytological features. A retrospective study of culture positive, fine needle aspiration biopsies of lymph nodes in children (<13 years) between 2003 and 2008. A total of 77 aspirates were available for evaluation with 67 (87%) patients having known HIV status. BCG occurred at a younger age (6 months), predominantly axillary lymph nodes (90%) compared with TB (5 years and 20% axillary lymph nodes). Amorphous necrosis was only seen in aspirates from TB lymph nodes, while in HIV negative children with TB, foamy macrophages were absent. On ZN staining there were more organisms in the BCG group and in HIV positive patients the organisms were present in both extra- and intracellular locations, whereas in the HIV negative patients the organisms were predominantly extracellular in location. Demographic and cytomorphologic features that can assist in distinguishing between the two mycobacterial species include: age of patient, location of the lymph node, and presence/absence of amorphous necrosis and foamy macrophages on FNAB. However the only reliable method to identify the mycobacterial species is by mycobacterial culture and/or PCR.

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

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

The diagnostic yield and safety of ultrasound-assisted transthoracic biopsy of mediastinal masses.

BACKGROUND: Ultrasound (US)-assisted transthoracic biopsy offers a less invasive alternative to surgical biopsy in the setting of mediastinal masses. OBJECTIVES: The aim of this 1-year prospective study was to assess the diagnostic yield and safety of a novel single-session sequential approach of US-assisted transthoracic fine-needle aspirations (TTFNA) with rapid on-site evaluation (ROSE) followed by cutting needle biopsies (CNB) performed by physicians on patients with anterosuperior mediastinal masses. METHODS: US-assisted TTFNA with ROSE was performed on 45 consecutive patients (49.5 ± 27.7 years, 24 males), immediately followed by CNB where a provisional diagnosis of epithelial carcinoma or tuberculosis could not be established, provided a safety range could be assured. RESULTS: TTFNA alone was deemed adequate by means of ROSE in 27 (60%) patients. CNB could be performed in 17 of the remaining 18. The on-site diagnosis corresponded to the final diagnosis in 26/45 (57.8%). An accurate cytological diagnosis was made in 33 (73.3%), and was more likely to be diagnostic in epithelial carcinoma and tuberculosis (28/30) than all other pathologies (5/15, p < 0.001). CNB yielded a diagnosis in 15/17 (88.2%). Overall, 42/45 patients were diagnosed by the single-session approach (93.3%). The final diagnoses included 41 neoplasms, with small cell lung cancer (n = 13) the commonest diagnosis. We observed no pneumothorax or major haemorrhage. CONCLUSIONS: A single-session sequential approach of US-assisted TTFNA with ROSE followed by CNB, where indicated, has a high diagnostic yield for anterosuperior mediastinal masses, is safe and offers an alternative to surgical biopsy.