SARJ Vol 22, No 3 (2016)

ISSN 2304-0017

SouthAfrican African South

Respiratory Respiratory Journal Journal VOLUME 22

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NUMBER 3

South African

Respiratory

Journal

OFFICIAL JOURNAL OF THE S.A. THORACIC SOCIETY

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SEPTEMBER 2016

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S4 FOXAIR® 50/250 and 50/500 ACCUHALER® - 42/21.5.4/0582; 0583. Each blister contains a mixture of salmeterol xinafoate equivalent to 50 µg of salmeterol and microfine fluticasone propionate (250 µg or 500 µg). Applicant: GlaxoSmithKline South Africa (Pty) Ltd. (Co. Reg. No. 1948/030135/07). 39 Hawkins Avenue, Epping Industria 1, Cape Town, 7460. For full prescribing information plese refer to the package insert approved by the Medicines Regulatory Authority. All adverse events should be reported by calling the Aspen Medical Hotline number or directly to GlaxoSmithKline on +27117456000. FO/0713/933 A16772 08/13

THE SOUTH AFRICAN

RESPIRATORY JOURNAL VOLUME 22 | NUMBER 3 | SEPTEMBER 2016

CONTENTS REVIEW 54

An approach to the solitary pulmonary nodule S Abraham, M J Vorster, S S Roy, C F N Koegelenberg

ORIGINAL ARTICLES

60

The effect of therapeutic pleural drainage on the short- and long-term sequelae of tuberculous pleural effusions E Wilken, H Fengels, F Swart, D Maree, J W Bruwer, E M Batubara, E M Irusen, C F N Koegelenberg 67 Diagnostic yield of transbronchial needle aspiration for lymphoma

B Sonnekus, J Steenkamp, M Louw, C F N Koegelenberg

CASE REPORT

73

Pulmonary puzzle: A rare case of dysphagia S Sinha Roy, C F N Koegelenberg, E M Irusen

76

BREATH-TAKING NEWS

79

PRODUCT NEWS

81 ABSTRACTS

SARJ EDITOR-IN-CHIEF Prof. K Dheda DEPUTY EDITOR Prof. C Koegelenberg SECTION EDITOR Breath-taking News: Prof. E Irusen EDITORIAL BOARD Prof. G Ainslie, Prof. E Bateman, Prof. R Green, Prof. E Irusen, Prof. M Jeebhay, Prof. P Jeena, Prof. U Lalloo, Prof. A Linegar, Prof. R Masekela, Dr K Nyamande, Dr J O’Brien, Dr R Raine, Prof. G Richards, Dr R van Zyl Smit, Prof. M Wong, Prof. H Zar INTERNATIONAL EDITORIAL BOARD Prof. Adithya Cattamanchi - USA Prof. Fan Chung - UK Prof. GB Migliori - Italy Prof. Surendra Sharma - India Prof. Wing Wai Yew - China PRESIDENT SA THORACIC SOCIETY Prof. U Lalloo

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REVIEW

An approach to the solitary pulmonary nodule S Abraham, MB ChB, MMed (Int), FCP (SA); M J Vorster, MB ChB, MRCP (UK), MMed (Int), FCP (SA); S S Roy, MBBS, DTCD, MD (Internal Medicine), FCCP; C F N Koegelenberg, MB ChB, MMed (Int), FCP (SA), FRCP (UK), Cert Pulmonology (SA), PhD Division of Pulmonology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Hospital, Cape Town, South Africa Corresponding author: S Abraham (shinu_29@yahoo.com)

Solitary pulmonary nodules may represent early lung cancer, which is potentially curable. The advent of improved imaging techniques, together with the worldwide implementation of screening programmes, has intensified the need for a structured approach to the management of pulmonary nodules. We present an overview of the current literature on risk stratification, characteristics and management of pulmonary nodules that are relevant to practitioners in South Africa.

S Afr Respir J 2016;22(3):54-60. DOI:10.7196/SARJ.2016.v22i3.83

In clinical practice, solitary pulmonary nodules (SPNs) represent a common challenge, as they may be indicative of early cancer that is curable; however, after extensive investigation the vast majority are found to be of benign aetiology. While advanced lung cancer survival rates remain low – 17% at 5 years – the diagnosis of early lung cancer (stage 1A) can be associated with a 5-year survival rate of 70 - 80%.[1] The best possibility for cure in potentially malignant SPNs is prompt diagnosis and surgery, while at the same time trying to avoid unnecessary intervention and surgery in patients with benign disease processes.[2] Traditionally an SPN is defined as a single, usually wellcircumscribed spherical opacity of ≤3 cm, completely surrounded by pulmonary parenchyma and not associated with lymphadenopathy, atelectasis or pleural effusion.[3] The new British Thoracic Society (BTS) guideline[4] extends the definition to include nodules in contact with the pleura. Most SPNs are asymptomatic and discovered incidentally.

The incidence of SPNs ranges from 0.2% in older radiographic studies to 40 - 60% in lung screening studies.[2] Lesions >3 cm are considered as masses and have a high likelihood of malignancy, requiring prompt diagnosis and management.

The differential diagnosis of SPNs (Table 1) is broad, with a variety of aetiologies, which include malignancies such as bronchogenic carcinoma, carcinoid tumours, lymphoma, and solitary pulmonary metastasis, and benign aetiologies such as granulomas and hamartomas[2] – the most common benign causes.

Low-dose computed tomography screening

With the increasing use of computed tomography (CT) of the chest, the detection of SPNs has become common.[5] The implementation of low-dose CT lung cancer screening is expected to increase the detection of SPNs. Several studies, including lung screening trials in smokers, suggest that the majority of nodules identified on CT are benign.[2,6-10] In the Pan-Canadian Early Detection of Lung Cancer and the British Columbia Cancer Agency studies, among the 7 008 and 5 021 nodules detected, respectively, only a total of 144 (1%) were

54 SARJ VOL. 22 NO. 3 2016

malignant.[7] The false-positive rate in the National Lung Screening Trial (NLST) was 96%.[10]

General evaluation of an SPN

The assessment of an SPN involves risk stratification of the individual patient, performing further imaging studies (if available), and formulating a management plan after taking into consideration the risks associated with various treatment strategies and individual patient preferences.

Risk stratification Principles

Estimation of the pretest probability of cancer in an SPN includes clinical assessment of individual risk, evaluation of radiological features to differentiate between benign and malignant nodules, and use of models using logistic regression. Logistic regression models use both clinical and radiological parameters to assess the pretest risk of malignancy. This risk assessment determines further management steps, which may include CT surveillance, further investigation (e.g. positron emission tomography (PET)-CT) and/ or biopsy (non-surgical or surgical).

Clinical assessment

Clinical risk stratification considers individual demographics and medical history and assesses the patient’s risk. Risk factors associated with a higher likelihood of malignancy include advanced age, current or ever smokers, time from smoking cessation, number of pack-years, emphysema, asbestos exposure, history of previous extrapulmonary malignancy, radiation therapy, idiopathic pulmonary fibrosis and HIV.[2,4] Chest radiography

SPNs (Fig. 1) are still commonly first detected on chest radiographs, and a diameter of 8 - 10 mm is usually required before they are visible. Certain patterns of calcification may point to a benign cause (discussed below).

REVIEW

Table 1. The differential diagnosis of a solitary pulmonary nodule Neoplastic Malignant Bronchogenic carcinoma Adenocarcinoma (including adenocarcinoma in situ (previously bronchoalveolar carcinoma)) Squamous cell carcinoma Large-cell lung carcinoma Small-cell lung cancer Metastasis Colon, breast, kidney, prostate, testicular cancer Extranodal lymphoma Pulmonary carcinoid Benign

Fig. 1. An example of an SPN seen on chest radiography. A nodule was noted in the right lower zone of a 50-year-old female smoker. A CT and an integrated PET-CT were done on the patient (Figs 2 and 4).

Pulmonary hamartoma Connective tissue and neural tumours Fibroma, neurofibroma, blastoma, sarcoma, lipoma, angioma Infectious Granulomas Tuberculosis Fungal (histoplasmosis, coccidioidomycosis, blastomycosis, cryptoccocosis) Atypical mycobacteria Bacterial (nocardiosis) Parasitic (Dirofilaria immitis) Lung abscess Round pneumonia Hydatid cyst Inflammatory Rheumatoid arthritis Sarcoidosis Granulomatosis with polyangitis Lipoid pneumonia Congenital Pulmonary sequestration Bronchogenic cyst Arteriovenous malformation Miscellaneous Pulmonary infarct Rounded atelectasis Mucoid impaction Progressive massive fibrosis

Fig. 2. A CT scan of the chest of the same patient as in Fig. 1, showing a 19 × 12 mm SPN in the right lower lobe.

Chest CT

In a patient with an indeterminate nodule identified by chest radiography, it is recommended that CT of the chest should be performed (preferably with thin sections through the nodule). The predictors on CT (Fig. 2) that could assist with the likelihood of malignancy in SPNs include: the nodule size, border, density (calcification, fat), growth rate or volume-doubling time (VDT), nodule attenuation and location.

Data from clinical trials indicate that the risk of malignancy rises with increasing nodule size.[6,7,11,12] More than 90% of nodules <2 cm in diameter are benign. However, subcentimeter nodules may represent an early stage of lung cancer. Data from the NLST suggested that the likelihood of malignancy increased

significantly from 1.7% for nodules 7 - 10 mm in diameter to 11.9%, 29.7% and 41.3% for nodules with a diameter of 11 - 20 mm, 21 30 mm and >30 mm, respectively.[10] Nodules with irregular, lobulated or spiculated (corona radiata) borders are associated with a progressively higher probability of malignancy than those with smooth borders. [6,13] The corona radiata sign consists of very fine linear strands extending 4 - 5 mm outward from the nodule.

Nevertheless, malignant SPNs may also present with a smooth border.

Certain types of calcification in SPNs indicate benign disease processes. There are six different patterns of calcification: central dense nidus; diffuse solid; laminated; pop­ corn; punctate; and dendriform. [14] Diffuse, central, laminated and popcorn calcification are considered to be benign[3,4,13,15,16] – the first three types are associated with granulomatous processes, with popcorn calcification typ­ ically occurring in a pulmonary hamar­ toma. The presence of intranodal fat density and popcorn calcification is specific for pulmonary hamartoma. All other patterns of calcification are suspicious of malignancy.

Stippled and eccentric calcification patterns are seen in malignant nodules and warrant further evaluation and workup.[17] Lung nodules containing fat include pulmonary hamartoma, lipoma and lipoid pneumonia.

Calcific metastases may occur in pri­mary sarcomas, such as osteosarcoma, chondro­ sarcoma and synovial sarcoma. [14] Primary carcinomas associated with metastases that may calcify include papillary and mucinous adenocarcinomas, and medullary carcinoma of the thyroid.[14] Studies have shown that 70% of lung cancers are located in the upper lobes.[4,6,7] As benign nodules can occur in the upper and lower lobes, location is not a good independent predictor of malignancy. Tuberculosis (TB) is common in the South African (SA) setting and classically affects the upper lobes.

Perifissural and subpleural solid nodules are likely to be benign if they are homogeneous, have a lentiform or triangular shape, measure <10 mm in size, and are within 1 cm of the fissure or the pleural surface.[18] Based on nodule attenuation on CT, SPNs can be classified as non-solid (ground glass), partly solid, or solid. Non-solid nodules have underlying bronchovascular structures visible

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REVIEW through them, while a partly solid nodule also contains solid regions that will mask visibility of the underlying bronchovascular structures.[19] New nomen­clature for SPNs has been adopted by the BTS guideline,[4] with classification of nodules into solid and subsolid; additionally, there is subclassification of subsolid nodules into part-solid and pure ground-glass nodules (pGGNs) (Fig. 3).

Solid lesions are more common in practice, but subsolid lesions have a higher likelihood of being malignant, with CT screening studies showing that the identification of a solid component in a partly solid nodule was an independent predictor of malignancy. [20] Pure ground-glass SPNs typically represent adenocarcinoma in situ, atypical adenomatous hyperplasia or minimally invasive adeno­carcinoma. [4] Increased growth or development of a solid component in a GGN is strongly associated with transformation to invasive adenocarcinoma. [2] The VDT for malignant bronchogenic tumours is rarely <1 month or >1 year.[21] The average doubling time for a malignant tumour is 120 days (range 7 - 590 days). The exception would be indolent tumours, such as adenocarcinoma in situ, which has a doubling time of up to 900 days. Doubling times <1 month may indicate infection, infarction, a lymphoma, or fast-growing metastases.[22,23] Data from the Dutch-Belgian Randomized Lung Cancer Screening Trial (Dutch acronym: NELSON) found that VDT in SPNs <400 days, 400 - 600 days, and >600 days at 3- and 12-month screening had 2-year cancer probabilities of 9.7%, 4.1% and 0.8% respectively.[24] Other characteristics suggestive of malignancy on CT include: vascular convergence, dilated bronchus leading to the nodule, presence of pseudocavitation or true cavitation.[16] Benign lesions usually have thinner, smoother walls <4 mm, thicker irregular walls >15 mm being suggestive of malignancy.[19,25,26] Nevertheless, there is overlap between the two, with thick-walled cavities also seen in benign infectious processes such as TB, fungal infections and rheumatoid nodules.[27] Pretest probability testing with a logistic model

There are various validated prediction models that use a combination of clinical and radiological features to assess the probability

56 SARJ VOL. 22 NO. 3 2016

Solid SPN

Partly solid Subsolid Pure ground glass

Fig. 3. A general classification of SPNs.

Fig. 4. The corresponding PET-CT of the patient in Fig. 2, showing a mass with FDG uptake.

The standardised uptake value was 7.06. A surgical biopsy was done, which revealed a poorly differentiated neuro-endocrine tumour. of malignancy. Prediction calculators are available online and also via medical applications for downloading on mobile devices. Current guidelines recommend their use in risk assessment.[4,16] The newest of these guidelines is the BTS guideline (2015), which recommends the use of the Brock and Herder models in its management algorithms.

The Bayesian model [12] uses the most important predictors of malignancy, i.e. spiculation, diameter and cavity wall thickness. Predictors of a benign aetiology are VDT >465 days and calcification. The Mayo Clinic model[6] uses six independent

predictors of malignancy, including three clinical risk factors (age, smoking status, history of cancer >5 years previously), and three radiological features (diameter, spiculation and upper-lobe location). The Veterans Administration model [11] uses independent predictors of positive smoking history, older age, larger nodule diameter and time since quitting smoking. The Brock University model[7] is based on the predictors of cancer, including older age, female sex, family history of lung cancer, emphysema, larger nodule size, location of the nodule in the upper lobe, SPN type, lower nodule count

REVIEW and spiculation. Lastly, the Herder model[28] uses the addition of PET-CT and a 4-point intensity score to the Mayo Clinic model to improve its accuracy.

Functional imaging and PET-CT

Various functional imaging modalities have been studied in patients with SPNs to distinguish malignant from benign nodules.

These include PET-CT, dynamic CT, dynamic magnetic resonance imaging (MRI) and dynamic single photon emission CT (SPECT).

Studies have shown similar sensitivities between these different modalities for the detection of malignancy.[29] 18-Fluorodeoxyglucose (FDG) PET-CT is, however, the preferred functional imaging modality, as it is more widely available and assists in clinical lung cancer staging (Fig. 4).

False-positive PET findings with standard uptake values >2.5 are often seen in infectious or inflammatory conditions, including TB, endemic mycoses (histoplasmosis), rheumatoid nodules, sarcoidosis and pneumonia.[30-32] False-negative results are seen in subcentimeter (<1 cm) nodules, subsolid nodules, malignancies with low metabolic activity (e.g. adenocarcinoma in situ, carcinoid) and hyperglycaemia.[33] Falsenegative results in the first three reflect the low mass of metabolically active malignant cells.

Biomarkers

Although some biomarkers have shown early interesting results, none has been validated for clinical use and none is currently recommended for use.[4]

General management of SPNs

Principles Most guideline recommendations on the evaluation and management of SPNs are based on low-quality evidence and expert opinion. Two of these guidelines include those by the Fleischner Society (Table 2) [34,35] and the American College of Chest Physicians (ACCP). [16] These guidelines use nodule size to determine further management, based on patient risk stratification. The ACCP guideline has similar recommendations as the Fleischner Society, pertaining to nodule size and further management (no follow-up, CT surveillance or biopsy). The ACCP guideline,

Table 2. Recommendations for the management of SPNs as per statements from the Fleischner Society[34,35] Nodule type and size Low risk

High risk

Solid nodules ≤4 mm

No follow-up

Follow-up at 12 months; if unchanged, no further follow-up

>4 - 6 mm

Follow-up at 12 months; if unchanged, no further follow-up

Initial follow-up CT at 6 - 12 months; then at 18 - 24 months if no change

>6 - 8 mm

Initial follow-up CT at 6 12 months; then at 18 - 24 months if no change

Initial follow-up CT at 3 - 6 months; then at 9 - 12 months and 24 months if no change

>8 mm

Follow-up CT at 3, 9 and 24 months

Same as low risk

Dynamic contrast-enhanced CT Consider PET-CT and/or biopsy Subsolid nodules (pGGNs) <5 mm

No follow-up needed

≥5 mm

Initial follow-up at 3 months; if persistent, annual CT for ≥3 years (FDGPET of limited value, potentially misleading and not recommended)

Subsolid nodules (partly solid nodules) <5 mm

Initial follow-up at 3 months; if persistent, annual CT for ≥3 years

≥5 mm

Initial follow-up at 3 months; if persistent, biopsy or surgical resection (consider PET-CT for partly solid nodules with a solid component >8 mm)

however, also incorporates surgical risk in their management algorithm. The new BTS guideline is based on a comprehensive review of the current literature and includes nodule volume and VDT in addition to nodule size.[4] Management options include serial CT surveillance, further imaging, non-surgical biopsy and surgical resection.

Decisions about further evaluation depend on clinical probability of malignancy determined by clinical, radiological and various logistic models, nodule character­istics such as size, attenuation (solid v. subsolid) and growth (VDT), as well as informed patient preference, associated risks and comorbidities that influence fitness for surgery.

The current BTS guideline recommends that the same diagnostic approach be applied to nodules that are discovered incidentally, via screening studies, in patients with a history of extrapulmonary malignancy, and in those with known lung malignancy. No consensus was reached on the risk of malignancy in SPNs in patients with a previous history of malignancy, with some studies indicating an increased risk and others showing no

difference.[36-39] Lung nodules detected in patients considered for radical cure should be evaluated on their own and not assumed to be malignant, as the probability of these being benign is high.

The BTS 2015 guideline addresses four groups of patients: (i) requiring no further follow-up; (ii) with solid nodules ≥5 <8 mm in diameter or volume <300 m3; (iii) with solid nodules with diameter ≥8 mm or volume ≥300 m3; and (iv) with subsolid nodules.

No further follow-up

No follow-up is required in patients with solid nodules with benign patterns of calcification, nodule size <5 mm (both solid and subsolid) or a volume <80 mm3, and solid perifissural or subpleural nodules <10 mm with triangular or lentiform shape. However, caution and follow-up are advised for perifissural nodules >10 mm, especially in patients with a history of extrapulmonary cancer.[4] Lung screening studies have provided evidence that nodules <5 mm or <100 mm3 have a low risk of malignancy, i.e. there is no

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REVIEW difference compared with individuals without pulmonary nodules.[24] However, because of lack of standardisation between volumetric determining programmes, the BTS has reduced the threshold value to 80 mm 3.

Studies of patients with perifissural nodes <10 mm showed that none of the nodules was malignant.[18]

Solid SPN <3 cm

Patient history Previous radiograph/CT Clinical setting Radiology pattern

No change for 2 years

Benign (<5 mm); calcified

Sputum, lavage, treatment Improvement

No further workup

Solid nodules ≥5 - <8 mm in diameter or volume ≥300 m3

The NELSON trial found an increased risk of 16.9% for malignancy in nodules with a volume ≥300 mm3, and 9.7% for lung nodules with a diameter >8 mm (Fig. 5).[24] In this group of patients with nodule size ≥8 mm and volume ≥300m 3 , the BTS recommendations include risk stratification using the Brock model. If the risk is low (<10%), serial CT follow-up is recommended, and if the risk is deemed to be high (>10%), further imaging with PETCT is indicated. Additional risk stratification is then suggested with the use of the Herder model.

Using the Herder risk stratification model, suggestions are as follows: (i) low risk (<10%) – can be followed-up by CT surveillance; (ii) intermediate risk (10 - 70%) – further evaluation such as non-surgical biopsy, excision biopsy or CT surveillance should be based on patient preference and associated comorbidities; and (iii) high risk (>70%) – surgical biopsy is the best option, with non-surgical treatment for those who are poor surgical candidates.

In facilities where volumetric measure­ ment can be done, follow-up of patients with solid nodules with inter val CT and determination of VDT at 1 year for nodules 5 - 6 mm, and at 3 months and 1 year for nodules with diameter ≥6 mm and volume ≥80 mm 3, is suggested. A volume change of ≥25% is defined as significant growth and requires further intervention (imaging, biopsy or surgery). Patients can be discharged if the volume change is <25% at 1 year, although if diameter is used to assess growth a 2-year follow-up

58 SARJ VOL. 22 NO. 3 2016

Possible malignancy

Possible infection

Solid nodules ≥5 - <8 mm in diameter or volume ≥80 - <300 mm3

The risk of malignancy in this group was found to be low (2.4%) in the NELSON trial, justifying conservative management with CT surveillance.

Increase in size

CT bronchus cancer protocol, including thin slices through nodule

No improvement

Benign calcification; or nodule <5 mm

≥5 mm - <8 mm

≥8 mm

Discharge

CT surveillance

Brock model (risk stratification)

Low risk (<10%)

High risk (>10%)

PET-CT

Herder model

Low risk (<10%)

Intermediate risk (10 - 70%) Patient preference and comorbidities

Non-surgical biopsy

High risk (>70%) Surgical biopsy

Non-surgical biopsy (high surgical risk)

Excision biopsy

Fig. 5. A suggested approach to SPNs (adapted from BTS and Murrmann et al.[40]). is required. A patient with VDT >600 days could be discharged or CT surveillance could be done based on patient preference.

A VDT 400 - 600 days should prompt a biopsy or surveillance based on patient preference, whereas a VDT <400 days should definitely indicate further workup and management.

Subsolid nodules

Subsolid nodules may represent slowgrowing indolent tumours and further management will be dependent on size, risk stratification in persistent nodules, growth and nodule subtype. For nodules ≥5 mm, a repeat CT scan is advised in 3 months. If the nodule disappears, the patient may be discharged. CT surveillance with intervals of 1, 2 and 4 years is suggested for patients with low risk (<10%). CT surveillance, CT-guided

biopsy, or resection should be considered in patients with a high risk (>10%), taking into account patient preference and surgical risk. Resection/non-surgical treatment or observation should be considered for pGGNs that enlarge ≥2 mm, considering patient preference and surgical risk. If observation is chosen, a repeat CT at a maximum interval of 6 months should be performed. Resection/ non-surgical treatment should be considered for patients with partly solid nodules that show an increase in solid component, pGGNs that develop a solid component, and pathologically proven malignancy, keeping in mind patient preference and surgical risk.

Biopsy Non-surgical biopsy

Options for non-surgical biopsy include bronchoscopy and CT-guided transthoracic

REVIEW needle aspiration (TTNA) or biopsy. The sensitivity of CT-TTNA was 90% in 11 studies, with the risk of pneumothorax between 4% and 8%.[20] Conventional bronchoscopy has a low yield and a low sensitivity of 13.5% reported in the NELSON study and is not recommended by the current BTS guideline.[4,24] Bronchoscopy yield can be augmented with fluoroscopy, radial endobronchial ultrasound and electromagnetic navigation bronchoscopy and is indicated if a bronchus sign is seen on CT. Surgical biopsy

Surgical resection is the gold standard and the definitive treatment for malignant nodules. Surgical approaches include video-assisted thoracoscopic surgery (VATS) or thoracotomy. Patients fit for surgery should undergo VATS wedge resection with progression to lobectomy and systematic sampling of mediastinal lymph nodes, if malignant. Sublobar resection (wedge resection and segmentectomy) was associated with worse outcomes in cases of stage 1 cancer.[41] Segmentectomy may be considered in patients in whom preservation of lung tissue will improve outcome. In patients who are not candidates for surgery, therapeutic alternatives include external beam radiation therapy and percutaneous radiofrequency ablation.[4]

SPN in the SA context

The World Health Organization (WHO) has rated SA as a highprevalence (>125/100 000) TB region, with statistics suggesting an estimated incidence of 450 000 active cases of TB in 2013. The incidence of benign granulomas is therefore exceedingly high, with incidental upper-lobe nodules being a common finding on imaging. In this setting, these findings would raise an already very high false-positive rate even further. This could lead to unnecessary investigations, high cost and associated morbidity. Even with the use of FDG-PET, the high false-positive rate would still limit accuracy, further complicating the evaluation of SPNs in our setting.[30]

Conclusion

The SPN remains a clinical challenge, with the potential of early malignancy. The 2015 BTS guideline assists with risk stratification and appropriate management of different patient groups. Benign granulomas in a high TB-endemic area such as SA can complicate the evaluation of SPNs. Risk stratification models and management algorithms need to be validated in this setting.

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DOI:10.1148/radiol.2391050343 20. Wahidi MM, Govert JA, Goudar RK, Gould MK, McCrory DC. Evidence for the treatment of patients with pulmonary nodules: When is it lung cancer? Chest 2007;132(3 Suppl):94S-107S. DOI:10.1378/chest.07-1352 21. Garland LH, Coulson W, Wollin E. The rate of growth and apparent duration of untreated primary bronchial carcinoma. Cancer 1963;16:694-707. DOI:10.1002/10970142(196306)16:6<694::AID-CNCR2820160603>3.0.CO;2-J 22. Collins VP, Loeffler RK, Tivey H. Observations on growth rates of human tumors. Am J Roentgenol Radium Ther Nucl Med 1956;76(5):988-1000.

23. Nathan MH, Collins VP, Adams RA. Differentiation of benign and malignant pulmonary nodules by growth rate. Radiology 1962;79:221-232. DOI:10.1148/79.2.221 24. Zhao YR, Xie X, de Koning HJ, Mali WP, Vliegenthart R, Oudkerk M. NELSON lung cancer screening study. Cancer Imaging 2011;11(1A):79-84. DOI:10.1102/14707330.2011.9020 25. Woodring JH, Fried AM, Chuang VP. Solitary cavities of the lung: Diagnostic implications of cavity wall thickness. AJR Am J Roentgenol 1980;135(6):1269-1271.

26. Woodring JH, Fried AM. Significance of wall thickness in solitary cavities of the lung: A follow-up study. AJR Am J Roentgenol 1983;140(3):473-474. DOI:10.2214/ ajr.135.6.1269 27. Gill RR, Matsusoka S, Hatabu H. Cavities in the lung in oncology patients: Imaging overview and differential diagnoses. Appl Radiol J Pract Imaging Manag 2010;39(6):10-21.

28. Herder GJ, van Tinteren H, Golding RP, et al. Clinical prediction model to characterize pulmonary nodules: Validation and added value of 18F-fluorodeoxyglucose positron emission tomography. Chest 2005;128(4):2490-2496. DOI:10.1378/chest.128.4.2490 29. Cronin P, Dwamena BA, Kelly AM, Carlos RC. Solitary pulmonary nodules: Meta-analytic comparison of cross-sectional imaging modalities for diagnosis of malignancy. Radiology 2008;246(3):772-782. DOI:10.1148/radiol.2463062148 30. Du Toit R, Shaw JA, Irusen EM, von Groote-Bidlingmaier F, Warwick JM, Koegelenberg CFN. The diagnostic accuracy of integrated positron emission tomography/computed tomography in the evaluation of pulmonary mass lesions in a tuberculosis-endemic area. S Afr Med J 2015;105(12):1049-1052. DOI:10.7196/SAMJ.2015.v105i12.10300 31. Deppen S, Putnam JB, Andrade G, et al. Accuracy of FDG-PET to diagnose lung cancer in a region of endemic granulomatous disease. Ann Thorac Surg 2011;92(2):428-432.

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REVIEW 32. Sathekge MM, Maes A, Pottel H, Stoltz A, van der Wiele C. Dual time-point FDG PET/CT for differentiating benign from malignant solitary pulmonary nodules in a TB endemic area. S Afr Med J 2010;100(9):598-601. DOI:10.7196/samj.4082 33. Nomori H, Watanabe K, Ohtsuka T, Naruke T, Suemasu K, Uno K. Evaluation of F-18 fluorodeoxyglucose (FDG) PET scanning for pulmonary nodules less than 3 cm in diameter, with special reference to the CT images. Lung Cancer 2004;45(1):19-27.

DOI:10.1016/j.lungcan.2004.01.009 34. MacMahon H, Austin JHM, Gamsu G, et al. Guidelines for management of small pulmonary nodules detected on CT scans: A statement from the Fleischner Society.

Radiology 2005;237(2):395-400. DOI:10.1148/radiol.2372041887 35. Naidich DP. Recommendations for the management of subsolid pulmonary nodules detected at CT: A statement from the Fleischner Society. Radiology 2013;266(1):304317. DOI:10.1148/radiol.12120628 36. Quint LE, Park CH, Iannettoni MD. Solitary pulmonary nodules in patients with extrapulmonary neoplasms. Radiology 2000;217(1):257-261. DOI:10.1148/ radiology.217.1.r00oc20257

37. Khokhar S, Vickers A, Moore MS, Mironov S, Stover DE, Feinstein MB. Significance of non-calcified pulmonary nodules in patients with extrapulmonary cancers. Thorax 2006;61(4):331-336. DOI:10.1136/thx.2005.051508 38. Mery CM, Pappas AN, Bueno R, et al. Relationship between a history of antecedent cancer and the probability of malignancy for a solitary pulmonary nodule. Chest 2004;125(6):2175-2181. DOI:10.1378/chest.125.6.2175 39. Hanamiya M, Aoki T, Yamashita Y, Kawanami S, Korogi Y. Frequency and significance of pulmonary nodules on thin-section CT in patients with extrapulmonary malignant neoplasms. Eur J Radiol 2012;81(1):152-157.

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The effect of therapeutic pleural drainage on the short- and longterm sequelae of tuberculous pleural effusions E Wilken, MB ChB, FCP; H Fengels, MD; F Swart, ND Clin Tech; D Maree, ND Clin Tech; J W Bruwer, MB ChB, FCP, Cert Pulm; E M Batubara, MD, FCCP, SBIM, SF-AP; E M Irusen, MB ChB, FCP, PhD; C F N Koegelenberg, MB ChB, FCP, FRCP, PhD Division of Pulmonology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Hospital, Cape Town, South Africa Corresponding author: E Wilken (elismawilken@gmail.com)

Background. Tuberculosis (TB) remains a common cause of pleural exudates in many parts of the globe. Pleural fibrosis with restriction is a well-known complication of tuberculous pleuritis. Current evidence suggests that pleural drainage offers little benefit over and above anti-TB treatment in improving pulmonary function.

Methods. We enrolled 20 patients with proven tuberculous pleural effusions (mean age 32.7 years, 10 males, 12 HIV-positive), and performed therapeutic pleural drainage in 10 randomly selected cases. Pulmonary function testing (PFT), chest radiography and transthoracic ultrasound were performed on all patients before treatment and at 7 - 10 days, 3 months and 6 months.

Results. Complete therapeutic drainage was achieved in only 4 of the 10 patients randomised to undergo drainage. No significant immediate benefit was achieved in the 10 patients assigned to intervention. However, compared with the non-intervention group, the intervention group showed significant changes in several functional parameters at 6 months, including changes in forced vital capacity from baseline (1.40 L v. 0.65 L; p<0.001), forced expiratory volume in 1 second (1.37 L v. 0.60 L; p=0.002), total lung capacity (1.76 L v. 0.88 L; p=0.034) and diffusion capacity for carbon monoxide (7.42 v. 2.19 mL/min/mmHg, p=0.013). No difference was observed in the change in 6-minute walking distance (113.4 m v. 126 m; p=0.798) compared with the control group at 6 months.

Conclusions. Therapeutic drainage may offer additional medium- and long-term functional benefits to patients with pleural TB, in addition to anti-TB drug therapy alone, as evident in the improvement in PFT results.

S Afr Respir J 2016;22(3):60-66. DOI:10.7196/SARJ.2016.v22i3.79

Tuberculosis (TB) is the most frequent cause of death due to infectious disease worldwide.[1,2] TB pleural involvement is the second most common extrapulmonary manifestation of TB after TB lymphadenitis.

It is well documented in both primary and post-primary TB.[3] Involvement ranges from tuberculous pleurisy to exudative and caseous pleurisy to frank empyema. [4] In the developed world, tuberculous pleural involvement remains rare with TB accounting for <1% of exudates. However, in the developing world, especially in the setting of HIV co-infection, TB may be associated with up to 80% of pleural effusions.[4]

60 SARJ VOL. 22 NO. 3 2016

Thoracocentesis is the initial mandatory diagnostic procedure, and typically reveals a lymphocytic exudate, rich in protein, glucose deplete and with elevated lactate dehydrogenase (LDH) and adenosine deaminase (ADA) levels. The diagnostic yield of thoracocentesis is ~93%, which could be improved to 100% with the addition of a thoracoscopic pleural biopsy.[5] Pleural fibrosis or fibrothorax is a well-described complication of tuberculous pleurisy.[4,6] Uncertainty remains regarding the prevalence of fibrothorax and permanent pleural thickening, with some sources suggesting a prevalence of 50%, while others suggest that it is as low

ORIGINAL RESEARCH as 5%.[4,7] This variation could be explained by differences in demographics and background TB prevalence. Many experienced thoracoscopists believe that complete drainage of the pleural effusion results in a reduction in the development of pleural fibrosis,[4,8] but empirical data showing a potential benefit of effective drainage of pleural effusion in the prevention of pleural fibrosis are lacking.

In 2003, Lai et al.[9] could not demonstrate a benefit of pleural drainage in the prevention of pleural fibrosis in a randomised trial, but the effectiveness of pleural drainage was not evaluated in that study. In a subsequent study, Chung et al.[10] showed that effective drainage of TB pleural effusion lowered the risk of fibrosis compared with partial drainage. Their data suggested that such drainage might in fact be of benefit in reducing the risk of developing residual pleural fibrosis. Owing to a lack of consensus, the current standard of care for TB pleural effusion does not include pleural drainage and only consists of anti-TB drugs.

Factors that significantly increase the probability of development of pleural fibrosis include the severity of the initial change in pleural glucose, pH and tumour necrosis factor-alpha levels.[7] It has also been suggested that the degree of pleural thickening can be estimated by the response to 2 weeks of antiTB treatment.[11] Additionally, a septated ultrasonographic appearance of the pleural effusion, a positive TB culture on pleural fluid and an elevated LDH level are also associated with an increased risk of developing pleural fibrosis.[12] Pulmonary function tests (PFTs) are an objective measure to monitor the response and effectiveness of treatment of TB pleural effusion. The 6-minute walking distance (6MWD) is used to determine objective functional exercise capacity.

A spectrum of sequelae is observed in patients with pleural fibrosis, ranging from asymptomatic radiographic abnorm­alities to severe restrictive ventilatory impair­ ment. [9,10,12,13]

Methods

Study design and population This randomised controlled interventional study was carried out from October 2012 to September 2013 in the Division of Pulmonology at Tygerberg Academic Hospital, a 1 200-bed hospital in Cape Town, South Africa (SA). It is one of two referral centres and renders a tertiary service to a population of approximately 1.5 million people. The incidence of pulmonary TB in the Western Cape Province is 933 cases per 100 000 population, the highest recorded incidence after China and India according to the World Health Organization.[14] Ethical approval for the study was obtained from the Stellenbosch University Human Research Ethics Committee (Ethics ref.: N12/07/040). Every patient gave informed consent to enrol in this study in writing.

Patients aged >18 years with a high clinical suspicion of TB and radiological evidence of a pleural effusion were enrolled. A high clinical suspicion included patients known to have HIV infection and those with a persistent cough lasting >3 weeks, haemoptysis, weight loss of >4 kg, intermittent fever for >3 weeks and drenching night sweats for >2 weeks. Patients were included if they could give written consent and had a chest radiograph (CXR) showing >30% involvement of the hemithorax and at least two clinical indicators to suggest TB. Any patient found not to have TB was excluded from the study. Other exclusion criteria were a recent history of invasive procedures in the pleural cavity or recent penetrating chest wall trauma.

A

Initial evaluation and management A baseline CXR with posteroanterior and lateral films along with spirometric assessment according to the guidelines of the American Thoracic Society (ATS) was performed on all patients.[15-18] Initial CXR effusion size was graded as moderate (<50% of a hemithorax), moderate to large (50 - 75% of a hemithorax) or large (>75% of a hemithorax). Spirometrics (MasterScreen Jaeger, Germany, version 02.00, 2011) included a flow-volume loop, diffusion capacity for carbon monoxide (DLCO) and plethysmography. To evaluate patients’ functional exercise capacity, we performed a 6MWD according to the ATS criteria[19] and graded symptoms according to Borg,[20] including dyspnoea and exhaustion with a visual analogue scale.

Participants were randomly allocated at a 1:1 ratio to either a control group or an intervention group at the onset of presentation. Diagnostic thoracocentesis (at least 50 ml of pleural fluid) and pleural biopsy (more than four samples) with an Abrams needle were performed in a sitting position and under ultrasound guidance according to standardised guidelines.[21-23] The intervention group received therapeutic once-off pleural fluid drainage with an Arrow percutaneous cavity drainage catheterisation set (Teleflex, SA). Thoracocentesis was suspended if spontaneous cessation of fluid drainage occurred or if the patient experienced discomfort with exacerbation of symptoms or vagal manifestations. The patient was observed and oxygen therapy given if saturation was <90%. After complete drainage, the efficacy was

B

Objective

To investigate the additional benefits of once-off pleural drainage in addition to medical management in the prevention of short- and long-term sequelae of tuberculous pleural effusions. The effectiveness of the intervention was measured by looking at changes in PFT results over time.

Fig. 1. Radiographs at baseline (A) and after 6 months of treatment (B), demonstrating pleural thickness.

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ORIGINAL RESEARCH assessed by an ultrasound scan (<0.5 cm of pleural fluid visible in the posterior-lateral recess) and chest radiography (<0.5 cm of blunting of the costophrenic angle). The measurements were defined as partial drainage (0.5 - 1.0 cm) or completely drained (<0.5 cm). Spirometric assessment (flow-volume and plethysmography) and 6MWD were repeated in all patients. Both groups were treated with standard anti-TB therapy.[24] Pleural fluid was analysed by means of routine biochemistry, including ADA, cytology and cell count. Liquid TB cultures of pleural fluid and tissue biopsy were performed with a BACTEC MGIT 960 System (Becton, Dickinson & Co, USA). TB was confirmed by the appearance of granulomas in the biopsy and a positive fluid or biopsy TB culture. Positive TB cultures were tested for drug resistance (GenoType MTBDRplus, Hain Life Science GmbH, Germany).[5] Surgical interventions (including decortication) were considered in patients with pleural empyema or persistent severe restriction (forced vital capacity (FVC) <50%) after completed medical treatment.[1] Patients who were found not to have TB were treated according to protocol for the diagnosis made and excluded from the study.

Follow-up All participants were followed up after 1 week. The laboratory results were reviewed, anti-TB treatment, where relevant, was continued for at least 6 months and further special investigations, where appropriate, were organised. This was all done according to the standard operating procedure at Tygerberg Academic Hospital. All patients with confirmed pleural TB were subsequently followed up at 3 and 6 months. The CXR (Fig. 1), spirometric assessments and a 6MWD were performed at each visit. The greatest linear width of pleural opacity on the erect PA CXR was classified as follows: <2 mm: radiologically normal; 2 - 4.9 mm: radiologically abnormal; 5 - 10 mm: pleural thickening; and >10 mm: fibrothorax.

Estimated overall pleural thickening was classified as involvement of less than one-third of the hemithorax, one-third to two-thirds of the hemithorax, or more than two-thirds of the hemithorax.

Statistical analysis The changes in FVC after 1 week and 3 and 6 months were compared with the baseline value. An unpaired t-test at an alpha level of 5% was used to compare the mean change in FVC between the intervention and control groups. Further key secondary endpoints were analysed in line with the primary endpoints (changes in forced expiratory volume in 1 second (FEV1), total lung capacity (TLC), DLCO and 6MWD after 1 week and 3 and 6 months). Missing values for assessment of change were replaced with zero, following a conservative strategy. Baseline characteristics were analysed using means and standard deviations (SDs) for continuous and absolute frequencies for categorical variables. A p-value of <0.05 was considered significant.

Outcome For a short-term sequelae primary outcome parameter we defined change in FVC in litres after 1 week, for medium term after 3 months and for long term after 6 months. Key secondary outcome parameters included changes in FEV1, TLC, DLCO and 6MWD and the prevalence of fibrothorax after 6 months of treatment. The need for surgery was taken as the main clinical long-term sequelae parameter.

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Results

Baseline observations and interventions Thirty-seven patients were referred for the study, of whom 13 were excluded (3 had empyemas, 3 had pneumonia, 3 had negative results on testing for TB, 1 was <18 years of age and 3 had other reasons).

All patients were randomised from the start, and either a diagnostic tap or therapeutic drainage was performed. Eleven patients were randomised to therapeutic pleural drainage, but 1 was lost to followup after the initial visit, leaving 10 patients with completed data in each study arm.

The mean age of the 20 patients was 32.7 years (SD 8.7); 12 were HIV-positive. The general characteristics of the group are summarised in Table 1 and the results of diagnostic thoracocentesis in Table 2.

The mean volume drained during therapeutic drainage was 1 139 mL (SD 711, range 250 - 2 700). Aspiration was abandoned in 6 patients owing to suspected re-expansion pulmonary oedema and/or discomfort.

Table 1. Clinical and radiological characteristics of the study population (N=20) Parameter

Study group (n=10)

Control group (n=10)

Age (years), mean (SD)

27.9 (6.8)

37.5 (10.63)

Weight (kg), mean (SD)

61.6 (14.1)

56.7 (10.14)

Height (cm), mean (SD)

164.0 (7.0)

164.45 (11.8)

Males/females, n

3/7

7/3

HIV-positive, n

4

8

Loculations, n

3

4

Left

4

5

Right

6

5

Effusion side, n

Effusion size, n

<50%

0

2

50 - 75%

7

8

>75%

3

0

Table 2. Pleural fluid and blood results in the study population (N=20) Pleural fluid ADA (U/L)

72.56

LDH (U/L)

749.1

Total protein (g/L)

63.6

Glucose (mmol/L)

4.1

pH

7.3

Lymphocytes (%)

81.55

Neutrophils (%)

13.0

Blood LDH (U/L)

293.11

Total protein (g/L)

80.8

Glucose (mmol/L)

5.1

ORIGINAL RESEARCH

Table 3. Lung function parameters (mean (SD)) of all study patients at baseline and immediately after drainage Initial assessment

Post drainage

Parameter

Variable

Not drained (n=10)

Therapeutic drainage (n=10)

p-value

Therapeutic drainage (n=10)

p-value

FVC

Absolute (L)

2.13 (0.61)

1.66 (0.48)

0.074

1.65 (0.43)

0.938

% predicted

55.67 (9.11)

43.0 (9.1)

0.006

43.6 (10.8)

0.887

FEV1

Absolute (L)

1.74 (4.49)

1.45 (0.41)

0.173

1.43 (0.35)

0.790

% predicted

53.71 (7.73)

43.9 (10.0)

0.024

43.6 (11.6)

0.932

TLC

Absolute (L)

4.01 (0.87)

3.00 (0.70)

0.010

3.40 (0.79)

0.047

% predicted

73.32 (20.12)

56.6 (13.8)

0.044

63.9 (13.7)

0.068

DLCO

Absolute (mL/min/ mmHg)

15.67 (4.44)

14.32 (3.49)

0.463

N/A

N/A

% predicted

55.19 (9.92)

50.2 (11.2)

0.303

N/A

N/A

6MWD

Absolute (m)

465.4 (100.54)

452.6 (110.5)

0.790

476.5 (102.7)

0.070

N/A = not applicable.

Table 4. Lung function parameters (mean (SD)) of all study patients after 1 week Follow-up, 1 week Therapeutic drainage (n=10)

p-value

Parameter

Variable

Not drained (n=10)

FVC

Absolute (L)

2.36 (0.62)

2.27 (0.60)

0.749

% predicted

61.9 (8.3)

58.9 (11.1)

0.496

FEV1

TLC (L)

DLCO

6MWT

Change from baseline (L)

0.23 (0.33)

0.61 (0.48)

0.054

% change

6.2 (8.6)

15.8 (12.4)

0.060

Absolute (L)

1.87 (0.53)

1.95 (0.62)

0.768

% predicted

58.1 (10.5)

58.6 (13.4)

0.929

Change from baseline (L)

0.13 (0.26)

0.50 (0.43)

0.034

% change

4.4 (8.3)

14.8 (12.6)

0.044

Absolute (L)

4.21 (0.74)

3.60 (0.70)

0.075

% predicted

76.4 (11.3)

67.6 (9.5)

0.077

Change from baseline (L)

0.21 (0.66)

0.60 (0.59)

0.173

% change

3.1 (14.0)

11.0 (10.8)

0.173

Absolute (mL/min/mmHg)

15.70 (4.33)

16.22 (3.79)

0.768

% predicted

55.4 (10.3)

56.5 (10.6)

0.818

Change from baseline (mL/min/ mmHg)

0.00 (1.60)

1.89 (2.03)

0.032

% change

0.25 (5.4)

6.4 (0.6)

0.047

Absolute (m)

501.1 (87.3)

485.6 (89.2)

0.701

Change from baseline (m)

35.7 (50.7)

33.0 (60.9)

0.914

Primary and key secondary outcomes Lung function parameters measured at baseline, 1 week, 3 months and 6 months are summarised in Tables 3 - 5.

With regard to the primary outcome variable, patients randomised to therapeutic drainage experienced a significantly greater

improvement in FVC than the control group at 3 months (mean difference 1.40 L (SD 0.44) in the intervention group v. 0.34 L (SD 0.46) in the control group; p<0.001) and at 6 months (1.40 L (SD 0.44) v. 0.65 L (SD 0.39); p<0.001) (Fig. 2A). The mean percentage predicted change in FVC from baseline in the

intervention group was significantly higher than in the control group at 3 months (36.3% (SD 9.4) v. 9.0% (SD 12.7); p<0.001) and 6 months (43.93% (SD 8.83) v. 16.38% (SD 11.38); p<0.001).

FEV1 in the intervention group improved significantly, with a mean change from baseline at 3 months of 1.08 L (SD 0.41) v.

0.38 L (SD 0.42); p=0.001 in the control group and 1.37 L (SD 0.56) v. 0.60 L (SD 0.34); p=0.002 at 6 months (Fig. 2B).

Patients randomised to therapeutic drainage also experienced significantly greater improvement in TLC, with a change of 1.45 L (SD 0.56) v. 0.56 L (SD 0.78); p=0.009 at 3 months, and 1.76 L (SD 0.94) v. 0.88 L (SD 0.76); p=0.034 at 6 months (Fig. 2C).

Changes in DLco after 3 months (mean change 6.43 mL/min/mmHg (SD 3.77) in the intervention group v. 0.57 mL/min/mmHg (SD 4.18) in the control group; p=0.005) and 6 months (7.42 mL/min/mmHg (SD 4.63) in the intervention group v. 2.19 mL/min/mmHg (SD 3.84) in the control group; p=0.013) were also statistically significant (Fig. 2D).

6MWD improved in both groups, being 113.5 m (SD 64.6) in the intervention group v. 85.9 m (SD 69.4) in the control group (p=0.369) at 3 months and 113.4 m (SD 131.02) in the intervention group v. 126 m (SD 78.8) in the control group (p=0.798) at 6 months. Improvement in the intervention group was not significantly superior to that in the control group (Fig. 2E).

As no patient showed severe restriction (FVC <50%) after 3 or 6 months, surgery was not considered in any patient.

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ORIGINAL RESEARCH

Table 5. Lung function parameters (mean (SD)) of all study patients after 3 and 6 months Follow-up, 3 months Therapeutic drainage (n=10)

Follow-up, 6 months Therapeutic drainage (n=10)

p-value

Parameter

Variable

Not drained (n=10)

p-value

Not drained (n=10)

FVC

Absolute (L)

2.46 (0.59)

3.06 (0.72)

0.059

2.78 (0.61)

3.38 (0.93)

0.108

% predicted

64.7 (9.6)

79.3 (11.2)

0.006

72.05 (8.85)

86.95 (11.01)

0.004

Change from baseline (L)

0.34 (0.46)

1.40 (0.44)

0.001

0.65 (0.39)

1.40 (0.44)

<0.001

% change

9.0 (12.7)

36.3 (9.4)

<0.001

16.38 (11.38)

43.93 (8.83)

<0.001

Absolute (L)

2.12 (0.62)

2.53 (0.61)

0.154

2.34 (0.65)

2.82 (0.81)

0.159

% predicted

67.5 (14.7)

76.4 (12.6)

0.163

71.02 (13.54)

84.37 (12.86)

0.036

Change from baseline (L)

0.38 (0.42)

1.08 (0.41)

0.001

0.60 (0.34)

1.37 (0.56)

0.002

FEV1

TLC

DLco

6MWD

% change

13.7 (14.3)

32.5 (11.2)

0.004

17.31 (11.27)

40.5 (12.17)

<0.001

Absolute (L)

4.57 (0.94)

4.45 (0.80)

0.760

4.89 (0.84)

4.76 (1.19)

0.783

% predicted

81.5 (15.9)

84.1 (9.5)

0.658

87.06 (11.26)

87.8 (9.03)

0.875

Change from baseline (L)

0.56 (0.78)

1.45 (0.56)

0.009

0.88 (0.76)

1.76 (0.94)

0.034

% change

8.2 (14.8)

27.5 (8.1)

0.002

13.74 (14.86)

31.19 (13.51)

0.013

Absolute (mL/min/mmHg)

16.17 (4.52)

20.75 (3.78)

0.028

17.86 (5.02)

21.74 (5.3)

0.11

% predicted

58.0 (10.8)

72.2 (6.8)

0.003

62.38 (10.76)

75.18 (10.8)

0.016

Change from baseline (mL/min/mmHg)

0.57 (4.18)

6.43 (3.77)

0.005

2.19 (3.84)

7.42 (4.63)

0.013

% change

2.0 (14.0)

22.1 (12.1)

0.004

7.19 (12.25)

25.03 (14.11)

0.007

Absolute (m)

551.3 (93.8)

566.1 (81.1)

0.708

591.4 (92.58)

566 (82.79)

0.523

Change from baseline (m)

85.9 (69.4)

113.5 (64.6)

0.369

126 (78.8)

113.4 (131.02) 0.798

Complications Initial pleural aspiration and biopsy were uncomplicated in all study patients. Re-expansion pulmonary oedema and/or patient discomfort resulted in the premature termination of 6 of the 10 attempts at complete pleural drainage. The procedure was stopped as soon as the patient experienced symptoms of distress or discomfort, and the patient was observed and given supplemental oxygen if the saturation was <90%. Patients recovered quickly, and no patient needed admission. The procedure was also abandoned if the drainage of fluid spontaneously ceased. No pneumothorax or major haemorrhage resulted.

Discussion

We found that at 3 and 6 monthsâ&#x20AC;&#x2122; follow-up, patients with confirmed tuberculous pleural effusions randomised to therapeutic pleural drainage showed significantly superior improvement in several lung function parameters to those who did not receive drainage. This included changes in FVC, FEV1, TLC and DLCO, despite the fact that complete drainage as per protocol was achieved in less than half of all patients randomised to undergo the intervention. Draining off as much fluid as possible seemed to be more beneficial than anti-TB treatment alone.

In 1996, Wyser et al.[25] investigated the influence of corticosteroids on TB pleural effusions and concluded that standard anti-TB therapy and early complete drainage are adequate for the treatment of TB pleurisy. Their study did not include a control group. A subsequent

64 SARJ VOL. 22 NO. 3 2016

randomised controlled trial by Lai et al.[9] found that the addition of pleural drainage to anti-TB medical treatment did not have a beneficial effect on restrictive pulmonary thickness (RPT) development or shorten the duration of fever or other clinical symptoms. Lai et al.[9] failed to show a significant improvement in FVC (treatment group 85.5% v. control group 88%; p=0.568), TLC and FEV1 were not measured, and effectiveness of drainage was not evaluated. Dyspnoea was the only proven benefit, and showed faster improvement in the drained group (median 4 days v. 8 days; p<0.001).

In contrast, a recent study by Bhuniya et al.[26] showed significant differences in mean percentage predicted FEV1 (drained group 87.62% v. control group 84.92%; p=0.02) and FVC (84.46 L v. 83.31 L; p=0.001) after 6 months, drainage being performed using pleural manometry.

They reported a lower appearance of RPT in patients who underwent drainage and commented that patients with therapeutic thoracocentesis experienced immediate relief from dyspnoea after drainage, although this finding was not substantiated with any objective measure.

Previous studies have reported immediate improvement in FVC and FEV1, with both showing an increase in excess of 10% after thoracocentesis of large pleural effusions.[27-29] We did not find any immediate improvement in FVC or FEV1 after the procedure, but this may be due to pain and coughing caused by the drainage process. TLC showed a significant immediate improvement (3.00 L before drainage v. 3.40 L after drainage; p=0.047).

We used the 6MWD to objectively evaluate performance-based functional exercise capacity. It is a cheap and easy test to perform,[19]

ORIGINAL RESEARCH

A 1.6 1.4 1.2 FVC (L)

1.0 0.8

Drained

0.6

Not drained

0.4 0.2 0

Start

7 - 10 days

3 months

6 months

B 1.6

1.4 FEV1 (L)

1.2 1.0 0.8

Drained

0.6

Not drained

0.4 0.2 0

Start

7 - 10 days

3 months

6 months

C 1.6 1.4

TLC (L)

1.2 1.0 0.8

Drained

0.6

Not drained

0.4 0.2 0

Start

7 - 10 days

3 months

6 months

D

DLCO (mL/min/mmHg)

8 7 6 5

Drained

4

Not drained

3 2 1 0

Start

7 - 10 days

3 months

6 months

E

140

and set pace. We did not find any difference in 6MWD (as measured

by Borg[20]) between the two groups at any time during follow-up. The minimal clinical important difference for the 6MWD is estimated to be between 54 m and 80 m,[30] which both groups achieved at 3 and 6 months. The lack of statistical significance could be explained by the study being under-powered for the test, or may suggest that a different objective test should have been used.[19] Another consideration is that both groups’ performance-based functional exercise capacity improved despite intervention.

On the other hand, most patients experienced clinical improvement of chest pain and relief of dyspnoea after drainage of the effusion.

The greatest dyspnoea relief was achieved immediately after drainage, which confirms findings of former studies.[25,26,31] Although our numbers were small, it appears that complete drainage seems to reduce RPT. Earlier studies reported that an RPT of >10 mm caused significant clinical symptoms in patients with pleural TB, with incidences ranging from 26% to 50.4%.[9,26,32] In our study there were twice as many patients with an RPT of >10 mm (60%) in the control group than in the intervention group (30%), which is in accordance with similar current studies.[32] In contrast to previous studies, [10,25] ours was a randomised controlled trial and as such we focused on FVC improvement and investigated the influence of drainage on all lung function parameters, including TLC and DL CO. Another difference to previous studies [9,10] is that we decided to use a single once-off drainage for achieving dryness of pleural effusion, not pigtail drainage over several days. The value of this is that once-off drainage is an available treatment procedure, simple to perform at primary healthcare level. Moreover, we evaluated effectiveness of drainage after the procedure.

Study limitations A limitation of our study is that despite randomisation, the two groups differed with regard to their baseline characteristics. From the outset, the intervention group had larger effusion sizes, higher dyspnoea grades and more restriction in lung function parameters. Nevertheless, the intervention group achieved significant improvement in primary and key secondary outcomes. Further limitations are the small number of patients and the inability to obtain complete dryness of effusion continuously, as defined in the protocol. Dyspnoea associated with pulmonary re-expansion is well known to limit the maximum volume drained.[31-36]

Conclusion

120

but unfortunately only measures the submaximal level of functional capacity, and the results are influenced by the patient’s own motivation

Acknowledgement. Funding was obtained from the Susan de Kock bursary for postgraduate study in 2013.

6MWD (m)

Fig. 2. Mean changes in absolute (A) FVC, (B) FEV1, (C) TLC, (D) DLCO and (E) 6MWD from baseline.

Therapeutic drainage may offer additional medium- and longterm functional benefits to patients with large tuberculous pleural effusions, as is evident by the statistically significant improvement in PFT results compared with anti-TB drugs alone. Pleurodesis is generally a safe procedure, and easy to perform in the primary care setting. We recommend draining the maximum amount of fluid the patient finds comfortable, or continuing until drainage stops spontaneously. This should be followed up by chest radiography to exclude any complications.

100

Drained

80

Not drained

60 40 20 0

Start

7 - 10 days

3 months

6 months

SARJ VOL. 22 NO. 3 2016

65

ORIGINAL RESEARCH References 1. World Health Organization. Global Tuberculosis Control: Surveillance, Planning, Finances. Geneva: WHO, 2008:19.

2. World Health Organization. Tuberculosis. http://www.who.int/mediacentre/ factsheets/fs104/en/ (accessed 15 March 2016).

3. Jantz MA, Antony VB. Pleural fibrosis. Clin Chest Med 2006;27(2):181-191.

DOI:10.1016/j.ccm.2005.12.003 4. Loddenkemper R, Antony VB. Pleural diseases. Eur Respir Monogr 2002;22:270-278.

5. Diacon AH, van de Wal BW, Wyser C, et al. Diagnostic tools in tuberculous pleurisy: A direct comparative study. Eur Respir J 2003;22(4):589-591. DOI:10.1183/0903193 6.03.00017103a 6. Bolliger CT, de Kock MA. Influence of a fibrothorax on the flow volume curve.

Respiration 1988;54(3):197-200. DOI:10.1159/000195522 7. De Pablo A, Villena V, Echave-Sustaeta J, Encuentra AL. Are pleural fluid parameters related to the development of residual pleural thickening in tuberculosis? Chest 1997;112(5):1293-1297. DOI:10.1378/chest.112.5.1293 8. Barbas CS, Cukier A, de Varvalho CR, et al. The relationship between pleural fluid findings and the development of pleural thickening in patients with pleural tuberculosis. Chest 1991;100(5):1264-1267. DOI:10.1378/chest.100.5.1264 9. Lai YF, Chao TY, Wang YH, Lin AS. Pigtail drainage in the treatment of tuberculous pleural effusions: A randomised study. Thorax 2003;58(2):149-152. DOI:10.1136/ thorax.58.2.149 10. Chung CL, Chen CH, Yeh CY. Early effective drainage in the treatment of loculated tuberculous pleurisy. Eur Respir J 2008;31(6):1261-1267.

DOI:10.1183/09031936.00122207 11. Wong PC. Management of tuberculous pleuritis: Can we do better? Respirology 2005;10(2):144-148. DOI:10.1111/j.1440-1843.2005.00689.x 12. Lai YF, Su MC, Weng HH, et al. Sonographic septation: A predictor of sequelae of tuberculous pleurisy after treatment. Thorax 2009;64(9):806-809. DOI:10.1136/ thx.2008.110197 13. Light RW. Update on tuberculous pleural effusion. Respirology 2010;15(3):451-458.

DOI:10.1111/j.1440-1843.2010.01723.x 14. World Health Organization. Global Tuberculosis Report 2012. Geneva: WHO, 2012.

15. Miller MR, Crapo R, Hankinson J, et al. General considerations for lung function testing. Eur Respir J 2005;26(1):153-161. DOI:10.1183/09031936.05.00034505 16. Miller MR, Hankinson J, Brusasco V, et al. Standardisation of spirometry. Eur Respir J 2005;26(2):319-338. DOI:10.1183/09031936.05.00034805 17. Wanger J, Clausen JL, Coates A, et al. Standardisation of the measurement of lung volumes. Eur Respir J 2005;26(3):511-522. DOI:10.1183/09031936.05.00035005 18. Pellegrino R, Viegi G, Brusasco V, et al. Interpretative strategies for lung function tests.

Eur Respir J 2005;26(5):948-968. DOI:10.1183/09031936.05.00035205 19. American Thoracic Society. ATS statement: Guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002;166(1):111-117. DOI:10.1164/ ajrccm.166.1.at1102 20. Borg G. Psychophysical bases of perceived exertion. Med Sci Sports Exerc 1982;14(5):377-381. DOI:10.1249/00005768-198205000-00012

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21. Koegelenberg CF, von Groote-Bidlingmaier F, Bolliger CT. Transthoracic ultrasonography for the respiratory physician. Respiration 2012;84(4):337-350.

DOI:10.1159/000339997 22. Colt H. Closed needle pleural biopsy. In: Light RW, Lee YC, eds. Textbook of Pleural Disease. 2nd ed. London: Hodder & Stoughton, 2008:557-559.

23. Raja OG, Lalor AJ. Modification to the technique of percutaneous pleural biopsy using Abramâ&#x20AC;&#x2122;s needle. Br J Dis Chest 1980;74(3):285-286. DOI:10.1016/00070971(80)90057-1 24. World Health Organization. Treatment of Tuberculosis Guidelines: Guidelines for National Programmes, 4th ed. Geneva: WHO, 2010.

25. Wyser C, Waltzl G, Smedema JP, Swart F, van Schalkwyk EM, van de Wal BW. Corticosteroids in the treatment of tuberculous pleurisy: A double blind, placebocontrolled randomized study. Chest 1996;110(2);333-338.

26. Bhuniya S, Arunabha DC, Choudhury S, Saha I, Roy TS, Saha M. Role of therapeutic thoracentesis in tuberculous pleural effusion. Ann Thorac Med 2012;7(4):215-219.

DOI:10.4103/1817-1737.102176 27. Brown NE, Zamel N, Aberman A. Changes in pulmonary mechanics and gas exchange following thoracocentesis. Chest 1978;74(5);540-542.

28. Cartaxo AM, Vargas FS, Salge JM. Improvement in the 6-min walk test and spirometry following thoracentesis for symptomatic pleural effusions. Chest 2011;139(6);1424-1429. DOI:10.1378/chest.10-1679 29. Zerahn B, Jensen BV, Olsen F, Petersen JR, Kanstrup IL. The effect of thoracentesis on lung function and transthoracic electrical bio impedance. Respir Med 1999;93(3);196201. DOI:10.1016/s0954-6111(99)90008-2 30. Wise RA, Brown CD. Minimal clinically important differences in the six-minute walk test and the incremental shuttle walk test. J Chron Obstruct Pulmon Dis 2005;2(1):125-129. DOI:10.1081/copd-200050527 31. Estenne M, Yernault JC, de Troyer A. Mechanism of relief of dyspnoea after thoracocentesis in patients with large pleural effusions. Am J Med 1983;74(5):813819. DOI:10.1016/0002-9343(83)91072-0 32. Candela A, Andujar J, HernaĂŠndez L, et al. Functional sequelae of tuberculous pleurisy in patients correctly treated. Chest 2003;123(6);1996-2000. DOI:10.1378/ chest.123.6.1996 33. Feller-Kopman D, Berkowitz D, Boiselle P, Ernst A. Large-volume thoracentesis and the risk of re-expansion pulmonary oedema. Ann Thorac Surg 2007;84(5):1656-1661.

DOI:10.1016/j.athoracsur.2007.06.038 34. Villena V, Lopez-Encuentra A, Pozo F, de-Palbo A, Martin-Escribano P. Measurement of pleural pressure during therapeutic thoracentresis. Am J Respir Crit Care Med 2000;162(4):1534-1538. DOI:10.1164/ajrccm.162.4.9907047 35. Light RW, Jenkinson SG, Minh VD, George RB. Observations on pleural fluid pressures as fluid is withdrawn during thoracentesis. Am Rev Respir Dis 1980;121(5):799-804.

36. Feller-Kopman D, Walkey A, Berkowitz D, Ernst A. The relationship of pleural pressure to symptom development during therapeutic throracentesis. Chest 2006;129(6);15561560. DOI:10.1378/chest.129.6.1556

ORIGINAL RESEARCH

Diagnostic yield of transbronchial needle aspiration for lymphoma B Sonnekus,1 MB ChB, MMed, FCP; J Steenkamp,2 MB ChB, FCPath; M Louw,3 MB ChB, MMed; C F N Koegelenberg,4 MB ChB, MMed, FCP, MRCP, Cert Pulmonology, PhD Department of Medicine, Stellenbosch University and Tygerberg Hospital, Cape Town, South Africa ivision of Haemato-Pathology, Department of Pathology and National Health Laboratory Service, Stellenbosch University and Tygerberg Hospital, Cape Town, D South Africa 3 Division of Anatomical Pathology, Department of Pathology and National Health Laboratory Service, Stellenbosch University and Tygerberg Hospital, Cape Town, South Africa 4 Division of Pulmonology, Department of Medicine, Stellenbosch University and Tygerberg Hospital, Cape Town, South Africa 1 2

Corresponding author: B Sonnekus (brentiasonnekus@yahoo.com)

Background. Transbronchial needle aspiration (TBNA) is a minimally invasive bronchoscopic technique that is cost-effective and safe for diagnosing mediastinal and hilar adenopathy in lung cancer, other malignancies, sarcoidosis and infectious processes such as tuberculosis.

Few studies have analysed the sensitivity, specificity and predictive values of TBNA for diagnosing lymphoma.

Objective. To evaluate the diagnostic yield of TBNA for diagnosing mediastinal and hilar adenopathy in suspected lymphoma.

Methods. We performed a retrospective analysis of collected data of patients with mediastinal and hilar adenopathy adjacent to the tracheobronchial tree detected by thoracic computed tomography, who underwent TBNA at Tygerberg Hospital between July 2010 and June 2013. We included 25 patients with suspected or proven lymphoma. Histology was used as the gold standard.

Results. Adequate samples for cytological evaluation were obtained for 22 (88%) patients. Cytological diagnosis was possible for 8 (32%).

For 17 (68%) who could not be diagnosed by TBNA alone, histology provided final diagnosis. Rapid on-site examination (ROSE) was performed in 23 (92%). In 17/23 (74%) cases, these had similar results to formal cytology. Only 4 (16%) had flow cytometry requested.

Twelve (48%) had lymphoma confirmed on histology. TBNA cytology had 100% specificity and positive predictive value for suspicion of lymphoma. Sensitivity was 33% and negative predictive value 62%.

Conclusion. TBNA is an appropriate first-line diagnostic procedure in evaluating mediastinal and hilar lymphadenopathy in suspected lymphoma. Biopsy should be the immediate second-line procedure when ROSE/cytology is suspicious of lymphoma or shows atypical cells.

Patients with negative TBNA cytology, but high clinical or radiological suspicion of lymphoma, should be further investigated.

S Afr Respir J 2016;22(3):67-72. DOI:10.7196/SARJ.2016.v22i3.80

Lymphoma is one of the top 10 most common cancers according to the Cancer Association of South Africa (CANSA) (last updated info, 2010). [1] The delayed diagnosis or misdiagnosis of lymphoma is an important clinical problem in SA. Owing to the varied clinical picture, especially in HIV-positive patients, symptoms may mimic other diseases, particularly tuberculosis (TB). The 2011 World Health Organization (WHO) report for SA revealed a treatment failure rate of 27% for smear-positive TB and 36% for smear-negative/extrapulmonary TB.[2] WHO and SA guidelines suggest empirical treatment of TB, particularly in HIVpositive patients.[3,4] However, these guidelines stress the importance of sample culture testing, with follow-up investigations and reviews of treatment response. TB responds rapidly in HIV-positive patients. [5] Lymphoma must be considered an important differential when TB cannot be confirmed in patients presenting with lymphadenopathy with/without constitutional symptoms.

In a retrospective study, conducted in rural KwaZulu-Natal, Puvaneswaran et al.[6] reviewed 21 patients attending a lymphoma clinic.

Of these patients, 13 were HIV-positive and 11 were on antiretroviral (ARV) therapy. They identified 18 (86%) patients who had undergone failed TB treatment in the 12 months before their histological confirmation of lymphoma. None had a confirmed TB culture before starting treatment. All these patients subjectively reported TB treatment failure, with a median duration of 5 months’ treatment. Only 7 (39%) patients reported being followed-up at 1 month post treatment initiation. Fine-needle aspiration (FNA) was suggested in the work-up

of all patients with lymphadenopathy, and lymph node (LN) biopsy for patients failing to respond to empirical TB treatment after 1 month.

It may also be difficult to distinguish TB from relapsed lymphoma.

Karakas et al.[7] evaluated the association of Hodgkin’s lymphoma (HL) and pulmonary TB, reviewing the medical records of 70 patients.

A total of 27 patients (38%) had mediastinal-pulmonary involvement initially, and systemic symptoms were present in 37 (52%) patients.

Fourteen patients (20%) had pulmonary TB: 3 had TB before HL, 2 had TB and HL concomitantly at initial diagnosis, 7 had TB during lymphoma therapy and 2 after the cessation of lymphoma treatment. Eleven patients with pulmonary TB had diffuse pulmonary infiltrations and mediastinal enlargement on computed tomography (CT) and X-ray. The radiologic differentiation could not be made on 9 patients who had a thoracic CT scan.

Lymphoma diagnosis depends on morphology, immunohisto­ chemistry and flow cytometry (FC) and, where appropriate, molecular studies to accurately categorise the lymphoma. An FNA is inadequate for initial diagnosis. An incisional or excisional biopsy is preferred to provide adequate tissue for these examinations.

Transbronchial needle aspiration (TBNA) is a minimally invasive bronchoscopic technique that is cost-effective and safe for diagnosing mediastinal and hilar adenopathy in patients with lung cancer, other malignancies, sarcoidosis and infectious processes such as TB.[8,9] Most of the studies on the diagnostic yield of TBNA for mediastinal and hilar adenopathy have been performed in patients with lung cancer. Few

SARJ VOL. 22 NO. 3 2016

67

ORIGINAL RESEARCH studies have analysed the sensitivity, specificity and predictive values of TBNA for diagnosing lymphoma. Therefore, it is difficult to compare the results among studies and perform a global evaluation of the technique.

In ill patients unable to undergo a definitive diagnostic procedure, TBNA is safe and has a high diagnostic yield. Ghamande et al.[10] evaluated TBNA in 8 ventilated patients. TBNA showed a sensitivity of 83%, specificity of 100%, positive predictive value (PPV) of 100%, and negative predictive value (NPV) of 50%. Diagnoses were carcinoma in 4 patients and post-transplantation lymphoproliferative disorder in 1 patient. Of the 3 patients with negative TBNA results, 2 underwent mediastinoscopy (MDS) (non-small-cell carcinoma and inflamed tissue). The 3rd patient could not undergo a MDS because of coagulopathy and no autopsy was performed. TBNA led to management changes in 5 (63%) patients. There were no complications from the TBNAs. FC has been shown to improve diagnostic yield. In a study of 285 patients, by Schmid et al.,[11] cytological specimens were retrospectively analysed and correlated with histology and follow-up.

Cytologically diagnosed malignancy was confirmed in all histologically examined cases. In 92% of reactive cytological cases, a benign process was diagnosed histologically. Correlation with histology showed a sensitivity of 98% and a specificity of 100% for cytology.

Another study by Gorczyca et al. [12] reviewed 100 patients presenting with mediastinal lesions. Samples were adequate for FC evaluation in 95%. Results showed that in 97%, 67%, 78%, 88% and 100% cases of B-cell lymphoma, T-cell lymphoma, carcinoma, T-cell acute lymphoblastic leukaemia/lymphoblastic lymphoma and thymoma/thymic hyperplasia, respectively, the diagnosis could be reached by FC alone. Excluding HL, the general sensitivity of FC in diagnosing mediastinal tumours was 92% and no false-positive (FP) results were encountered. Flow methodology has the advantage of rapid turnaround time as well as high sensitivity, enabling patients with large anterior mediastinal masses and/or superior vena cava syndrome to begin treatment promptly.

MDS is currently used extensively for the diagnosis of thoracic disease and staging of malignancies.[13] Positron-emission tomography (PET) scans have recently raised doubts as to the importance of MDS in the diagnosis and staging of lung cancer, with sensitivity and specificity almost approaching that of MDS.[14] However, since histological diagnosis is the issue, especially where a differentiation needs to be made between sarcoidosis, TB and lymphoma, MDS remains the diagnostic procedure of choice. In a study by Nalladaru et al.,[15] MDS resulted in a definitive diagnosis in 97% of patients with isolated mediastinal lymphadenopathy.

Sonar-guided FNA procedures (endoscopic ultrasound (EUS) and endobronchial ultrasound (EBUS)) are on the rise, especially for the diagnosis of primary and metastatic lesions. This has been increasingly noted for lung, oesophageal and pancreatic carcinomas.

Determining a definitive diagnosis of lymphoma by aspiration cytology is particularly important for patients whose condition may be too unstable to undergo general anaesthesia and open surgical biopsy. Earlier studies have demonstrated that EUS-FNA biopsy is a safe and effective procedure without significant complications. It also is less costly than other methods of obtaining tissue for diagnosis, including MDS, thoracotomy and CT-guided biopsies.[16] EUS-FNA allows access to deep-seated LNs and allows sampling of lesions that are small (<25 mm) and may be difficult to sample using other techniques.[17]

68 SARJ VOL. 22 NO. 3 2016

Nunez et al.[18] analysed 1 338 cases of EUS and EBUS-FNAB of deep-seated LNs. Results showed that, in association with FC and/ or immunohistochemical analysis, EUS-FNAB was 89% sensitive and 100% specific in the diagnosis of primary and recurrent deep-seated non-HL and HL. Currently, the diagnosis of lymphoma is based on the WHO classification system. A study by Yasuda et al.[19] of 152 patients with lymphoma showed that EUS-FNAB was able to determine the subclassification, based on the WHO classification, in 89% of cases.

Objective

The purpose of this study was to evaluate the diagnostic yield of TBNA for diagnosing mediastinal and hilar adenopathy from suspected lymphoma in a cohort of patients evaluated at Tygerberg Hospital over a 3-year period (July 2010 - June 2013).

Methods

Study design and population We performed a retrospective analysis of the collected data of patients with thoracic CT-detected mediastinal and hilar adenopathy adjacent to the tracheobronchial tree (with the short axis ≥1 cm) who underwent TBNA. Approximately 1 000 bronchoscopies are performed annually at Tygerberg Hospital. TBNAs are performed by experienced bronchoscopists, and registrars under their supervision.

We included all adult patients who underwent bronchoscopy for evaluation of mediastinal or hilar lymph adenopathy secondary to suspected lymphoma. Histology obtained from any method was used as the gold standard. Approval was granted by Stellenbosch University Health Research Ethics Committee (HREC ref.: S13/10/192).

TBNA materials and methods The Respiratory Division’s bronchoscopy reports were used as source documents. In general, patients underwent conscious sedation with intravenous propofol. Bronchoscopy was performed transnasally/orally using 2% lignocaine jelly/xylocaine spray as local anaesthesia. TBNA of selected mediastinal or hilar adenopathy stations was performed. The insertion point was determined after an analysis of thoracic CT with or without PET-CT. In most (84%) cases, aspiration was not ultrasoundguided as the hospital obtained EBUS after the start of the study period; therefore, EBUS was used in only 4 (16%) patients. A cytopathologist was present during most (92%) procedures and made an immediate microscopic evaluation (rapid on-site evaluation (ROSE)) of the cytology samples. Suspected lymphoma was defined as cytology compatible with or suggestive of lymphoma. Suspected malignancy included atypical cells, undifferentiated malignant cells or an abnormal cell population.

Data collection interpretation Samples with high lymphoid cellularity (suggesting an LN puncture), neoplastic cells or cytological findings that allowed for a specific diagnosis were considered adequate. Samples with too few cells for cytological evaluation or tracheobronchial wall cellularity (suggesting superficial puncture) were considered non-adequate. Clinical data included patient demographics, HIV status, current/previous TB or malignancies, LN involvement, ROSE, cytological diagnosis, FC results, histological diagnosis and procedural complications.

Samples with a cytological diagnosis of lymphoma confirmed by a surgical technique were considered true positives (TPs) and FPs indicated cases with confirmed negative histology. Cases yielding only

ORIGINAL RESEARCH a lymphoid cellularity in patients with specific pathologies such as carcinomas, TB or sarcoidosis on surgical biopsies were considered true negatives (TNs). False-negatives (FNs) indicated cases with negative cytology, but positive histology.

Statistical analysis Qualitative variables were reported as absolute frequencies and percentages, and numeric variables as median (range). Sensitivity, specificity, PPV and NPV were determined using the standard definitions.

Results

Population description Data from 78 patients with clinical or radiological suspicion of lymphoma were evaluated for the study. All underwent bronchoscopy and TBNA of mediastinal and/or hilar LNs. Patients with histological tissue confirmation of cytological diagnosis were included. The final study population comprised 25 patients. The median age of the patients was 44 (18 - 82) years and 16 (64%) were male. Seven (28%) patients were HIV-positive and of these, 5 (71%) were on ARV

Table 1. Patient characteristics, TBNA and biopsy results Known malignancy and TB

HIV

ROSE

TBNA cytology

HL

–

Atypical cells

HL

HL

+

Nil specific

Reactive lymphocytes (EBUS)

DLBCL

+

? Lymphoma

? DLBCL

FL

Unknown

Atypical cells

Atypical cells

FL/DLBCL CLL

CLL

–

CLL

SLL

CLL

+

CLL

Reactive lymphocytes Abnormal cell population

CLL

–

Nil specific

Reactive lymphocytes

AML

–

Nil specific

Reactive lymphocytes

Flow cytometry

TB

Tissue, histology LN, HL

–

LN, HL LN, DLBCL

+

LN, DLBCL

–

Arm mass, SLL

LN, SLL

Scalp mass, SLL –

Skin macules, necrotising granuloma

–

Atypical cells

? HL

–

LN, HL

–

Nil specific

Normal mucosa

–

LN, HL

–

Nil specific

Mucinous (EBUS)

–

Mediastinoscopy, HL

+

NSCLC

Undifferentiated malignant cells

Previous TB 2010

+

Lymphoid

Reactive lymphocytes

–

Spleen, marginal zone lymphoma

Empirical TB treatment

–

Lymphocytes

Reactive lymphocytes

–

LN, squamous Ca metastasis

–

Adeno Ca

Normal mucosa

–

Reactive LN

Reactive lymphocytes (EBUS) Granuloma

–

Endobronchial, granuloma

–

Granuloma

Granuloma

–

Transbronchial, granuloma

+

Granuloma

Granuloma

–

Endobronchial, granuloma

–

Necrotising granuloma

Necrotising granuloma

+

Endobronchial, granuloma

–

Lymphocytes/ macrophages

Reactive lymphocytes

–

Mediastinoscopy, granuloma

–

Normal

Reactive lymphocytes (EBUS)

–

Endobronchial, granuloma

Too few cells

–

Mediastinoscopy, necrotising granuloma

– Empirical TB treatment

Empirical TB treatment Previous TB 2011

–

Inconclusive

LN, primary effusion lymphoma

Retroperitoneal, adeno Ca metastasis –

Insufficient

Transhepatic, GIST

Unknown

Myxoid cells

Myxoid

–

Mediastinoscopy, reactive LN/bronchial cyst

+

Granuloma

Normal mucosa

–

Mediastinoscopy, reactive LN

Ca = carcinoma; CLL = chronic lymphocytic leukaemia; DLBCL = diffuse large B-cell lymphoma; FL = follicular lymphoma; GIST = gastrointestinal stromal tumour; HL = Hodgkin’s lymphoma; NSCLC = non-small-cell lung cancer; SLL = small lymphocytic lymphoma.

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ORIGINAL RESEARCH therapy. Their CD4 counts varied from 32 1 537 cells/mm3. The patient characteristics and final diagnoses are presented in Table 1.

All patients had a contrasted CT scan. Eight (32%) were known to have haematological malignancy: 2 with HL, 1 diffuse large B-cell lymphoma (DLBCL), 1 follicular lymphoma (FL), 3 chronic lymphocytic leukaemia/ small lymphocytic lymphoma (CLL/SLL), 1 acute myeloid leukaemia (AML). Twelve (48%) patients had lymphoma confirmed on a histological sample: 5 (42%) HL, 2 (17%) DLBCL, 3 (25%) CLL/SLL, 1 (8%) splenic/ nodal marginal zone lymphoma, 1 (8%) primary effusion lymphoma.

The smallest axis diameter of the 38 studied LNs was 10 mm (range 10 - 52 mm); 23 (61%) were smaller than 20 mm. A mean of 3.6 (range 1 - 9) passes were performed.

TBNA validity and reliability Adequate samples for cytological evaluation were obtained from 22 (88%) patients.

Cytological diagnosis could be made for 8 (32%) patients, including suspected lymphoma (n=4) and granuloma (n=4).

Samples were considered non-adequate for 3 (12%) patients (normal mucosa and too few cells). FC was requested for only 4 (16%).

TB cultures were performed for 19 (76%).

Of these 2 (11%) were positive. Histology provided the final diagnosis for all cases, with 12 lymphoma cases confirmed.

ROSE was performed in 23 (92%). In 17/23 (74%) cases similar results were obtained to formal cytology. In the lymphoma subgroup, ROSE showed 7/12 (58%) cells suspicious of malignancy (2 CLL, 3 atypical cells, 1 possible lymphoma, 1 non-small-cell lung cancer) and 5 (42%) were non-diagnostic (4 nil specific and 1 lymphoid) with sensitivity for suspicion of malignancy 58% and specificity 100%. All ROSE and cytology samples suggestive of malignancy were confirmed by histology, indicating excellent PPV. In the lymphoma subgroup, 7/12 (58%) patients had cytology suspicious of malignancy (HL, CLL/SLL, possible HL, possible DLBCL, atypical cells, undifferen­ tiated malignant cells, abnormal cell population). Only 2 (17%) had a specific cytological diagnosis (both patients were known to have the same haematological malignancy). Another 2 had cytology results suggestive of lymphoma (1 known with DLBCL and 1 newly diagnosed with HL). Cytology was FN for malignancy in

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5/12 (42%) of the lymphoma subgroup (3 reactive lymphocytes, 1 normal mucosa, 1 mucinous). TBNA sensitivity for suspecting lymphoma was 33% and specificity 100%.

In patients with known haematological malignancies, TBNA cytology showed atypical cells in 5 (63%) and 3 (37%) had FN results. Only 2 (25%) had a definitive diagnosis and 1 (13%) a suggestive diagnosis of lymphoma. In the 5 newly diagnosed lymphoma patients, TBNA cytology showed atypical cells in 2 (40%) and FN results in 3 (60%). Only 1 (20%) showed cytology suggestive of lymphoma.

Of the study population, 8/25 (32%) had granulomatous inflammation on histology (6 non-necrotising and 2 necrotising). One of these had a positive TB culture. All 4 cases of cytological granulomatous inflammation were confirmed by histology, with TBNA sensitivity of 50% and specificity of 100%.

FC was performed on 4 (16%) TBNA samples. The routine immuno­phenotypic panel was: CD3, CD4, CD5, CD8, CD10, CD19, CD20, CD22, CD23, CD38, CD45, FMC-7, kappa and lambda (CD 45 gating strategy). One sample was insufficient for analysis. The other samples demonstrated 1 CLL, 1 FL relapse/transformation into DLBCL and 1 was inconclusive. Sensitivity was 50% and specificity 100%. From the source population, 19/78 (25%) had FC performed.

Lymphoma subtyping was as follows: 5 patients had classic HL (1 nodular sclerosis, 1 mixed cellularity, 1 lymphocyte rich, 1 mixed cellularity nodular sclerosis, 1 lymphocyte depleted), 3 patients had CLL/SLL, 2 patients had DLBCL, 1 patient had splenic and nodal marginal zone lymphoma and 1 patient had primary effusion lymphoma.

MDS was performed in 5 (20%) patients.

One patient had HL. The results are shown in Table 2.

Peripheral LN biopsy confirmed 8/12 (67%) lymphomas, soft-tissue biopsy 2 (17%) and splenectomy 1 (8%). MDS yielded 1 (8%)

undiagnosed HL. Lymphoma could be confirmed in 10 (82%) with minor surgical procedures (peripheral LN or soft-tissue biopsy) and only 2 (17%) required major surgical procedures (MDS or laparotomy).

Complications Complications related to TBNA occurred in 3 patients: 1 case of mild, self-limited bleeding at the puncture site, 1 patient was too restless to complete the procedure and 1 patient had laryngospasm.

Discussion

There is a question as to the accuracy of fineneedle aspiration cytology (FNAC) in the diagnosis of lymphomas, as the tumours often contain malignant and reactive elements and the FNAC may only have sampled the reactive regions. The inherent characteristics of lymphoma (i.e. fibrosis in classic HL) may also prevent cytomorphologists from obtaining enough material for several analyses. Visualising LN changes may help with selecting the right aspiration area and overcome problems with partial fibrotic changes in the affected LN.[20] Another disadvantage of FNAC is that it does not provide the cellular architecture required for accurate subtyping of the lymphoma. The sensitivity of all FNA for the diagnosis of lymphoma (published 2004 - 2014) has been reported to range between 25% and 95%.[21] As a result of the deficiencies of FNAC, LN excision or core needle biopsy is required and is the recommended second-line diagnostic procedure. All suspicious LNs should be biopsied following FNA, even if FNA is reported normal or demonstrating reactive changes only.[22] Histological confirmation and subtyping of lymphoma remains the standard precondition for chemotherapy.

TBNA/EBUS-TBNA cell block samples[23] and EBUS transbronchial needle forceps biopsies[24] may overcome these deficiencies.

Table 2. Results from mediastinoscopy Cytology result

Final diagnosis

Mucinous

Hodgkin’s lymphoma (extranodal) lymphocyte depleted/diffuse fibrosis type

Reactive lymphocytes

Non-necrotising granulomatous inflammation and anthracosis

Normal mucosa

Reactive LN with anthracosis, fibrosis and scarring

Myxoid

Reactive LN and bronchial cyst

Too few cells

Necrotising granulomatous inflammation

ORIGINAL RESEARCH A limited number of study patients had sonar-guided LN aspiration. In the lymphoma subgroup, no tissue suitable for immunohistochemical analysis (cell block or forceps biopsy) was submitted from TBNA samples. There were also a limited number of FC tests requested. This may explain the low sensitivity (33%) demonstrated by our study.

The only study done in the last 10 years evaluating the diagnostic yield of conventional (blind) TBNA in the diagnosis of lymphoma (using cytology and/or histology needles) was by Fernández-Villar et al.[25] in 2010, on 15 patients with lymphoma. They also demonstrated TBNA specificity and PPV of 100%, but poor sensitivity (36%) and NPV (10%). Other studies evaluating conventional TBNA had a limited number of patients with lymphoma. Sharafkhaneh et al.[26] had 4 patients, Szlubowski et al.[27] 2 patients, Selcuk et al.[28] 1 patient and Aliyali et al.[29] 2 patients, with sensitivity ranging from 0% - 50%. Most studies focused on lung carcinoma, metastatic disease and sarcoidosis.

Most other recent studies looked at EBUS-guided TBNA (developed in 2002). It was traditionally thought that the small samples of mediastinal LNs obtained by EBUS are inadequate for the diagnosis of lymphoma, as treatment regimens for lymphoma are dependent on the specific subtype and histological grade.

Kennedy et al.[30] carried out a retrospective study in 2007 that included 25 patients with mediastinal adenopathy and suspected lymphomas. EBUS-TBNA (in combination with cytology and immunohistochemistry with/without FC) demonstrated sensitivity, specificity, PPV and NPV of 90%, 100%, 100% and 93%, respectively.

In 2010, Steinfort et al.[31] reviewed data from 55 patients with suspected lymphoma who underwent EBUS-TBNA (using a 22-gauge needle and preparing a cell block for immunohistochemical analysis) to evaluate mediastinal lymphadenopathy. They showed that EBUSTBNA provided a diagnosis in 16/21 (76%) of the lymphoma cases, although 4 patients required further surgical biopsy to completely characterise lymphoma subtypes. Sensitivity and specificity for definitive diagnosis of lymphoma were 57% and 100%, respectively.

Another study published in 2014 showed similar results.

Senturk et al. [32] evaluated EBUS-TBNA (with cell block for immunohistochemistry) in 15 patients with lymphoma. A definitive pathological diagnosis and histological typing were achieved in 87% of patients. Specificity, NPV and diagnostic accuracy were calculated as 100%, 97% and 97%, respectively.

In these studies, though FC was not routinely requested, tissue for immunohistochemical analysis was submitted. This could explain the increased sensitivity for a definitive diagnosis and subtyping of lymphoma, obviating the need for more invasive surgical biopsy.

Recently, a new 22-gauge needle (SonoTip EBUS Pro with stainless steel) was introduced in Japan, showing promising results.[33] The low cost and few complications justify the continued use of conventional TBNA as the initial diagnostic test for mediastinal and hilar adenopathy, especially when other techniques, such as EBUSTBNA, are unavailable. The diagnostic yield of conventional TBNA could be improved by FC or adequate tissue sampling (with cell block preparation) for immunohistochemical analysis.

In our institution, TBNA is a first-line diagnostic procedure for the initial evaluation of mediastinal and/or hilar lymph adenopathy, while FC is not currently used on a routine basis. If lymphoma is suspected, FC of TBNA samples should be encouraged, as it has been shown to have an excellent correlation with histology. In most (84%) patients, aspiration was not ultrasound guided. Since beginning the study, our

hospital has obtained EBUS, and the use of sonar-guided aspiration (+/– biopsy) and improved specimen preparation (including a cell block) should improve TBNA yield for all pathologies.

Study limitations Our study was retrospective and included a small number of patients from a single centre. Neither FC nor cell block preparation was routinely used in the evaluation of samples, and EBUS was only acquired towards the end of the study period. With most studies in the last 10 years that evaluate diagnostic yield of TBNA being sonarguided, it is difficult to compare our results. A larger, randomised controlled prospective study comparing conventional TBNA, FC or cell block preparation, EBUS-TBNA and EBUS transbronchial needle forceps biopsy could overcome these limitations.

Conclusion

In our study, transbronchial FNAC had a low sensitivity, but high rule-in value for the diagnosis of lymphoma in patients presenting with mediastinal or hilar adenopathy. It is an appropriate first-line diagnostic procedure, but further invasive sampling is required for histological confirmation and subtyping of lymphoma, and in cases where TBNA cytology is negative but clinical or radiological suspicion of lymphoma is high. This could be obviated by the routine request of FC, preparing a cell block during TBNA/EBUS-TBNA and performing transbronchial needle forceps biopsy during EBUS-TBNA. The main advantage of TBNA was shown to be in evaluating persistent disease.

It is possible to provide a definitive diagnosis of new or persistent lymphoma using TBNA, but this is not sufficient to exclude new or persistent lymphoma. If ROSE/cytology is suspicious of lymphoma or shows atypical cells, excisional or incisional biopsy should be the immediate second-line diagnostic step.

References

1. Herbst MC. CANSA Statistics 2010 National Cancer Registry Report. Fact Sheet on the Top Ten Cancers per Population Group, October 2015.

2. Floyd K, Glaziouet P, Timimi H, et al. Global Tuberculosis Report 2015, 20th edition.

Geneva: World Health Organization, 2015.

3. The South African National Tuberculosis Control Programme. Practical Guidelines.

Pretoria: Department of Health, 2004.

4. World Health Organization. Treatment of Tuberculosis Guidelines. Geneva: WHO, 2010.

5. Wilson D, Nachega J, Morroni C, et al. Diagnosing smear-negative tuberculosis using case definitions and treatment response in HIV-infected adults. Int J Tuber Lung Dis 2006;10(1):31-38.

6. Puvaneswaran B, Shoba B. Misdiagnosis of tuberculosis in patients with lymphoma.

S Afr Med J 2013;103(1):32-33.

7. Karakas Z, Agaoglu L, Taravari B, et al. Pulmonary tuberculosis in children with Hodgkin’s lymphoma. Hematol J 2003;4(1):78-81. DOI:10.1038/sj.thj.6200219 8. Dasgupta A, Mehta AC. Transbronchial needle aspiration. An underused diagnostic technique. Clin Chest Med 1999;20:39-51.

9. Wang KP, Metha A, Turner JF. Transbronchial needle aspiration for cytology and histology specimens. In: Flexible Bronchoscopy, 2nd ed. Cambridge: Blackwell Publishing, 2004:117-137.

10. Ghamande S, Rafanan A, Dweik R, Arroliga AC, Mehta AC. Role of transbronchial needle aspiration in patients receiving mechanical ventilation. Chest 2002;122(3):985989. DOI:10.1378/chest.122.3.985 11. Schmid S, Tinguely M, Cione P, Moch H, Bode B. Flow cytometry as an accurate tool to complement fine needle aspiration cytology in the diagnosis of low grade malignant lymphomas. Cytopathology 2010;22(6):397-406. DOI:10.1111/j.13652303.2010.00801.x 12. Gorczyca W, Tugulea S, Liu Z, et al. Flow cytometry in the diagnosis of mediastinal tumors with emphasis on differentiating thymocytes from precursor t-lymphoblastic lymphoma/leukemia. Leuk Lymphoma 2004;45(3):529-538. DOI:10.1080/10428190 310001598008

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ORIGINAL RESEARCH 13. Carlens E. Mediastinoscopy: A method for inspection and tissue biopsy in the superior mediastinum. Dis Chest 1959;36:343-349.

14. Lee BE, Redwine J, Foster C, et al. Mediastinoscopy might not be necessary inpatients with non–small cell lung cancer with mediastinal lymph nodes having a maximum standardized uptake value of less than 5.3. J Thorac Cardiovasc Surg 2008;135(3):615619. DOI:10.1016/j.jtcvs.2007.09.029 15. Nalladaru ZM, Wessels A. The role of mediastinoscopy for diagnosis of isolated mediastinal lymphadenopathy. Indian J Surg 2011;73(4):284-286. DOI:10.1007/s12262-011-0282-x 16. Catalano MF, Nayar R, Gress F, et al. EUS-guided fine needle aspiration in mediastinal lymphadenopathy of unknown etiology. Gastrointest Endosc 2002;55(7):863-869.

DOI:10.1067/mge.2002.124637 17. Jhala NC, Jhala D, Eltoum I, et al. Endoscopic ultrasound-guided fine-needle aspiration biopsy: A powerful tool to obtain samples from small lesions. Cancer 2004;102(4):239-246. DOI:10.1002/cncr.20451 18. Nunez AL, Jhala NC, Carroll AJ, et al. Endoscopic ultrasound and endobronchial ultrasound-guided fine-needle aspiration of deep-seated lymphadenopathy: Analysis of 1 338 cases. Cytojournal 2012;9(1):14. DOI:10.4103/1742-6413.95845 19. Yasuda I, Goto N, Tsurumi H, et al. Endoscopic ultrasound-guided fine needle aspiration biopsy for diagnosis of lymphoproliferative disorders: Feasibility of immunohistological, flow cytometric, and cytogenetic assessments. Am J Gastroenterol 2012;107(3):397-404. DOI:10.1038/ajg.2011.350 20. Kuvezdić KG, Aurer I, Ries S. FNA based diagnosis of head and neck nodal lymphoma.

Coll Antropol 2010;34(1):7-12.

21. Health Quality Ontario. The Accuracy of Fine-Needle Aspiration Cytology in the Diagnosis of Lymphoma. Toronto: HQO, 2014:1-19.

22. Morris-Stiff G, Cheang P, Key S, et al. Does the surgeon still have a role to play in the diagnosis and management of lymphomas? World J Surg Oncol 2008;6(1):13.

DOI:10.1186/1477-7819-6-13 23. Sanz-Santos J, Serra P, Andreo F, et al. Contribution of cell blocks obtained through endobronchial ultrasound-guided transbronchial needle aspiration to the diagnosis of lung cancer. BMC Cancer 2012;12(1):34. DOI:10.1186/1471-2407-12-34

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24. Herth FJF, Schuler H, Gompelmann D, et al. Endobronchial ultrasound-guided lymph node biopsy with transbronchial needle forceps: A pilot study. Eur Respir J 2012;39(2):373-377. DOI:10.1183/09031936.00033311 25. Fernández-Villar A, Botana M, Leiro V, et al. Validity and reliability of transbronchial needle aspiration for diagnosing mediastinal adenopathies. BMC Pulm Med 2010;10(1):24. DOI:10.1186/1471-2466-10-24 26. Sharafkhaneh A, Baaklini W, Gorin AB, Green L. Yield of transbronchial needle aspiration in diagnosis of mediastinal lesions. Chest 2003;124(6):2131-2135.

DOI:10.1378/chest.124.6.2131 27. Szlubowski A, Kuzdzał J, Soja J. Transbronchial needle aspiration as a diagnostic method in lung cancer and non-malignant mediastinal adenopathy. Pneumonol Alergol Pol 2007;75(1):5-12.

28. Selçuk ZT, Firat P. The diagnostic yield of transbronchial needle aspiration in superior vena cava syndrome. Lung Cancer 2003;42(2):183-188. DOI:10.1016/s01695002(03)00293-9 29. Aliyali M, Shafigh E. Diagnostic yield of transbronchial needle aspiration in intrathoracic lymphadenopathy. Tanaffos 2008;7(2):23-27.

30. Kennedy MP, Jimenez CA, Bruzzi JF, et al. Endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of lymphoma. Thorax 2008;63(4):360-365.

31. Steinfort DP, Conron M, Tsui A, et al. Endobronchial ultrasound-guided transbronchial needle aspiration for the evaluation of suspected lymphoma. J Thorac Oncol 2010;5(6):804-809. DOI:10.1097/jto.0b013e3181d873be 32. Senturk A, Babaoglu E, Kilic H, et al. Endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of lymphoma. Asian Pac J Cancer Prev 2014;15(10):4169-4173.

33. Izumo T, Sasada S, Watanabe J, et al. Comparison of two 22 G aspiration needles for histologic sampling during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Jpn J Clin Oncol 2014;44(9):841-845. DOI:10.1093/jjco/ hyu095

CASE REPORT

Pulmonary puzzle: A rare case of dysphagia S Sinha Roy, MBBS, DTCD, MD, FCCP; C F N Koegelenberg, MB ChB, MMed (Int), FCP (SA), FRCP (UK), Cert Pulm (SA), PhD; E M Irusen, MB ChB, FCP (SA), FCCP, PhD Division of Pulmonology, Department of Medicine, Stellenbosch University and Tygerberg Hospital, Cape Town, South Africa Corresponding author: S Sinha Roy (sinharoy@gmail.com) S Afr Respir J 2016;22(3):73-75. DOI:10.7196/SARJ.2016.v22i3.81

Case report

A 58-year-old man presented with a longstanding history of dysphagia and sensation of something lodged in the back of his throat. He had no significant past medical history, was a smoker (30 pack-years) and used >60 units of alcohol per week. A physical examination was unremarkable. The patient was referred to the respiratory clinic at Tygerberg Hospital, Cape Town, by a specialist physician who was concerned about the patient’s abnormal chest radiograph (Fig. 1).

The chest radiograph showed that the normal left-sided aortic arch and the usual companion descending aorta were absent. The arch coursed to the right with the descending aorta also on the right. A computed tomography (CT) scan (Figs 2 and 3) and reconstructions (Figs 4 and 5) confirmed the right-sided aortic arch with a retrooesophageal aberrant left subclavian artery and formation of a Kommerell’s diverticulum at the origin. In the absence of major complications, he was managed conservatively.

develops. The arch is formed by the left fourth aortic arch vessel while the right fourth vessel regresses.[1] The two dorsal aortas fuse (or the right dorsal aorta involutes) to form the descending aorta, and the ventral aortic limbs fuse to form the aortic sac. In individuals with a right-sided aortic arch, the right dorsal aorta and right fourth

Discussion

The prevalence of a right-sided aortic arch among adults is ~1/1 000 2 000 of the population.[1] With this rare congenital anomaly, the aortic arch and the descending thoracic aorta are situated in the right hemithorax. During the third week of gestation, the aortic arch

Fig. 1. The patient’s chest radiograph that prompted the referral.

Fig. 2. Contrasted CT thorax mediastinal view showing a right-sided aortic arch with its branches: (A) the aortic arch (right-sided); (B) superior vena cava; (C) right subclavian artery; (D) right common carotid artery; (E) left common carotid artery; (F) aberrant left subclavian artery; and (G) left brachiocephalic vein draining into SVC.

Fig. 3. Contrasted CT scan of the patient’s thorax, mediastinal view, showing aberrant left subclavian artery with formation of a Kommerell’s diverticulum: (A) the aortic arch (right-sided) indenting on the trachea; (B) Kommerell’s diverticulum; and (C) aberrant left subclavian artery forming the diverticulum.

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CASE REPORT branchial arch persist and the distal left dorsal aorta disappears.[1] These variants may have occasional complications, mostly tracheobronchial or oesophageal compression and, rarely, disturbances of normal blood flow patterns,[2] e.g. cerebral ischaemia because of reversal of flow through the vertebrobasilar vasculature. Several types have been described[1,3] (Fig. 6). Type I (15 - 20% of cases) involves a rightsided aortic arch with mirror-image branching. This type is usually associated with congenital heart disease, the most common being tetralogy of Fallot or pulmonary stenosis. Type II is the most common variety (around 80% of all cases), in which a right-sided aortic arch is present with an aberrant left subclavian artery. The vessels originate in the following order: left common carotid, right common carotid, right

Fig. 4. CT scan of patient’s thorax, reconstructed view showing right arch and its branches.

A

B

A C

B

subclavian and left subclavian artery. A Kommerell’s diverticulum develops at the junction of the aberrant left subclavian artery with the right aortic arch and may cause compressive features[3,4] such as dysphagia, dyspnoea, stridor, wheezing, cough, choking spells or chest pain. The dysphagia caused by the aberrant left subclavian artery causing a vascular ring formation is sometimes referred to as dysphagia pseudolusoria.[1] The type III malformation is very rare: a right-sided aortic arch is present with isolation of the left subclavian artery. The left subclavian artery does not arise from the arch or

Fig. 5. CT scan of thorax of patient, reconstructed view showing aberrant left subclavian artery originating from right arch from its posteromedial aspect with the formation of Kommerell’s diverticulum: (A) the aberrant left subclavian artery and (B) Kommerell’s diverticulum. Note the origin of the aberrant left subclavian artery below the right subclavian artery.

A

E

B

E F

D G

Fig. 6. The three main variations seen in patients with right-sided aortas: type I, mirror image aortic arch; type II, aberrant left subclavian artery; type III, isolated subclavian artery. (A) the right subclavian artery; (B) right common carotid artery; (C) brachiocephalic trunk; (D) aberrant left subclavian artery; (E) left common carotid artery; (F) ductus arteriosus; and (G) pulmonary trunk.

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CASE REPORT the descending aorta. It may be associated with vertebrobasilar insufficiency and subclavian steal syndrome. This variety may also be associated with congenital heart disease.

The causes of right-sided aortic arch are unknown. In some patients, 22q11 deletions have been found.[5] This deletion is responsible for the DiGeorge, velocardiofacial and conotruncal face anomaly syndromes, which are often referred to by the unified terms CATCH-22 syndrome or chromosome 22q11 deletion syndrome.

A right-sided aortic arch alone is usually asymptomatic and diagnosed incidentally. During pregnancy, a prenatal ultrasound may reveal the abnormal course of the arch. Chest radiography demonstrates an absent left aortic knuckle and left-sided descending aorta. The right-sided aortic arch is discernible, often at a relatively higher plane, and may project like a mass in the immediate right lower paratracheal region (this, in fact, represents the most common misdiagnosis). The course of the right-sided descending aorta can then be traced. The lower trachea may be pushed to the left or indented

by the right arch. Rarely, the arch may be associated with aneurysmal dilatation and other anomalies of position and branching of the aorta. A CT scan of the thorax will delineate the exact anatomical abnormality. Magnetic resonance angiography and a barium swallow test may be considered, to better demonstrate the abnormalities and vascular anomalies.

References 1. Kau T, Sinzig M, Gasser J, et al. Aortic development and anomalies. Semin Intervent Radiol 2007;24(2):141-152. DOI:10.1055/s-2007-980040 2. BiaĹ&#x201A;owas J, Hreczecha J, Grzybiak M. Right-sided aortic arch. Folia Morphol 2000;59(3):211-216.

3. Cina CS, Arena GO, Bruin G, Clase CM. Kommerellâ&#x20AC;&#x2122;s diverticulum and aneurysmal right-sided aortic arch: A case report and review of the literature. J Vasc Surg 2000;32(6):1208-1214. DOI:10.1067/mva.2000.108012 4. Salanitri J. MR angiography of aberrant left subclavian artery arising from right-sided thoracic aortic arch. Br J Radiol 2005;78(934):961-966. DOI:10.1259/bjr/20210494 5. McElhinney DB, McDonald-McGinn D, Zackai EH, Goldmuntz E. Cardiovascular anomalies in patients diagnosed with a chromosome 22q11 deletion beyond 6 months of age. Pediatrics 2001;108(6):E104. DOI:10.1542/peds.108.6.e104

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BREATH-TAKING NEWS

COPD sine COPD Currently, almost all physicians rigidly apply the Global Initiative for Obstructive Lung Disease (GOLD) definition for chronic obstructive pulmonary disease (COPD), exemplified by the post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) <0.70 as being diagnostic.[1] However, there are emerging data to suggest that this may not be definitive.

The SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) research group recently reported on an observational study involving 2 736 current or former smokers.[2] They measured their respiratory symptoms with the COPD Assessment Test (CAT), spirometry and 6-minute walk distance, and performed a high-resolution computed tomography (HRCT) scan of the chest. Respiratory symptoms were present in 50% of subjects with spirometry in the normal range. These participants also had a mean (standard deviation (SD)) rate of exacerbations per year that was significantly higher than that of asymptomatic smokers (0.27 (0.67) v. 0.08 (0.31), p<0.001). They also had greater limitation of activity, mildly reduced FEV 1/FVC and inspiratory capacity, and more airway wall thickening seen on HRCT scan than the asymptomatic group. When categorised according to the CAT scores, this current and ex-smoker group with a score ≥10 had an exacerbation rate approximately twice that of the group spirometrically defined as COPD with a score of <10. Among this apparent non-COPD group, 42% were taking bronchodilators and 23% inhaled corticosteroid.

These data are consistent with an additional report by the Genetic Epidemiology of COPD (COPD Gene) investigators.[3] They found one or more respiratory-related impairments in 54.1% (2 375/4 388)

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of smokers or ex-smokers with normal spirometry. This group had worse quality of life than the never-smokers (mean St George’s Respiratory Questionnaire total score 17.0 (18.0) v. 3.8 (6.8), p<0 .001) and a lower 6-minute walk distance, and 42.3% (127/300) had computed tomography (CT) evidence of emphysema or airway thickening.

It appears that appreciable numbers of smokers who do not meet the GOLD criteria for COPD have significant symptoms, exacerbations, imaging evidence of airways disease and are receiving medication. These data suggest that we need to be circumspect about the GOLD definition, carefully evaluate at-risk patients for symptoms and treat appropriately.

E M Irusen Professor and Head, Division of Pulmonology, Department of Medicine, Stellenbosch University and Tygerberg Academic Hospital, Cape Town, South Africa 1. Vestbo J, Hurd SS, Agusti AG, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.

Am J Respir Crit Care Med 2013;187(4):347-365. DOI:10.1164/rccm.201204-0596PP 2. Woodruff PG, Barr G, Bleecker E, et al. Clinical significance of symptoms in smokers with preserved pulmonary function. N Engl J Med 2016;374(19):1811-1821.

DOI:10.1056/NEJMoa1505971 3. Regan EA, Lynch DA, Curran-Everett D, et al. Clinical and radiologic disease in smokers with normal spirometry. JAMA Intern Med 2015;175(9):1539-1549.

DOI:10.1001/jamainternmed.2015.2735

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BREATH-TAKING NEWS

Elevated blood eosinophil count and exacerbations of COPD Chronic obstructive pulmonary disease (COPD) is a major cause of global morbidity and mortality, currently listed as the fourth-leading cause of death. Exacerbation is the foremost contributor to worsening lung function, impairment in quality of life, need for urgent care or hospitalisation and cost of care in COPD.[1] Factors predicting exacerbation frequency and thus providing subsequent optimal treatment strategies are presently a major focus in respiratory research.

Watz et al.[2] reported on a post-hoc analysis of the WISDOM trial.[3] In this 1-year, double-blind, parallel-group study, 2 485 patients with severe COPD were enrolled, and inhaled corticosteroids (ICS) were withdrawn in one group over a 12-week period. The trial showed a similar time to first exacerbation in both groups but a significant (40 mL) drop in forced expiratory volume in 1 second (FEV1) in the ICS withdrawal group. When stratifying this cohort of patients according to the blood eosinophil count, those with an elevated count >2% (46% of subjects) had a significant increase in the rate of moderate or severe exacerbations, with a rate ratio of 1.22 (95% confidence interval (CI) 1.02 - 1.48), while an eosinophilia of ≥4% had a rate ratio of 1.63 (95% CI 1.19 - 2.24) and a blood eosinophil count of 300 cells/µL reached statistical significance. Interestingly, neither atopy nor IgE were predictive of exacerbations after withdrawal of ICS. There remain many unanswered questions, such as the optimal dose of ICS required to attenuate eosinophilia. To date, there is no plausible biological mechanism to explain this association between blood eosinophils and ICS response. The peripheral blood eosinophil count appears to correlate with sputum eosinophilia and eosinophilic inflammation.[4] However, treatment with ICS does not appear to

lower the blood eosinophil count[5] and this may point towards a nonIgE mediated anti-inflammatory effect.

Peripheral blood eosinophilia is a convenient biomarker to measure, with clear cut-off values that may potentially be used to select patients that benefit from ICS use for exacerbations and other endpoints of clinical efficacy in COPD. Morné Vorster Pulmonology Fellow, Division of Pulmonology, Department of Medicine, Stellenbosch University and Tygerberg Academic Hospital, South Africa 1. Vedel-Krogh S, Nielsen SF, Lange P, Vestbo J, Nordestgaard BG. Blood eosinophils and exacerbations in chronic obstructive pulmonary disease. The Copenhagen General Population Study. Am J Respir Crit Care Med 2016;193(9):965-974. DOI:10.1164/ rccm.201509-1869OC 2. Watz H, Tetzlaff K, Wouters EFM, et al. Blood eosinophil count and exacerbations in severe chronic obstructive pulmonary disease after withdrawal of inhaled corticosteroids: A post-hoc analysis of the WISDOM trial. Lancet Respir 2016;4(5):390-398. DOI:10.1016/S2213-2600(16)00100-4 3. Magnussen H, Disse B, Rodriguez-Roisin R, et al. Withdrawal of inhaled glucocorticoids and exacerbations of COPD. N Engl J Med 2014;371(14):1285-1294.

DOI:10.1056/NEJMoa1407154 4. Singh D, Kolsum U, Brightling CE, Locantore N, Agusti A. Eosinophilic inflammation in COPD: Prevalence and clinical characteristics. Eur Respir J 2014;44(6):1697-1700.

DOI:10.1183/09031936.00162414 5. Barnes NC, Sharma R, Lettis S, Calverley PM. Blood eosinophils as a marker of response to inhaled corticosteroids in COPD. Eur Respir Journal 2016;47:1374-1382.

DOI:10.1183/13993003.01370-2015

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PRODUCT NEWS NEW Antistatic Chamber: small, solid and effective ®

Aspen is proud to announce the launch of VORTEX , an innovative aluminium antistatic holding chamber with ‘cyclone twist’ principle, as an addition to our respiratory portfolio.

NEW Antistatic Chamber: small, solid andsolid effective NEW Antistatic Chamber: small, and effective ® [1]

VORTEX inhalation aid is suitable in providing: ® ® • High lung deposition, lowis throat deposition Aspen proud to launch announce launch of VORTEX , an innovative aluminium antistaticholding holding AspenAntistatic is proud toChamber: announce the ofthe VORTEX , an innovative aluminium antistatic NEW small, solid and effective • High dosage consistency chambertwist’ with ‘cyclone twist’as principle, as an to addition to our respiratory portfolio. chamber with ‘cyclone principle, an addition our respiratory portfolio.

• Disinfectable, ergonomic SmartTouch masks ®

Aspen is proud to announce® the launch of VORTEX , an innovative aluminium antistatic holding [1] VORTEX inhalation aid is suitable in[1]providing: ® chamber ‘cyclone twist’ principle, as an addition to our respiratory portfolio. inhalation aid is suitable in providing: VORTEXwith • High lung deposition, low throat deposition

• High lung deposition, throat deposition • High low dosage consistency ®

[1]

• Disinfectable, ergonomic SmartTouch masks inhalation aid is suitable in providing: VORTEX • High dosage consistency ••High lung deposition, low throat deposition Disinfectable, ergonomic SmartTouch masks • High dosage consistency • Disinfectable, ergonomic SmartTouch masks

Reference: 1. Laube BL, Janssens HM, de Jongh FHC, et al. What the pulmonary specialist should know about the new inhalation therapies. Eur Respir J 2011;37:1308-1331.

Reference: 1. Laube BL, Janssens HM, de Jongh FHC, et al. What the pulmonary specialist should know about the new inhalation therapies. Eur Respir J 2011;37:1308-1331.

Reference: 1. Laube BL, Janssens HM, de Jongh FHC, et al. What the pulmonary specialist should know about the new inhalation therapies. Eur Respir J 2011;37:1308-1331.

Reference: 1. Laube BL, Janssens HM, de Jongh FHC, et al. What the pulmonary specialist should know about the new inhalation therapies. Eur Respir J 2011;37:1308-1331.

1 1

78 SARJ VOL. 22 NO. 3 2016

PRODUCT NEWS Rivaroxaban reduces length of hospital stay in patients with symptomatic venous thromboembolism The phase III EINSTEIN deep vein thrombosis (DVT) and EINSTEIN pulmonary embolism (PE) trials demonstrated the potential of oral rivaroxaban (Xarelto, Bayer) – 15 mg twice daily for 21 days, followed by 20 mg once daily – for the treatment of venous thromboembolism (VTE), a term that embraces DVT and PE. A subsequent study by van Bellen et al.,[1] published in Current Medical Research and Opinion in 2014, was undertaken to assess the length of initial hospitalisation in patients presenting with either symptomatic DVT or PE using hospitalisation records from these trials.

The authors found that overall 52% of EINSTEIN DVT patients and 90% of EINSTEIN PE patients were admitted to hospital. The proportion of hospitalised DVT patients with a length of stay 5 days or fewer, receiving rivaroxaban, was 54% compared with 31% for those receiving enoxaparin/vitamin K antagonist (VKA), the current standard of care for the treatment of patients with symptomatic DVT and PE. For patients with PE, the corresponding values were 45% and 33%. Stays of 6 - 10 days were observed in 29% of rivaroxaban-treated patients compared with 45% for enoxaparin/VKA-treated patients for DVT. For patients with PE, these values were 39% and 46% in the rivaroxaban and enoxaparin/ VKA groups, respectively. Overall, length of stay was significantly shorter in the rivaroxaban group, compared with the enoxaparin/VKA group across all analyses performed (p<0.0001).

VTE is associated with significant morbidity and mortality and therefore carries a considerable healthcare burden. Rivaroxaban is as effective as enoxaparin/VKA for the treatment of acute symptomatic DVT or PE, with the additional benefit of significantly reducing the period of hospitalisation in patients being treated for an initial DVT or PE. ‘Coupled with improved patient treatment satisfaction and no requirement for routine monitoring or dose adjustment, this presents strong advantages for treating patients with VTE with rivaroxaban,’ the authors wrote.

They concluded that a single-drug regimen with rivaroxaban may reduce the burden on healthcare systems and patients by providing effective and well-tolerated treatment. ‘The convenience of a single-drug approach with oral rivaroxaban has the potential to allow discharge based on a patient’s clinical condition and to facilitate the transition from in-hospital to outpatient care. […] However, assessment of patient risk is still warranted to identify candidates who can safely receive outpatient treatment, and patient monitoring is essential to ensure adherence to the specified dosing regimen.’

Reference

1. van Bellen B, Bamber L, Correa de Carvalho F, et al. Reduction in the length of stay with rivaroxaban as a single-drug regimen for the treatment of deep vein thrombosis and pulmonary embolism. Curr Med Res Opin 2014; 30(5):829-837. [http://dx.doi.org/10.1185/03007995.2013.879439]

For full prescribing information, refer to the package insert approved by the Medicines Regulatory Authority (MCC).

PHARMACOLOGICAL CLASSIFICATION: A.8.2 Anticoagulants.

S4 XARELTO® 10. Reg. No.: 42/8.2/1046. Each film-coated tablet contains rivaroxaban 10 mg.

INDICATION: Prevention of VTE in patients undergoing major orthopaedic surgery of the lower limbs.

S4 XARELTO® 15 and XARELTO® 20. Reg. No.: 46/8.2/0111 and 46/8.2/0112. Each film-coated tablet contains rivaroxaban 15 mg or 20 mg, respectively.

INDICATIONS: Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation; Treatment of DVT and for the prevention of recurrent DVT and PE; Treatment of PE and for the prevention of recurrent PE and DVT. Bayer (Pty) Ltd, Co. Reg. No.: 1968/011192/07, 27 Wrench Road, Isando, 1609. Tel: 011 921 5044 Fax: 011 921 5041.

L.ZA.GM.06.2014.1007

© Bayer HealthCare Pharmaceuticals June 2014

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Scholarships for 2016: Calls for SATS scholarships will be announced shortly after the congress: Training fellowships Research grants Travel scholarships Keep an look out on the Website or contact the scholarship comittee: Richard.vanzyl-smit@uct.ac.za

ABSTRACTS

Abstracts of presentations at the congress of the South African Thoracic Society in Johannesburg, 18 - 21 August 2016 The use of propofol for sedation in medical thoracoscopy M Vorster

Stellenbosch University and Tygerberg Hospital, Cape Town, South Africa mvorster@sun.ac.za

Introduction. Propofol has been shown to be safe for sedation during flexible bronchoscopy, but data for its use in medical thoracoscopy are limited.

Objectives. We initiated a multicentre randomised study, to compare both the safety and adequacy of medical thoracoscopy performed with two different conscious sedation regimens (midazolam/fentanyl v. propofol/fentanyl) administered by a non-specialist anaesthetist.

Methods. Either propofol or midazolam was given in boluses.

Fentanyl was used in all. Procedure time, complications and patient discomfort were defined and documented. The adequacy of the sedation according to the endoscopist and recovery time were measured.

Results. We enrolled 38 patients (mean 67.5 (standard deviation (11.9)) years, 23 males), with 18 patients randomised to propofol and 20 to midazolam. We observed no differences in procedure time (37.6 v. 36.2 min, p=0.57), recovery time (20.1 v. 20.8 min, p=0.86), or adequacy of sedation as perceived by the endoscopist (p=0.73).

There were, however, 10 adverse events observed in the propofol group compared with 4 in the midazolam group (p=0.04). Adverse events in the propofol group included desaturation responsive to supplementary oxygen (n=6), desaturation requiring temporary bag valve ventilation (n=1), hypotension requiring intravenous fluid resuscitation (n=2) and the need to abort the procedure (n=1); this compared with the midazolam group which included desaturation responsive to supplementary oxygen (n=3) and hypotension not requiring intervention (n=1).

Conclusion. Propofol is not the drug of choice for sedation during medical thoracoscopy, given the increased risk of complications.

Inhaler technique in an urban pulmonologist population group J Vanderwagen,1 C Smith2

Clifford Smith practice, Johannesburg, South Africa Morningside Clinic, Johannesburg, South Africa csmithtrials@mweb.co.za 1 2

Objective. To prospectively evaluate the use of inhaler therapy, primarily focusing on the origin of the initial inhaler training and the effects of regular monitoring of inhaler use.

Methods. We conducted a prospective study on 200 consecutive adult patients using either an metered-dose inhaler (MDI) or dry-powder inhaler (DPI) in a pulmonology practice, for the treatment of asthma, chronic obstructive pulmonary disease (COPD) or asthma-COPD overlap syndrome (ACOS). The data apply to a single evaluation

episode per patient and no patients were evaluated twice. Each patient was assessed by J Vanderwagen irrespective of their previous teaching.

Results. Overall, 45% of MDI technique was adequate whereas 79% of DPI technique was found to be adequate (p<0.001). When initial MDI teaching was performed by family members, general practitioners, hospital staff, pharmacy staff and self, inadequate technique was found (p<0.05). Similarly, inadequate technique was seen in the DPI group when taught by family members, general practitioners, hospital staff and pharmacy staff (p<0.001). Initial teaching in a specialist or pulmonology practice showed 100% adequacy. A total of 59% of the patients using DPI were using the Accuhaler, and 41% the Turbuhaler; however, the percentage of inadequate inhaler technique in the Accuhaler was 28%, while the percentage of inadequate inhaler use in the Turbuhaler group was lower, at 10% (p<0.001).

Conclusions. Inhaler technique was shown to be suboptimal.

There was no correlation in the duration of inhaler use and technique. Patients initially taught by specialists and pulmonologists showed superior technique. DPI technique was found to be superior to MDI technique. In comparing two DPI devices, it was found that although the Accuhaler was more widely used (68% Accuhaler v.

32% Turbuhaler), Turbuhaler technique was superior to Accuhaler (Turbuhaler 90% adequate and Accuhaler 72% adequate).

The microbiome in children with HIVassociated bronchiectasis: A crosssectional study R Masekela

University of KwaZulu-Natal, Durban, South Africa mphahleler@ukzn.ac.za

Objective. To determine the lung microbial community in HIVassociated bronchiectasis (BX) and its impact on exacerbations.

Methods. We conducted a cross-sectional study of 26 children (68% male; mean age 10.8 years) with BX and a control group of 6 children with cystic fibrosis (CF). A total of 32 samples were collected, with 1 during an exacerbation (n=8 BX and n=3 CF). Sputum samples were processed with 16S rRNA pyrosequencing.

Results. The average (standard deviation) number of operational taxonomic units (OTUs) detected among BX samples was 298 (67), with 434 (90) for CF. The relative abundance of Proteobacteria was higher in BX (72.3%) compared with CF (40.1%). The average relative abundance of Firmicutes was higher with CF (49.0%) v. BX (22.2%).

Higher within-community heterogeneity was associated with CF (H’=5.39 (0.38) and 1 – D=0.99 (0.00)) than with BX (H’=4.45 (0.49) and 1 – D=0.96 (0.04)). The bacterial assemblage of exacerbation samples was not significantly different from non-exacerbation samples for either disease groups (ANOSIM R=0.050, RBX=0.082, RCF=–0.083; p>0.05). In the BX group there was no correlation between FEV1% or FEF25/75% and predominant community (R=0.154, p=0.470 and R=0.178, p=0.403), respectively.

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ABSTRACTS Conclusion. Microbial diversity is lower in BX and level of immunosuppression does not affect this. Exacerbations did not affect community diversity levels.

An analysis of outcomes in children with cystic fibrosis in a tertiary African centre: A retrospective study R Mphahlele, R Masekela, V Naidoo, S Thula University of KwaZulu-Natal, Durban, South Africa mphahleler@ukzn.ac.za

Background. Cystic fibrosis (CF) is a common genetic disorder in whites that has become increasingly prevalent in populations of African descent. The clinical presentation in African children with CF is commonly related to nutritional and growth abnormalities.

Objective. To describe clinical, laboratory and spirometric characteristics of children followed up at the CF Clinic at Inkosi Albert Luthuli Central Hospital, Durban, South Africa.

Methods. A retrospective chart review of clinical, laboratory and spirometric data of patients registered from January 2013 to January 2016 was conducted.

Results. The data were reviewed for 15 patients (mean age 132 months, range 26 - 219 months), with 53% males. A total of 60% of these children were white, and 26.7% were of black African descent.

Collectively, the mean age of diagnosis was 45 months (range 0 - 156), although this was higher in the non-whites (at 104 months, range 48 - 156) v. 1.3 months (range 0 - 3) in whites. The white group had better nutritional status when compared with non-whites, with BMI 17.2 kg/m2 v. 14.5 kg/m2, respectively. Age at diagnosis had a negative correlation with weight-for-age z-score (–0.61, p<0.05) and BMI (–0.54, p<0.05). The mean FEV1% predicted was 70.0 (range 16.1 120.2). FEV1% predicted had a positive correlation with both weight z-score (0.83; p<0.001) and BMI (0.59; p<0.05). Chronic Pseudomonas infection occurred only in two patients, both of whom were above the age of 16 years. On mutational analysis, five of the non-white patients had no mutations identified on the 30 panel mutation used for testing. phelF508.del was the most commonly identified mutation in whites, with four homozygotes and four heterozygotes.

Conclusion. Cystic fibrosis is diagnosed late in non-white children in South Africa, affecting their growth and lung functions. There is a need for a genetic panel that includes mutations specific to children of African descent.

Haemoptysis in patients with HIV and immunocompetent patients with aspergillomas A Peter,1 G Candy2

Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa Department of Clinical Chemistry, University of the Witwatersrand, Johannesburg, South Africa alanpeter@ymail.com 1

2

Objective. To contrast the presentation of HIV-positive and HIVnegative patients presenting with haemoptysis due to aspergillomas.

Methods. A retrospective study was conducted of 89 inpatient medical records of patients presenting with haemoptysis due to aspergillomas,

82 SARJ VOL. 22 NO. 3 2016

referred to the pulmonology unit at Chris Hani Baragwanath Academic Hospital, Soweto, between 2006 and 2012.

Results. Of the 89 patients, 44 (49%) were HIV-positive and 45 were HIV-negative. A total of 9 (20.4%) HIV-positive patients presented with minor haemoptysis (1 - 150 mL/24 h), 25 (57%) with moderate haemoptysis (150 - <500 mL/24 h) and 10 (22.7%) with massive haemoptysis (>500 mL/24 h). In the HIV-negative group, the distribution of severity of haemoptysis was 6 (13.3%) minor, 32 (71.1%) moderate and 7 (15.5%) massive (p=0.37). A total of 5 (11%) of the HIV-negative patients were admitted for repeat haemoptysis, while 6 (13%) of the HIV-positive group presented with repeat haemoptysis. Bronchial artery embolisation (BAE) was performed in patients who presented with massive haemoptysis or in those whose haemoptysis worsened. In the HIV-positive group, 11 (25%) had a BAE and 6 (13.6%) patients had blood transfusions. In the HIVnegative group, 11 (24%) had a BAE and 3 (6.6%) were transfused (p=0.23). In the HIV-positive group, 43/44 patients had a CD4 count measured: the mean CD4 was 291 cells/mm3. The mean CD4 counts in the severity categories were: minor CD4 231 cells/mm3, moderate 294 cells/mm3 and massive 332 cells/mm3 (p=0.55). In the HIVpositive group there were 4 deaths, while there were 3 deaths in the HIV-negative group (p=0.65).

Conclusion. There was no significant difference in HIV-positive v. HIV-negative patients presenting with haemoptysis with aspergillomas.

Spectrum and determinants of lung function in HIV- infected adolescents on antiretroviral therapy in Cape Town, South Africa L Githinji, D Gray, S Hlengwa, H Zar University of Cape Town, South Africa gthlea001@myuct.ac.za

Introduction. Over 90% of HIV-infected children live in sub-Saharan Africa. Although lung disease is very common, there is limited information on the spectrum and determinants of chronic lung disease in HIV-infected adolescents and the impact of antiretroviral therapy (ART).

Objective. To investigate lung function in HIV-infected adolescents on ART in Cape Town, South Africa, in a prospective, longitudinal cohort: the Cape Town Adolescent Antiretroviral Cohort (CTAAC).

Methods. HIV-infected adolescents aged 9 - 14 years with at least 6 months of ART and enrolled in the CTAAC underwent lung function testing. Spirometry, single-breath carbon monoxide diffusion test, forced oscillation technique, nitrogen multiple breath wash-out and 6-minute walk test were done at enrolment. Demographic and clinical parameters were also collected. Appropriate statistical tests were used.

Results. A total of 515 HIV-infected adolescents and 110 HIV-negative controls were enrolled. The mean (SD) age was 12 (1.6) years; 52% were male. HIV infection was significantly associated with lower lung function outcome after adjusting for age, sex and height. HIV infection was associated with a lower carbon monoxide transfer factor (TLCO) compared with HIV uninfected (95% confidence interval (CI) –1.20 –0.01; p=0.0048), lower forced expiratory volume in 1 second (FEV1) (95% CI –0.20 - –0.05, p=0.001), lower functional residual capacity

ABSTRACTS (FRC) (95% CI –0.20 - –0.04, p=0.004) and lower compliance (95% CI –0.011 - –0.005, p<0.001). Pneumonia and previous tuberculosis (TB) were significantly associated with lower FEV1 (n=461, 95% CI –0.18 - 0.04, p=0.001 and n=426, 95% CI –0.13 - –0.004, p=0.037, respectively). ART duration was significantly associated with FEV1 (n=486, 95% CI –0.024 - –0.004, p=0.006).

Conclusion. HIV-infected adolescents on ART have significantly lower lung function than matched HIV-negative adolescents. ART duration and history of past respiratory illnesses were significantly associated with lung function outcomes.

Behcet’s disease: A case of multisystem disease D Parris, R Green

Steve Biko Academic Hospital, Pretoria, South Africa drdeniseparris@gmail.com

Introduction. Behcet’s disease (BD) is a multisystem, multiorgan disease, with complex clinical manifestaions. BD may present with cutaneous, neurological, pulmonary, vascular, gastrointestinal, genitourinary and rheumatological manifestations. The most important feature of BD is a widespread vasculitis that involves both arteries and veins of all sizes.

Case report. A previously well 12-year-old girl presented with a history of right-sided pleuritic chest pain, shortness of breath, coughing, abdominal pain, abdominal distension and anorexia for 2 weeks.

Chest X-ray revealed a massive right-sided pleural effusion. Septic markers were not suggestive of infection. HIV testing was negative, as was testing for tuberculosis and auto-immunity. A pleural biopsy revealed non-caseous granulomata. Computed tomography scan documented multiple thrombi in small, medium and large vessels. The most significant thrombus formation was in the right internal jugular vein and the right subclavian vein. The thrombi extended into the sigmoid and transverse sinuses. Multiple lymph nodes were present in the mediastinum and abdomen. Biopsy results of the lung revealed a marked capillaritis, vasculitis, arteritis, involving vessels of various sizes. Histology was compatible with BD.

Pulmonary hydatid disease at Inkosi Albert Luthuli Central Hospital: A case series M Ndlovu, S Thula, R Mphahlele, R Masekela University of KwaZulu-Natal, Durban, South Africa mphahleler@ukzn.ac.za

Background. Hydatid disease is a parasitic infection caused by a tapeworm of the genus Echinococcus. In humans, Echinococcus granulosus is responsible for causing cystic disease. There has been a rise in the incidence of pulmonary hydatid disease in South African children, and most cases require surgical management, which is usually associated with significant morbidity.

Objective. To report on the different presentations of pulmonary hydatid disease in children referred to Inkosi Albert Luthuli Central Hospital (IALCH).

Methods. A retrospective chart review of clinical, laboratory and radiological data of paediatric patients with pulmonary hydatid cysts

admitted to IALCH between January 2015 and December 2015 was conducted.

Results. A total of 10 patients were reviewed; 80% were males and 20% were females. The mean age at diagnosis of lung disease was 8.0 (range 4.0 - 12.5) years. There was an average (standard deviation) delay of 6.1 (5.5) months between first presentation of lung disease and actual diagnosis of hydatid disease. All the patients were from the Eastern Cape: 70% were from Mthatha, 20% from Tsolo and the remaining 10% from Libode area. A total of 7/10 patients reported exposure to dogs, sheep or cattle. Overall, 70% had positive indirect haemagglutination assay (IHA) and 55% had positive eosinophilia.

There was no correlation between IHA and eosinophilia (p=0.193).

There was correlation between delay in diagnosis and the IHA or eosinophilia results (p=0.58). In terms of anatomical localisation, the number of cysts in the right or left lung was similar, with 40% in the right, 40% in the left and only 20% with bilateral disease. Of the 2 patients who had bilateral disease, 1 had extrapulmonary cysts in the liver and spleen. Overall, 70% required surgical management.

The mean length of intensive care unit stay was 2.6 (range 0 - 6) days.

Conclusion. Hydatid lung disease is still common in the Eastern Cape of South Africa, with the majority of children exposed to known risk factors. Despite this knowledge, there is a significant delay in diagnosis of hydatid pulmonary cysts.

An unusual case of an anterior mediastinal mass in a child with cystic lung disease S Chaya, H Zar, M Zampoli, A Vanker, D Gray, K Pillay

Division of Paediatric Pulmonology, Department of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital, Cape Town; and Medical Research Council Unit on Child & Adolescent Health, University of Cape Town, South Africa shaakira.chaya@gmail.com

Introduction. Langerhans histiocytosis (LCH) is a rare disease that is characterised by monoclonal proliferation of dendritic cells. We describe a rare example of multiorgan (lungs, skin and bone marrow) LCH presenting with an anterior mediastinal mass, cystic lung disease and typical skin features.

Case report. A 7-month-old, HIV-unexposed male of a mixed-race ethnicity, presented with a 6-day history of progressive shortness of breath and increased work of breathing. Examination revealed a hyperpigmented papular vesicular rash with a symmetrical distribution mainly in the trunk, groin, neck, scalp and both the hands and feet. The chest radiograph showed multiple cystic lesions with a possible mediastinal mass that filled the right hemithorax on the frontal projection, while the computed tomography scan demonstrated a heterogeneous enhancing large anterior mediastinal mass. Punch biopsies of skin were in keeping with a diagnosis of Langerhans cell histiocytosis. The bone marrow trephine biopsy was very cellular and demonstrated morphological and immunohistochemical features suggestive of involvement by Langerhans cells/Langerhans cell histiocytosis.

Discussion. The presence of an anterior mediastinal mass with cystic lung disease is rare but highly suggestive of LCH. LCH is part of a spectrum of histiocytic disorders, and is divided into three classes.

It is most common in children between 1 and 4 years of age, with

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ABSTRACTS a peak incidence of about 0.1 - 1 per 100 000 children. Symptoms range from asymptomatic (with infiltrations noted on chest X-ray) to severe symptomatic respiratory disease. These may be nonspecific and include dyspnoea, cough, chest pain, wheezing, fatigue or tachypnoea. Chest pain may be associated with a pneumothorax.

Treatment protocols are based on whether there is single or multiorgan involvement. Children who present at a younger age with multisystemic disease have a high mortality.

Effects of early-life pneumonia on lung function in the first 2 years of life in black and mixed-race African infants L McMillan

University of Cape Town, South Africa laurenmcmillan.za@gmail.com

Background. Infection in the first year of life in African infants has been shown to result in lower lung function at 1 year. It is unknown if this effect persists.

Methods. Infants enrolled in the Drakenstein Child Health birth cohort had lung function tested at ages 6 weeks, 1 and 2 years.

Results. A total of 182 children were tested both at 6 weeks, 1 year and 2 years of age. Lung function was tracked from 6 weeks through to 1 and 2 years. Pneumonia during the first 2 years of life was independently associated with decreased tidal volume (average 2.62 mL lower, 95% confidence interval (CI) –4.15 - 1.09) and increased respiratory rate (average 5% higher, 95% CI 1.02 - 1.08). This effect on respiratory rate was stronger if the pneumonia incidence occurred within the first year of life (average 5% higher, 95% CI 1.02 - 1.09), but tidal volume was more affected if pneumonia occurred in the second year of life (average 3.57 mL lower, 95% CI –6.6 - –0.54). The effect on tidal volume at 2 years of age was stronger if the infant required hospitalisation (average 2.17 mL reduction, 95% CI –4.22 - –0.11).

Conclusions. Early-life pneumonia results in lower lung function at 2 years of age, an effect independent of baseline lung function.

Preventing early-life pneumonia will help optimise early lung growth and function as well as strengthening respiratory health in later childhood.

Overnight oximetry as a screening tool for moderate-severe obstructive sleep apnoea in children in a resourceconstrained setting N Abousetta, A Vanker, M Zampoli University of Cape Town, South Africa nesrinabuosetta@yahoo.com

Introduction. Obstructive sleep apnoea (OSA) is common in paediatrics yet often overlooked, as symptom-based screening is unreliable. Polysomnography is regarded as the gold standard for OSA diagnosis, but its utility in resource-constrained settings is limited.

Overnight oximetry and the McGill score is a validated screening tool for moderate-to-severe OSA. Objective. To describe the spectrum of OSA severity in children referred for overnight oximetry at RCWMCH, and report the impact of overnight oximetry on management of children with suspected OSA.

84 SARJ VOL. 22 NO. 3 2016

Methods. A retrospective descriptive study was conducted of patients screened for OSA by overnight oximetry at RCWMCH from December 2012 to December 2014. Clinical data were retrieved from the oximetry database and medical records. Recordings of 6 hours or more were considered adequate and included in the study.

OSA severity was determined using the McGill score. Details on management and outcome were documented.

Results. A total of 153 patients were studied; 99 (65%) were males and median age was 31.6 months (interquartile range (IQR) 15.8 - 61.1). A total of 123 (80%) patients presented with history of snoring, 85 (56%) reported apnoea and 19 (12%) a history of frequent awakenings. A further 107 (70%) patients reported hyperactivity during the day. Risk factors for OSA included obesity (10%), facial abnormalities (17%), cerebral palsy (7%), Down syndrome (9%), prematurity (10%), and neuromuscular disorders 23 (15%). McGill’s score classified patients as no/mild OSA (n=65 (42%)), moderate OSA (n=25 (16%)), severe OSA (n=25 (16%)) and very severe OSA (n=38 (25%)). Eighty-five (56%) patients were referred for surgery and 35 (23%) had urgent surgery. The median time to surgery was 15 days (IQR 5 - 110).

Conclusion. Overnight oximetry is a simple and useful tool to assess severity of OSA and prioritise appropriate management in the setting of the South African public health system.

Evaluation of the knowledge and correct use of metered-dose inhalers by healthcare professionals and medical students in Gauteng H Maepa, C Menezes, M Wong

University of the Witwatersrand, Johannesburg, South Africa hlanjwa.maepa@gmail.com

Introduction. Incorrect use of metered-dose inhalers (MDIs) accounts significantly for poor disease control in asthma and chronic obstructive pulmonary disease (COPD). Knowledge and application of the correct inhaler technique by both patients and their healthcare providers are essential to minimise morbidity and mortality.

Methods. Data for this study were collected prospectively by administering a questionnaire to doctors, nurses and finalyear medical students at Helen Joseph Hospital and Chris Hani Baragwanath Academic Hospital in the Departments of Internal Medicine, Emergency Medicine and Pulmonology. The questionnaire gauged their perceptions and level of knowledge of MDI technique. In addition, study participants were requested to demonstrate their inhaler technique using a placebo inhaler device.

Use of the MDI was evaluated using a scoring system, whereby one point was allocated to each of the six sequential steps mandatory for correct technique.

Results. The total sample of 195 participants comprised 130 females (67%) and 65 males. Of these, 133 (68%) were qualified medical staff, and 62 were final-year medical students. Overall, only 16% demonstrated adequate MDI technique. There was no difference between medical students and qualified medical staff regarding their knowledge of MDI technique (p=0.5243). Fifty-seven per cent of participants did not demonstrate MDI technique to patients, or check their inhaler technique in clinical practice. There was no relationship between knowledge of correct MDI technique and the healthcare

ABSTRACTS providers’ practice of demonstrating (p=0.0728) and/or observing patients’ inhaler technique (p=0.1564).

Conclusions. Healthcare professionals and final-year medical students have poor knowledge of inhaler technique and are ill-prepared to teach patients. Also of concern is that the majority do not routinely demonstrate or observe patients’ inhaler technique.

Eosinophilic pneumonia: A case report N P K Banda,1 N Vorajee,2 M Wong1

hris Hani Baragwanath Academic Hospital and University of the C Witwatersrand, Johannesburg, South Africa 2 Anatomical Pathology, National Institute for Occupational Health, National Health Laboratory Services, Johannesburg, South Africa npkbanda2000@yahoo.com 1

Case report. A 20-year-old man was referred to Chris Hani Baragwanath Academic Hospital in March 2015 with a 2-week history of cough, fever, dyspnoea, weight loss and night sweats. He denied any history of chest pain, wheezing, asthma, skin rash, joint pain, sinusitis, allergies, drug ingestion, travel history or residence in a rural area. He admitted to a brief period of tobacco smoking. Physical examination was unremarkable, except for severe respiratory failure. The chest X-ray and high-resolution computed tomography scan showed diffuse ground-glass opacification. The initial clinical suspicion was that of pneumocystis pneumonia. However, HIV serology and PCR were negative. Sputum analysis was unhelpful. The full blood count, urea and electrolytes, 1,3β-D-glucan, ANCA, ANA, ACE and stool examination were normal. Serum total IgE was raised (265 kU/L). Abdominal ultrasound examination was normal. During his hospital admission he developed a spontaneous left pneumothorax, which required intercostal drainage. An open lung biopsy showed features of eosinophilic pneumonia. High-dose corticosteroids failed to produce any clinical improvement; however, there was a definite clinical response to 2 cycles of intravenous cyclophosphamide. He was then lost to follow-up, but traced in May 2016. He is significantly better, and able to perform activities of daily living while using domiciliary oxygen intermittently.

Discussion. This is an unusual case of idiopathic eosinophilic pneumonia as there was no significant response to corticosteroids.

As a last resort, cyclophosphamide was administered, resulting in definite clinical improvement. We were unable to find any similar case in the literature. Follow-up of this patient will be continued with great interest.

The prevalence and management of rifampicin-resistant tuberculosis at Chris Hani Baragwanath Academic Hospital R Narsing

Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa raj4065@yahoo.com

Introduction. Pulmonary tuberculosis (TB) causes a substantial burden of disease in sub-Saharan Africa and worldwide. In 2014 the WHO reported approximately nine million new cases of TB in 2013 globally. Of the new TB cases reported, there were approximately 480 000 cases of multidrug-resistant (MDR)-TB. Drug resistance remains a significant hindering factor in the management of TB

worldwide. The implications are numerous, comprising poorer patient outcomes, cost implications, disease complications and mortality.

Objective. To describe the prevalence and management of rifampicin resistance diagnosed at Chris Hani Baragwanath Academic Hospital during a 2-year period, using variables including the presence of HIV co-infection, previous TB history, clinically relevant laboratory tests, drug therapy used and mortality rate.

Methods. The study design is a retrospective cross-sectional descriptive study assessing patients with rifampicin-resistant tuberculosis confirmed on GeneXpert test and whether adequate treatment was instituted compared with the recommended national guidelines. A total of 70 participants’ inpatient files were reviewed and the relevant data were extracted. Descriptive statistics were used.

Results. The prevalence of rifampicin-resistant TB during the 2-year period was 9.7%. The prevalence rates were 3.05%, 2.63% and 4.02% for rifampicin-monoresistant (RMR)-, MDR- and ‘not classified’ TB, respectively. The patients were on average 36 years old. Overall, 83% of participants were co-infected with HIV and had an average CD4 count of 91 cells/mm3, and 59% of patients had a history of previous TB, of which 90.2% had completed their treatment regimens. The average time take to obtain the GeneXpert result was 3.36 days post admission.

The response to the submission of confirmatory tests was poor, with only 60% of line probe assay and 25.7% of drug susceptibility testing tests being submitted. Only 59% of patients were on appropriate drug therapy following their diagnosis, and there was an 18.6% mortality rate.

Conclusion. There still remains a significant burden of disease with drug-resistant TB, which is compounded by the HIV epidemic.

National departmental guidelines have been designed to aid in controlling the problem, but this study demonstrates that there is poor implementation and adherence to the guidelines. Educating healthcare providers with current guidelines and management tools (confirmatory tests, drug therapy and referral systems) is essential to help minimise the burden of disease.

Factors affecting compliance and control of asthma at the Division of Pulmonology, Chris Hani Baragwanath Academic Hospital: A prospective study A van Blydenstein, M Wong

Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa savanblydenstein@gmail.com

Introduction. Less than half of asthmatic patients at the Respiratory Outpatient Department (ROPD), Chris Hani Baragwanath Academic Hospital (CHBAH), are well controlled, despite very few admissions or exacerbations in the previous year.

Objectives. To describe the cohort of patients, in terms of personal health history, comorbidities and indicators of asthma severity and control, and to describe the factors influencing control of asthma, hoping to identify factors that could be addressed to improve control in the defined cohort.

Methods. This study was a prospective analysis of asthmatic patients attending the ROPD at CHBAH, who presented for scheduled outpatient visits. Data collected included demographics, spirometry, symptoms, treatment, severity and control of asthma.

SARJ VOL. 22 NO. 3 2016

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ABSTRACTS Results. Of 137 patient files reviewed, 89% were female. The mean (SD) age was 51.49 (0.14) years. Only 32.12% of patients were well controlled.

Common triggers for asthma included passive smoking (34.3%), house dust mites (32.8%) and other (36.5%). While 86.9% were assessed as being adherent to treatment, 44.5% of the cohort did not receive all medications prescribed by the doctor. Mistakes in inhaler technique were made in 46% of the patients, with the most common (16.1%) being not breathing in slowly and deeply after dispensing medication from the canister. Steps omitted in inhaler technique were associated with intensive care unit admissions (p=0.022).

Conclusion. In this population of mostly middle-aged female asthmatics, less than half the patients were well controlled, with two contributing factors being poor inhaler technique and patients not receiving all medications prescribed. These factors are avoidable, and every effort should be made to rectify them to improve control in this population.

It will be prudent to remember that it is as a consequence of the principles of open cardiothoracic surgery that the foundation for the meteoric rise in video-assisted thoracoscopic surgery (VATS) has been established. It is imperative that every surgeon practising VATS has the ability to safely convert to an open procedure. The principles of open surgery start with meticulous patient selection, as this is fundamental for good outcomes. Surgical selection considers the indication for surgery, cardiorespiratory function and radiological investigations. Intraoperative principles include: aspects of anaesthesia (type of anaesthesia, analgesia and lung isolation); and the type of surgical incision and surgical dissection (lung, vascular and mediastinal lymph nodes). In addition, principles for surgery for bronchial carcinoma and inflammatory lung disease – most notably that of lung resection for cavitatory disease both for active and sequelar TB – should be noted. Postoperative pain control is key to rehabilitation and resumption of normal function.

First rib resection by VATS

Massive haemoptysis

ivan@schewitz.com

mdalexg@hotmail.com

First rib resection for outlet obstruction is an operation that should only be performed when medical therapy fails. The supraclavicular and transaxillary approaches are currently the most commonly utilised approaches. Technically, both approaches are difficult, with potential brachial plexus and vascular injuries. video-assisted thoracoscopic surgery techniques have been proposed that give superior visualisation and exposure, and simplify the risk attached to the operation. I will report on my first two cases with a review of the literature, describing the technique and the potential complications.

Current consensus advocates bronchial artery embolisation (BAE) as the initial form of therapy for massive haemoptysis with radiologically localised disease, even if emergency lung resection is deemed suitable. Massive haemoptysis has been associated with an extremely high mortality. Death is usually due to asphyxiation rather than exsanguination. Conservative management of massive haemoptysis has a mortality of 50 - 100%. Mortality rates for surgery for massive haemoptysis vary between 7 and 18% .This increases up to 40% when emergency surgery is undertaken in the presence of active haemoptysis. Mortality is not affected by the aetiology, tuberculosis activity, lack of therapy, age or sex of the patient. The most significant factor influencing outcomes is soiling or aspiration involving the contralateral normal lung. BAE may be used either as a temporising measure or definitive therapy. When used as a temporising measure, it is thought to allow sufficient time for adequate resuscitation of the patient and clearing of blood from the bronchial tree prior to lung resection. However, up to 20 - 45% of patients have recurrent haemoptysis within the first month following BAE.

I Schewitz

Aetiology of pleural effusion – an African perspective K M Hossain, R F Chauke ivan@schewitz.com

Objective. To evaluate the common causes of pleural effusion in an African context.

Methods. We conducted a retrospective study at Dr George Mukhari Hospital (a tertiary teaching hospital), Pretoria, South Africa, investigating the aetiology of pleural effusion among patients admitted to the Cardiothoracic Unit during a period of 2 years (2010 - 2012).

Results. Of the 237 patients admitted, records of 120 patients were available for study, of which 50 were incomplete and excluded from analysis. We analysed 70 patients’ data and found that in 72%, pleural effusion was due to tuberculosis (TB), in 17% malignant causes and in the rest nonspecific pleuritic. Of the malignant aetiologies, a high percentage (40%) was due to mesothelioma.

Conclusion. TB was found to be the most common cause of pleural effusion in our patients, in line with studies published from other African countries but different from Western countries. We also found a high percentage of malignant pleural effusions due to mesothelioma.

Principles of open surgery G Alexander

mdalexg@hotmail.com

86 SARJ VOL. 22 NO. 3 2016

G Alexander

Avoiding barotrauma in the operating theatre: Non-intubated thoracotomy I Schewitz

ivan@schewitz.com

Barotrauma is an avoidable but poorly recognised complication of intraoperative ventilation. I will be presenting my early experience of my cases, with the potential complications. In thoracic surgery, the gold standard is use of the double-lumen endotracheal tube. This is often complicated by incomplete collapse of the operated lung and incorrect positioning, and often takes a considerable amount of time to position, even with the use of an intubating bronchoscope.

With adequate modern anaesthesia it is possible to perform complex procedures such as a video-assisted lobectomy without the need of an endotracheal tube. This avoids the trauma of intubation, the

ABSTRACTS complications of barotrauma and often gives better collapse of the lung than with the standard double-lumen approach.

Surgical management of mediastinal compression caused by massive retrosternal goiter with cardiopulmonary bypass: A case report R Fourie, R J Correia, J J Jordaan, M Myburg, F E Smit rentiaf@yahoo.co.za

Introduction. Most goiters grow slowly and are asymptomatic.

Compressive symptoms appear late but can be life-threatening, especially during surgery. Complete airway obstruction and cardiovascular collapse can occur during the induction of general anaesthesia, as intubation of the tortuous, compressed trachea is difficult. Also, positive pressure ventilation increases pre-existing superior vena cava obstruction, resulting in cardiovascular collapse.

Surgery of compressive thoracic masses on the mediastinum is challenging. Cardiopulmonary bypass (CPB) facilitating the excision of tumours is controversial.

Case report. A 56-year-old obese male presented with intermitted haemoptysis. He had dyspnoea, hoarseness and dysphagia. He was known to have hyperthyroidism and had had a previous partial thyroidectomy. Comorbid diseases included hypertension and obstructive sleep apnoea. Imaging revealed a superior mediastinal mass displacing the trachea, and mediastinal vasculature and severe tracheal narrowing. Histological diagnosis after computed tomography-guided biopsy was that of normal thyroid tissue. In theater, awake-intubation with flexible bronchoscope was attempted, but it failed owing to the narrow, displaced trachea. Using a femoral block, the femoral vessels were cannulated while the patient was sedated in a semi-supine position. Another attempt at intubation after initiation of CPB failed. Retrosternal goiter was removed via sternotomy and the patient was intubated.

Discussion. Retrosternal goiter should be treated in both symptomatic and asymptomatic patients to prevent rapid deterioration and airway obstruction. Medical treatment is unsuccessful for goiter post thyroidectomy. Surgery is high risk due to decompensation at induction and difficult airway management. CPB is used in thoracic surgery for tracheal resection and reconstruction and if masses are adherent to or infiltrating the great vessels. The role of CPB in critical lower airway obstruction is controversial. CPB is the ultimate solution to the â&#x20AC;&#x2DC;impossible airwayâ&#x20AC;&#x2122;.

Peptide receptor radionuclide therapy as a novel treatment for malignant mesothelioma: Case reports R Fourie, M Vorster, M Sathekge, F E Smit rentiaf@yahoo.co.za

Introduction. Malignant pleural mesothelioma (MPM) is a fatal disease. The prognosis is modestly influenced by conventional oncological treatments. MPM is a radiosensitive tumour, but external beam radiation therapy is not used owing to the problem of irradiating normal lung tissue. Targeted radionuclide therapy delivers the maximum possible radiation dose to the tumour while sparing

healthy tissues. Theranostics allows for the diagnosis and therapy of malignancies by the substitution of a radioisotope used for imaging (Gallium-68) with one used for therapy (Lutetium-177). Uptake of a diagnostic tracer will determine whether a patient will benefit from peptide receptor radionuclide therapy (PRRT).

Case report. Patient X (53-year-old female) and patient Y (55-yearold male) both presented with dyspnoea from pleural effusion.

Both patients had a known asbestos exposure history. Histological diagnosis of sarcomatoid mesothelioma was made in patient X, and patient Y was diagnosed with epitheloid mesothelioma. Both patients underwent a Ga-68-NOTA-ANG positron emission tomographycomputed tomography study, which demonstrated increased tracer accumulation in the pleura. The intensity of the uptake in the pleura exceeds that of the liver, which predicts a favourable response to therapy, when substituting Gallium-68 with a therapeutic isotope such as Lutetium-177.

Discussion. Surgery, chemotherapy and radiotherapy fail to improve the life expectancy of patients with MPM. The appeal of PRRT lies in the reduced toxicity owing to the affinity for specific receptors or certain tissues, which results in the maximisation of the effect where it is needed. Receptor-mediated endocytosis of radiolabelled peptides is important, as radionuclides emitting therapeutic particles have very short path lengths, and are only effective over a short distance from their target DNA. These cases indicate that PRRT might be a treatment option in future in patients with MPM.

Mediastinal tumours M Coetzee

marichelleb@gmail.com

Mediastinal tumours represent a wide range of disease states.

The location and mass composition have important implications for diagnosing mediastinal masses. Common causes of anterior mediastinal masses include the following: thymoma, thyroid disease, teratoma and lymphoma. Masses of the middle mediastinum are typical congenital cysts, while those from the posterior mediastinum are often neurogenic in nature. Clinical presentation can range from being asymptomatic to causing pain, cough and dyspnoea. The likelihood of malignancy is influenced primarily by mass location, patient age and the absence or presence of symptoms. Chest radiograph and computed tomography scanning as well as biochemical studies can identify and characterise mediastinal masses, but a tissue diagnosis is almost always required to complete the diagnosis.

Resection of tumours of the chest wall: Durban experience R Madansein

Department of Cardiothoracic Surgery, University of KwaZulu-Natal, Inkosi Albert Luthuli Central and King DinuZulu Hospitals, Durban, South Africa rajhmunmad@ialch.co.za

A talk on tumours of the chest wall would be incomplete without a tribute to Prof. B le Roux, the founder of our unit in Durban, and his pioneering work on the use of acrylic sandwich for chest wall reconstruction. Our work encompasses primary chest wall tumours, secondary chest wall involvement, usually due to underlying

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87

ABSTRACTS pulmonary pathology, and pseudo-tumours of the chest wall, of which tuberculosis is the most common. While most diseases seen during Prof. Le Roux’s time have not changed, the surgical techniques to reconstruct the chest wall, availability of newer prosthetic materials and use of myocutaneous flaps have allowed us to resect larger sections of chest wall and safely get adequate cover. We will discuss chest wall resections and the 10 years’ experience with chest wall resections in our unit.

Comparison of outcomes between primary and secondary lung decortication in patients with empyema thoracis, admitted to Dr George Mukhari Academic Hospital J M Sekgololo,1 R F Chauke2

epartment of Cardiothoracic Surgery, Sefako Makgatho Health Sciences D University, Dr George Mukhari Academic Hospital, Pretoria, South Africa 2 Department of Cardiothoracic Surgery, Sefako Makgatho Health Sciences University, and Dr George Mukhari Academic Hospital, Pretoria, South Africa motshedi.sekgololo@gmail.com 1

Background. We examined all the patients with empyema thoracis admitted in our unit to compare the outcomes between primary and secondary lung decortication. The primary decortication was defined as a primary procedure, without prior attempt of pleural space evacuation with either chest tube or previous decortication. Secondary decortication was defined as decortication following failed lung expansion after initial pleural space drainage or after failed primary decortication. Anecdotally, secondary decortication is associated with increased complications including prolonged length of hospital stay due to respiratory complications or wound complications, compared with primary decortication. From a literature search, there is currently no study that directly compares outcomes of these two procedures, hence it was interesting study on which to embark.

Methods. We included all patients who presented to our unit with empyema thoracis from 1 January 2011 to 31 December 2014 in a retrospective, quantitative, descriptive study. In this study, 32 patients were analysed with a male:female ratio of 1:1. Thirteen patients underwent primary decortication and 19 underwent secondary

88 SARJ VOL. 22 NO. 3 2016

decortication. A combination of both sequential and random sampling was used. We compared the postoperative outcomes of the two groups.

The Fisher exact test was used to compare percentages, including the rates of complications between primary and secondary decortication.

Mean values were compared using the t-test. The frequency of other variables was also determined.

Results. There was significant statistical difference in length of hospital stay (intensive care unit (ICU) and ward) and complications between patients who underwent primary v. secondary decortication.

The primary and secondary decortication mean (standard deviation) values for days spent in ICU were 2.21 (0.43) days and 2.84 (1.07) days, respectively (p<0.029). The mean values for days in the ward between two groups were 2.79 (1.31) days and 4.05 (1.78) days, respectively (p<0.032). There was no statistical difference in terms of age, CD4 (only for HIV patients) and adenosine aminase (ADA) between patients who underwent primary against secondary decortication.

The primary and secondary decortication mean values for age were 40.0 (11.66) years and 33.4 (10.34) years (p<0.094). The mean values for CD4 count (HIV-positive patients) between the two groups were 312.8 (227.13) cells/mm3 and 244.20 (168.39) cells/mm3 (p<0.499). The mean values of ADA between the two groups were 57.6 (26.66) IU/L and 76.21 (42.22) IU/L (p<0.200). The frequency of complications were: wounds sepsis for seconday decortication (4 (21.05%)) – for primary decortication there was none; 1 (5.26%) recurrent empyema following secondary decortication, with none after primary; and 1 (5.26%) chest wall abscess following secondary decortication, with none for primary.

Conclusion. The patients who underwent secondary lung decortication had a longer hospital stay (both in ICU and ward) than those who underwent primary decortication. There were increased frequencies of complications for patients who underwent secondary decortication v. primary decortication. There was no statistical difference between demography (age), CD4 count (HIV patients) and ADA. The frequency of complications (recurrent empyema, chest wall abscess and wound sepsis) was higher for secondary decortication. Note: The results obtained are preliminary and must not be considered as conclusive. Further data are still being collected to complete this study.

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Indication (2)

VORTEX® with a mouthpiece

VORTEX® with mouthpiece and baby mask ‘Ladybug’

To be used in conjunction with medication sprays or "metered dose inhalers" in the treatment of respiratory tract diseases.

VORTEX® with mouthpiece and child mask ‘Frog’

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SEP (Excl VAT)

SEP (Incl VAT)

216379001

R 267,27

R 304,69

216375001

R 291,66

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S3 FLIXOTIDE® 50/125/250 INHALER CFC-FREE. Reg No.: 35/21.5.1/0377-0082/3. Delivers 50/125/250 µg of fluticasone propionate per actuation. INDICATIONS: Prophylactic management of atopic asthma in adults and children of 6 years and older. CONTRA-INDICATIONS: History of allergy to any of its components.

PREGNANCY AND LACTATION: Safety not established. DOSAGE AND DIRECTIONS FOR USE: For inhalation use only. Should be taken regularly even when asymptomatic. The onset of therapeutic effect is 4 to 7 days. Should not be used for relief in acute attacks but for routine long term management. Patients will require a fast- and short-acting inhaled bronchodilator to relieve acute symptoms. If patients find that relief with short-acting bronchodilator treatment becomes less effective or they need more inhalations than usual, medical attention must be sought. Adults and children over 16 years of age: 100-1000 µg twice daily.

Starting dose should be appropriate for severity of the disease. Dose may be adjusted until control is achieved or reduced to the minimum effective dose, according to the individual response. Children over 6 years of age: 50-100 µg twice daily. The dose may be adjusted until control is achieved and should be reduced to the minimum effective dose according to the individual response. Special patient groups: No dose adjustment in elderly patients. For the transfer of patients being treated with oral corticosteroids: Patients treated with systemic steroids for long periods of time or at a high dose may have adrenocortical suppression and adrenocortical function should be monitored regularly and their dose of systemic steroid reduced cautiously. After approximately a week, gradual withdrawal of the systemic steroid may be commenced. Decrements in dosages should be appropriate to the level of maintenance systemic steroid, and introduced at not less than weekly intervals. In some patients on oral corticosteroids the dose reduction or replacement with inhaled corticosteroids may not be possible. Some patients feel unwell in a non-specific way during the withdrawal phase despite maintenance or even improvement of the respiratory function. They should be encouraged to persevere with inhaled fluticasone propionate and to continue withdrawal of systemic steroid, unless there are objective signs of adrenal insufficiency. SIDE EFFECTS AND SPECIAL PRECAUTIONS: Treatment should not be stopped abruptly as adrenal insufficiency may be precipitated. Candidiasis of the mouth and throat (thrush) may occur. May be helpful to rinse out mouth with water after use. Symptomatic candidiasis can be treated with topical anti-fungal therapy whilst continuing treatment. Hoarsenes. Paradoxical bronchospasm with an immediate increase in wheezing. Treat immediately with a fast-acting inhaled bronchodilator.

Treatment should be discontinued immediately, the patient assessed, and if necessary alternative therapy instituted. Cutaneous hypersensitivity. Systemic corticosteroid effects may occur. Patients transferred from other inhaled steroids or oral steroids remain at risk of impaired adrenal reserve for a considerable time after transferring to inhaled fluticasone propionate. Increasing use to control symptoms indicates deterioration of asthma control and patient should be reassessed. Sudden and progressive deterioration in asthma control is potentially life-threatening and may have several causes. Consideration should be given to increasing corticosteroid dosage if not caused by otherwise treatable causes of deterioration. Severe asthma requires regular medical assessment as death may occur. Sudden worsening of symptoms may require increased corticosteroid dosage which should be administered under urgent medical supervision. Patients weaned off oral steroids whose adrenocortical function is still impaired should carry a steroid warning card indicating that they may need supplementary systemic steroid during periods of stress, e.g. worsening asthma attacks, chest infections, major intercurrent illness, surgery, trauma, etc. Inhaled therapy may unmask underlying eosinophilic conditions (e.g. Churg Strauss syndrome). These cases have usually been associated with reduction or withdrawal of oral corticosteroid therapy. Similarly replacement of systemic steroid treatment with inhaled therapy may unmask allergies such as allergic rhinitis or eczema previously controlled by the systemic drug. These allergies should be symptomatically treated with antihistamine and/or topical preparations, including topical steroids. Patients in a medical or surgical emergency, who require high doses of inhaled steroids and/or intermittent treatment with oral steroids, are at risk of impaired adrenal reserve. The extent of the adrenal impairment may require specialist advice before elective procedures. The possibility of residual impaired adrenal response and elective situations likely to produce stress and appropriate corticosteroid treatment must be considered. Lack of response or severe exacerbations of asthma should be treated by increasing the dose of inhaled fluticasone propionate or by giving a systemic steroid and/or an antibiotic if there is an infection. Special care is necessary in patients with active or quiescent pulmonary tuberculosis. Patients on corticosteroid therapy may have adrenocortical suppression. MANAGEMENT OF OVERDOSAGE: Monitoring of adrenal reserve may be indicated. Treatment with inhaled fluticasone propionate should be continued at a dose sufficient to control asthma. APPLICANT: GlaxoSmithKline South Africa (Pty) Ltd; (Co. reg. no.1948/030135/07). 39 Hawkins Avenue, Epping Industria 1, Cape Town, 7460.

Reference: 1. Laube BL, Janssens HM, de Jongh FHC, et al. What the pulmonary specialist should know about the new inhalation therapies. Eur Respir J 2011;37:1308-1331. 2. VORTEX® package insert.

For full prescribing information, please refer to the package inserts approved by the Medicines Regulatory Authority.

All adverse events should be reported by calling the Aspen Medical Hotline number or directly to GlaxoSmithKline on +27 11 745 6000.

ZAF/FP/0004/15a A19615 04/16

The South African Respiratory Journal acknowledges with thanks the invaluable sponsorship of the following companies: Aspen GSK Division Bayer Healthcare