Application of 18F-FDG PET-CT in the management of pulmonary nodule and mass - a pictorial review.

BACKGROUND: Lung cancer is one of the leading causes of cancer-related mortality worldwide. Pulmonary nodules are commonly encountered in clinical practice because of the recent implementation of low-dose CT lung screening programme, incidental finding on cardiac CT or CT for nonthoracic related disease. 18F-FDG PET-CT plays an important role in the management of pulmonary nodules. METHODS: In this pictorial review, we present six different scenarios of using 18F-FDG PET-CT in the management of suspicious pulmonary nodule or mass. The advantages and limitations of 18F-FDG PET-CT and Herder model are discussed. RESULTS: 18F-FDG PET-CT with risk assessment using Herder model provides added value in characterising indeterminate pulmonary nodules. Besides, 18F-FDG PET-CT is valuable to guide the site of biopsy and provide accurate staging of lung cancer. CONCLUSION: To further improve its diagnostic accuracy, careful history taking, and CT morphological evaluation should be taken into consideration when interpreting 18FFDG PET-CT findings in patients with these nodules.

Anaplastic lymphoma kinase (ALK) mutations in patients with adenocarcinoma of the lung.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death. Approximately 2-16% of NSCLC patients with wild-type epidermal growth factor receptor (EGFR) harbour anaplastic lymphoma kinase (ALK) mutations. Both EGFR and ALK mutations occur most commonly in Asian patients with NSCLC. As targeted therapy is available for NSCLC patients with these mutations, it is important to establish reliable assays and testing strategies to identify those most likely to benefit from this therapy. MATERIALS AND METHODS: Patients diagnosed with adenocarcinoma of the lung between 2010 and 2014 were tested for EGFR mutations. Of these, 92 cases were identified as EGFR wild type and suitable candidates for ALK testing utilising immunohistochemistry and the rabbit monoclonal antibody D5F3. The reliability of the IHC was confirmed by validating the results against those achieved by fluorescence in situ hybridisation (FISH) to detect ALK gene rearrangements. RESULTS: Twelve (13%) cases were positive for ALK expression using immunohistochemistry. Of the 18 evaluable cases tested by FISH, there was 100% agreement with respect to ALK rearrangement/ALK expression between the assays, with 11 cases ALK negative and 7 cases ALK positive by both assays. ALK tumour expression was significantly more common in female compared to male patients (29.6% vs. 6.2%, P < 0.001), detected exclusively in patients that had never smoked (P < 0.001) and more frequently in metastases (22.7%) than in primary tumours (10%) (P = 0.047). CONCLUSIONS: Detection of ALK expression by IHC is reliable and the most practical way of identifying NSCLC patients likely to benefit from crizotinib treatment.

First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study.

BACKGROUND: The phase III, randomized, open-label ENSURE study (NCT01342965) evaluated first-line erlotinib versus gemcitabine/cisplatin (GP) in patients from China, Malaysia and the Philippines with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients ≥18 years old with histologically/cytologically confirmed stage IIIB/IV EGFR mutation-positive NSCLC and Eastern Cooperative Oncology Group performance status 0-2 were randomized 1:1 to receive erlotinib (oral; 150 mg once daily until progression/unacceptable toxicity) or GP [G 1250 mg/m(2) i.v. days 1 and 8 (3-weekly cycle); P 75 mg/m(2) i.v. day 1, (3-weekly cycle) for up to four cycles]. Primary end point: investigator-assessed progression-free survival (PFS). Other end points include objective response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 217 patients were randomized: 110 to erlotinib and 107 to GP. Investigator-assessed median PFS was 11.0 months versus 5.5 months, erlotinib versus GP, respectively [hazard ratio (HR), 0.34, 95% confidence interval (CI) 0.22-0.51; log-rank P < 0.0001]. Independent Review Committee-assessed median PFS was consistent (HR, 0.42). Median OS was 26.3 versus 25.5 months, erlotinib versus GP, respectively (HR, 0.91, 95% CI 0.63-1.31; log-rank P = .607). ORR was 62.7% for erlotinib and 33.6% for GP. Treatment-related serious adverse events (AEs) occurred in 2.7% versus 10.6% of erlotinib and GP patients, respectively. The most common grade ≥3 AEs were rash (6.4%) with erlotinib, and neutropenia (25.0%), leukopenia (14.4%), and anemia (12.5%) with GP. CONCLUSION: These analyses demonstrate that first-line erlotinib provides a statistically significant improvement in PFS versus GP in Asian patients with EGFR mutation-positive NSCLC (NCT01342965).

Patients' beliefs and behaviors related to treatment adherence in patients with asthma requiring maintenance treatment in Asia.

OBJECTIVES: To identify patients' beliefs or behaviors related to treatment adherence and to assess association between asthma control and adherence in Asian patients with asthma. METHODS: We conducted a cross-sectional observational study of adult patients with asthma from specialist clinics in six Asian countries. Patients who were deemed by their treating physicians to require a maintenance treatment with an inhaler for at least 1 year were recruited. Patients completed a 12-item questionnaire related to health beliefs and behaviors, the 8-item Morisky Medication Adherence Scale (MMAS-8), the Asthma Control Test (ACT™), and the Standardized Asthma Quality of Life Questionnaire (AQLQ-S). RESULTS: Of the 1054 patients recruited, 99% were current users of inhaled corticosteroids. The mean ACT score was 20.0 ± 4.5 and 64% had well-controlled asthma. The mean MMAS-8 score was 5.5 ± 2.0 and 53% were adherent. Adherence was significantly associated with patients' understanding of the disease and inhaler techniques, and with patients' acceptance of inhaler medicines in terms of benefits, safety, convenience, and cost (p < 0.01 for all). In multivariate analysis, three questions related to patients' acceptance of inhaler medicines remained significantly associated with poor adherence, after adjusting for potential confounders: "I am not sure inhaler type medicines work well" (p = 0.001), "Taking medicines more than once a day is inconvenient" (p = 0.002), and "Sometimes I skip my inhaler to use it over a longer period" (p < 0.001). CONCLUSIONS: Our study showed that patients' acceptance of the benefits, convenience and cost of inhaler medications have a significant impact on treatment adherence in the participating Asian countries.

Prevalence of bronchial asthma among orang asli in peninsular malaysia.

A survey was carried out to determine the prevalence of bronchial asthma and their contributing risk factors among Orang Asli subgroups living in Malaysia using IUATLD questionnaire and spirometry without being discriminatory towards age or gender. Of the 1171 distributed questionnaires, 716 (61.1%) comprising of 62.7% Semai Pahang, 51.3% Temiar, 74.2% Mah Meri, 65.6% Semai Perak, 53.6% Temuan, 53.8% Semelai, 61.1% Jakun and 67.4% Orang Kuala subgroups completed their questionnaire and were included in the data analysis. Participants comprised 549 (76.7%) children and 167 (23.3%) adults, age between 1 to 83 years old, 304 (42.5%) males and 412 (57.5%) females. The overall prevalence of bronchial asthma was 1.4% of which 1.5% was children, 1.3% adults, 1.0% male and 1.7% female, respectively. Of the 8 subgroups surveyed, 5 out of 10 confirmed asthma cases were Semai Pahang, followed by 3 cases among Mah Meri, and one case each among Temuan and Semai Perak subgroups, respectively. This study also demonstrated that the prevalence of self-reported and confirmed bronchial asthma tend to be higher among those who had close contact with pets, smoking individuals and among those who had a family history of asthma.

The diagnosis of lung cancer in the era of interventional pulmonology.

Advances in bronchoscopic and other interventional pulmonology technologies have expanded the sampling procedures pulmonologist can use to diagnose lung cancer and accurately stage the mediastinum. Among the modalities available to the interventional pulmonologist are endobronchial ultrasound-guided transbronchial needles aspiration (EBUS-TBNA) and transoesophageal bronchoscopic ultrasound-guided fine-needle aspiration (EUS-B-FNA) for sampling peribronchial/perioesophageal central lesions and for mediastinal lymph node staging, as well as navigational bronchoscopy and radial probe endobronchial ultrasound (RP-EBUS) for the diagnosis of peripheral lung cancer. The role of the interventional pulmonologist in this setting is to apply these procedures based on the correct interpretation of clinical and radiological findings in order to maximise the chances of achieving the diagnosis and obtaining sufficient tissue for molecular biomarker testing to guide targeted therapies for advanced non-small cell lung cancer. The safest and the highest diagnosis-yielding modality should be chosen to avoid a repeat sampling procedure if the first one is non-diagnostic. The choice of site and biopsy modality are influenced by tumour location, patient comorbidities, availability of equipment and local expertise. This review provides a concise state-of-the art account of the interventional pulmonology procedures in the diagnosis and staging of lung cancer.

Seropositivity and risk factors of Toxocara canis infection in adult asthmatic patients.

This cross-sectional study involving 86 adult asthmatic patients aimed to determine the relationship between Toxocara seropositivity and severity of asthma in adult asthmatics and investigate the risk factors for Toxocara infection. In all cases, T. canis IgG level was measured using an anti-Toxocara IgG enzyme-linked immunosorbent assay kit. Total serum IgE and eosinophil count were also determined. The anti-Toxocara IgG seropositivity was 68.6% among asthmatic patients. There were no statistically significant associations between Toxocara seroprevalence and other risk factors, clinical symptoms of asthma and high level of total serum IgE and eosinophilia. Pet ownership could be an important risk factor for Toxocariasis. Having a pet at home and wheezing were significantly associated with Toxocara seropositivity in adult asthmatic patients.

Relationship between various cytokines implicated in asthma.

Asthma is a complex disorder involving immunologic, environmental, genetic and other factors. Today, asthma is the most common disease encountered in clinical medicine in both children and adults worldwide. Asthma is characterized by increased responsiveness of the tracheobronchial tree resulting in chronic swelling and inflammation of the airways recognized to be controlled by the T-helper 2 (Th2) lymphocytes, which secrete cytokines to increase the production of IgE by B cells. There are many cytokines implicated in the development of the chronic inflammatory processes that are often observed in asthma. Ultimately, these cytokines cause the release of mediators such as histamine and leukotrienes (LT), which in turn promote airway remodeling, bronchial hyperresponsiveness and bronchoconstriction. The CD4+ T-lymphocytes from the airways of asthmatics express a panel of cytokines that represent the Th2 cells. The knowledge derived from numerous experimental and clinical studies have allowed physicians and scientists to understand the normal functions of these cytokines and their roles in the pathogenesis of asthma. The main focus of this review is to accentuate the relationship between various cytokines implicated in human asthma. However, some key findings from animal models will be highlighted to support the discoveries from clinical studies.

Gastro-oesophageal reflux disease in 'difficult-to-control' asthma: prevalence and response to treatment with acid suppressive therapy.

BACKGROUND: The causal association between gastro-oesophageal reflux disease (GERD) and difficult-to-control asthma is unclear. AIM: To determine the prevalence of GERD and response to proton pump inhibitor therapy in patients with difficult-to-control asthma. METHODS: Consecutive patients with difficult-to-control asthma as defined by persistent and recurrent symptoms despite on optimal asthmatic medications were recruited for the study. GERD was diagnosed by symptoms, gastroscopy and 24-h oesophageal pH monitoring. All patients were prescribed a course of lansoprazole 30 mg daily for 8 weeks. Improvement to treatment was assessed by a change in pulmonary symptom score and also by patient's subjective assessment of improvement. RESULTS: Seventeen of 30 (56.7%) patients with difficult-to-control asthma were diagnosed with GERD. Pulmonary symptom score improved significantly only in patients with GERD (35.0 to 21.0; P = 0.002). Twelve of 16 (75%) patients with GERD reported an improvement in asthma symptoms; 1 of 11 (9.1%) without GERD reported mild symptom improvement. There was no significant change in peak expiratory flow rate and forced expiratory volume. CONCLUSIONS: More than half of patients with difficult-to-control asthma were diagnosed with GERD. In these patients the severity of asthma improved significantly with potent acid suppression therapy. This underlines the critical role of acid reflux in this subset of patients with difficult-to-control asthma.

Pleural effusions: role of commonly available investigations.

INTRODUCTION: Previous studies have reported high rates of undetermined causes of pleural effusions. We aimed to find out the proportion of pleural effusions in which the aetiology is uncertain despite commonly available investigations. METHODS: A prospective study was carried out at the University of Malaya Medical Centre from May 2001 to January 2002. All patients with pleural effusion admitted to the medical wards and non-medical wards during that period were included in the study. RESULTS: Of 111 patients with pleural effusion, malignancy was the commonest cause of pleural effusion (34.2 percent), followed by tuberculosis (22.5 percent) and parapneumonic effusions (18.9 percent). There were only two patients (1.8 percent) with undetermined cause despite extensive investigations. Carcinoma of the lung was the commonest cause of malignant effusions and bronchoscopic biopsy gave the highest yield of histological diagnosis (66 percent), followed by pleural fluid cytology (59 percent) and pleural biopsy (50 percent). The combination of these three procedures increased the diagnostic yield to 96 percent. In tuberculous pleural effusion, pleural fluid staining for acid-fast bacilli was negative in all cases but mycobacterial culture was positive in 24 percent of cases while pleural biopsy gave a better yield of 68.8 percent. Examination of sputum and bronchoalveolar lavage specimens confirmed the diagnosis of tuberculosis in 40 percent of cases. A combination of these investigations yielded the diagnosis in 92 percent of patients with tuberculous effusion. CONCLUSION: Malignancy is the commonest cause of pleural effusion, followed by tuberculosis and pneumonia, in patients treated in a teaching hospital in Malaysia. The number of undetermined causes could be minimised with a combination of readily-available and established investigations.

Melioidosis: a potentially life threatening infection.

Melioidosis is caused by the gram-negative bacillus, Burkholderia pseudomallei. It is endemic in tropical Australia and in Southeast Asian countries. The overall mortality from this infection remains extremely high despite recent advancement in its treatment. This review discuss about clinical manifestations, diagnosis and management of melioidosis.

Serum cancer antigen 125 in patients with pleural effusions.

We studied the prevalence of raised serum CA125 in patients with pleural effusions and explored factors affecting its level. Sixty four patients with benign effusions and 36 patients with malignant effusions admitted to the University Malaya Medical Centre from May 2001 to January 2002 were included in the study. There were no significant differences in age, gender and ethnicity of the patients with benign and malignant effusions. There was also no difference in the frequency of the side of pleural effusion between the two groups but compared to benign effusions, a higher proportion of malignant effusions was moderate to large in size (66% versus 39%, p = 0.011). Serum CA125 levels were above 35U/dL in 83.3% and 78.1% of patients with malignant and benign effusions, respectively (p = 0.532). All patients with underlying malignancy and 95.3% of patients with benign effusions had pleural fluid CA125 levels above 35U/dL (p = 0.187). The median levels of CA125 were higher in the pleural fluid than in the serum in all aetiological groups. Higher serum CA125 levels were more likely to be found in patients with moderate to large effusions (p = 0.015), malignant effusions (p = 0.001) and in female patients (0.016). Serum CA125 level showed significant correlation with pleural fluid CA125 level (r = 0.532, p < 0.001) but not with pleural fluid total white blood cell count (r = -0.092, p = 0.362), red blood cell count (r = -0.082, p = 0.417) and lactate dehydrogenase level (r = 0.062, p = 0.541). We conclude that serum CA125 is commonly elevated in patients with benign and malignant pleural effusions.

Tracheobronchial stenting is safe and effective in relieving upper airway obstruction.

Many studies have shown that tracheobronchial stenting is effective in relieving respiratory distress secondary to major airway obstruction due to lung or oesophageal cancer. A retrospective review on the benefits and complications of self-expandable metallic stent (SEMS) insertion through flexible bronchoscopy for the palliative treatment of upper airway obstruction in University Malaya Medical Centre was performed. Ten patients underwent this procedure. Relief of dyspnoea was immediate following stent insertion in all patients. Stent migration occurred in one patient and three patients had restenosis of the central airway. We conclude that tracheobronchial stenting via flexible bronchoscopy is feasible and safe.

Squamous cell carcinoma antigen as an adjunct tumour marker in primary carcinoma of the lung.

AIMS: To determine (1) the detection rate of primary carcinoma of the lung by serological assay of CEA (carcinoembryonic antigen); and (2) whether addition of seroassay of squamous cell carcinoma related antigen before treatment improves detection sensitivity. METHODS: A prospective study spanning 27 months was conducted at the University Hospital, Kuala Lumpur. Serum CEA (Abbott IMx) and serum squamous cell carcinoma antigen (Abbott IMx) from patients clinically suspected of having primary carcinoma of the lung, were assayed using the microparticle enzyme immunoassay method. RESULTS: Thirty seven cases of histologically confirmed primary lung carcinoma were studied. Of these, 17 were squamous cell carcinomas, 10 adenocarcinomas, nine small cell carcinomas, and one large cell carcinoma. The patients' ages ranged from 34-82 years. The male:female ratio was 3.6:1. Squamous cell carcinoma antigen was raised above the cutoff value of 1.5 ng/ml in 94.1% of squamous cell carcinomas, 20.0% of adenocarcinomas, and 11.1% of small cell carcinomas. By comparison, CEA was raised above the cutoff value of 3.0 ng/ml in 70.6% of squamous cell carcinomas, 77.8% of small cell carcinomas, and 100% of adenocarcinomas. CEA and squamous cell carcinoma antigen were not raised in the patient with large cell carcinoma and in 14 healthy volunteers. None of 15 patients with a variety of benign lung diseases showed a rise of CEA, while two patients--a 25 year old Indian woman with pneumonia and a 64 year old Malay man with bronchial asthma--had raised squamous cell carcinoma antigen values above the cutoff. Serum CEA and squamous cell carcinoma antigen values did not seem to correlate with stage or degree of differentiation of the tumours. CONCLUSIONS: The findings suggest that CEA is a good general marker for carcinoma, particularly adenocarcinoma. In contrast, squamous cell carcinoma antigen is more specific for squamous carcinoma.

Awareness of the ozone layer and acceptance of a new CFC-free metered dose inhaler among asthmatic patients.

SETTING: University of Malaya Medical Centre, Kuala Lumpur, Malaysia. OBJECTIVE: To assess the awareness of the ozone layer and the acceptance of the new non-chlorofluorocarbon (CFC) propellant hydrofluoroalkane 134a salbutamol pressurised metered dose inhaler (MDI) Airomir among asthmatic patients. DESIGN: A total of 113 consecutive asthmatic patients aged 12 years and above from the out- and in-patient services of the hospital were interviewed using a questionnaire. RESULTS: Sixty-five per cent of the patients were aware of the existence of the ozone layer, 23% that CFCs play a role in ozone depletion, and only 10% that current MDIs contained CFCs. All the patients felt that pressurised MDIs should be made CFC-free after they had considered the role of CFCs in the destruction of the ozone layer. Eighty-one per cent of 94 patients who preferred the Airomir inhaler over a multi-dose dry powder inhaler for administering bronchodilator medications were willing to switch to the new inhaler once it became available on the market. CONCLUSION: Awareness of the damaging effect of CFCs on the ozone layer among asthmatic patients would encourage them to change to an ozone-friendly, CFC-free pressurised MDI.

Delay in the diagnosis and treatment of pulmonary tuberculosis in patients attending a university teaching hospital.

SETTING: University Hospital, Kuala Lumpur, Malaysia. OBJECTIVE: To investigate patient and doctor delays in the diagnosis and treatment of pulmonary tuberculosis in patients attending a tertiary teaching hospital. DESIGN: A total of 97 patients with newly diagnosed pulmonary tuberculosis at our hospital were interviewed to study the process of case-finding since the onset of symptoms. Time intervals between onset, first medical consultation and the final diagnosis and commencement of antituberculosis treatment were determined. Demographic and clinical features were evaluated for their effect on these intervals. RESULTS: 36 cases were sputum smear-positive and 61 were smear-negative. Tuberculosis was eventually confirmed in 32 of the smear-negative cases. The medians of patient delay, doctor delay and total delay were 2 weeks, 7 weeks and 12.5 weeks, respectively. The majority of the patients consulted private general practitioners but the diagnosis of tuberculosis was rarely suspected; chest X-ray and sputum examinations were under-utilized. CONCLUSION: To shorten patient delay the public should be educated about the symptoms of tuberculosis and the importance of early medical consultation. Private general practitioners should be more alert to the diagnostic possibility of tuberculosis and refer the patients promptly to the government hospitals for appropriate investigation.

The role of 67gallium scintigraphy and high resolution computed tomography as predictors of disease activity in sputum smear-negative pulmonary tuberculosis.

SETTING: University Hospital, Kuala Lumpur, Malaysia. OBJECTIVE: To determine whether 67Gallium (Ga) scintigraphy and high resolution computed tomography (HRCT) of the lung improve the diagnostic accuracy of sputum smear-negative active pulmonary tuberculosis. DESIGN: Patients suspected of having active pulmonary tuberculosis but who were sputum smear-negative underwent 67Ga scintigraphic and HRCT scanning of the lung. Results of these scans were correlated with results of bacteriology and histopathology as well as clinical data on follow-up. RESULTS: Although none of the patients was culture-positive for Mycobacterium tuberculosis, 14 were considered to have active disease either because of positive direct smears of respiratory tract specimens other than sputum, positive histopathology, or clinical and radiological improvement following antituberculosis chemotherapy. A positive 67Ga scan had a sensitivity of 100% and a specificity of 83% for active pulmonary tuberculosis. Of the HRCT findings, the presence of centrilobular lesions had a 93% sensitivity and 100% specificity in determining disease activity in this group of patients. CONCLUSION: Both 67Ga scintigraphic and HRCT scans are helpful in determining disease activity in sputum smear-negative pulmonary tuberculosis.

Tuberculous pleurisy as a manifestation of primary and reactivation disease in a region with a high prevalence of tuberculosis.

SETTING: A teaching hospital in Malaysia. OBJECTIVE: To review the demographic and clinical features of patients with pleural tuberculosis (TB). DESIGN: Retrospective chart and chest radiograph review. RESULTS: The chest radiograph of 54 (61.4%) of a total of 88 patients with pleural TB did not show any lung infiltrate (considered a manifestation of primary TB), while that of 32 (36.3%) patients showed infiltrates in the upper lobes or superior segment of the lower lobes, or the presence of parenchymal scarring in the upper lobes (typical of reactivation TB). Additionally, the chest radiograph of two (2.3%) patients showed miliary mottling (also classified as having primary TB). The mean age of patients with primary versus reactivation tuberculous pleurisy was 36.3 (+/-14.8) years and 44.6 (+/-19.3) years, respectively (P = 0.041). The median duration of symptoms before presentation was 14 days and 60 days in patients with primary and reactivation disease, respectively (P = 0.001). CONCLUSION: In Malaysia, where the prevalence of TB is high, tuberculous pleurisy is more commonly a manifestation of primary rather than reactivation disease. Patients with primary TB pleurisy are younger and have a shorter duration of symptoms than those with reactivation TB pleurisy.