G.C. Ooi

White Matter Anisotropy in Post-Treatment Childhood Cancer Survivors: Preliminary Evidence of Association With Neurocognitive Function

PURPOSE We aim to determine if the loss of white matter fractional anisotropy (FA), measured by diffusion tensor magnetic resonance imaging (DTI), in post-treatment childhood medulloblastoma (MED) and acute lymphoblastic leukemia (ALL) survivors correlate with intelligence quotient (IQ) scores. MATERIALS AND METHODS MED and ALL survivors (n = 30; 20 male, 10 female; age range, 6.0 to 22.1 years; mean, 13.1 years) were recruited for DTI and IQ tests. In this cross-sectional study, age-matched normal control (n = 55; 32 male, 23 female; age range, 6.0 to 23 years; mean, 12.1 years) DTI was obtained to compute percentage difference in white matter FA (DeltaFA%) for each patient compared with the age-matched control group. Multivariate regression analysis was performed to determine the relationships between DeltaFA%, age at treatment, irradiation dose, time interval from treatment, and full-scale IQ (FSIQ), verbal IQ (VIQ), and performance IQ (PIQ). Receiver operating characteristics curves were used to determine the best DeltaFA% cutoffs for predicting FSIQ, VIQ, and PIQ of less than 85. RESULTS DeltaFA% had a significant effect on FSIQ (adjusted r2 = 0.439; P < .001), VIQ (adjusted r(2) = 0.237; P = .028), and PIQ (adjusted r(2) = 0.491; P < .001) after adjusting for the effects of age at treatment, irradiation dose, and time interval from treatment. The best DeltaFA% value to predict less than 85 scores in FSIQ, VIQ, and PIQ was -3.3% with specificities of 100% and sensitivities ranging from 77.8% to 87.5%. CONCLUSION Our preliminary findings suggest that white matter FA may be a clinically useful biomarker for the assessment of treatment-related neurotoxicity in post-treatment childhood cancer survivors.

Inhaled fluticasone in bronchiectasis: a 12 month study

Background: The clinical efficacy of inhaled corticosteroid (ICS) treatment has not been evaluated in bronchiectasis, despite the presence of chronic airway inflammation. Methods: After three consecutive weekly visits, 86 patients were randomised to receive either fluticasone 500 μg twice daily (n = 43, 23F, mean (SD) age 57.7 (14.4) years) or matched placebo (n = 43, 34F, 59.2 (14.2) years) and reviewed regularly for 52 weeks in a double blind fashion. Results: 35 and 38 patients in the fluticasone and placebo groups completed the study. Significantly more patients on ICS than on placebo showed improvement in 24 hour sputum volume (OR 2.5, 95% CI 1.1 to 6.0, p = 0.03) but not in exacerbation frequency, forced expiratory volume in 1 second, forced vital capacity, or sputum purulence score. Significantly more patients with Pseudomonas aeruginosa infection receiving fluticasone showed improvement in 24 hour sputum volume (OR 13.5, 95% CI 1.8 to 100.2, p = 0.03) and exacerbation frequency (OR 13.3, 95% CI 1.8 to 100.2, p = 0.01) than those given placebo. Logistic regression models revealed a significantly better response in sputum volume with fluticasone treatment than with placebo among subgroups of patients with 24 hour sputum volume <30 ml (p = 0.04), exacerbation frequency ⩽2/year (p = 0.04), and sputum purulence score >5 (p = 0.03). Conclusions: ICS treatment is beneficial to patients with bronchiectasis, particularly those with P aerurginosa infection.

Overexpression of matrix metalloproteinase‐8 and ‐9 in bronchiectatic airways in vivo

The progressive bronchial dilatation in bronchiectasis is likely to be the result of continued airway matrix destruction, although little is known about the role of neutrophil matrix metalloproteinases (MMPs) in this process. Immunohistochemistry has been used to investigate the expression and cellular localisation of MMP‐8 and MMP‐9 in bronchiectatic airways in vivo. Endobronchial biopsies were taken from 25 bronchiectatic patients, and from the right lower lobe in 14 control subjects. MMP‐8, MMP‐9, neutrophils and macrophages were stained with monoclonal antibodies and quantified as positive cell·mm−2 of the lamina propria by using an image analysis system. There were significantly higher densities of MMP‐8 and MMP‐9 positive cells in the lamina propria of bronchiectatic than control airways. In bronchiectatic airways, the densities of MMP‐8 and MMP‐9 positive cells correlated with each other and with neutrophil density, but not with macrophage density. In control airways, a significant correlation was found between MMP‐8 with neutrophil and MMP‐9 with macrophage densities. An overexpression of neutrophil matrix metalloproteinases in bronchiectatic airways could help explain the continuation of airway destruction in bronchiectasis. In view of the clinical availability of matrix metalloproteinase antagonists, the results presented here could have a significant impact on the development of novel therapies of this untreatable disease.

Transarterial chemoembolization for inoperable, early stage hepatocellular carcinoma in patients with Child-Pugh grade A and B: results of a comparative study in 96 Chinese patients

Transarterial chemoembolization for inoperable, early stage hepatocellular carcinoma in patients with Child-Pugh grade A and B: Results of a comparative study in 96 Chinese patients

Prevalence and extent of calcification over aorta, coronary and carotid arteries in patients with rheumatoid arthritis

Objective.  To evaluate the prevalence and pattern of arterial calcification in patients with rheumatoid arthritis (RA).

The Evaluation of Wallerian Degeneration in Chronic Paediatric Middle Cerebral Artery Infarction Using Diffusion Tensor MR Imaging

Background: The long-term neuromotor outcome in paediatric strokes ranges from normal to varying degrees of hemiplegia. We evaluated the indices of diffusion tensor magnetic resonance imaging (DTI), fractional anisotropy and mean diffusivity to determine if these indices can identify and quantify the presence of Wallerian degeneration in paediatric patients with chronic middle cerebral artery infarction, and to determine if these quantitative parameters correlate with the neuromotor outcome. Methods: Eleven children (mean age 8.1 years) with evidence of unilateral middle cerebral artery stroke on magnetic resonance imaging and 10 control subjects (mean age 8.7 years) were studied. Neuromotor outcome was based on functions of the affected hand: mild (n = 3), moderate (n = 6), and severe (n = 2) hemiparesis. Fractional anisotropy and mean diffusivity of the ipsilateral corticospinal tract were compared with matched contralateral regions using the Mann-Whitney U test. Spearman’s test was performed to study the relationship between neuromotor outcome and the following: ipsilateral-to-contralateral ratio of fractional anisotropy, mean diffusivity and cerebral peduncle area, and the largest infarction size. Results: For control subjects, there were no significant differences in fractional anisotropy and mean diffusivity of the corticospinal tract between the right and left side. For patients, fractional anisotropy decreased by 18% and mean diffusivity increased by 8% in the ipsilateral compared to the contralateral corticospinal tract. Neuromotor outcome correlated with the ipsilateral-to-contralateral ratio of fractional anisotropy (r = –0.638, p = 0.035) but not with the mean diffusivity ratio, cerebral peduncle area ratio and largest infarction size. Conclusion: DTI can be used to detect and quantify Wallerian degeneration in chronic paediatric middle cerebral artery infarction. Our preliminary data show that loss of anisotropy in the corticospinal tract correlates with neuromotor outcome.

Magnetic resonance screening of iron status in transfusion‐dependent β‐thalassaemia patients

The clinical utility of dual sequence (T1‐ and T2‐weighted) magnetic resonance (MR) imaging in estimating liver iron concentration (LIC) in 32 transfusion‐dependent β‐thalassaemia major (24 females; age 18·5±5·9 years) patients on desferrioxamine was evaluated. Signal intensity ratios (SIR) between liver, spleen and pancreas to psoas muscle were determined on both sequences. Relationships between clinical and MR parameters, and accuracy of SIR thresholds in determining adequacy of chelation from LIC were analysed. Liver T1‐ and T2‐SIR were related to LIC (P < 0·001). T1‐SIR < 0·60 predicted severe iron overload (LIC > 15 mg/g) with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 100%, 87%, 33% and 100% respectively. T2‐SIR < 0·1 yielded 100% sensitivity, 93% specificity, 50% PPV and 100% NPV. T1‐SIR ≥ 1·1 predicted LIC < 7 mg/g with 69% sensitivity, 88% specificity, 85% PPV and 74% NPV. T2‐SIR ≥ 0·20 yielded 56·5% sensitivity, 94% specificity, 90% PPV and 71% NPV. LIC correlated with liver T1‐SIR, liver T2‐SIR and serum ferritin (r = −0·76, −0·65, 0·47, respectively; P < 0·01). Serum ferritin was inversely related to liver T1‐SIR, liver T2‐SIR and spleen T2‐SIR (r = −0·35, −0·43, −0·40, respectively; P < 0·05). Mean total transfusion burden was not related to any MR parameter. Although neither MR sequence was a highly accurate predictor of LIC, SIR thresholds are useful to determine presence of iron overload and adequacy of chelation treatment.

Systemic lupus erythematosus patients with respiratory symptoms: the value of HRCT

Ten Chinese patients with systemic lupus erythematosus (SLE) and with persistent respiratory symptoms were evaluated with high resolution computed tomography (HRCT), chest radiographs and lung function tests. Fourteen of 15 HRCT scans performed were abnormal. The predominant disease pattern, seen in 60% of patients, was one of chronic interstitial lung disease with honeycombing, architectural distortion, parenchymal bands, pleural irregularity, and a lower zone predominance. Three of 10 patients had histological evidence of either lung fibrosis or interstitial pneumonitis. Airways disease and pleural thickening were seen in 20% and 87% of scans, respectively. Pleural thickening and honeycombing were present in 53% and 20% of chest radiographs, respectively. All concurrent lung function tests were abnormal. Reduced diffusion capacity of carbon monoxide (DLCO/VA) was observed in 60% of lung function tests. There was no correlation between duration of disease and DLCO/VA. However, pathological reduction of DLCO/VA was seen in 71% of patients with honeycombing, and 88% of patients with ground glass opacity. Our study has documented a high incidence of HRCT features of chronic lung destruction and a lower zone predominance in SLE patients with persistent respiratory symptoms.

Pulmonary sequelae of treatment for breast cancer: A prospective study

PURPOSE To prospectively study the effects of loco-regional radiotherapy in women with breast cancer. METHODS AND MATERIALS Thirty consecutive patients with breast resection underwent clinical, lung function, radiographic, and thoracic high-resolution computed tomography evaluation before and at 1, 3, 6, and 12 months after adjuvant radiotherapy. Chemotherapy was also administered to 15 patients. RESULTS Nineteen patients reported mild respiratory symptoms at 1 month, which resolved completely at 6 months after radiotherapy. Opacities were present on 80% of chest radiographs and in all patients on high-resolution computed tomography by 3 months. These opacities became compact and persisted on high-resolution computed tomography at 12 months. Lung function indices, including FEV1, FVC, TLC, and DLCO, progressively declined after radiotherapy, and was irreversible at 12 months (p < 0.05). Patients who received chemotherapy did not have significantly different lung function indices compared with their counterparts at all time points (p > 0.05). CONCLUSIONS Our results have shown that adjuvant loco-regional radiotherapy, a common practice in breast cancer treatment, is associated with irreversible reduction in lung function parameters. These changes are accompanied by radiological evidence of persistent lung injury. Further studies should be performed to evaluate the incidence and long-term pulmonary sequelae of current treatment for breast cancer.

High-Resolution Computed Tomography of Bronchiolitis Obliterans Syndrome after Bone Marrow Transplantation

High-resolution computed tomography (HRCT) has been described to be useful in assessing bronchiolitis obliterans (BO) syndrome in the transplanted lung. Currently, BO syndrome is diagnosed if lung function deterioration shows persistent or progressive irreversible airflow obstruction, with FEV1 of less than 80% of baseline values, without clinical evidence of infection. The aim of this study is to assess the value of HRCT in evaluating BO syndrome after allogenic bone marrow transplantation (BMT). Fourteen HRCT scans were performed in 6 women and 3 men with moderately severe irreversible airflow obstruction and a clinical diagnosis of BO syndrome after BMT. Two patients had normal HRCT scans. In the remaining 7 patients, 7 of 11 HRCT scans were abnormal, with non-specific findings of bronchial dilatation (1), consolidation (2), hypoattenuated areas (4) and vascular attenuation (4). In comparison with the consistency of positive HRCT findings of BO syndrome in transplanted lungs, HRCT surveillance for BO syndrome in post-BMT patients with clinically established disease is of limited value, unless other pulmonary complications such as opportunistic infections are to be excluded.