O Jung Kwon

Clinical Significance of Differentiation of Mycobacterium massiliense from Mycobacterium abscessus

RATIONALE Mycobacterium massiliense has been recognized as a separate species from Mycobacterium abscessus; however, little is known regarding the clinical impact of this differentiation. OBJECTIVES To compare clinical features and treatment outcomes between patients with M. abscessus lung disease and those with M. massiliense lung disease. METHODS We performed molecular identification of stored clinical isolates of M. abscessus complex and compared clinical characteristics and treatment outcomes between 64 patients with M. abscessus lung disease and 81 patients with M. massiliense lung disease. MEASUREMENTS AND MAIN RESULTS The clinical and radiographic manifestations of disease caused by each species were similar. Standardized combination antibiotic therapy, including a clarithromycin-containing regimen in combination with an initial 4-week course of cefoxitin and amikacin, was given to 57 patients (24 with M. abscessus and 33 with M. massiliense) for more than 12 months. The proportion of patients with sputum conversion and maintenance of negative sputum cultures was higher in patients with M. massiliense infection (88%) than in those with M. abscessus infection (25%; P < 0.001). Inducible resistance to clarithromycin (minimal inhibitory concentrations ≥ 32 μg/ml) was found in all tested M. abscessus isolates (n = 19), but in none of the M. massiliense isolates (n = 28). CONCLUSIONS Treatment response rates to combination antibiotic therapy including clarithromycin were much higher in patients with M. massiliense lung disease than in those with M. abscessus lung disease. The inducible resistance to clarithromycin could explain the lack of efficacy of clarithromycin-containing antibiotic therapy against M. abscessus lung disease.

Antibiotic treatment of Mycobacterium abscessus lung disease: a retrospective analysis of 65 patients.

RATIONALE The optimal therapeutic regimen and duration of treatment for Mycobacterium abscessus lung disease is not well established. OBJECTIVES To assess the efficacy of a standardized combination antibiotic therapy for the treatment of M. abscessus lung disease. METHODS Sixty-five patients (11 males, 55 females, median age 55 yr) with M. abscessus lung disease were treated with clarithromycin, ciprofloxacin, and doxycycline, together with an initial regimen of amikacin and cefoxitin for the first 4 weeks of hospitalization. MEASUREMENTS AND MAIN RESULTS Treatment response rates were 83% for symptoms and 74% for high-resolution computed tomography. Sputum conversion and maintenance of negative sputum cultures for more than 12 months was achieved in 38 (58%) patients. These rates were significantly lower in patients whose isolates were resistant to clarithromycin (17%, 2/12) compared with those whose isolates were susceptible or intermediate to clarithromycin (64%, 21/33; P = 0.007). Neutropenia and thrombocytopenia associated with cefoxitin developed in 33 (51%) and 4 (6%) patients, respectively. Drug-induced hepatotoxicity occurred in 10 (15%) patients. Because of these adverse reactions, cefoxitin was discontinued in 39 (60%) patients after treatment for a median of 22 days. CONCLUSIONS Standardized combination antibiotic therapy was moderately effective in treating M. abscessus lung disease. However, frequent adverse reactions and the potential for long-duration hospitalization are important problems that remain to be solved.

Non–Small Cell Lung Cancer Staging: Efficacy Comparison of Integrated PET/CT versus 3.0-T Whole-Body MR Imaging

PURPOSE To compare prospectively the diagnostic efficacies of integrated positron emission tomography (PET)/computed tomography (CT) and 3.0-T whole-body magnetic resonance (MR) imaging for determining TNM stages in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS Institutional review board approval and informed consent were obtained. The study included 165 patients (125 men, 40 women; mean age, 61 years) with NSCLC proved at pathologic examination who underwent both unenhanced PET/CT and whole-body MR imaging. Pathologic findings for T (n = 123) and N (n = 150) staging and pathologic or follow-up imaging findings (n = 154) for M staging were reference standards. The efficacies of PET/CT and whole-body MR imaging for lung cancer staging were compared by using the McNemar test. RESULTS Primary tumors (n = 123 patients) were correctly staged in 101 (82%) patients at PET/CT and in 106 (86%) patients at whole-body MR imaging (P = .263). N stages (n = 150 patients) were correctly determined in 105 (70%) patients at PET/CT and in 102 (68%) patients at whole-body MR imaging (P = .880). Thirty-one (20%) of 154 patients had metastatic lesions. Accuracy for detecting metastases was 86% (133 of 154 patients) at PET/CT, and that at whole-body MR imaging was 86% (132 of 154 patients) (P > .99). Although the differences were not statistically significant, whole-body MR imaging was more useful for detecting brain and hepatic metastases, whereas PET/CT was more useful for detecting lymph node and soft-tissue metastases. CONCLUSION Both PET/CT and 3.0-T whole-body MR imaging appear to provide acceptable accuracy and comparable efficacy for NSCLC staging, but for M-stage determination, each modality has its own advantages.

Computed tomography in pulmonary artery sarcoma: distinguishing features from pulmonary embolic disease.

Objective: The purpose of this study was to present the computed tomography (CT) findings of pulmonary artery sarcoma in 7 patients with a focus on the distinguishing features of pulmonary embolic disease. Methods: For the 9 years from December 1993 to November 2002, we treated 7 patients with pathologically proven pulmonary artery sarcoma, and during the 2 years from December 2000 to November 2002, we treated 40 patients with acute (n = 33) or chronic (n = 7) pulmonary embolism. In these patients, pulmonary embolism was diagnosed from serial CT or clinical findings. Two chest radiologists, blinded to the diagnoses, independently reviewed the scans of all 47 patients in random order, and the so-documented CT features of sarcoma and pulmonary embolism were compared by using Fisher exact test or the generalized estimating equations test. Results: The two most frequent CT findings of pulmonary artery sarcomas were a low-attenuation filling defect occupying the entire luminal diameter of the main (n = 1) or proximal (n = 6) pulmonary artery and an expansion of any segment of the pulmonary artery with extensive intraluminal filling defect, as observed in six (86%) of 7 patients. In contrast, the finding of a lesion occupying the entire luminal diameter at the level of proximal pulmonary arteries was absent in all 40 patients with pulmonary embolism (P < 0.0001) (κ = 0.9111). Expansion of the pulmonary arteries was seen in one (3%) of 40 patients with pulmonary embolism (P < 0.0001) (κ = 0.9108). Extraluminal extension was observed in 5 of 7 (71%) patients with sarcoma, but in no patient with an embolism (P < 0.0001) (κ = 0.8773). Conclusion: CT can help differentiate pulmonary artery sarcoma from pulmonary embolism by indicating a low-attenuation filling defect occupying the entire luminal diameter of the proximal or main pulmonary artery, expansion of the involved arteries, or extraluminal tumor extension.

Treatment Outcomes for HIV-Uninfected Patients with Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis

BACKGROUND Multidrug-resistant (MDR) tuberculosis (TB) is more difficult to treat than is drug-susceptible TB. To elucidate the optimal therapy for MDR TB, we assessed the treatment outcomes and prognostic factors for patients with MDR TB. METHODS This study included patients who received an individualized treatment regimen for MDR TB at Samsung Medical Center, a tertiary referral hospital in Seoul, Korea, from January 1995 through December 2004. To identify the prognostic factors related to favorable treatment outcomes, univariate comparison and multiple logistic regression were performed. RESULTS Of 155 patients, 18 (12%) had newly diagnosed MDR TB, 81 (52%) had previously received treatment with first-line drugs, and 56 (36%) had received treatment with second-line drugs. The isolated strains were resistant to a median of 5 drugs. Twenty-seven patients (17%) had extensively drug-resistant (XDR) TB at the start of treatment. Outcome assessment revealed that 102 patients (66%) were cured or completed therapy. The treatment success rates did not differ significantly between patients with non-XDR MDR TB and those with XDR TB (66% vs. 67%). Surgical resection was performed more frequently for patients with XDR TB than for those with non-XDR MDR TB (48% vs. 17%). Combined surgical resection, body mass index >/=18.5 (calculated as the weight in kilograms divided by the square of the height in meters), use of >4 effective drugs, and a negative sputum smear result were independent predictors of a favorable outcome. CONCLUSIONS Early aggressive treatment comprising at least 4 effective drugs and surgical resection, when indicated, may improve the outcome for patients with MDR TB or XDR TB.

Clinical characteristics and treatment outcomes of chronic necrotizing pulmonary aspergillosis: a review of 43 cases

OBJECTIVES Chronic necrotizing pulmonary aspergillosis (CNPA) is uncommon, and the optimal therapeutic regimen has not been established. In a retrospective cohort study, we investigated the clinical characteristics and treatment outcomes of patients with CNPA. METHODS We reviewed the medical records of all patients who had been diagnosed with CNPA at our institution over the last 10 years. RESULTS Forty-three patients were identified. Their median age was 60 years (interquartile range (IQR) 45-65 years), and 34 (79%) of the patients were men. The most common underlying lung disease was pulmonary tuberculosis (n=40, 93%). After CNPA was diagnosed, all patients were treated with antifungal drugs, including oral itraconazole (n=39, 91%) or intravenous amphotericin B (n=4, 9%). Seventeen (40%) patients discontinued therapy early (<3 months), 14 patients due to death and three to loss of follow-up. Twenty-six (60%) patients received oral itraconazole at a daily dose of 200-400mg for more than 3 months. The median treatment duration was 6 months (IQR 6-12 months). In these 26 patients, clinical improvement was observed in 15 (58%) and radiological improvement was observed in 11 (42%). Ten (38%) patients showed no improvement. Twenty-two (51%) patients died, including 18 (42%) CNPA-related deaths, during a median follow-up of 15 months (IQR 2.5-32 months). The median survival time was 62 months. CONCLUSIONS CNPA is difficult to treat and often has a poor outcome. Further studies with more patients are needed to identify the optimal therapy for patients with CNPA.

Improved Detection of Second Primary Cancer Using Integrated [18F] Fluorodeoxyglucose Positron Emission Tomography and Computed Tomography for Initial Tumor Staging

PURPOSE This study evaluated prospectively the value of integrated whole-body positron emission tomography and computed tomography (PET/CT) using [18F] fluorodeoxyglucose (FDG) in detecting a second primary cancer at the time of the initial staging in comparison with a conventional staging work-up (CSW). METHODS The participants were 547 patients diagnosed with cancer who underwent FDG PET/CT imaging for the initial staging. An additional diagnostic evaluation was performed when there were abnormal findings indicative of a second primary cancer on either PET/CT or CSW considering the site and the biologic behavior of the alleged primary tumor. RESULTS A total of 27 second primary malignant tumors were identified in 26 of the 547 patients (4.8%). FDG PET/CT found 45 lesions indicative of a second primary cancer, of which 24 lesions were proved to be a second primary cancer, seven were clinically unexpected metastases, and 14 lesions were benign. Therefore, sensitivity and positive predictive value of FDG PET/CT in detecting a second primary cancer or an unexpected metastasis were 91% (31 of 34) and 69% (31 of 45), respectively. In contrast, CSW could not identify 16 second primary cancers and one metastatic lesion. CONCLUSION FDG PET/CT at the time of the initial staging is useful for screening a second primary cancer with a high sensitivity. An additional diagnostic work-up is essential when abnormal findings, which are indicative of a second primary cancer, are obtained on PET/CT images to rule out the presence of either a second primary cancer or an unexpected metastasis.

Diagnosis and Treatment of Nontuberculous Mycobacterial Pulmonary Diseases: A Korean Perspective

The incidence of pulmonary disease caused by nontuberculous mycobacteria (NTM) appears to be increasing worldwide. In Korea, M. avium complex and M. abscessus account for most of the pathogens encountered, whilst M. kansasii is a relatively uncommon cause of NTM pulmonary diseases. NTM pulmonary disease is highly complex in terms of its clinical presentation and management. Because its clinical features are indistinguishable from those of pulmonary tuberculosis and NTMs are ubiquitous in the environment, the isolation and identification of causative organisms are mandatory for diagnosis, and some specific diagnostic criteria have been proposed. The treatment of NTM pulmonary disease depends on the infecting species, but decisions concerning the institution of treatment are never easy. Treatment requires the use of multiple drugs for 18 to 24 months. Thus, treatment is expensive, often has significant side effects, and is frequently not curative. Therefore, clinicians should be confident that there is sufficient pathology to warrant prolonged, multidrug treatment regimens. In all of the situations, outcomes can be best optimized only when clinicians, radiologists, and laboratories work cooperatively.

Clinical Significance of the Differentiation Between Mycobacterium avium and Mycobacterium intracellulare in M avium Complex Lung Disease

BACKGROUND Mycobacterium avium and Mycobacterium intracellulare are grouped together as the M avium complex; however, little is known about the clinical impact of this species differentiation. This study compared the clinical features and prognoses of patients with M avium and M intracellulare lung disease. METHODS From 2000 to 2009, 590 patients were given a new diagnosis of M avium complex lung disease; 323 (55%) had M avium lung disease, and 267 (45%) had M intracellulare lung disease. RESULTS Compared with the patients with M avium lung disease, the patients with M intracellulare lung disease were more likely to have the following characteristics: older age (64 vs 59 years, P = .002), a lower BMI (19.5 kg/m² vs 20.6 kg/m², P < .001), respiratory symptoms such as cough (84% vs 74%, P = .005), a history of previous treatment for TB (51% vs 31%, P < .001), the fibrocavitary form of the disease (26% vs 13%, P < .001), smear-positive sputum (56% vs 38%, P < .001), antibiotic therapy during the 24 months of follow-up (58% vs 42%, P < .001), and an unfavorable microbiologic response after combination antibiotic treatment (56% vs 74%, P = .001). CONCLUSIONS Patients with M intracellulare lung disease exhibited a more severe presentation and had a worse prognosis than patients with M avium lung disease in terms of disease progression and treatment response. Therefore, species differentiation between M avium and M intracellulare may have prognostic and therapeutic implications.

Natural History of Pure Ground-Glass Opacity Lung Nodules Detected by Low-Dose CT Scan

BACKGROUND Although focal ground-glass opacity (GGO) lung nodules are generally reported to grow slowly, their natural course is unclear. The purpose of this study was to elucidate the natural course of screening-detected pure GGO lung nodules in patients with no history of malignancy. METHODS We retrospectively reviewed the database of subjects who had undergone screenings involving low-dose CT scans. We included patients with pure GGO lung nodules who were followed for > 2 years after the initial screening. RESULTS Between June 1997 and September 2006, 122 pure GGO nodules were found in 89 patients. The median nodule size was 5.5 mm (range, 3-20 mm) in the largest diameter on initial low-dose CT scan. The median follow-up period per patient was 59 months. On a per-person basis, the frequency of growth was 13.5% (12 of 89 patients). On a per-nodule basis, the frequency of growth was 9.8% (12 of 122 nodules). Nodule growth was significantly associated with initial size and new development of an internal solid portion. The median volume doubling time was 769 days for growing pure GGO nodules. A total of 11 growing nodules were surgically validated, and all lesions were confirmed as primary lung cancer. CONCLUSIONS About 90% of the screening-detected pure GGO lung nodules did not grow during long-term follow-up in subjects with no history of malignancy and most growing nodules had an indolent clinical course. A strategy of long-term follow-up and selective surgery for growing nodules should be considered for pure GGO lung nodules.