A randomized phase III trial of stereotactic radiosurgery (SRS) versus observation for patients with asymptomatic cerebral oligo-metastases in non-small-cell lung cancer.

BACKGROUND: It is unclear whether treating brain metastasis before starting systemic chemotherapy can improve survival compared with upfront chemotherapy in non-small-cell lung cancer (NSCLC) with asymptomatic cerebral oligo-metastases. PATIENTS AND METHODS: We undertook a randomized, controlled trial of 105 patients with one to four brain metastases, admitted to Samsung Medical Center between 2008 and 2013. Patients were randomly assigned to receive stereotactic radiosurgery (SRS) (49 patients) followed by chemotherapy or upfront chemotherapy (49 patients). The primary end point was overall survival (OS) and secondary end points included central nervous system (CNS) progression-free survival, progression to symptomatic brain metastasis and brain functional outcome. RESULTS: The median age was 58 years (range, 29-85) with ECOG 0-1 performance status, and 40% of patients were never smokers. Most patients had adenocarcinoma, and about half of patients had only one brain metastasis, while the rest had multiple cerebral metastases. The median OS time was 14.6 months [95% confidence interval (CI), 9.2-20.0] in the SRS group and 15.3 months (95% CI, 7.2-23.4) for the upfront chemotherapy group (P = 0.418). There was no significant difference in time to CNS disease progression [median, 9.4 months (SRS) versus 6.6 months (upfront chemotherapy), P = 0.248]. Symptomatic progression of brain metastases was observed more frequently in the upfront chemotherapy group (26.5%) than the SRS group (18.4%) but without statistical significance. CONCLUSIONS: Although this study included smaller sample size than initially anticipated due to early termination, SRS followed by chemotherapy did not improve OS in oligo-brain metastases NSCLC patients compared with upfront chemotherapy. Further study with large number of patients should be needed to confirm the use of upfront chemotherapy alone in this subgroup of patients. CLINICAL TRIALS NUMBER: NCT01301560.

Toxocariasis as a cause of new pulmonary infiltrates.

SETTING: Patients with new pulmonary infiltrates on chest computed tomography (CT) scans at a tertiary centre in South Korea. OBJECTIVE: To demonstrate associations among radiological changes, blood eosinophilia (E) and Toxocara (T) seropositivity. DESIGN: We retrospectively reviewed blood eosinophilia, Toxocara seropositivity, history of raw meat intake and radiological features, and divided study patients into four groups according to blood eosinophilia and Toxocara seropositivity. RESULTS: Among 150 patients, 62 were E- and T-positive (E+T+), 45 were E-negative and T-positive (E-T+), 7 were E-positive and T-negative (E+T-), and 36 were E- and T-negative (E-T-). History of raw meat intake was found in 95 (63%) patients. The type and number of lesions on CT did not show any significant differences among the four groups. Among 119 patients who were not diagnosed with a specific disease, transient or migrating lesions were seen in 93% of E+T+, 93% of E-T+, 80% of E+T- and 52% of E-T- patients (P < 0.0001). Furthermore, the frequencies of migrating or new lesions and improvement were significantly higher in the Toxocara-positive group (88/95, 93%) than in the Toxocara-negative group (14/24, 58%; P = 0.002). CONCLUSION: Transient and migratory pulmonary infiltrates on chest CT scans were associated with blood eosinophilia and Toxocara seropositivity. Clinicians should consider asymptomatic toxocariasis as a cause of unexplained new pulmonary infiltrates in countries with dietary habits of raw meat intake.

Initial lactate level and mortality in septic shock patients with hepatic dysfunction.

An elevated serum lactate level is associated with morbidity and mortality in patients with severe sepsis and septic shock. In patients with hepatic dysfunction, however an elevated serum lactate level may be due to either impaired lactate clearance or excessive production. Thus, we evaluated whether the initial serum lactate level was also associated with mortality in septic shock patients with hepatic dysfunction. A retrospective observational study enrolled 307 patients with septic shock admitted to the intensive care unit (ICU) between May 2007 and July 2009. Hepatic dysfunction was defined as a serum total bilirubin > 34.2 micromol/l (2 mg/dl). Selected patients were divided into high (> or = 4 mmol/l) and low (< 4 mmol/l) lactate groups, according to the initial serum lactate level. Of 307 patients with septic shock, 118 (38%) patients with hepatic dysfunction were eligible for this study. The median lactate levels were 5.9 (interquartile range 4.7 to 9.0) and 2.6 (interquartile range 1.7 to 3.2) mmol/l for the high and low lactate groups respectively (P < 0.001). The initial serum lactate level was strongly associated with in hospital mortality in a univariate analysis (P < 0.001). After adjusting for potential confounding factors, the initial serum lactate level remained significantly associated with in-hospital mortality (odds ratio 1.281, 95% confidence interval 1.097 to 1.496, P = 0.002). In conclusion, the serum lactate level could be useful in predicting the outcome of patients with septic shock regardless of hepatic dysfunction.

Pulmonary paragonimiasis mimicking lung cancer in a tertiary referral centre in Korea.

OBJECTIVE AND DESIGN: To determine how pulmonary paragonimiasis may be confused with lung cancer, we retrospectively analysed the clinical and radiological characteristics of 47 patients (27 males, median age 55 years; interquartile range 49-61) with serologically or histopathologically confirmed pulmonary paragonimiasis seen between October 2004 and December 2009. RESULTS: Respiratory symptoms were present in 29 (62%) patients; the remaining 18 (38%) were asymptomatic. Chest radiography (CXR) revealed intrapulmonary parenchymal lesions (n = 35, 75%) more frequently than pleural lesions (n = 11, 23%). Of the 47 patients, 28 (60%) were referred for suspected lung cancer. The majority of these patients had no symptoms, and 22 (79%) patients with suspected lung cancer had nodular or mass lesions on CXR. As a result, additional diagnostic procedures were performed to make an accurate diagnosis in these patients, including bronchoscopy in 20, transthoracic lung biopsy in 11 and fluorodeoxyglucose positron emission tomography in seven. Surgical lung resection was performed unnecessarily in six patients. CONCLUSIONS: Pulmonary paragonimiasis presenting with nodular or mass lesions on CXR is common. Clinicians should therefore include pulmonary paragonimiasis in the differential diagnosis of asymptomatic nodular lesions in the lung in patients who have lived in or travelled to paragonimiasis-endemic areas.

Predictors of persistent airway stenosis in patients with endobronchial tuberculosis.

SETTING: The university and municipal hospitals in Seoul, Korea. OBJECTIVE: To evaluate the predictors of persistent airway stenosis following anti-tuberculosis chemotherapy in patients with endobronchial tuberculosis (TB). DESIGN: Diagnosis of TB was confirmed by microbiology or histopathology. Bronchoscopic examinations revealed that patients had endobronchial lesions compatible with endobronchial TB. Study subjects had at least one follow-up bronchoscopy to evaluate their treatment response. Treatment response was determined by changes in the degree or extent of airway stenosis between the first and last bronchoscopic examinations. RESULTS: Sixty-seven subjects were recruited retrospectively from Seoul National University Hospital and Seoul National University Boramae Hospital. Persistent bronchostenosis occurred in 41.8% of the patients. In multivariate regression analysis, age >45 years (OR 3.65), pure or combined fibrostenotic subtype (OR 5.54) and duration from onset of chief complaint to the initiation of anti-tuberculosis chemotherapy >90 days (OR 5.98) were identified as independent predictors of persistent airway stenosis. Oral corticosteroids (prednisolone equivalent >or=30 mg/d) did not reduce the frequency of persistent airway stenosis. CONCLUSION: Early diagnosis and early administration of anti-tuberculosis chemotherapy before involvement of the deeper airways is important to prevent the development of unwanted sequelae of bronchostenosis.

Low serum concentrations of anti-tuberculosis drugs and determinants of their serum levels.

SETTING: Low serum concentrations of anti-tuberculosis drugs have occasionally been associated with treatment failure. OBJECTIVE: To determine the prevalence of low serum concentrations of anti-tuberculosis drugs and to identify the determinants of drug concentrations. DESIGN: Venous blood was obtained 2 h after drug ingestion, and serum levels of isoniazid (INH), rifampicin (RMP), ethambutol (EMB), pyrazinamide (PZA), acetyl INH and 25-desacetyl RMP were analysed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Patients with human immunodeficiency virus co-infection and gastrointestinal disease or diarrhoea were excluded. RESULTS: Among 69 enrolled TB patients, the prevalence of a low 2 h serum concentration of at least one anti-tuberculosis drug was 46.4%. Prevalences of a low concentration of INH, RMP, EMB or PZA were 15.2%, 23.5%, 22.4% and 4.5%, respectively. By multivariate linear regression analysis, the serum concentrations of INH, RMP and PZA were positively associated with dose per kg of body weight (P < 0.05). Moreover, INH concentration was associated with acetyl INH/INH ratio (beta = -8.588, P < 0.001) and EMB concentration was associated with calculated creatinine clearance (beta = -0.025, P < 0.001). CONCLUSION: Low concentrations of anti-tuberculosis drugs are common, and although the clinical significance of low concentrations remains uncertain, it may be necessary to optimise drug doses by therapeutic drug monitoring, especially in patients with an inadequate clinical response to chemotherapy.