Gender-Based Impact of Epidermal Growth Factor Receptor Mutation in Patients With Nonsmall Cell Lung Cancer and Previous Tuberculosis

The association between tuberculosis (TB) and lung cancer is well known. However, carcinogenesis of TB and its connection with epidermal growth factor receptor (EGFR) mutation remains unclear. This study aimed to determine this connection to see if TB can affect the outcome of patients with lung cancer.This is a retrospective cohort study of patients with lung cancer receiving EGFR-tyrosine kinase inhibitors (TKIs) between 1996 and 2010 using the National Health Insurance Research Database of Taiwan. Because therapeutic response was required to apply EGFR-TKIs for >90 days, only patients with a follow-up of >120 days were studied and a responder was defined as intake of EGFR-TKIs >90 days. Predictors of EGFR-TKI response and survival were identified using logistic and Cox regression analyses, respectively.There were 8265 patients analyzed, including 6073 (73.5%) EGFR-TKI responder and 2192 (26.5%) nonresponder. A history of TB was found in 1.2% and 1.8% of the 2 groups, respectively. Comparing to male with pulmonary TB history, female with or without pulmonary TB history and male without pulmonary TB history all had a better EGFR-TKI response and 1-year progression-free survival (PFS). Gender and TB history were not independent prognostic factors of 2-year overall survival. The findings were similar in the subpopulation without chronic obstructive pulmonary disease, malignancies other than lung cancer, and low-income status.TB has a gender-dependent impact, with better EGFR-TKI response and 1-year PFS in female patients with lung cancer. The carcinogenesis and inflammation of TB may be different between genders.     

Performance assessment of the DR. MTBC Screen assay and the BD ProbeTec ET system for direct detection of Mycobacterium tuberculosis in respiratory specimens

The performance of the DR. MTBC PCR-based assay and the BD ProbeTec ET Mycobacterium tuberculosis Complex Direct Detection (DTB) assay for the direct detection of Mycobacterium tuberculosis was evaluated using 1,066 consecutive clinical respiratory samples collected from 494 patients who did not have old cases of pulmonary tuberculosis and were not receiving antituberculosis treatment at National Taiwan University Hospital from January to February 2005. The results of both assays were compared to the "gold standard" of combined culture results and clinical diagnosis. The overall sensitivity and specificity of the DR. MTBC Screen assay were 56.6% and 98.9%, respectively, and of the DTB assay were 63.2% and 98.4%, respectively. The positive and negative predictive values for the DR. MTBC Screen assay were 84.5% and 95.4%, respectively, and for the DTB assay were 81.7% and 96.0%, respectively. The DR. MTBC Screen assay produced 11 false-positive results for 11 patients, including three samples yielding non-M. tuberculosis mycobacteria (one each for M. abscessus, a mixture of M. abscessus and M. chelonae, and unidentified non-tuberculosis mycobacteria). The DTB assay produced 15 false-positive results for 13 patients, including five samples from four patients yielding non-tuberculosis mycobacteria (two for M. abscessus, one for a mixture of M. abscessus and M. chelonae, and two for unidentified non-tuberculosis mycobacteria). This study demonstrated that the DR. MTBC Screen assay has a similar diagnostic value but fewer false-positive results than the DTB assay for respiratory specimens.     

Factors influencing time to smear conversion in patients with smear-positive pulmonary tuberculosis

Background and objective:   Persistent smear-positivity in patients with pulmonary tuberculosis has been shown to predict an unfavourable outcome. This study was conducted to identify the factors influencing time to sputum smear conversion.
Methods:   From July 2003 to June 2007, all patients with smear-positive and culture-confirmed pulmonary tuberculosis, who had attended a medical centre and a local teaching hospital, were identified. Factors that might have influenced time to smear conversion were investigated using time-to-event analysis.
Results:   Altogether 305 patients (mean age: 58.6 years) were studied. Diabetes mellitus was the most common underlying comorbidity. Eight patients (2.6%) had AIDS. After 2 months of treatment, 34 (11.1%) patients remained smear- and culture-positive. Cox proportional hazard regression analysis indicated that the presence of a cavity on CXR, smear grading and the first 2-month treatment regimen were independent factors influencing the time to sputum smear conversion. Among patients who had received isoniazid in the first 2 months of treatment, the time to sputum smear conversion in the 24 patients whose isolate showed isoniazid resistance was not different from that in the 236 patients whose isolate was isoniazid-susceptible (hazard ratio 1.061; 95% CI: 0.697–1.616).
Conclusions:   This analysis revealed that 11.1% of tuberculosis patients remained smear-positive after 2 months of treatment. Patients with cavitation, higher smear grading and those who had not used isoniazid, rifampicin, ethambutol and pyrazinamide continuously in the initial treatment phase had a longer time to sputum smear conversion.     

Lower gastrointestinal tract tuberculosis: an important but neglected disease

Purpose  

Difficulties in early and accurate diagnosis of intestinal tuberculosis lead to frequent misdiagnosis even in endemic areas. This study aimed to investigate clinical and laboratory characteristics of patients with lower gastrointestinal tract tuberculosis (LGITB).     

Mycobacterium tuberculosis inducing disseminated intravascular coagulation

Disseminated intravascular coagulation (DIC) can develop infrequently in patients with tuberculosis and has a very high mortality rate. We conducted a retrospective study to evaluate the incidence of tuberculosis-induced DIC and to investigate the clinical manifestation, outcome, and prognostic factors of such patients. From January 2002 to December 2003, all culture-proven tuberculosis patients who developed DIC before starting anti-tuberculosis treatments were selected for this study. Patients who had other clinical conditions or were infected by other pathogens that may have been responsible for their DIC were excluded. Survival analysis was performed for each variable with possible prognostic significance. Our results showed that 27 (3.2%) out of the 833 patients with culture-proven tuberculosis had tuberculosis-induced DIC with a mortality rate of 63.0%. The most common clinical manifestations were fever (63.0%) and multiple patches of pulmonary consolidation (59.3%). Seven (25.9%) patients had disseminated tuberculosis. Twelve (44.4%) developed acute respiratory distress syndrome and three (11.1%) were associated with hemophagocytosis. Twenty-four (88.9%) patients had findings that were unusual for an acute bacterial infection, such as positive acid-fast smear, miliary pulmonary lesions, lymphocytotic exudative pleural effusion, and mediastinal lymphadenopathy. Early anti-tuberculosis treatment significantly improved survival. In conclusion, tuberculosis can cause DIC. Patients with non-miliary, non-disseminated tuberculosis could also develop the rare clinical manifestation. Since the prognosis was very poor in patients not treated at an early stage, a high index of suspicion is required, especially in those with clinical findings suggestive of tuberculosis.     

Performance assessment of a nested-PCR assay (the RAPID BAP-MTB) and the BD ProbeTec ET system for detection of Mycobacterium tuberculosis in clinical specimens

The performance of a nested PCR-based assay (the RAPID BAP-MTB; AsiaGen, Taichung, Taiwan) and the BD ProbeTec ET (DTB) system (Becton Dickinson, Sparks, Md.) for detection of Mycobacterium tuberculosis was evaluated with 600 consecutive clinical samples. These samples, including 552 respiratory specimens and 48 nonrespiratory specimens, were collected from 333 patients treated at National Taiwan University Hospital from September to October 2003. The results of both assays were compared to the gold standard of combined culture results and clinical diagnosis. The overall sensitivity and specificity of the RAPID BAP-MTB assay for respiratory specimens were 66.7% and 97.2%, respectively, and for the DTB assay they were 56.7% and 95.3%, respectively. The positive and negative predictive values for the RAPID BAP-MTB were 74.1% and 96.0%, respectively, and for the DTB assay they were 59.6% and 94.7%, respectively. For smear-negative samples, the sensitivity of the RAPID BAP-MTB and DTB assays was 57.1% and 40.5%, respectively. The RAPID BAP-MTB assay produced 14 false-positive results in 14 samples, including one of the six samples yielding Mycobacterium abscessus, one of the six samples yielding Mycobacterium avium intracellulare, one sample from a patient with a history of pulmonary tuberculosis with complete treatment, and three samples from three patients with a previous diagnosis of tuberculosis who were under treatment at the time of specimen collection. Among the 48 nonrespiratory specimens, the RAPID BAP-MTB assay was positive in one biopsy sample from a patient with lumbar tuberculous spondylitis and one pus sample from a patient with tuberculous cervical lymphadenopathy. Our results showed that the RAPID BAP-MTB assay is better than the DTB assay for both respiratory specimens and nonrespiratory specimens. The overall time for processing this assay is only 5 h. In addition, its diagnostic accuracy in smear-negative samples is as high as in smear-positive samples.