Antifactor Xa Levels in Critically Ill Korean Patients Receiving Enoxaparin for Thromboprophylaxis: A Prospective Observational Study

The aim of this study was to investigate antifactor Xa (aFXa) levels after once daily dose of 40 mg of enoxaparin and to evaluate factors influencing aFXa levels among Korean intensive care unit (ICU) patients. This prospective observational study was conducted between August and December 2011 in medical ICUs at Samsung Medical Center. AFXa levels between 0.1 and 0.3 U/mL were considered to be effective for antithrombotic activity. Fifty-five patients were included. The median aFXa levels were 0.22 (IQR 0.17-0.26) at 4 hr, 0.06 (IQR 0.02-0.1) at 12 hr, and 0 U/mL (IQR 0-0.03) at 24 hr. The numbers of patients showing effective antithrombotic aFXa levels were 48 (87.3%), 18 (32.7%), and 0 (0%) at 4, 12 and 24 hr, respectively. At 12 hr, higher sequential organ failure assessment (SOFA) scores and hyperbilirubinemia were significantly associated with low aFXa levels (OR, 0.58; 95% CI, 0.36-0.93; P = 0.02 and 0.06; 0.003-0.87; 0.04, respectively). Once daily dose of 40 mg of enoxaparin is inadequate for maintaining effective antithrombotic aFXa levels, and the inadequacy is more salient for patients with high SOFA scores and hyperbilirubinemia.     

The Clinical,Radiological, and Bronchoscopic Findings and Outcomes in Patients with Benign Tracheobronchial Tumors

Purpose

We evaluated the characteristics of and treatment outcomes in patients with benign tracheobronchial tumors.

Materials and Methods

We reviewed the records of patients with benign tracheobronchial tumors who underwent bronchoscopic intervention with mechanical removal and Nd: YAG laser cauterization, and evaluated the characteristics and treatment outcomes of 55 patients with hamartomas, leiomyomas, papillomas, typical carcinoids, or schwannomas seen between April 1999 and July 2012.

Results

The most common tumors were hamartoma (n=24), leiomyoma (n=16), papilloma (n=7), typical carcinoid (n=5), and schwannoma (n=3). Forty-one patients (75%) had symptoms. On chest computed tomography, 35 patients (64%) had round or ovoid lesions, accompanied by atelectasis (n=26, 47%) or obstructive pneumonia (n=17, 31%). Fatty components (n=9, 16%) and calcifications (n=7, 13%) were observed only in hamartomas, leiomyomas, and typical carcinoids. At bronchoscopy, the typical findings were categorized according to tumor shape, surface, color, and visible vessels. Fifty (91%) patients underwent complete resection. Forty patients (73%) achieved successful bronchoscopic removal defined as complete resection without complications or recurrence. Recurrences occurred in four papillomas, one leiomyoma, and one typical carcinoid. The proportions of tumor types (p=0.029) differed between the successful and unsuccessful removal groups, and a pedunculated base (p<0.001) and no spontaneous bleeding (p=0.037) were more frequent in the successful removal group.

Conclusion

We described clinical, radiological, and typical bronchoscopic findings in patients with benign tracheobronchial tumors; these findings might help to differentiate such tumors. Bronchoscopic intervention was a useful treatment modality, and tumor type, pedunculated base, and vascularity may influence successful tumor removal.     

Treatment of isoniazid-resistant pulmonary tuberculosis

Background  

Although resistance to isoniazid (INH) is the most common form of drug resistance seen among Mycobacterium tuberculosis isolates, there have been few studies on the efficacy and optimal duration of treatment for patients with INH-resistant tuberculosis (TB).     

Occult nodal metastasis in patients with non‐small cell lung cancer at clinical stage IA by PET/CT

Background and objective: The introduction of ¹⁸F‐FDG PET/CT has enhanced the diagnostic accuracy of nodal staging for non‐small cell lung cancer (NSCLC). We analysed risk factors for occult nodal metastasis in patients with clinical stage IA NSCLC as determined by ¹⁸F‐FDG PET/CT. Methods: Data for 147 patients diagnosed as clinical stage IA NSCLC by PET/CT from 2005 to 2007 were retrospectively reviewed. All study patients underwent ¹⁸F‐FDG PET/CT for lung cancer staging. They also underwent cervical mediastinoscopy or systematic lymph node dissection. Results: Cervical mediastinoscopy was performed in 78 patients (53.1%), and N2 involvement was detected in 3.8% (3/78) of these patients. Thoracotomy with systematic lymph node dissection was done in 144 patients. Four patients (2.8%, 4/144) were diagnosed with N2 disease after systematic lymph node dissection. Total N2 involvement was 4.8% (7/147). As 9.5% (14/147) of study patients had N1 disease, 14.3% (21/147) of patients had occult nodal (N1 or N2) metastasis. In univariate analyses, larger tumour size and a higher primary tumour maximum standardized uptake value >7.3 (SUV_max) were associated with occult nodal metastasis. Multivariate analysis demonstrated that a primary tumour SUV_max >7.3 was an independent predictor of occult nodal metastasis (odds ratio: 7.574; P = 0.001). Conclusions: Preoperative PET/CT scans contribute to reduce the frequency of occult nodal metastasis compared with those reported in the pre‐PET/CT era. The higher SUV_max in primary tumour was an independent predictor of occult nodal metastasis in patients with clinical stage IA NSCLC by PET/CT.     

Routine screening by brain magnetic resonance imaging decreased the brain metastasis rate following surgery for lung adenocarcinoma

Since May 1999, the institutional guidelines of Samsung Medical Center, Seoul, Korea, have required preoperative magnetic resonance (MR) screening of the brain in all patients with lung adenocarcinoma. To investigate the brain metastasis and survival rates since the adoption of this guideline, we retrospectively reviewed the medical records of patients who underwent complete lung resection between January 1995 and December 2000. Recurrence rate, recurrence site, and survival were investigated and compared between patients with lung adenocarcinoma who underwent complete resection before May 1999, who did not undergo MR screening of the brain (non-MR group, n=160), and those after May 1999, who did receive MR screening of the brain (MR group, n=86). The brain metastasis rate was lower in the MR group than in the non-MR group (p<0.05), especially for the first 2 years. However, the recurrence rate at sites other than the brain was similar between the two groups. The 5-year survival was higher in the MR group (59%) than in the non-MR group (45%, p<0.05). Even in patients with stage I cancer, brain metastasis was diagnosed more frequently in the non-MR group (5%) than in the MR group (2%). Preoperative MR screening of the brain can help early detection of brain metastases in the patients with lung adenocarcinoma prior to surgical resection and lead to increase postoperative survival in patients with operable lung adenocarcinoma.     

Prevalence of gastroesophageal reflux disease in patients with nontuberculous mycobacterial lung disease

BACKGROUND: Knowledge of the relationship between respiratory disorders and gastroesophageal reflux disease (GERD) is increasing. However, the association between GERD and pulmonary disease caused by nontuberculous mycobacteria (NTM) has not been studied in detail. We investigated the prevalence of GERD in patients with the nodular bronchiectatic form of NTM lung disease. METHODS: Fifty-eight patients with the nodular bronchiectatic form of NTM lung disease underwent ambulatory 24-h esophageal pH monitoring. Of the 58 patients, 27 patients were identified as having Mycobacterium avium complex infection (15 with Mycobacterium intracellulare and 12 with M avium), and 31 patients had Mycobacterium abscessus pulmonary infection. RESULTS: The prevalence of GERD in patients with the nodular bronchiectatic form of NTM lung disease was 26% (15 of 58 patients). Only 27% (4 of 15 patients) had typical GERD symptoms. No statistically significant differences were found between patients with GERD and those without GERD with regard to age, sex, body mass index, or pulmonary function test results. However, patients with GERD were more likely to have a sputum smear that was positive for acid-fast bacilli (12 of 15 patients, 80%), compared with patients without GERD (19 of 43 patients, 44%) [p = 0.033]. In addition, bronchiectasis and bronchiolitis were observed in more lobes in patients with GERD than in patients without GERD (p = 0.008 and p = 0.005, respectively). CONCLUSIONS: Patients with the nodular bronchiectatic form of NTM lung disease have a high prevalence of increased esophageal acid exposure, usually without typical GERD symptoms.     

In vitro antimicrobial susceptibility of Mycobacterium abscessus in Korea

Mycobacterium abscessus is the second most common etiology of pulmonary disease caused by nontuberculous mycobacteria in Korea. Although antimicrobial susceptibility tests are important for appropriate patient management in M. abscessus lung disease, the tests have never been investigated in Korea. Seventy-four isolates of M. abscessus recovered from patient respiratory samples were tested against eight antimicrobial agents following the guidelines set forth by the National Committee for Clinical Laboratory Standards. Of the parenteral antibiotics, amikacin (99%, 73/74) and cefoxitin (99%, 73/74) were active against most isolates. Imipenem (55%, 36/66) and tobramycin (36%, 27/74) had activity against moderate number of isolates. Of the oral antibiotics, clarithromycin (91%, 67/74) was active against the majority of isolates. Moxifloxacin (73%, 54/74) and ciprofloxacin (57%, 42/74) had activity against a moderate number of isolates. Doxycycline was the least active, inhibiting only 7% (5/74) of isolates. In conclusion, the variations in susceptibility within M. abscessus isolates to currently available antimicrobials suggest that the antimicrobial susceptibilities of any clinically significant M. abscessus isolate be needed individually.     

Mediastinal nodal staging of nonsmall cell lung cancer using integrated 18F-FDG PET/CT in a tuberculosis-endemic country: diagnostic efficacy in 674 patients

BACKGROUND: Integrated (18)fluorine fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) has shown somewhat variable sensitivity and specificity for mediastinal nodal staging in granulomatous disease endemic areas. The purpose of the study was to prospectively evaluate the efficacy of PET/CT for mediastinal nodal staging in nonsmall cell lung cancer (NSCLC) patients in a tuberculosis-endemic country. METHODS: Prospective assessment of the diagnostic efficacy of integrated PET/CT for detecting mediastinal nodal metastasis was performed in 674 patients (M:F ratio = 502:172; mean age, 61 years) with NSCLC. Patients underwent an integrated PET/CT examination and subsequent surgical nodal staging (by mediastinoscopy only in 121 patients and by thoracotomy in 553). Nodes showing greater (18)F-FDG uptake than mediastinum at PET without benign calcification or high attenuation >70 household unit (HU) at unenhanced CT were regarded as being positive for malignancy. The histologic nodal assessment results were used as reference standards. RESULTS: Of 2477 mediastinal nodal stations evaluated in 674 patients, 275 (11%) stations in 180 (27%) patients proved to be malignant. On a per-person basis, the overall sensitivity, specificity, and accuracy of PET/CT for mediastinal nodal staging were 61% (110 of 180), 96% (473 of 494), and 86% (583 of 674), respectively. On a per-nodal station basis, they were 46% (126 of 275), 98% (2154 of 2202), and 92% (2280 of 2477). CONCLUSIONS: Integrated PET/CT provides high specificity and reasonably high accuracy, but somewhat low sensitivity for mediastinal nodal staging of NSCLCs. The high specificity is achieved at the expense of sensitivity by interpreting calcified nodes or nodes with high attenuation at CT, even with high FDG uptake at PET, as benign in a tuberculosis-endemic region.     

Aberrant methylation of the FHIT gene in chronic smokers with early stage squamous cell carcinoma of the lung

Fragile histidine triad (FHIT) gene plays an important role in the pathogenesis of lung cancer. However, the clinicopathological significance of CpG island hypermethylation of FHIT gene in non-small cell lung cancer (NSCLC) remains to be elucidated. We studied FHIT methylation in 254 NSCLCs in order to further understand the clinicopathological and prognostic significance of FHIT methylation in NSCLC. Methylation status of the FHIT gene was examined using Methylation-Specific PCR. All statistical analyses were two-sided, with a 5% type I error rate. Hypermethylation of the FHIT gene occurred more frequently in squamous cell carcinoma than adenocarcinoma. For 93 adenocarcinomas there was no statistically significant association between FHIT methylation and age, gender, smoking history, pathologic stage and p16 methylation. However, FHIT methylation in 125 squamous cell carcinomas was associated with exposure to tobacco smoke and p16 methylation, but not with age, gender and pathologic stage. Hypermethylation of FHIT in squamous cell carcinomas occurred more frequently in current smokers (45%) than in never-smokers (13%). FHIT methylation was significantly associated with p16 methylation in current- and ex-smokers (P = 0.02 and P = 0.01, respectively) with squamous cell carcinoma and in patients with pathologic stage I squamous cell carcinoma (P = 0.001). Patients with p16 methylation were 3.74 times [95% confidence interval (CI) = 1.62 - 7.95; P = 0.001] more likely to have FHIT methylation in squamous cell carcinoma. FHIT methylation in squamous cell carcinoma occurred at a 4.62 times (95% CI = 1.26 - 34.97; P = 0.02) higher prevalence in current smokers than in never-smokers. No prognostic effect of FHIT methylation was observed in stage I and stage II NSCLCs. In conclusion, hypermethylation of the FHIT gene did not have a prognostic significance in early stage NSCLCs. The FHIT methylation is associated with the p16 methylation and smoking in squamous cell carcinoma, suggesting that FHIT may cooperate with p16 for the development of squamous cell carcinoma of lung in individuals exposed to tobacco smoke.     

Replacement of a tracheal defect with a tissue-engineered prosthesis: early results from animal experiments

OBJECTIVES: The major problems in the development of tracheal prosthesis are anastomotic dehiscence and stenosis, caused by poor epithelialization of the prosthetic graft. We developed a novel tracheal prosthesis with viable mucosa transplanted from the oral cavity and reported excellent long-term results after thoracic tracheal replacements in dogs. In the current study, we used tissue-engineering techniques to construct a mucosal prosthetic lining from skin cells and evaluated its usefulness in tracheal replacement. METHODS: Abdominal skin patches (5 x 10 cm) were harvested from 10 adult mongrel dogs. The epithelial cells were separated, cultured in vitro for 4 weeks, and then seeded onto a porous polylactic glycolic acid scaffold (6 x 8 cm) to construct a lining mucosa. This was then mounted onto the prosthesis framework, made with polypropylene mesh reinforced with polypropylene rings. The mucosa-lined prosthesis was wrapped with the greater omentum of the same dog and placed in the peritoneal cavity for 1 week. Complete surgical resection and replacement of a thoracic tracheal segment (5 cm in length, just above the carina) was then performed using the prosthesis. RESULTS: The animals regained full activity and survived with normal activity. Bronchoscopy at 1 week and at 1 and 2 months revealed no stenosis in the anastomosis. CONCLUSIONS: This highly biocompatible tracheal prosthesis could prove useful for the reconstruction of large, circumferential tracheal defects.