Outcome differences between recanalized malignant central airway obstruction from endoluminal disease versus extrinsic compression.

We compared the outcome of Nd:YAG laser therapy with stent placement for malignant central airway obstruction (CAO) at our center over a 10-year period. This is a retrospective review of patients undergoing Nd:YAG laser therapy or self-expanding metal stent (SEMS) placement for malignant CAO between November 2007 and October 2017. Seventy-two patients were recanalized for malignant CAO. The median (range) age was 63 (23-86) years, with 49 (68%) males. Patients underwent either laser therapy alone (N = 36), stent placement alone (N = 30), or both (N = 6). The wavelength of Nd:YAG laser used was 1064 nm, and median (range) laser energy used was 25 (15-35) W, in 377 (115-1107) pulses. Fifty-one (71%) patients died with median survival of 7.2 months. In subgroup analysis, 21 (58.3%) vs. 25 (83.3%), p = 0.03 patients died in the "laser resection" vs. "stent placement" group with longer median survival of 12.4 months in the former vs. 4.5 months, p = 0.0004 in the later. Esophageal cancer and left main bronchus involvement were significantly more common (10 (33.3%) vs. 0, p = 0.0001, and 16 (53.3%) vs. 8 (22.2%), p = 0.01), in the stent placement vs. laser resection group, respectively. Trachea or main bronchi involvement and respiratory failure on presentation requiring mechanical ventilation correlated with poorer survival. The immediate restoration of luminal patency, complication rate, and 30-day mortality was similar among the two groups. The median (range) energy used for laser therapy was 25 (15-35) W. Median of 377 pulses was used for the duration of 287.5 s. The results were compared using a Wilcoxon two-sample test, and Fischer exact test with p values considered indicative of a significant difference if less than 0.05. In patients requiring recanalization of malignant CAO, the extrinsic compression from esophageal cancer, trachea or main bronchi involvement, respiratory failure on presentation requiring mechanical ventilation, and stent placement correlated with poorer survival. Interventional pulmonology training program should emphasize on dedicated training in laser therapy as it is associated with improved survival.

Using whole genome amplification (WGA) of low-volume biopsies to assess the prognostic role of EGFR, KRAS, p53, and CMET mutations in advanced-stage non-small cell lung cancer (NSCLC).

BACKGROUND: Progression of non-small cell lung cancer (NSCLC) from early- to late-stage may signify the accumulation of gene mutations. An advanced-stage tumor's mutation profile may also have prognostic value, guiding treatment decisions. Mutation detection of multiple genes is limited by the low amount of deoxyribonucleic acid extracted from low-volume diagnostic lung biopsies. We explored whole genome amplification (WGA) to enable multiple molecular analyses. METHODS: Eighty-eight advanced-stage NSCLC patients were enrolled. Their low-volume lung biopsies underwent WGA before direct sequencing for epidermal growth factor receptor (EGFR), KRAS (rat sarcoma virus), p53, and CMET (mesenchymal-epithelial transition factor) mutations. Overall survival impact was examined. Surgically-resected tumors from 133 early-stage NSCLC patients were sequenced for EGFR, KRAS and p53 mutations. We compared the mutation frequencies of both groups. RESULTS: It is feasible for low-volume lung biopsies to undergo WGA for mutational analysis. KRAS and CMET mutations have a deleterious effect on overall survival, hazard ratios 5.05 (p = 0.009) and 23.65 (p = 0.005), respectively. EGFR and p53 mutations, however, do not have a survival impact. There also does not seem to be significant differences in the frequency of mutations in EGFR, KRAS, and p53 between early- and advanced-stage disease: 20% versus 24% (p = 0.48), 29% versus 27% (p = 0.75), 10% versus 6% (p = 0.27), respectively. CONCLUSIONS: In advanced-stage NSCLC, KRAS, and CMET mutations suggest poor prognosis, whereas EGFR and p53 mutations do not seem to have survival impact. Mutations in EGFR, KRAS and p53 are unlikely to be responsible for the progression of NSCLC from early- to late-stage disease. WGA may be used to expand starting deoxyribonucleic acid from low-volume lung biopsies for further analysis of advanced-stage NSCLC.

Detection and comparison of epidermal growth factor receptor mutations in cells and fluid of malignant pleural effusion in non-small cell lung cancer.

Cells or cell-free fluid of malignant pleural effusion could be important clinical specimen for epidermal growth factor receptor (EGFR) mutation screening in advanced non-small cell lung cancer (NSCLC) patients. However, their usefulness in mutation detection has not been well compared. In this study we recruited 26 East Asian NSCLC patients with malignant pleural effusion, determined the mutation status of EGFR in both cells and matched cell-free fluid with the use of sequencing and mutant-enriched PCR. After comparing the mutation spectrums, we found both the cells and cell-free pleural fluid may be feasible clinical specimen for EGFR mutation detection in unresectable NSCLC given sensitive genotyping assays employed. Direct sequencing could miss a significant portion of mutations in these heterogeneous specimens. More sensitive methods, such as mutant-enriched PCR and gene scan, could provide more reliable mutational information.

An alternative approach to determining therapeutic choices in advanced non-small cell lung carcinoma (NSCLC): maximizing the diagnostic procedure and the use of low-volume lung biopsies.

BACKGROUND: Accurate mutational analysis, especially epidermal growth factor receptor (EGFR) mutations, of diagnostic biopsies from all Asian NSCLC patients is crucial to their clinical management, but faces problems. Here, we explore, within usual hospital constraints, the practicalities of incorporating mutational analysis in every newly diagnosed case of NSCLC, namely, maximizing tissue acquisition during the diagnostic procedure and determining the maximum quantity and quality of DNA sequence data available from these biopsies. METHODS: Sixty-eight Chinese patients were enrolled. Thirty-five underwent surgical resections for early-stage tumors. Thirty-three underwent diagnostic procedures, i.e., needle aspirates under bronchoscopic or computed tomographic/fluoroscopic guidance, or forceps biopsies via bronchoscopy. Separate samples for research purposes were obtained from these 33 patients during the diagnostic procedure. All samples were analyzed for mutations in EGFR exons 18 to 21, p53 exons 4 to 9, and Kras exon 2. RESULTS: No deaths occurred in this study. Success rates in obtaining sequence data from surgical samples versus low-volume samples for EGFR, p53, and Kras were 100% versus 85%, 100% versus 82%, and 100% versus 85%, respectively. Sequencing nine polymerase chain reaction products from each low-volume sample resulted in the exhaustion of all extracted DNA from three samples. CONCLUSIONS: Acquiring a separate low-volume lung biopsy sample for mutational analysis in lung cancer patients during the diagnostic procedure is feasible and may be a valuable complement to the usual diagnostic workflow in future.

An Audit of medical thoracoscopy and talc poudrage for pneumothorax prevention in advanced COPD.

OBJECTIVES: To prospectively study all patients with COPD and spontaneous pneumothorax (SP) who underwent thoracoscopic talc poudrage (TP) under local anesthesia to determine its efficacy and safety in recurrence prevention. METHODS: Data on clinical measurements, complications, duration of chest tube drainage, length of hospital stay, and outcome were collected. RESULTS: Forty-one patients (38 men and 3 women) with a mean (+/- SD) age of 70.7 +/- 7.2 years were treated. All patients had COPD, with a mean FEV(1) of 41 +/- 14% predicted. The majority of SPs measured 20 to 50% in size, and 34% were recurrent. Three grams of talc were insufflated into the pleural cavity without complications. Thirteen patients (32%) complained of pain, 5 (12%) developed fever, 27 (66%) had subcutaneous emphysema, and 7 (17%) had prolonged air leaks. Postoperative chest tube drainage and hospital stay were 4 and 5 days, respectively. Success was 95% after a median follow-up of 35 months. Four patients with FEV(1) of < 40% predicted died within 30 days of the procedure, yielding a mortality rate of 10%. FEV(1) (in liters), FEV(1) (in % predicted), and ischemic heart disease were risk factors that influenced early mortality. CONCLUSION: Thoracoscopic TP is effective for pneumothorax prevention and can be performed with acceptable mortality in patients with advanced COPD.

Acute respiratory distress syndrome in critically ill patients with severe acute respiratory syndrome.

CONTEXT: Severe acute respiratory syndrome (SARS) is an emerging infectious disease with a 25% incidence of progression to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and mortality exceeding 10%. OBJECTIVE: To describe the clinical spectrum and outcomes of ALI/ARDS in patients with SARS-related critical illness. DESIGN, SETTING, AND PATIENTS: Retrospective case series of adult patients with probable SARS admitted to the intensive care unit (ICU) of a hospital in Singapore between March 6 and June 6, 2003. MAIN OUTCOME MEASURES: The primary outcome measure was 28-day mortality after symptom onset. RESULTS: Of 199 patients hospitalized with SARS, 46 (23%) were admitted to the ICU, including 45 who fulfilled criteria for ALI/ARDS. Mortality at 28 days for the entire cohort was 20 (10.1%) of 199 and for ICU patients was 17 (37%) of 46. Intensive care unit mortality at 13 weeks was 24 (52.2%) of 46. Nineteen of 24 ICU deaths occurred late (> or =7 days after ICU admission) and were attributed to complications related to severe ARDS, multiorgan failure, thromboembolic complications, or septicemic shock. ARDS was characterized by ease of derecruitment of alveoli and paucity of airway secretion, bronchospasm, or dynamic hyperinflation. Lower Acute Physiology and Chronic Health Evaluation II scores and higher baseline ratios of PaO2 to fraction of inspired oxygen were associated with earlier recovery. CONCLUSIONS: Critically ill patients with SARS and ALI/ARDS had characteristic clinical findings, high rates of complications; and high mortality. These findings may provide useful information for optimizing supportive care for SARS-related critical illness.