Cheng-Yu Chang

Successful Erlotinib Rechallenge after Gefitinib-Induced Acute Interstitial Pneumonia

Case 1 A 62-year-old nonsmoker man who suffered from a weight loss of 2 kg in 2 months was found to have lung adenocarcinoma with multiple metastases. He received gefitinib (Iressa; AstraZeneca, Wilmington, DE) 250 mg/d as a first-line treatment. Excellent response to gefitinib is noted in his fourth week of treatment. However, fever, dry cough, and dyspnea developed in the sixth week of gefitinib treatment. Pulse oximetry showed a 84% oxyhemoglobin saturation, whereas chest computed tomography revealed bilateral ground-glass opacities (Figure 1A). Gefitinib was discontinued immediately, and methylprednisolone 1.77mg/kg/d was initiated. There was no clinical evidence of tumor progression. No pathologic microorganism was isolated in both sputum and blood cultures, and serology test results for Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila were all negative. There was clinical improvement on the sixth day of steroid therapy and erlotinib (Tarceva; Genentech, OSI Pharmaceuticals, Melville, NY) 150 mg/d was administered concurrently. No pulmonary toxicity recurred because the erlotinib rechallenge and partial tumor remission was achieved (Figure 1B). Progressive disease with leptomeningeal metastasis was documented 7 months later.

Gefitinib-Related Interstitial Lung Disease in Taiwanese Patients With Non–Small-Cell Lung Cancer

BACKGROUND Gefitinib (Iressa; AstreZeneca, Wilmington, DE) is effective in the treatment of NSCLC, especially in the Asian population. However, ILD is usually a serious pulmonary adverse effect and almost leads to cessation of gefitinib treatment. In this study, we investigated the incidence, clinical features, and prognosis of gefitinib-related ILD in Taiwanese patients with NSCLC. PATIENTS AND METHODS This was a retrospective observational study conducted in 2 medical centers and a local teaching hospital. RESULTS A total of 1080 patients with NSCLC, who received at least 1 dose (250 mg per day) of gefitinib treatment, were enrolled. Of these, 42 patients were diagnosed with ILD. Twenty-five of the 42 patients were diagnosed with gefitinib-related ILD (incidence, 2.3%). The main manifestations of ILD included dyspnea, cough, and hypoxemia. Six of the 25 patients (24%) with gefitinib-related ILD required invasive mechanical ventilation and all patients were treated with steroids. Twenty-two patients (88%) discontinued gefitinib treatment without further rechallenge. Ten (40%) patients died directly from ILD and in-hospital mortality was 52%. Eleven patients received subsequent cytotoxic chemotherapy with a mean of 33.5 days after ILD events. Kaplan-Meier analysis demonstrated that gefitinib nonresponder and gefitinib use rather than first-line treatment were associated with poor prognosis when ILD developed during gefitinib treatment. CONCLUSION Taiwanese patients with NSCLC had a relatively high incidence of ILD during gefitinib treatment. Gefitinib-related ILD is usually life-threatening, especially in gefitinib nonresponders and gefitinib use rather than first-line treatment.

Successful Treatment of Severe Heatstroke With Therapeutic Hypothermia by a Noninvasive External Cooling System

Heatstroke is a life-threatening disease; however, no pharmacologic treatment has proven to be effective. In severe cases with multiple organ dysfunction, the mortality remains high and many patients inevitably develop permanent neurologic damage. We report a near-fatal case of exertional heatstroke with multiple organ dysfunction, including generalized convulsions, acute lung injury, and disseminated intravascular coagulation, successfully treated with induced therapeutic hypothermia (33°C [91.4°F]) by a noninvasive external cooling system. After treatment, the patient completely recovered, without any neurologic sequelae during 1 year of follow-up. To our knowledge, this is the first reported case of using therapeutic hypothermia in heatstroke.

Bacterial pneumonia following acute ischemic stroke

Background: The most common serious complication following acute ischemic stroke is pneumonia, which may increase mortality and worsen clinical outcomes. The purpose of this study was to investigate the predictors of 30‐day mortality in patients with pneumonia following acute ischemic stroke. Methods: From June 2006 to May 2011, we retrospectively included 51 patients with pneumonia following acute ischemic stroke. We analyzed the clinical features, microbiologic data, and outcomes. Predictors of 30‐day mortality were investigated by univariate and multivariate analysis. Results: The acute ischemic strokes were caused by large‐artery atherosclerosis in 37 (72.5%) of the 51 patients. We found that the most common pathogen responsible for poststroke pneumonia was Klebsiella pneumoniae, followed by Pseudomonas aeruginosa and Escherichia coli. Ultimately, 12 patients died of progressive sepsis due to pneumonia after the acute ischemic stroke. The 30‐day mortality rate was 23.5%. In the univariate analysis, patients who died within 30 days had higher National Institutes of Health Stroke Scale scores, higher CURB‐65 scores, elevated instability of hemodynamic status, and lower Glasgow Coma Scale (GCS) scores. In Cox regression analysis, a GCS score of <9 on the day of pneumonia onset was only significant indicator for 30‐day mortality (hazard ratio, 6.72; 95% confidence interval, 2.12–21.30, p = 0.001). Conclusion: Pneumonia after acute ischemic stroke is a severe complication. Once stroke‐related pneumonia develops, neurologic assessment, CURB‐65 score, and shock can be used to predict the ultimate prognosis.

Adenoid cystic carcinoma of trachea treated with tumor curettage and adjuvant intensity modulated radiation therapy.

Primary tracheal tumors are rare, accounting for only 0.2% of all thoracic cancers. Adenoid cystic carcinoma (ACC) is the second most common tracheal malignancy. Most ACC patients present with dyspnea, and the symptoms often mimic those of asthma or chronic bronchitis. We report the case of a 79-year-old female patient who presented with dyspnea and wheezing, but showed poor response to bronchodilator treatment. Bronchoscopy revealed a lobulated tumor over the lower third of the trachea, and biopsy revealed adenoid cystic carcinoma. Tumor curettage followed by intensity modulated radiation therapy was performed, and the patient eventually recovered. This case demonstrates that such less invasive management also leads to a favorable outcome.

Risk factors in patients with AFB smear-positive sputum who receive inappropriate antituberculous treatment

Background Acid-fast bacilli (AFB) smear-positive sputum is usually an initial clue in the diagnosis of pulmonary tuberculosis (TB); however, the test is not disease-specific. Nontuberculous mycobacterium-related colonization or lung disease often has AFB smear-positive sputum results, and physicians may prescribe unnecessary antituberculous drugs for these patients. The aim of this study was to analyze the clinical characteristics of patients with AFB smear-positive sputum who received unnecessary anti-TB treatment. Methods and patients From January 2008 to July 2011, we retrospectively enrolled 97 patients with AFB smear-positive sputum who did not have pulmonary TB according to mycobacterial cultures and clinical judgment. We analyzed the clinical and radiographic features of the patients who received inappropriate and unnecessary anti-TB treatment. Preliminary analyses of chisquare and Fisher’s exact tests were applied to determine factors unlikely to be associated with the independent variables. The relationship between independent covariates was then analyzed using multivariate logistic regression. Results Of the 97 enrolled patients, 25 (25.8%) were diagnosed with pulmonary TB and prescribed anti-TB drugs (mostly a combination of isoniazid, rifampicin, ethambutol, and pyrazinamide). The other 72 (74.2%) patients were not initially diagnosed with pulmonary TB and were classified as the control group. Compared to the control group, the patients who received inappropriate anti-TB treatment had more chronic cough as presentation symptom and heavy AFB Ziehl–Neelsen staining in sputum (>10/100 fields, grading 2+ to 4+). There were no significant differences in the radiographic analysis between the two groups. Conclusion Among the patients with AFB smear-positive sputum that did not have pulmonary TB, chronic cough and heavy AFB staining (2+ to 4+) were risk factors for the inappropriate administration of unnecessary anti-TB treatment.

Both gefitinib and erlotinib induced drug-related interstitial lung disease in a patient with pulmonary adenocarcinoma

Treatment for non-small-cell lung cancer with gefitinib and erlotinib is efficacious. However, while many studies have reported on gefitinib-related interstitial lung disease (ILD), less published data are available regarding erlotinib-induced ILD. Here, we report a case of pulmonary adenocarcinoma who developed ILD due to gefitinib initially and erlotinib thereafter. The two episodes of ILD were treated successfully with the discontinuation of the tyrosine kinase inhibitors and high-dose intravenous corticosteroids.

Video-assisted thoracoscopic surgical decortication in the elderly with thoracic empyema: Five years' experience

Background Video‐assisted thoracoscopic surgery (VATS) with decortication is a major treatment for thoracic empyema in the fibropurulent stage. Compared to open thoracotomy, VATS decortication has similar efficacy but fewer postoperative complications in the treatment of thoracic empyema. The role of VATS decortication in the elderly had rarely been investigated. Methods From January 2006 to August 2011, we retrospectively enrolled 33 patients older than 65 years diagnosed as thoracic empyema and treated with VATS decortication. We analyzed the outcomes of this geriatric population, including surgical effectiveness, postoperative morbidity, and mortality. Results A total of 33 patients with mean age of 73.6 ± 7.1 years received VATS decortication for their empyema. Twenty‐one (63.6%) patients were male. Only one patient died of progressive sepsis, due to pulmonary infection 9 days after VATS decortication. The 30‐day mortality was 3% after the surgery. The major etiology (87.9%) of thoracic empyema was pneumonia. The main causes of postoperation morbidity included respiratory failure requiring mechanical ventilation for >7 days (15.2%) and septic shock (15.2%), followed by persistent air leakage for >7 days (9.1%). Twenty‐four (75%) of 32 patients had good re‐expansion of the affected lung 3 months after VATS decortication. Conclusion We concluded that VATS decortication in the treatment of thoracic empyema is effective in elderly patients. The major concerns of postoperative complications are respiratory failure and sepsis.

The value of positron emission tomography in early detection of lung cancer in high‐risk population: a systematic review

Background:  Early detection trials with chest radiography and sputum cytology were ineffective in decreasing lung cancer mortality. The advent of low‐dose spiral chest computed tomography (LDCT) provided clinicians with a new tool that could be with early diagnosis; however, this also raised significant concerns regarding the systematic use of LDCT with its high false‐positive rate for benign nodules. At this time, there is limited information about the true role of PET (positron emission tomography) for early detection of lung cancer.

Imaging patterns and prognosis of patients with gefitinib-related interstitial lung disease.

PURPOSE We aimed to summarize the imaging findings of 25 patients with gefitinib-related interstitial lung disease (ILD), and identify the factors related to prognosis of gefitinib-related ILD in patients with non-small-cell-lung cancer. MATERIALS AND METHODS Diagnosis of gefitinib-induced ILD by at least two chest radiologists was based on a review and analysis of the chest radiography and CT findings plus clinical data in the medical records. All patients were diagnosed with Stage III - IV non-small-cell carcinoma (adenocarcinoma (n = 24), bronchioalveolar cell carcinoma (n = 1)) and essential clinical data such as gefitinib as first-line use and survival status were recorded and analyzed to determine whether these were prognosis predictors. The imaging findings were classified into four patterns according to the previous largest study in Japan. RESULTS The 25 chest radiographs were classified as Pattern A (n = 8), Pattern B (n = 3), Pattern C (n = 6), and pattern D (n = 8). Likewise the 23 CT images were classified as pattern A (n = 8; 34.8%), B (n = 3; 13%), C (n = 5; 21.7%), and D (n = 7; 30.4%). The mortality rate was significantly higher in patients with pattern D than in patients with the other patterns. Pattern D imaging findings were also significantly correlated with non first-line use of gefitinib (p = 0.007). CONCLUSIONS We found an increase in mortality rate in patients with gefitinib associated ILD/pattern D compared to other radiological patterns. Familiarity with these imaging patterns can facilitate early and accurate diagnosis and help physicians gauge clinical prognosis of gefitinib-related ILD.