다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

BACKGROUND Most patients with non-small-cell lung cancer have no response to the tyrosine kinase inhibitor gefitinib, which targets the epidermal growth factor receptor (EGFR). However, about 10 percent of patients have a rapid and often dramatic clinical response. The molecular mechanisms underlying sensitivity to gefitinib are unknown. METHODS We searched for mutations in the EGFR gene in primary tumors from patients with non-small-cell lung cancer who had a response to gefitinib, those who did not have a response, and those who had not been exposed to gefitinib. The functional consequences of identified mutations were evaluated after the mutant proteins were expressed in cultured cells. RESULTS Somatic mutations were identified in the tyrosine kinase domain of the EGFR gene in eight of nine patients with gefitinib-responsive lung cancer, as compared with none of the seven patients with no response (P<0.001). Mutations were either small, in-frame deletions or amino acid substitutions clustered around the ATP-binding pocket of the tyrosine kinase domain. Similar mutations were detected in tumors from 2 of 25 patients with primary non-small-cell lung cancer who had not been exposed to gefitinib (8 percent). All mutations were heterozygous, and identical mutations were observed in multiple patients, suggesting an additive specific gain of function. In vitro, EGFR mutants demonstrated enhanced tyrosine kinase activity in response to epidermal growth factor and increased sensitivity to inhibition by gefitinib. CONCLUSIONS A subgroup of patients with non-small-cell lung cancer have specific mutations in the EGFR gene, which correlate with clinical responsiveness to the tyrosine kinase inhibitor gefitinib. These mutations lead to increased growth factor signaling and confer susceptibility to the inhibitor. Screening for such mutations in lung cancers may identify patients who will have a response to gefitinib.

/pdf/activating-mutations-in-the-epidermal-growth-factor-receptor-4a7r2t8eq0.pdf

Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib

Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. Methods: The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Gr...

/pdf/2015-american-thyroid-association-management-guidelines-for-32kri8vrhd.pdf

2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer.

Receptor tyrosine kinase genes were sequenced in nonsmall cell lung cancer (NSCLC) and matched normal tissue. Somatic mutations of the epidermal growth factor receptor gene EGFR were found in 15 of 58 unselected tumors from Japan and 1 of 61 from the United States. Treatment with the EGFR kinase inhibitor gefitinib (Iressa) causes tumor regression in some patients with NSCLC, more frequently in Japan. EGFR mutations were found in additional lung cancer samples from U.S. patients who responded to gefitinib therapy and in a lung adenocarcinoma cell line that was hypersensitive to growth inhibition by gefitinib, but not in gefitinibinsensitive tumors or cell lines. These results suggest that EGFR mutations may predict sensitivity to gefitinib. Protein kinase activation by somatic mutation or

https://science.sciencemag.org/content/sci/early/2004/04/29/science.1099314.full.pdf

EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy.

Introduction Retrospective and anecdotal evidence have been used to suggest that bronchoscopy in patients with IPF could be associated with an increased risk of acute exacerbations or acute respiratory deterioration. We aim to clarify the safety of BAL in patients with IPF in the prospectively recruited PROFILE cohort. Methods Patients diagnosed with IPF within the past 6 months were invited to participate in the PROFILE study. Patients were assessed at baseline, 1, 3, and 6 months and annually for 3 years. Fibreoptic bronchoscopy with BAL was performed at baseline in a subset of the Royal Brompton portion of the cohort. The procedure involved installation of 240 ml of warm saline in four aliquots into the right middle lobe followed by gentle aspiration by hand.Continuous variables are presented as means (±SD) and categorical variables as proportions. Differences between subject groups were evaluated with the use of the Mann–Whitney test for continuous variables and Fisher exact test for categorical variables. Time-to-event curves were calculated using the Kaplan–Meier method and compared with the use of the log-rank test. Results 302 patients were prospectively recruited, of whom 223 underwent bronchoscopy (74%). The 79 IPF patients who did not undergo BAL were older (71.6 vs. 67.8 years, P=0.001) and had a lower DLCo (39.2% vs. 47.6%, P=0.001) compared to subjects undergoing bronchoscopy. All subjects in the bronchoscopy cohort tolerated the procedure well. A leukocyte differential profile was determined in all cases and no immediate ( Conclusions Bronchoscopy is a safe and well tolerated procedure in patients with IPF supporting its use as part of the diagnostic assessment of interstitial lung disease and as a research tool.

P7 The safety of bronchoalveolar lavage in patients with idiopathic pulmonary fibrosis

A previously well 35 year old man who currently smoked cigarettes (40 pack years) was referred because of a history of dyspnoea on exertion that had gradually got worse during the two months before presentation and a cough that was initially productive but then dry. He regularly smoked crack cocaine and took cocaine intranasally. 

At presentation he had hypoxaemia (partial pressure of oxygen 57 mm Hg), with a respiratory rate of 20 breaths/min. Physical examination showed only bilateral fine inspiratory crackles at the middle and lower zones of the chest. Initial blood tests were unremarkable. He had no signs of collagen tissue disorder, his autoantibody profile was negative, and HIV screening was negative. Chest radiography showed a bilateral reticular pattern at the middle and lower zones and bilateral infiltrates in the lower zones of the lung. Pulmonary function testing showed a restrictive pattern (total lung capacity 49%, forced expiratory volume in one second 48%, forced vital capacity 47%, diffusing capacity of the lung for carbon monoxide 36%).

A 12 lead resting electrocardiogram showed sinus rhythm and an echocardiogram showed no abnormalities and no indirect evidence of pulmonary hypertension. Baseline saturation was 96% with a heart rate of 100 beats/min. During the six minute walking distance test he desaturated to 83% after three minutes and having completed 110 m. He underwent high resolution computed tomography of the chest (figs 1 and 2⇓ ⇓).



Fig 1 High resolution computed tomography of the chest: upper lung zones





Fig 2 High resolution computed tomography of the chest: lower lung zones

Andrew G. Nicholson

Papers

P7 The safety of bronchoalveolar lavage in patients with idiopathic pulmonary fibrosis

A 35 year old smoker with shortness of breath