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.

P2.06-05 Multimodality Therapy Using Total Pleurectomy in Malignant Pleural Mesothelioma: Long-Term Outcomes in 150 Consecutive Cases

A female non-smoker in her thirties was referred to the chest clinic with a 6-month history of a dry cough, breathlessness and general malaise.

Her chest x ray showed diffuse bilateral ground-glass opacity (fig 1). Her autoimmune profile was negative. An HIV test was negative. Lung function tests showed a restrictive pattern with moderately reduced transfer factor.



Figure 1 
Chest x ray: diffuse bilateral ground-glass opacity.



A high resolution CT (HRCT) showed bilateral ground-glass opacity, more marked on the right, with no evidence of mediastinal or hilar lymphadenopathy (fig 2).



Figure 2 
High …

https://thorax.bmj.com/content/thoraxjnl/64/7/644.full.pdf

A woman in her mid 30s with a dry cough and breathlessness.

Editor,—The report of Hacking et al ,1 of a series of infants with very early onset interstitial lung disease (ILD) with good prognosis, is of great clinical interest but sadly represents a lost investigative opportunity.

Firstly, their statement that percutaneous open lung biopsy has fewer side effects than open lung biopsy (OLB) is not supported by any direct comparative trial, and cannot be allowed to stand. Indeed, the largest published series using this technique2 was heavily criticised both for the number of complications and the often non-diagnostic samples obtained.3 4 By contrast OLB is safe,5 permits direct inspection of the site of biopsy, and allows the acquisition of specimens large enough to determine the lung architecture in order more precisely to classify the different types of paediatric ILD. OLB thus allows appreciation of the distribution of disease involvement within the acinus, allowing more … 

Dr D Hacking, Paediatric Specialist Registrar, Department of Paediatrics, Wexham Park Hospital, Slough, UK (hackandmack{at}lwcdial.net).

https://adc.bmj.com/content/archdischild/85/2/172.3.full.pdf

Methodology for assessing patterns of interstitial pneumonia in children

1 A comparative analysis of cancer hotspot mutation profiles in circulating tumour cells, circulating tumour DNA and matched primary lung tumour

Background Childhood interstitial and diffuse lung diseases (chILD) encompass a broad spectrum of rare pulmonary disorders. In most developing Middle Eastern countries, chILD is still underdiagnosed. Our objective was to describe and investigate patients diagnosed with chILD in a tertiary university hospital in Egypt. Methods We analysed data of consecutive subjects (aged Results 22 subjects were enrolled over 24 months. Median age at diagnosis was 7 years (range 3.5–14 years). The most common manifestations were dyspnoea (100%), cough (90.9%), clubbing (95.5%) and tachypnoea (90.9%). Systematic evaluation led to the following diagnoses: hypersensitivity pneumonitis (n=3), idiopathic interstitial pneumonias (n=4), chILD related to chronic granulomatous disease (n=3), chILD related to small airways disease (n=3), post-infectious chILD (n=2), Langerhans cell histiocytosis (n=2), idiopathic pulmonary haemosiderosis (n=2), granulomatous lymphocytic interstitial lung disease (n=1), systemic sclerosis (n=1) and familial interstitial lung disease (n=1). Among the subjects who completed the diagnostic evaluation (n=19), treatment was changed in 13 (68.4%) subjects. Conclusion Systematic evaluation and multidisciplinary peer review of chILD patients at our tertiary hospital led to changes in management in 68% of the patients. This study highlights the need for an Egyptian chILD network with genetic testing, as well as the value of collaborating with international groups in improving healthcare for children with chILD.

https://openres.ersjournals.com/content/erjor/7/2/00880-2020.full.pdf

Andrew G. Nicholson

Papers

P2.06-05 Multimodality Therapy Using Total Pleurectomy in Malignant Pleural Mesothelioma: Long-Term Outcomes in 150 Consecutive Cases

A woman in her mid 30s with a dry cough and breathlessness.

Methodology for assessing patterns of interstitial pneumonia in children

1 A comparative analysis of cancer hotspot mutation profiles in circulating tumour cells, circulating tumour DNA and matched primary lung tumour

Spectrum of childhood interstitial and diffuse lung diseases at a tertiary hospital in Egypt.