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.

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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.

Update on mesothelioma diagnosis and classification

Klippel-Trenaunay syndrome (KTS) is a rare congenital disorder with pathognomonic capillarylymphatic-venous malformation (CLVM) of an extremity in association with soft-tissue and/or skeletal overgrowth. Truncal manifestation of the disorder is uncommon and rarely symptomatic but can result in chylothorax. We report on our experience with the management of chylothorax in Klippel-Trenaunay syndrome, in a unique case of a 57-year-old female patient with metachronous bilateral chylothoraces requiring sequential surgical pleurodesis procedures, to draw attention to potential challenges posed by the pathophysiology of this uncommon manifestation. In our experience, surgical management of chylothorax in KTS should be minimally invasive. Thoracic duct ligation is not recommended, mainly due to overexpression of lymphatic collaterals, and because of theoretically possible reflux of chyle to the lower part of the body. Pleural biopsies anywhere but the point of entry should be avoided as they may result to significant concomitant chyle leak. Limited intra-operative tissue handling is advised, to reduce the risk of prolonged leakage, and utilisation of modern local haemostats should be prioritised over cauterization techniques. Nutritional status plays an essential role in chylothorax treatment, we recommend intraoperative insertion of a central line for post-operative total parenteral nutrition as a standard and lastly, considering the course of our case, we further recommend contralateral prophylactic pleurodesis or concurrent bilateral pleurodesis in KTS patients with chylothorax.

/pdf/a-rare-manifestation-of-klippel-trenaunay-syndrome-with-4v2e6urila.pdf

A rare manifestation of Klippel-Trenaunay syndrome with bilateral chylothorax requiring surgical management—a case report

Background: The PATHways survey aimed to capture pathologists’ perspectives on current diagnostic pathways, the increasing role of molecular diagnostic tests, and improvement opportunities for optimising pathways to ensure equitable and timely access. Here we report the results for breast cancer (BC) testing. 

PATHways UK survey: Pathology perceptions on current biomarker testing and pathways for breast cancer in England

/pdf/author-correction-integrated-genomics-point-to-immune-1b8n49zc.pdf

Andrew G. Nicholson

Papers

Update on mesothelioma diagnosis and classification

A rare manifestation of Klippel-Trenaunay syndrome with bilateral chylothorax requiring surgical management—a case report

PATHways UK survey: Pathology perceptions on current biomarker testing and pathways for breast cancer in England

Author Correction: Integrated genomics point to immune vulnerabilities in pleural mesothelioma

E12-03: Intra-operative pathology consultation - novel approaches to frozen section