Genetic Background Analysis of Protein C Deficiency Demonstrates a Recurrent Mutation Associated with Venous Thrombosis in Chinese Population

Background: Protein C (PC) is one of the most important physiological inhibitors of coagulation proteases. Hereditary PC deficiency causes a predisposition to venous thrombosis (VT). The genetic characteristics of PC deficiency in the Chinese population remain unknown. Methods: Thirty-four unrelated probands diagnosed with hereditary PC deficiency were investigated. PC activity and antigen levels were measured. Mutation analysis was performed by sequencing the PROC gene. In silico analyses, including PolyPhen-2, SIFT, multiple sequence alignment, splicing prediction, and protein molecular modeling were performed to predict the consequences of each variant identified. One recurrent mutation and its relative risk for thrombosis in relatives were analyzed in 11 families. The recurrent mutation was subsequently detected in a case (VT patients)-control study, and the adjusted odds ratio (OR) for VT risk was calculated by logistic regression analysis. Results: A total of 18 different mutations, including 12 novel variants, were identified. One common mutation, PROC c.565C.T (rs146922325:C.T), was found in 17 of the 34 probands. The family study showed that first-degree relatives bearing this variant had an 8.8-fold (95%CI = 1.1–71.6) increased risk of venous thrombosis. The case-control (1003 vs. 1031) study identified this mutation in 5.88 % patients and in 0.87 % controls, respectively. The mutant allele conferred a high predisposition to venous thrombosis (adjusted OR = 7.34, 95%CI = 3.61–14.94). The plasma PC activity and antigen levels i

The IASLC/ITMIG thymic epithelial tumors staging project: Proposals for the T component for the forthcoming (8th) edition of the TNM classification of malignant tumors

Despite longstanding recognition of thymic epithelial neoplasms, there is no official American Joint Committee on Cancer/ Union for International Cancer Control stage classification. This article summarizes proposals for classification of the T component of stage classification for use in the 8th edition of the tumor, node, metastasis classification for malignant tumors. This represents the output of the International Association for the Study of Lung Cancer and the International Thymic Malignancies Interest Group Staging and Prognostics Factor Committee, which assembled and analyzed a worldwide database of 10,808 patients with thymic malignancies from 105 sites. The committee proposes division of the T component into four categories, representing levels of invasion. T1 includes tumors localized to the thymus and anterior mediastinal fat, regardless of capsular invasion, up to and including infiltration through the mediastinal pleura. Invasion of the pericardium is designated as T2. T3 includes tumors with direct involvement of a group of mediastinal structures either singly or in combination: lung, brachiocephalic vein, superior vena cava, chest wall, and phrenic nerve. Invasion of more central structures constitutes T4: aorta and arch vessels, intrapericardial pulmonary artery, myocardium, trachea, and esophagus. Size did not emerge as a useful descriptor for stage classification. This classification of T categories, combined with a classification of N and M categories, provides a basis for a robust tumor, node, metastasis classification system for the 8th edition of American Joint Committee on Cancer/Union for International Cancer Control stage classification

Monitoring and management of lung cancer patients following curative-intent treatment: clinical utility of 2-deoxy-2-[fluorine-18]fluoro-d-glucose positron emission tomography/computed tomography

Shigeki Sawada, Hiroshi Suehisa, Tsuyoshi Ueno, Ryujiro Sugimoto, Motohiro Yamashita Department of Thoracic Surgery, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan Abstract: A large number of studies have demonstrated that 2-deoxy-2-[fluorine-18]fluoro-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) is superior to conventional modalities for the diagnosis of lung cancer and the evaluation of the extent of the disease. However, the efficacy of PET/CT in a follow-up surveillance setting following curative-intent treatments for lung cancer has not yet been established. We reviewed previous papers and evaluated the potential efficacy of PET-CT in the setting of follow-up surveillance. The following are our findings: 1) PET/CT is considered to be superior or equivalent to conventional modalities for the detection of local recurrence. However, inflammatory changes and fibrosis after treatments in local areas often result in false-positive findings; 2) the detection of asymptomatic distant metastasis is considered to be an advantage of PET/CT in a follow-up setting. However, it should be noted that detection of brain metastasis with PET/CT has some limitation, similar to its use in pretreatment staging; 3) additional radiation exposure and higher medical cost arising from the use of PET/CT should be taken into consideration, particularly in patients who might not have cancer after curative-intent treatment and are expected to have a long lifespan. The absence of any data regarding survival benefits and/or improvements in quality of life is another critical issue. In summary, PET/CT is considered to be more accurate and sensitive than conventional modalities for the detection of asymptomatic recurrence after curative-intent treatments. These advantages could modify subsequent management in patients with suspected recurrence and might contribute to the selection of appropriate treatments for recurrence. Therefore, PET/CT may be an alternative to conventional follow-up modalities. However, several important issues remain to be solved. PET/CT in a follow-up surveillance setting is generally not recommended in clinical practice at the moment. Keywords: lung cancer, follow-up surveillance, FDG-PET/C