Contribution of double strand break repair gene XRCC3 genotypes to nasopharyngeal carcinoma risk in Taiwan.

The DNA double strand break repair protein XRCC3 plays a central role in removing double strand breaks from the genome and defects in cellular repair capacity is closely related to human cancer initiation. Therefore, we aimed to investigate the contribution of XRCC3 genotypes to individual nasopharyngeal carcinoma (NPC) susceptibility. In this hospital-based population research, the genotyping and analyzing of XRCC3 rs1799794, rs45603942, rs861530, rs3212057, rs1799796, rs861539, rs28903081 in a large Taiwanese population was performed. Totally, 176 NPC patients and 880 age- and gender-matched healthy controls were genotyped and analyzed by PCR-RFLP method. The results showed that there was a differential distribution among NPC and control subjects in the genotypic (P = 0.000488) and allelic (P = 0.0002) frequencies of XRCC3 rs861539. As for the gene-environment interaction, we have firstly provided evidence showing that there is an obvious joint effect of XRCC3 rs861539 CT and TT genotypes with individual smoking habits on increased NPC risk. In conclusion, the T allele of XRCC3 rs861539, interacts with smoking habit in increasing NPC risk, may be an early detection marker for NPC.

The current progress and future prospects of personalized radiogenomic cancer study.

During the last twenty years, mounting studies have supported the hypothesis that there is a genetic component that plays an important role in clinically observed variability in individual tissue/organ toxicity after radiotherapy. We propose the term "Personalized Radiogenomics" for the translational study of individual genetic variations that may associate with or contribute to the responses of tissues to radiation therapy used in the treatment of all types of cancer. The missions of personalized radiogenomic research are 1) to reveal the related genes, proteins, and biological pathways responsible for non-tumor or tumor tissue toxicity resulting from radiotherapy that could be targeted with radio-sensitizing and/or radio-protective agents, and 2) to identify specific genetic markers that can be used in risk prediction and evaluation models before and after clinical cancer surgery. For the members of the Terry Fox Cancer Research Lab in China Medical University and Hospital, the long-term goal is to develop SNP-based risk models that can be used to stratify patients to more precisely tailored radiotherapy protocols. Worldwide, the field has evolved over the last two decades in parallel with rapid advances in genetic and genomic technology, moving step by step from narrowly focused candidate gene studies to large-scale, collaborative genome-wide association studies. This article will summarize the candidate gene association studies published so far from the Terry Fox Cancer Research Lab as well as worldwide on the risk of radiation-related cancers and highlight some wholegenome association studies showing feasibility in fulfilling the dream of personalized radiogenomic cancer therapy.

The role of apurinic/apyrimidinic endonuclease DNA repair gene in endometriosis.

BACKGROUND/AIM: The altered cellular repair capacity plays a critical role in genomic instability and carcinogenesis. We aimed at evaluating the contribution of the polymorphic variant in apurinic/apyriminidinic endonuclease (APEX1) gene to its mRNA and protein levels and the risk of endometriosis. PATIENTS AND METHODS: In the current case-control study, 153 endometriosis patients and 636 non-endometriosis controls were recruited. APEX1 Asp(148)Glu (rs1130409) genotyping was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). At the same time, twenty eight endometriosis tissue samples with different genotypes were examined regarding their expression levels of APEX1 mRNA and protein by quantitative reverse transcription-polymerase chain reaction (q-PCR) and western blotting, respectively. RESULTS: Compared with wild-type TT genotype, TG and GG genotypes of APEX1 Asp(148)Glu had a risk of endometriosis of 0.93- and 0.87-fold. The results from in vivo transcriptional (RNA) and translational (protein) level analysis revealed that the APEX1 mRNA and protein were of similar levels among the endometriosis tissues of people carrying TT, TG, or GG genotypes. There was no joint effect of APEX1 Asp(148)Glu genotype with menarche, pregnancy, smoking or alcohol drinking lifestyles on endometriosis risk. CONCLUSION: The APEX1 Asp(148)Glu genotype correlates well with its mRNA and protein expression among endometriosis patients and may not serve as a sensitive marker for prediction of endometriosis risk in Taiwan.

Contribution of DNA double-strand break repair gene XRCC3 genotypes to oral cancer susceptibility in Taiwan.

The DNA repair gene X-ray repair cross complementing protein 3 (XRCC3) is thought to play a major role in double-strand break repair and in maintaining genomic stability. Very possibly, defective double-strand break repair of cells can lead to carcinogenesis. Therefore, a case-control study was performed to reveal the contribution of XRCC3 genotypes to individual oral cancer susceptibility. In this hospital-based research, the association of XRCC3 rs1799794, rs45603942, rs861530, rs3212057, rs1799796, rs861539, rs28903081 genotypes with oral cancer risk in a Taiwanese population was investigated. In total, 788 patients with oral cancer and 956 age- and gender-matched healthy controls were genotyped. The results showed that there was significant differential distribution among oral cancer and controls in the genotypic (p=0.001428) and allelic (p=0.0013) frequencies of XRCC3 rs861539. As for the other polymorphisms, there was no difference between case and control groups. In gene-lifestyle interaction analysis, we have provided the first evidence showing that there is an obvious joint effect of XRCC3 rs861539 genotype with individual areca chewing habits on oral cancer risk. In conclusion, the T allele of XRCC3 rs861539, which has an interaction with areca chewing habit in oral carcinogenesis, may be an early marker for oral cancer in Taiwanese.

Ventricular hemodynamics using cardiac computed tomography and optical flow method.

Ventricular hemodynamics plays an important role in assessing cardiac function in clinical practice. The aim of this study was to determine the ventricular hemodynamics based on contrast movement in the left ventricle (LV) between the phases in a cardiac cycle recorded using an electrocardiography (ECG) with cardiac computed tomography (CT) and optical flow method. Cardiac CT data were acquired at 120 kV and 280 mA with a 350 ms gantry rotation, which covered one cardiac cycle, on the 640-slice CT scanner with ECG for a selected patient without heart disease. Ventricular hemodynamics (mm/phase) were calculated using the optical flow method based on contrast changes with ECG phases in anterior-posterior, lateral and superior-inferior directions. Local hemodynamic information of the LV with color coating was presented. The visualization of the functional information made the hemodynamic observation easy.

Density features of screened lung tumors in low-dose computed tomography.

RATIONALE AND OBJECTIVES: Using low-dose computed tomography (LDCT), small and heterogeneous lung tumors are detected in screening. The criteria for assessing detected tumors are crucial for determining follow-up or resection strategies. The purpose of this study was to investigate the capacity of density features in differentiating lung tumors. MATERIALS AND METHODS: From July 2008 to December 2011, 48 surgically confirmed tumors (29 malignancies, comprising 17 cases of adenocarcinoma and 12 cases of adenocarcinoma in situ [AdIs], and 19 benignancies, comprising 11 cases of atypical adenomatous hyperplasia [AAH] and eight cases of benign non-AAH) in 38 patients were retrospectively evaluated, indicating that the positive predictive value (PPV) of physicians is 60.4% (29/48). Three types of density features, tumor disappearance rate (TDR), mean, and entropy, were obtained from the CT values of detected tumors. RESULTS: Entropy is capable of differentiating malignancy from benignancy but is limited in differentiating AdIs from benign non-AAH. The combination of entropy and TDR is effective for predicting malignancy with an accuracy of 87.5% (42/48) and a PPV of 89.7% (26/29), improving the PPV of physicians by 29.3%. The combination of entropy and mean adequately clarifies the four pathology groups with an accuracy of 72.9% (35/48). For tumors with a mean below -400 Hounsfield units, the criterion of an entropy larger than 5.4 might be appropriate for diagnosing malignancy. For others, the pathology is either benign non-AAH or adenocarcinoma; adenocarcinoma has a higher entropy than benign non-AAH, with the exception of tuberculoma. CONCLUSIONS: Combining density features enables differentiating heterogeneous lung tumors in LDCT.

Management of distal left main coronary artery aneurysm.

Aneurysms of the left main coronary artery are extremely rare. The cause of such aneurysms is uncertain. Although the treatment of distal left main aneurysms is very complicated, definitive treatment is necessary because the aneurysm may grow further and cause embolism or rupture. Herein, we report a case of acute myocardial infarction caused by aneurysm of the distal left main coronary artery, which was successfully treated by performing coronary artery bypass surgery, followed by implantation of a polytetrafluoroethylene-covered stent.

Association of C-reactive protein and homocysteine with subclinical coronary plaque subtype and stenosis using low-dose MDCT coronary angiography.

OBJECTIVES: Given the uncertainty regarding the relationship of C-reactive protein (CRP) and homocysteine (Hcy) to atherosclerotic burden, our aim was to determine whether CRP and Hcy are related to the presence of subclinical coronary plaque and stenosis. METHODS: We did a cross-sectional analysis of data gathered on 1248 consecutive, newly self-referred, middle-aged subjects who underwent health check ups at China Medical University Hospital. Participants had at least one cardiac risk factor, but no known coronary heart disease. Low-dose multidetector computed tomography coronary angiography (MDCT-CA) was used to measure coronary artery stenosis and identify plaque subtypes. RESULTS: Subjects were divided into quartiles based on levels of high-sensitivity (hs)-CRP and Hcy. hs-CRP level and Hcy level were associated with the relative proportion of plaque subtypes; Hcy level (P<0.05) but not hs-CRP level (P>0.05) was associated with prevalence of artery segment stenosis. After multivariate adjustment for traditional cardiovascular risk factors through logistic regression analysis, neither hs-CRP level nor Hcy level was independently associated with coronary plaque subtypes and stenosis (P>0.05). CONCLUSIONS: Subclinical atherosclerosis is mildly increased in subjects with higher CRP and Hcy levels, but this association is not independent of traditional cardiovascular risk factors. CRP and Hcy are poor predictors of atherosclerotic burden and coronary stenosis.

Impact of the new lung cancer staging system for a predominantly advanced-disease patient population.

INTRODUCTION: To investigate the feasibility and clinical impact of the 7th edition of the "Tumor, Node, Metastasis" (TNM) classification scheme in lung cancer as proposed by the International Association for the Study of Lung Cancer (IASLC) for non-small cell lung cancer. METHODS: We evaluated the feasibility of the new staging system in our routine biweekly multidisciplinary lung cancer staging conference compared with the 6th TNM staging in a prospective manner from April 2008 to June 2009. The impact of IASLC staging versus the 6th TNM staging was observed at three levels: change in substaging, staging, and clinical management (based on the discussion within the staging conference). RESULTS: From 348 patients discussed during these conferences, 226 eligible non-small cell lung cancer patients newly diagnosed within the study period were reviewed and clinically staged. The majority were elderly (median age, 67 years) and men (58%). Of these, 23 patients had different staging, and four patients had different substaging in the IASLC staging compared with the 6th TNM staging. An impact on clinical management was seen in 2.7% (6 of 226) of these patients because of coding ipsilateral different-lobe metastasis as T4 instead of M1. CONCLUSIONS: The new staging system was clinically feasible and resulted in some (27 of 226, 12%) differences in staging. An impact on clinical decision making was occasionally seen within our institutional practice. Further studies are needed to investigate the comprehensive and long-term impact of the new staging system.

Metallic stents for rescuing a patient with severe upper airway compression due to aortic aneurysm.

Aortic aneurysm is usually a potentially life-threatening medical problem, with a 5-year survival rate of 20% if there is no surgical repair. Upper airway compression due to aortic aneurysm usually presents with wheezing, coughing, hemoptysis, dyspnea, or pneumonitis. We report a 78-year-old male patient with a history of chronic obstructive pulmonary disease who was admitted to our emergency department because of wheezing dyspnea for 2 days. Acute chronic obstructive pulmonary disease exacerbation with respiratory failure was impressed, but the patient had poor response to bronchodilators and systemic steroids treatment. Because chest radiography revealed a widening of the upper mediastinum and right lower lung collapse, fiberoptic bronchoscopy was performed and revealed narrowing at the lower portion of trachea and orifice of right main bronchus. Chest computed tomography scan showed aortic aneurysm involving the aortic arch and near the entire thoracic aorta. Because of his poor condition, surgery for aortic aneurysm was not suggested by the thoracic surgeons. We deployed expandable metallic stents in the right main stem bronchi and in the distal trachea. The patient was then weaned from mechanical ventilation a few days later.

Role of chest computed tomography in head and neck cancer.

OBJECTIVES: To evaluate the role of chest computed tomography (CT) in patients with head and neck squamous cell carcinoma (HNSCC) and to determine the optimal timing and predictive factors for positive findings. DESIGN: Retrospective analysis. SETTING: Tertiary referral center. PATIENTS: Two hundred seventy screening chest CT scans performed in 192 patients with HNSCC during a 42-month period were reviewed. MAIN OUTCOME MEASURES: The scans were categorized as new cases, follow-up cases, or recurrent cases. The results were classified as abnormal or normal. Scans of patients having a radiologic diagnosis of a malignant neoplasm of the lung or an indeterminate lesion were considered abnormal. Factors correlating with an abnormal chest CT scan or development of malignant neoplasm of the lung were analyzed, including the timing of imaging and the patients' clinicopathologic data. RESULTS: Seventy-nine scans (29.3%) were considered abnormal. The rate of an abnormal scan was significantly higher in the follow-up case group (44.2%) than in the new case group (14.2%) (P < .001). Ten of 15 indeterminate scans (66.7%) with small (<1 cm) solitary pulmonary nodules showed disease progression on subsequent follow-up scans, changing the patients' diagnoses to a malignant neoplasm of the lung. The predictive factors for development of a malignant neoplasm of the lung were initial N2 or N3 disease, stage IV disease, recurrent disease, and distant metastasis to another site. CONCLUSIONS: Chest CT is recommended for high-risk patients, especially during the follow-up period. Intensified evaluation and management are mandatory for indeterminate small solitary pulmonary nodules because of the high rate of malignant neoplasms.

The role of false lumen size in prediction of in-hospital complications after acute type B aortic dissection.

OBJECTIVES: The aim of this study was to determine whether false lumen size predicts in-hospital complications for acute type B aortic dissection. BACKGROUND: The incidence of complications developing in patients with acute type B aortic dissection has been high. However, methods for recognizing high-risk patients have not been well-studied. We used quantitative analysis by computed tomography (CT) to predict the occurrence of in-hospital complications. METHODS: Fifty-five consecutive patients with acute type B aortic dissection documented by CT imaging were analyzed. They were divided into groups, with and without in-hospital complications, and compared regarding maximal aortic diameter (MAD), maximal false lumen area (MFLA), minimal true lumen area (MTLA), branch-vessel involvement (BVI), and longitudinal length (LL) of aortic dissection. RESULTS: There were 31 patients with a stable course (group 1) and 24 patients who developed complications (group 2). The MFLA of group 2 was significantly larger than that of group 1 (group 1 vs. group 2=577.7+/-273.2 mm2 vs. 1,899.3+/-1,642.4 mm2, p<0.001). The BVI number was also higher in group 2 (group 1 vs. group 2=1.0+/-1.1 vs. 3.3+/-2.0, p<0.001). On multivariate analysis, only MFLA and BVI number were independent predictors of in-hospital complications. Patients with initial MFLA>or=922 mm2 or BVI number>or=2 showed a significantly higher incidence of in-hospital complications than the other patients (p<0.001). CONCLUSIONS: A large MFLA and a higher BVI number are powerful predictors of in-hospital complications after acute type B aortic dissection.

Electron beam computed tomography evidence of aortic calcification as an independent determinant of coronary artery calcification.

BACKGROUND: Imaging of the aorta has received less attention than imaging of the coronary beds, despite the possible link between aortic and coronary artery disease (CAD). Electron beam computed tomography (EBCT) with 100 ms scanning speed can eliminate pulsation-related motion artifacts. The goals of this study were to evaluate EBCT-detected subclinical atherosclerosis over the whole aorta as in routine abdominal and thoracic CT scans and analyze whether or not the measurements of aortic calcification (AC) can independently predict the presence of coronary artery calcification (CAC), which is a surrogate marker of CAD. METHODS: A consecutive series of 196 adults (male:female, 127:69; mean age, 65.9 +/- 10.5 years) were enrolled for EBCT examinations of the coronary arteries and whole aorta. CAC and AC were calculated by the Agatston method. Major cardiovascular risk factors were also recorded. RESULTS: The greatest amount of AC was seen at the abdominal aorta, followed by the descending aortic arch, thoracic aorta, and ascending aorta. Total AC was significantly correlated with CAC (r = 0.51, p < 0.001). After adjustment for major cardiovascular risk factors of age, gender, diabetes, hypertension, hypercholesterolemia, and family history, the three independent significant determinants of CAC were abdominal AC, thoracic descending AC, and male gender (model r2 = 0.495, p < 0.001). For receiver operating characteristic analysis in predicting the presence of CAC, the threshold of descending AC was 11, with 68.3% sensitivity and 75.0% specificity. The optimal threshold of abdominal AC was 123, with 74.1% sensitivity and 67.9% specificity. CONCLUSION: AC values in different portions of the aorta are independent predictors for the presence of CAC.

Middle lobe syndrome as the pulmonary manifestation of primary Sjögren's syndrome.

Middle lobe syndrome - recurrent atelectasis and/or bronchiectasis involving the right middle lobe and/or lingula - has, up to now, not been reported as the pulmonary manifestation of primary Sjögren's syndrome. We describe a patient in whom lymphocytic bronchiolitis in the atelectatic lobes was proved histologically from two separate transbronchial biopsies. The atelectasis responded well to glucocorticoid treatment, suggesting that the peribronchiolar lymphocytic infiltrates may have played an important role in the development of middle lobe syndrome in this patient.

Sonographically guided core needle biopsy of soft tissue neoplasms.

PURPOSE: This study was conducted to evaluate the usefulness of sonography (US)-guided needle biopsy in the diagnosis of soft tissue masses. PATIENTS AND METHODS: Thirty-seven patients with a mean age of 49 years were enrolled in the study. The size of the biopsy needle was selected according to the kind of tumor suspected (ie, primary or metastatic). In patients with suspected metastases, smaller biopsy needles were used; in patients with suspected primary tumors, larger needles were used so that larger specimens could be obtained. Prebiopsy color Doppler sonography (CDUS) was routinely used to guide the cutting needle to areas of the lesion showing sufficient vascularity. From 3 to 6 cores were obtained, depending on their quality. We compared the diagnoses yielded by the core biopsy and the final histopathologic analysis of the resected tumor by classifying the results as "concordant" or "discordant." RESULTS: A total of 37 tumors were examined. Final diagnoses were 24 malignant tumors (6 metastases and 18 primary tumors) and 13 benign tumors. The lesions were diagnosed correctly as either benign or malignant in 35 of the 36 cases for which needle biopsy specimens were adequate, with only 1 misdiagnosis. The diagnoses were concordant in 33 cases (17 primary malignant tumors, 6 metastatic tumors, and 10 benign tumors) and were discordant diagnosis in the other 4 cases (1 primary malignant tumor and 3 benign tumors). No complications were attributable to the needle biopsy. CONCLUSIONS: US-guided percutaneous core needle biopsy of soft tissue neoplasms is an easy, safe, and useful procedure. It can be considered a first-line procedure for the acquisition of tissue specimens adequate for histopathologic diagnosis.

Percutaneous retrieval of 20 centrally dislodged Port-A catheter fragments.

A total of 20 patients with centrally embolized Port-A catheter fragments underwent the percutaneous retrieval procedures at our hospital. The causes of the dislodgement of these catheters included bad connection between the port and catheter, angulation or distortion at the anastomosis site, severing the catheter during insertion and removal of the catheter, improper catheter position and fatigue of the catheter. Consequently, improper procedure handling by the inexperienced surgeons could be considered as the most frequent cause of embolization. The percutaneous retrieval procedures were successful in all centrally embolized fragments. Of 20 successful retrievals, 16 were performed will loop snare catheters and 4 with Dormia basket retrievers.

Percutaneous retrieval of intravascular foreign bodies: experience with 19 cases.

From April 1994 to June 2002, 17 catheter fragments and two guidewires became intravascular foreign bodies during venous catheterization at our hospital. Retrievals of these 19 foreign bodies were performed percutaneously with loop snare techniques (10 cases), Dormia basket retrievers (eight cases) and grasping forceps (one case). The percutaneous retrieval procedures were successful in 18 of 19 cases. A broken Port-A catheter fragment anchored and entrapped in the vascular wall of the right brachiocephalic vein failed to be removed. No complication was noted during or after these percutaneous procedures. Our experience indicates that intravascular foreign bodies can be removed easily, safely, and successfully with currently available percutaneous methods. As a result, major surgical procedures can be avoided if interventional radiologists are familiar with a variety of techniques for the removal of the expanding spectrum of intravascular foreign bodies currently encountered.