Keon Hyun Jo

Somatic mutations of the ERBB4 kinase domain in human cancers.

The EGFR family consists of 4 receptor tyrosine kinases, EGFR (ERBB1), ERBB2 (HER2), ERBB3 (HER3) and ERBB4 (HER4). Recent reports revealed that the kinase domains of both EGFR (ERBB1) and ERBB2 gene were somatically mutated in human cancers, raising the possibility that the other ERBB members possess somatic mutations in human cancers. Here, we performed mutational analysis of the ERBB4 kinase domain by polymerase chain reaction–single‐strand conformation polymorphism assay in 595 cancer tissues from stomach, lung, colon and breast. We detected the ERBB4 somatic mutations in 3 of 180 gastric carcinomas (1.7%), 3 of 104 colorectal carcinomas (2.9%), 5 of 217 nonsmall cell lung cancers (2.3%) and 1 of 94 breast carcinomas (1.1%). The 12 ERBB4 mutations consisted of 1 in‐frame duplication mutation and 8 missense mutations in the exons, and 3 mutations in the introns. We simultaneously analyzed the somatic mutations of EGFR, ERBB2, K‐RAS, PIK3CA and BRAF genes in the 12 samples with the ERBB4 mutations and found that 1 gastric carcinoma with ERBB4 mutation also harbored K‐RAS gene mutation. Our study demonstrated that in addition to EGFR and ERBB2, somatic mutation of the kinase domain of ERBB4 occurs in the common human cancers, and suggested that alterations of ERBB4‐mediated signaling pathway by ERBB4 mutations may contribute to the development of human cancers.

Clinical Significance of Vascular Endothelial Growth Factors (VEGF)-C and -D in Resected Non-Small Cell Lung Cancer

PURPOSE Lymphatic spread of tumor is an important prognostic factor for patients with non-small cell lung carcinoma (NSCLC). Vascular endothelial growth factor-C (VEGF-C) and VEGF-D play important roles in lymphangiogenesis via the VEGF receptor 3 (VEGFR-3). We sought to determine whether VEGF-C, VEGF-D and VEGFR-3 are involved in the clinical outcomes of patients with resected NSCLC. MATERIALS AND METHODS Using immunohistochemical staining, we investigated the protein expressions of VEGF-C, VEGF-D and VEGFR-3 in the tissue array specimens from patients who underwent resection for NSCLC. The immunoreactivity for p53 was also examined. The clinicopathological implications of these molecules were statistically analyzed. RESULTS Analysis of a total of 118 specimens showed that VEGF-C, VEGF-D and their co-expression were significantly associated with more advanced regional lymph node metastasis (p=0.019, p=0.044 and p=0.026, respectively, N2 versus N0 and N1). A VEGFR-3 expression had a strong correlation with peritumoral lymphatic invasion (p=0.047). On the multivariate analysis for survival and recurrence, pathologic N2 lymph node metastasis was the only independent prognostic factor, but none of the investigated molecules showed any statistical correlation with recurrence and survival. CONCLUSIONS The present study revealed that high expressions of VEGF-C and VEGF-D were strongly associated with more advanced regional lymph node metastasis in patients with resected NSCLC.

Clinical experience of spontaneous pneumomediastinum: diagnosis and treatment

BACKGROUND Spontaneous pneumomediastinum (SPM) is a benign disease with a variety degree of severity but definite treatment modality is not clearly identified with its rarity. The purpose of this study was to review our experience and discuss the management of SPM according to the severity of disease. METHODS From March 1996 to December 2012, total 64 patients were enrolled and classified as mild, moderate and severe groups and subsequent clinical courses were analyzed retrospectively. RESULTS Fifty-one were males and 13 were females (M:F =3.9:1) with a mean age of 18 years old (range: 10-30 years old). Thirty-six patients were in mild, 22 in moderate and 6 in severe group. Chief complaints were chest pain (50 cases; 78.1%), neck pain (35 cases; 54.7%), dyspnea (18 cases; 28.1%), odynophagia (9 cases; 14.1%) and precipitating factors were coughing in 12 cases, feeding problems in 9 cases, and vomiting in 7 cases; however, 34 patients (53.1%) had no precipitating signs. All patients received oxygen therapy (100%), prophylactic antibiotics in 57 patients (89.1%), and pain medications in 47 patients (73.4%). The mean hospital stay was 4.6 days (range: 1-10 days). There was an increased linear trend according to time to visit (P=0.023) but clinical course demonstrated no significant trend between groups. CONCLUSIONS These data demonstrated that there was no difference in symptom, clinical course and SPM was adequately treated with conservative management regardless of the degree of severity of SPM.

Infective endocarditis in transcatheter aortic valve implantation

An 85-year old man with a history of transcatheter aortic valve implantation (TAVI) for severe symptomatic aortic stenosis was readmitted with cerebral stroke accompanied by fever. An infected prosthetic valve was revealed by echocardiography (Supplementary Video 1) and retrieved successfully with a surgical approach (Fig. 1). Supplementary material (Video 1) is available at EJCTS online. Video 1: Transoesophageal echocardiographic evaulation showing shaggy materials attached to the prosthetic valve with 1-cm floating linear vegetations.

Cardiac perforation caused by bone cement embolism.

MOTS CLÉS Embolisation ; We report a case of right ventricle perforation caused by bone cement embolism in an 86-year-old woman who had complained of progressive chest pain and fever for 6 days. She had a percutaneous vertebroplasty due to a compression fracture of L3—4, 5 years previously. A chest X-ray obtained on admission showed a linear fishbone-like radiopaque material within the cardiac shadow (Fig. 1A). A computed tomography (CT) scan showed this structure to be stuck in the ventricular septum, penetrating the right ventricular free wall. There was no evidence of pulmonary cement embolism on chest CT scan. A transthoracic echocardiogram confirmed that the hyperechoic linear structure, embedded in the apical

Docetaxel Monotherapy as Second-Line Treatment for Pretreated Advanced Non-Small Cell Lung Cancer Patients

Background Second-line chemotherapy offers advanced non-small cell lung cancer (NSCLC) patients a small, but significant increase in survival. Docetaxel is usually administered as a 3-week schedule, yet there is significant toxicity with this therapy. Therefore, a weekly schedule has been explored in several previous trials. In this retrospective study, we compared the efficacy and safety of a weekly schedule and a 3-week schedule of docetaxel monotherapy in a second-line setting. Methods Docetaxel was administered as 75 mg/m2 on day 1 every 3 weeks or as 37.5 mg/m2 on day 1 and 8 every 3 weeks until disease progression or severe toxicity developed. Results From October 2003 to March 2006, a total of 37 patients received docetaxel monotherapy and 36 patients could be evaluated. A total of 135 cycles were administered and then evaluated. The median overall survival was 13.3 months (95% confidence interval: 6.3~20.3) for the weekly schedule and 10.7 months (95% confidence interval: 8.3~13.0) for the 3-week schedule (p=0.41). The median time to progression was 3.0 months (95% confidence interval: 1.9~4.0) and 2.8 months (95% confidence interval: 1.0~4.6), respectively (p=0.41). The response rate was 16.7% for the weekly schedule and 21.1% for the 3-week schedule. The major form of hematologic toxicity was grade 3-4 neutropenia (3-week: 38.9%, weekly: 9.5%). The non-hematologic toxicities were similar between the two schedules. There were no treatment-related deaths. Conclusions A docetaxel weekly schedule was very tolerable and it had comparable activity to that of the 3-week docetaxel schedule. Considering the efficacy and tolerability, a docetaxel weekly schedule can be an alternative schedule for the standard treatment of NSCLC in a second-line setting.

Concomitant Aortoesophageal and Aortobronchial Fistula After Endovascular Aortic Repair

d a u g d 75-year-old man was admitted with excruciating chest pain and hemodynamic collapse 2 months earlier. mergency computed tomographic scan showed a rupured thoracic aorta with mediastinal hematoma (Fig 1A). n endovascular stent-graft was deployed along the decending thoracic aorta through emergency angiogram (Fig B). Completion angiogram showed successful exclusion of he ruptured descending thoracic aorta (Fig 1C). The patient was readmitted with recurrent pneumonia nd intermittent hemoptysis 4 months later. A computed omographic scan on readmission showed crescenthaped air bubbles around the endovascular stent-grafted

Postoperative acute superior mesenteric venous thrombosis after cardiac surgery in a patient with anti-phospholipid syndrome.

Fig. 1. A 45-year-old female was admitted with chest pain and dyspnoea for 2 days. She had a medical history of anti-phospholipid syndrome. Coronary angiogram showed total occlusion of left circumflex artery (A). Moreover, severe ischaemic mitral regurgitation without papillary muscle rupture was found on echocardiography (ECG showing regular sinus rhythm) (B). Preoperative computerised tomography (CT) scan showed no abnormal findings of abdominal visceral and vascular structures (C-1 and C-2). After myocardial revascularisation and mitral valvuloplasty, extubation was performed with minimal inotropic support (dopamine 9 mg/kg/min) 8 h later. However, mild LLQ abdominal discomfort was developed on postoperative 1 day. CA, coeliac axis; ECG, electrocardiography; LLQ, left lower quadrant; SMA, superior mesenteric artery.

Changes of cardiac troponin I and operative mortality of coronary artery bypass.

Background Recently, cardiac troponin I has been used to detect myocardial injury because of its superior cardiac specificity. However, there has been debate about the appropriate timing and cutoff level of cardiac troponin I to detect perioperative myocardial injury after coronary artery bypass grafting. The objective of this study was to define the relationship between operative mortality and changes in cardiac troponin I after isolated coronary artery bypass. Patients and methods A retrospective analysis was carried out on data of 218 isolated coronary artery bypass patients who were operated on between June 2009 and February 2012. All patients followed an institutional perioperative management protocol that included 6 cardiac troponin I measurements (preoperatively and 0, 12, 24, 36, and 48 h after coronary artery bypass). According to the patterns of cardiac troponin I, the patient cohort was divided into 2 groups. Group 1 was patients in whom cardiac troponin I levels decreased 24 h after the operation, and group 2 comprised the patients with cardiac troponin I levels that did not decrease or even increased after 24 h. Results The operative mortality was 4.1% (9/218). Group 2 showed significantly higher mortality (5/25, 20%) than group 1 (4/193, 2.1%). Conclusion An elevated cardiac troponin I level is common after coronary artery bypass. A persistently high level of cardiac troponin I after 24 h is an important predictor of operative mortality after coronary artery bypass surgery.

Total occlusion of both right-sided pulmonary veins after radiofrequency ablation for atrial fibrillation.

Fig. 1. For ectopic origin from the right superior pulmonary vein, the encircling ablatio under the electroanatomic mapping system 7 months earlier. The patient was anticoa 2.0—2.5 for 6 months after the procedure. On admission, the chest radiograph showe After thoracostomy tube drainage, multiple interstitial infiltrate of the right-sided tomographic scan (B). In addition, complete occlusion of the right-sided pulmonary v LLA, left atrial appendage; LIPV, left inferior pulmonary vein; LSPV, left superior p occlusion of right-sided pulmonary veins.