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.

Left atrial and left ventricular diastolic function after the maze procedure for atrial fibrillation in mitral valve disease: degenerative versus rheumatic.

The present study was aimed to compare the left atrial and left ventricular diastolic functions amongst the rheumatic and degenerative mitral valve disease patients in atrial fibrillation who reverted to normal sinus rhythm following Cox-maze procedure. We prospectively investigated the left atrial and left ventricular function with Doppler echocardiography, by dividing into the rheumatic (N = 105) and the degenerative group (N = 47). Over the follow-up period (mean: 4.4 ± 1.2 years in the rheumatic group, 4.8 ± 1.3 years in the degenerative group), the rheumatic group showed statistically significant decrease in A' velocity and E' velocity, on contrary to degenerative group (A' velocity: mean decrease of 0.43 ± 0.13 cm/s in the rheumatic group, mean increase of 0.57 ± 0.11 cm/s in the degenerative group, p = 0.029, E' velocity: mean decrease of 0.23 ± 0.17 cm/s in the rheumatic group, mean increase of 0.21 ± 0.15 cm/s in the degenerative group, p = 0.031). In addition, the rheumatic group showed statistically significant increase in E/E' ratio than the degenerative group (mean increase of 4.49 ± 1.98 in the rheumatic group, mean increase of 1.74 ± 1.52 in the degenerative group, p = 0.047). Despite successful sinus rhythm restoration, the progressive loss of LA function as well as LV diastolic function is more prominent in the rheumatic group than the degenerative group. Therefore, differentiated strategies for postoperative surveillance are needed according to the pathology of mitral valve disease.

Lymphatic vessel invasion in pathologic stage I and II non-small cell lung tumors.

PURPOSE: Tumor node-metastasis staging is essential for predicting the prognosis of patients with non-small cell lung cancer (NSCLC); however, its accuracy remains limited. The aim of this study was to establish the significant predictors of outcome for patients with pathologic stage I or II NSCLC. METHODS: We reviewed the records of patients with pathologic stage I and II NSCLC retrospectively. After the exclusion of those who underwent sublobar resection, received neoadjuvant treatment, or died within 30 days of surgery, 271 patients treated between January, 2004 and December, 2010 were analyzed. We investigated whether lymphatic vessel invasion (LVI) grade was associated with prognosis in stage I or II NSCLC. RESULTS: The median age of the patients was 64 years. Of the 198 and 73 patients with pathologic stage I and stage II disease, respectively, 73 (26.9%) had LVI. Thirteen patients had a high degree of LVI. Although LVI was not associated with overall survival (p = 0.13), a high degree of LVI was associated with poor survival (p < 0.001). Multivariate analysis revealed that diabetes mellitus (p = 0.001), tumor size (p < 0.001), LVI grade (p < 0.001), and pathologic stage II (p = 0.040) were all associated with overall survival. CONCLUSIONS: A higher grade of LVI was predictive of a worse prognosis. Further study is required to establish the prognostic role of moderate and marked LVI in NSCLC.

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.

Pain after median sternotomy: collateral damage or mitigatable byproduct?

BACKGROUND: Postoperative acute pain can cause anxiety and decrease the quality of life in patients. Acute sternal bone pain after cardiac surgery can persist for long time. OBJECTIVE: The aim of this study is to explore the relationships between the degree of sternal misalignment and the degree of acute sternal pain after coronary artery bypass grafting surgery (CABG). METHODS: We retrospectively reviewed postoperative coronary computed tomographic (CT) angiography and medical records in 104 patients who received CABG between May 1, 2009 and January 31, 2011. CT scan was classified into five categories, and we compared the degree of misalignment and subjective pain via numerical rating scale (NRS) system. RESULTS: Positive correlation was noted between NRS and the degree of sternal misalignment (Pearson correlation coefficient 0.660, p = 0.000). CONCLUSION: Postoperative sternal pain is related to the degree of misalignment of the sternal halves. It would be appropriate for surgeons to approximate the sternal halves accurately to decrease the postoperative sternal wound pain in the first place.

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.

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.

ERBB2 kinase domain mutation in the lung squamous cell carcinoma.

Mounting evidence exists that the activation of proto-oncogene by somatic mutation plays an important roles in the development of human cancers. Recent reports revealed that the kinase domain of ERBB2 gene, a proto-oncogene, is somatically mutated in the lung adenocarcinomas, suggesting the mutated ERBB2 gene may act as an oncogene in human cancers. The purpose of this was to see whether the ERBB2 kinase domain is mutated in other lung cancer types besides the adenocarcinoma. Here, we performed mutational analysis of the ERBB2 kinase domain by polymerase chain reaction-single strand conformation polymorphism assay in 114 non-adenocarcinoma type non-small cell lung cancers (NSCLCs) tissue samples, including 100 squamous cell carcinomas, three adenosquamous carcinomas and 11 large cell carcinomas. We detected the ERBB2 kinase domain mutation in one squamous cell carcinoma (1.0%). The detected ERBB2 mutation showed G to C transversion at bp 2305 (2305G>C), which would result in the substitution of Asp to His at codon 769 (D769H). The amino acid D769 is located in the alpha-helix within the kinase domain, which is important in the binding of ATP with ERBB2. We simultaneously analyzed the somatic mutations of EGFR, K-RAS, PIK3CA and BRAF genes in the squamous cell carcinoma with the ERBB2 mutation, and found that the tumor did not harbor any EGFR or ERBB2 or K-RAS or PIK3CA or BRAF gene mutation, either. This study demonstrated that in addition to lung adenocarcinoma ERBB2 kinase domain mutation could occur in lung squamous cell carcinomas, and suggested that alterations of ERBB2-mediated signaling pathway by ERBB2 mutations may occasionally contribute to the development of lung squamous cell carcinomas.

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.