Shih-Chun Lee

Prognostic significance of global histone modifications in resected squamous cell carcinoma of the esophagus

Patterns of global histone modifications have been recently suggested as outcome predictors in cancer patients. To date, there has been no report on the prognostic significance of global histone modifications in esophageal squamous cell carcinoma. We investigated the role of global histone modification as outcome predictor in patients undergoing esophagectomy for esophageal squamous cell carcinoma. A retrospective clinicopathologic analysis was undertaken of 97 patients with esophageal squamous cell carcinoma who recovered from esophagectomy. Immunohistochemical expression of five histone modification markers, acetylated histone 3 lysine 18 (H3K18Ac), acetylated histone 4 lysine 12 (H4K12Ac), dimethylated histone 4 arginine 3 (H4R3diMe), dimethylated histone 3 lysine 4 (H3 K4diMe), and trimethylated histone 3 lysine 27 (H3K27triMe) was assessed in paraffin-embedded tumor samples. Results were analyzed in relation to patients’ clinicopathologic parameters. There was a positive relationship between tumor differentiation and H3K18Ac (P<0.001), H4R3diMe (P=0.003), and H3K27triMe (P<0.001). Expression of H3K27triMe correlated positively with nodal (N) status (P=0.012) and stage (P=0.025). Univariate analysis showed that better survival in patients with low expression of H3K18Ac (P=0.038) and H3K27triMe (P=0.003). Multivariate analysis showed that nodal status, metastasis status (M), and expression of H3K27triMe predicted survival independently (P<0.001, P=0.016, and 0.048, respectively). Low expression of H3K18Ac and H3K27triMe correlated with better prognosis of patients with esophageal squamous cell carcinoma, especially for those of early stages. We hypothesize that expression of H3K27triMe may be considered as a significant survival predictor for patients with esophageal squamous cell carcinoma.

The impact of smoking in primary spontaneous pneumothorax.

BACKGROUND The crucial role of cigarette smoking in the development of pneumothorax is unclear because nonsmokers can also develop primary spontaneous pneumothorax. The purpose of this study was to clarify the pathophysiologic effects of cigarette smoking and its clinical correlations in primary spontaneous pneumothorax. METHODS Included were 115 specimens of lung tissue from patients with primary spontaneous pneumothorax who underwent video-assisted thoracoscopic surgery from January 2001 to December 2002. We reviewed the clinical features of 56 smokers and 59 nonsmokers with an average follow-up of 67 months. The pathologic findings of resected lung specimens were analyzed retrospectively. RESULTS There were no statistical differences in sex, age, body height, body weight, body mass index, or the presence of blebs/bullae on computed tomography scans of the lung or under thoracoscopy between the 2 groups. In the smoking group, patients had more extensive respiratory bronchiolitis (P < .001), a high prevalence of tobacco pigmentation (P < .001), and a higher recurrence rate without or after surgery than the nonsmoking group (57% vs 22%, P = .001 and 8.9% vs 1.7%, P = .02, respectively). Patients with extensive respiratory bronchiolitis had significantly higher nonoperative and postoperative recurrences than patients with nonextensive respiratory bronchiolitis (P = .004 and P < .001, respectively). CONCLUSION Cigarette smoking is associated with the pathophysiologic consequences of extensive respiratory bronchiolitis, which had a significant impact on the recurrence rates of primary spontaneous pneumothorax.

Cortactin, fascin, and survivin expression associated with clinicopathological parameters in esophageal squamous cell carcinoma

Cortactin, fascin, and survivin have been documented in several human cancers and play important roles in tumor progression. We collected 57 surgical specimens, including esophageal squamous cell carcinomas (SqCC; 7 well-differentiated, 15 moderately differentiated, and 24 poorly differentiated), 3 dysplasias, and 8 normal esophageal tissues. Tissue microarrays were constructed and the immunostaining scores for cortactin, fascin, and survivin were assessed. In 46 SqCC specimens, we examined the relationship between the expression of three biomarkers and tumor differentiation or clinical parameters. Higher immunostaining scores for cortactin, fascin, and survivin correlated positively with tumor differentiation of esophageal SqCC. Univariate survival analysis showed significantly worse prognosis in patients with high scores of cortactin (>or=290), fascin (>or=245), and survivin (score >or= 175), poor differentiation, T4 stage, positive for lymph node metastasis, and positive for distant metastasis. In multivariate survival analysis, high scores of survivin (>or=175) and poor differentiation were independent risk factors for worse prognosis. Our results demonstrated that higher expression of survivin may be related to tumor progression and it is an independent risk factor for poor survival time of esophageal SqCC. Survivin may be a good biomarker to be applied in clinic to predict the prognosis of esophageal SqCC.

Simultaneous bilateral primary spontaneous pneumothorax

Objective:  While primary spontaneous pneumothorax (PSP) is common in adolescents and young adults, simultaneous bilateral PSP (SBPSP) is rare and can be life‐threatening if it progresses to tension pneumothorax. This study reviewed cases of PSP to identify the clinical features of SBPSP.

The Extract of Hibiscus syriacus Inducing Apoptosis by Activating p53 and AIF in Human Lung Cancer Cells

Natural products including plants, microorganisms and marine life provide rich resources for anticancer drug discovery. The root bark of Hibiscus syriacus has been used as an antipyretic, anthelmintic and antifungal agent in Asia. The antiproliferative effects of H. syriacus on human lung cancer cells were evaluated with bio-assays. The apoptotic activity was detected by Hoechst 33342 DNA staining and annexin V staining. The expression of caspases, p53, apoptosis induced factor (AIF), Bcl-2 and Bax were evaluated with Western blotting. The in vivo anticancer activity was evaluated using A549-xenograft model. The acetone extract of H. syriacus (HS-AE) exhibited a better cytotoxic effect on lung cancer cells than its methanol extract (HS-ME) or water extract (HS-WE). The IC(50) values of HS-AE on A549 (adenocarcinoma), H209 (squamous cell carcinoma) or H661 (large cell carcinoma) lung cancer cells ranged from 14 to 22 microg/ml after 48 hours of treatment. After 48 hours of exposure, HS-AE (15 microg/ml) induced A549 cell apoptosis to 48 +/- 3.6% of the control. Using Western blotting, HS-AE appears to suppress the expression of p53 and AIF. The results of the in vivo study showed that HS-AE suppresses growth in A549 subcutaneous xenograft tumors. These results indicate that HS-AE exerts significant and dose-dependent antiproliferative effects on cancer cells in vitro and in vivo, which prompts us to further evaluate and elucidate the bioactive component(s) of H. syriacus.

Middle mediastinal thymoma

Abstract:  Thymoma is a common primary neoplasm of the anterior mediastinum. However, it can also arise in other locations, including the neck, the posterior mediastinum, the lung, base of the skull and the pleural cavity. There are only three previous case reports of thymoma located in the middle mediastinum. This report describes a patient together with a review of the literature on middle mediastinal thymoma.

Effect of body positions on hemodynamics and gas exchange in anesthetized pigs shortly after pneumonectomy.

Positional changes are thought to affect hemodynamics, respiratory mechanics, and gas exchange after pneumonectomy. The objective of this study was to compare hemodynamic and respiratory parameters and gas exchange in different positions before and after pneumonectomy. Twenty pigs were anesthetized and mechanically ventilated. Seven received right-side pneumonectomy, seven received left-side pneumonectomy, and six were anesthetized but did not receive surgery and served as controls. Hemodynamic and respiratory parameters and blood gas values were measured in different positions (supine and right and left lateral decubitus). Minute mechanical ventilation was controlled throughout. Pneumonectomy resulted in significant reductions in MAP, accompanied by significant decreases in cardiac index, stroke volume index, global ejection fraction, and global end-diastolic volume index. Mean pulmonary arterial pressure and pulmonary vascular resistance index increased. PaCO2, airway resistance, and peak airway pressure increased, whereas PaO2 and lung compliance decreased. Hemodynamic and respiratory parameters and gas exchange were also significantly affected by changes in position with pneumonectomy. Mean arterial pressure, cardiac index, stroke volume index, global ejection fraction, and global end-diastolic volume index were significantly lower in the supine than in the right or left lateral decubitus position. PaO2 was significantly higher in a lateral position, with the remaining lung uppermost. Our findings suggest that avoiding the supine positioning after pneumonectomy may facilitate improvements in hemodynamics and a decreased risk of hypoxemia. The optimal position for gas exchange after pneumonectomy is a lateral position, with the remaining lung in the uppermost position.

Influences of pleural effusion on respiratory mechanics, gas exchange, hemodynamics, and recruitment effects in acute respiratory distress syndrome

BACKGROUND Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) cause substantial morbidity and mortality despite improvements in the understanding of lung injury and advances in treatment. Recruitment maneuver (RM) with high sustained airway pressures is proposed as an adjunct to mechanical ventilation to maintain alveolar patency. In addition, RM has been advocated to improve pulmonary gas exchange. However, many factors may influence responses to RM and the effect of pleural effusion (PLE) is unknown. METHOD There were four groups in this study (n = 6 in each group). Group A was the control group, group B was the PLE group, group C was ARDS with RM, and group D was ARDS with PLE and RM. RM was performed in groups C and D, consisting of a peak pressure of 45 cm H2O with positive end-expiratory pressure of 35 cm H2O sustained for 1 min. Arterial blood gas, systemic and pulmonary hemodynamics, lung water, and respiratory mechanics were measured throughout. RESULT After the induction of ALI/ARDS, there were significant decreases in partial pressure of oxygen in arterial blood, mean arterial pressure, systemic vascular resistance, and lung compliance. There were also significant increases in the alveolar-arterial O2 tension difference, partial pressure of arterial carbon dioxide, mean pulmonary arterial pressure, pulmonary vascular resistance, and lung water. The RM improved oxygenation, which was attenuated by PLE. CONCLUSIONS ALI/ARDS leads to poor oxygenation and hemodynamics. RM results in improved oxygenation, but this improvement is attenuated by PLE.

Prognostic value of 18-FDG uptake in early stage NSCLC.

BACKGROUND We assessed whether the standard uptake of 18-fluorodeoxyglucose (18-FDG) in non-small cell lung cancers (NSCLC) differed between stage I and non-stage I tumors. METHODS We reviewed 163 patients with NSCLC who underwent surgical lymph node dissection after tumor resection in 2002-2003. Patients with clinical stage I NSCLC who were investigated with preoperative positron emission tomography integrated computed tomography (PET-CT) scans using 18-FDG uptake were included; those with N2 disease were excluded. We reviewed 55 patients with a mean follow-up of 68 months. RESULTS We analyzed 36 patients with stage I (Group 1) and 19 patients with non-stage I NSCLC (Group 2; 8 stage II, 7 stage III and 4 stage IV). There were no statistical differences in sex, age, tumor size, histological type, location or tumor differentiation between the groups. Group 1 had lower maximum standard 18-FDG uptake values (SUVmax) than Group 2 (4.9 +/- 2.7 vs. 8.1 +/- 3.8; P = 0.001). Using multiple logistic regression, patients with higher preoperative SUVmax and serum carcinoembryonic antigen (CEA) levels showed advanced tumor stages postoperatively (SUVmax > 4.7, odds ratio 7.65; CEA > 3.5 ng/mL, odds ratio 8.39). High 18-FDG uptake was significantly associated with reduced median survival (62.69 months for SUVmax < 4.7 and 40.89 months for SUVmax > 4.7). CONCLUSIONS High preoperative 18-FDG uptake of tumors was significantly associated with reduced overall patient survival. The SUVmax of the tumor and serum CEA levels demonstrated aggressive tumors and could be helpful preoperatively when considering patients for induction therapy or resection.

Spontaneous regression of a mediastinal thymoma

Thymoma is a common tumor in the anterior mediastinum. Thymoma may be symptomatic, but 20% to 30% of affected patients have symptoms related to compression of the mediastinum. Surgical excision is the keystone of therapy. Reports of the spontaneous regression of thymoma are rare in the English-language literature. Here we present a case of spontaneous remission of a mediastinal thymoma and a review of the literature.