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Biomedical subjects

Yung-Chie Lee

Publications and source records attributed to Yung-Chie Lee.

At least 19 recordsLinked to original sources

Long-term outcome and effects of oral bosentan therapy in Taiwanese patients with advanced idiopathic pulmonary arterial hypertension.

STUDY DESIGN: We report on the long-term outcome and effects of bosentan treatment in Taiwanese patients with advanced (functional class III or IV) idiopathic pulmonary arterial hypertension (IPAH). MATERIALS AND METHODS: IPAH patients on stable bosentan therapy for more than 12 months and regularly monitored were eligible for this prospective uncontrolled study. Patients were evaluated for several clinical parameters, both measured at the time of initiation of bosentan therapy and after 12 months on therapy: New York Heart Association functional class (NYHA FC), change in 6-min walk distance (6MWD), right ventricle ejection fraction (RVEF), cardiothoracic ratio (CTR), and pulmonary functional status. RESULTS: Twelve of 15 patients met eligibility requirements and were enrolled. Their mean age was 37.6+/-12.9 years and 92% were female. Six (50%) patients were in NYHA FC IV and the others were in NYHA FC III at baseline. Three (25%) patients were chronic hepatitis C virus (HCV) carriers, with normal liver function. After 12 months of bosentan treatment, 6-MWD, RVEF, and pulmonary function all increased significantly. CTR and NYHA FC both decreased significantly. Oral bosentan was well tolerated and there was no episode of liver dysfunction that required adjustment of the bosentan dosage or discontinuance of therapy. CONCLUSION: Long-term treatment with oral bosentan appears to have beneficial effects on functional status, exercise capacity, right heart function, and pulmonary function in Taiwanese patients with advanced IPAH, regardless of whether or not they presented with chronic HCV infection.

Adult↗

Perioperative extracorporeal membrane oxygenation support for critical pediatric airway surgery.

Extracorporeal membrane oxygenation (ECMO) has been used for cardiopulmonary support in neonates, infants, and adults. We report the application of ECMO for critical airway surgery when mechanical ventilation cannot provide adequate gas exchange. Three pediatric patients underwent emergency ECMO establishment because of hypercapnia that could not be managed by conventional mechanical ventilation. The pathology included: (1) left pulmonary artery sling with long-segment tracheal stenosis; (2) absence of the right intermediate bronchus and abnormal origin of the right lower bronchus arising from the left main bronchus; (3) right-lung agenesis with long-segment tracheobronchial stenosis. Venoarterial ECMO was established. Before ECMO, the arterial pH values were 7.28, 7.0, and 7.08, and the PaCO2 values were 111.8, 112.0, and 208.7 mmHg for each patient, respectively. After ECMO support, respiratory acidosis was reversed. The patients then underwent surgical intervention. The surgical procedures included: (1) slide tracheoplasty and reimplantation of the left pulmonary artery; (2) resection of the stenotic tracheal segment and reconstruction of the bronchial tree; (3) tracheal dilatation and stent implantation. The ECMO durations were 11, 5, and 16 h, respectively. All patients were successfully weaned off ECMO without complications. In conclusion, ECMO provided adequate ventilation support for patients undergoing critical tracheobronchial reconstruction when conventional mechanical ventilation could not maintain adequate gas exchange.

Acidosis, Respiratory↗

Clonality and prognostic implications of p53 and epidermal growth factor receptor somatic aberrations in multiple primary lung cancers.

PURPOSE: For treatment decision and prognostic applications, we evaluated p53/epidermal growth factor receptor (EGFR) somatic aberrations in multiple primary lung cancers to differentiate multifocal tumors from intrapulmonary metastasis. EXPERIMENTAL DESIGN: Fifty-eight multiple primary lung cancers of 1,037 patients in a 10-year period were identified to investigate somatic mutations and altered expression of p53 and EGFR for clonality assessment. Genomic DNA was extracted from microdissected cells of paraffin-embedded multiple primary lung cancer tissues. Overexpression and somatic mutations in exons of p53 (exons 5-8) and tyrosine kinase domain of EGFR (exons 18-22) were examined by immunohistochemical staining and DNA sequencing, respectively. RESULTS: High frequency of somatic mutations in p53 (33 of 58, 56.9%) and/or EGFR (44 of 58, 75.9%) resulted in high discrimination rate of tumor clonality (50 of 58, 86.2%) of multiple primary lung cancers. Twenty-two cases (37.9%) were assessed as having the same clonality and 28 cases (48.3%) were determined as having different clonality, which further supported the carcinogenic theory of field cancerization. Notably, the occurrence of lymph node metastasis was more commonly observed in tumors with the same clonality (P = 0.045) and was associated with poor patient 5-year survival rate (P = 0.001). However, no correlation was found between tumor clonality and patient survival (P = 0.630). The EGFR somatic aberrations in 58 multiple primary lung cancers, including vascular invasion associated with EGFR overexpression (P = 0.012) and mutation (P = 0.025), further suggested the potential benefits of target therapy of inoperable multiple primary lung cancers. CONCLUSIONS: Our results suggest that analysis of somatic alterations in p53 and EGFR can significantly improve the clonality assessment and impact management of multiple primary lung cancer patients.

DNA Mutational Analysis↗

Prognostic factors for pulmonary metastasectomy in hepatocellular carcinoma.

PURPOSE: To identify the prognostic factors for pulmonary metastasectomy (PM-ectomy) in hepatocellular carcinoma (HCC). PATIENTS AND METHODS: We conducted a retrospective review of patients with pulmonary metastases (PM) from HCC who had undergone curative PM-ectomy at National Taiwan University Hospital between 1990 and 2004. Univariate (log-rank) and multivariate (Cox's model) analyses of survival were used to identify the significant prognostic factors. RESULTS: In total, 34 patients were eligible for curative PM-ectomy. The overall survival rates (Kaplan-Meier) after PM-ectomy were 65.2% and 27.5% at 2 and 5 years, respectively. High alpha-fetoprotein level, positive hepatic resection margin, and short disease-free interval (DFI) were unfavorable factors for overall survival from univariate analysis, however, only DFI (P = 0.028) was identified as an independently prognostic factor by multivariate analysis. Bilateral distribution and more PMs were unfavorable factors for PM-free survival from univariate analysis, with only PM number identified as an independent prognostic factor by multivariate analysis (P = 0.017). CONCLUSION: Patients with longer DFIs and fewer PMs can benefit from PM-ectomy in HCC.

Adult↗

Bronchoscopic gluing for post-lung-transplant bronchopleural fistula.

A 44-year-old female patient diagnosed as pulmonary lymphangioleiomyomatosis with respiratory failure underwent bilateral sequential lung transplantation using an entire left lung and a post-lower-lobectomy right lung due to pneumonia. Persistent air leakage during cough was noted and bronchoscopy 12 days after transplantation demonstrated post-lobectomy bronchial stump dehiscence with a large bronchopleural fistula. We applied twice tissue glue instillation on the dehiscent bronchial stump through flexible bronchoscopy. The air leak improved and the patient was discharged 3 months after transplantation uneventfully. Two months after discharge, bronchoscopy showed complete healing of the dehiscent bronchial stump. Now, she lives independently without oxygen support.

Adult↗

Treatment of mediastinal immature teratoma in a child with precocious puberty and Klinefelter's syndrome.

Teratoma is the most common germ cell tumor, which can be divided into the mature and the immature histologically. Concurrent Klinefelter's syndrome may be overlooked in a patient with a germ cell tumor. This is because the tumor that secrets alpha-fetoprotein and beta human chorionic gonadotropin can mimic puberty in a patient with Klinefelter's syndrome, masking the usual clinical signs. In reviewing the literature on the subject, the role of neoadjuvant and adjuvant chemotherapy remains ill-defined for the immature teratoma. Age-dependent prognosis seems to demonstrate that children with immature teratomas have a better outcome. We share the experience of treating a child with immature teratoma with surgical excision alone, and it ended in a local recurrence.

Antineoplastic Combined Chemotherapy Protocols↗

Validation of a computer-based bronchoscopy simulator developed in Taiwan.

BACKGROUND/PURPOSE: Conventional training in bronchoscopy may increase patient's discomfort and procedure-related morbidity. Computer-based bronchoscopy simulator (CBBS) permits the acquisition and evaluation of the necessary skills through a realistic bronchoscopic experience. This study was conducted to validate the use of a CBBS system developed in Taiwan as a learning and assessment tool. METHODS: Twenty novice bronchoscopists and 10 expert bronchoscopists were enrolled as subjects in this prospective study. The 20 novice bronchoscopists were randomized into two groups, which received conventional bronchoscopic training or CBBS training and then completed a satisfaction survey. Subsequently, the novices who received CBBS training underwent an observational performance trial and the results were compared with those of expert bronchoscopists. All 10 expert bronchoscopists completed a realism survey and observational trial after CBBS performance. RESULTS: The satisfaction survey showed that the CBBS training program significantly increased participants' satisfaction (p = 0.002) and interest in learning (p < 0.001). The realism survey by the 10 expert bronchoscopists indicated that CBBS provides a favorable degree of realism with regard to the mechanical and visual parameters examined. Analysis of the performance results showed that the following parameters were capable of differentiating the participants by level of expertise: total procedure time (p = 0.002), percentage of bronchial segments entered (p = 0.012), percentage of bronchial segments identified (p < 0.001), percentage of repeated bronchial segments entered (p = 0.004), percentage of pathologies identified (p < 0.001), number of times that the bronchoscope tip collided with airway walls (p = 0.013), and number of times oral instruction was needed (p = 0.01). CONCLUSION: CBBS is a valid training method that increases interest in learning and provides a favorable degree of virtual realism. It can also distinguish various levels of competence at actual bronchoscopy and may have a useful role in the bronchoscopic training curriculum.

Bronchoscopy↗

Video-assisted thoracoscopic excision of intradiaphragmatic bronchogenic cysts: two cases.

We report two cases of bronchogenic cyst in the diaphragm. Case 1 was a female patient with hepatocellular carcinoma. Computed tomography showed a tumor in the right lower lung and metastasis was suspected initially because of underlying disease and imaging findings. Case 2 was a female patient who presented with prolonged intermittent cough. Computed tomography showed a tumor in the left lower lung. Both tumors were excised by video-assisted thoracoscopic surgery, and the diagnosis was confirmed by histopathology.

Aged↗

Additional minocycline pleurodesis after thoracoscopic surgery for primary spontaneous pneumothorax.

RATIONALE: Ipsilateral recurrence rates of spontaneous pneumothorax after video-assisted thoracoscopic surgery are higher than rates after open thoracotomy. OBJECTIVES: This study was conducted to determine whether additional minocycline pleurodesis would be effective in diminishing recurrence after video-assisted thoracoscopic surgery treatment of primary spontaneous pneumothorax. METHODS: Between June 2001 and February 2004, 202 patients with primary spontaneous pneumothorax were treated by conventional or needlescopic video-assisted thoracoscopic surgery. The procedures included resection of blebs and mechanical pleurodesis by scrubbing the parietal pleura. After the operation, patients were randomly assigned to additional minocycline pleurodesis (103 patients) or to observation (99 patients). MAIN RESULTS: Patients in the minocycline group had higher intensity chest pain and required a higher accumulated dose of meperidine. Short-term results showed that the two groups had comparable chest drainage duration, postoperative hospital stay, and complication rates. Patients in the minocycline group demonstrated a trend of decreased rate of prolonged air leaks (1.9 vs. 6.1%, p = 0.100). After a mean follow-up of 29 mo (12-47 mo), recurrent ipsilateral pneumothorax was noted in two patients in the minocycline group and eight patients in the observation group (p = 0.044 by the Kaplan-Meier method and log-rank test). Postoperative long-term residual chest pain and pulmonary function were comparable in both groups. CONCLUSIONS: Although associated with intense immediate chest pain, additional minocycline pleurodesis is a safe and convenient procedure that can reduce the rate of ipsilateral recurrence after thoracoscopic treatment for primary spontaneous pneumothorax.

Adult↗

The associations of p53 overexpression with p53 codon 72 genetic polymorphism in esophageal cancer.

Variations in p53 codon 72 have been identified as significant predisposing factors for various cancers, but molecular mechanisms remain unclear. We investigated associations of p53 overexpression with codon 72 variants and other factors with esophageal cancer. Status of p53 overexpression was determined by immunohistochemical staining. Codon 72 polymorphisms and mutation of p53 was identified by PCR-RFLP and direct sequencing from exons 4 to 9, respectively. We evaluated 126 patients who underwent esophagectomy in the National Taiwan University Hospital, and found that the status of p53 overexpression was significantly influenced by presence of codon 72 polymorphisms. After adjustment for other possible confounders, the incidence of p53 overexpression was significantly decreased in patients with Pro/Pro genotype with an odds ratio (OR) of 0.21 (95% CI: 0.067-0.64) (p = 0.0065) compared with incidence in patients with Arg/Arg genotype. The incidence of p53 overexpression was additively increased with environmental exposure to cigarette smoke, alcohol, and areca quid. When compared with individuals exposed to only one of these environmental risk factors, patients who had exposure to two or three risk factors had ORs of 6.11 (95% CI: 1.80-20.75) and 6.22 (95% CI: 1.81-21.34) for p53 overexpression, respectively. Elderly patients (age >70 years) were also more likely to have p53 overexpression, with an OR of 5.63 (95% CI: 1.53-20.64) compared with overexpression among patients aged less than 55 years. Forty-one patients received further evaluation of p53 mutation. There was also a higher incidence of, but without reaching a statistical significance, p53 mutation in patients with p53 overexpression (OR[95% CI]: 2.18 [0.52-9.6]) and codon 72 Arg/Arg genotype (OR [95% CI] of 0.8 [0.13-4.2], comparing genotypes of Pro/Pro and Arg/Pro with Arg/Arg). Our data provide the first observations that the presence of p53 codon 72 variants can be a significant factor influencing p53 overexpression in esophageal cancer, with overexpression also influenced by combined or prolonged environmental exposures.

Aged↗

Transcription repressor slug promotes carcinoma invasion and predicts outcome of patients with lung adenocarcinoma.

PURPOSE: In a previous genome-wide gene expression profiling analysis using an invasion cancer cell lines model, we have identified Slug as selectively overexpressed in the highly invasive cancer cells. Here, we investigated the clinical significance of Slug in lung adenocarcinoma and the role of Slug in the process of cancer cell invasion and metastasis. EXPERIMENTAL DESIGN: Real-time quantitative reverse transcription-PCR was used to investigate Slug mRNA in surgically resected lung adenocarcinoma of 54 patients and its correlation with survival. We overexpressed Slug in a lung adenocarcinoma cell line with very low Slug levels and investigated the in vitro and in vivo effects of Slug expression. RESULTS: High expression of Slug mRNA in lung cancer tissue was significantly associated with postoperative relapse (P = 0.03) and shorter patient survival (P < 0.001). The overexpression of Slug enhanced xenograft tumor growth and increased microvessel counts in angiogenesis assay. Both inducible and constitutive overexpression of Slug suppressed the expression of E-cadherin and increased the in vitro invasive ability. Zymography revealed increased matrix metalloproteinase-2 activity in Slug overexpressed cells. ELISA, reverse transcription-PCR, and immunohistochemistry confirmed the increase of matrix metalloproteinase-2 proteins and mRNA in Slug overexpressed cells and xenograft tumors. CONCLUSIONS: Slug expression can predict the clinical outcome of lung adenocarcinoma patients. Slug is a novel invasion-promoting gene in lung adenocarcinoma.

Adenocarcinoma↗

Elevation of telomerase activity positively correlates to poor prognosis of patients with non-small cell lung cancer.

Increased telomerase activity has been found in various types of human malignancies, including lung cancer. However, the correlation between the level of telomerase activity and the clinical characteristics of lung cancer patients remains unclear. The levels of telomerase activity in lung cancer specimens and adjacent non-neoplastic tissues obtained from 68 patients who underwent surgery were measured by using a non-radioactive quantitative method. Clinical and pathologic parameters were evaluated with respect to the level of telomerase activity. Prominent telomerase activity was detected in 58 (85.3%) lung cancer tissues and 21 (30.9%) adjacent non-neoplastic tissues. There was a trend of increase in relative telomerase activity in regard to the advanced pathological stage, and lymph node metastasis. Using Cox regression analysis, we found that every 100 unit of increase in relative telomerase activity was associated with an increase in the hazard ratio of death by 13% after controlling for other variables such as age, gender, and stage (Hazard ratio=1.13; 95% CI: 1.03-1.23, P=0.006). For patients with stage I disease, an increase of every 100unit of relative telomerase activity was associated with an even higher increase of 33% in the hazard ratio of death (Hazard ratio=1.33; 95% CI: 1.07-1.65, P=0.011) and a 16% increase in the hazard of disease recurrence (Hazard ratio=1.16, 95% CI: 1.01-1.33, P=0.032). The level of telomerase activity is positively correlated with the risk of recurrence and mortality of lung cancer. The level of telomerase activity would predict the prognosis of lung cancer patients.

Adult↗

An esophageal mass with coexistent Mycobacterium chelonae and Candida albicans infections in an immunocompetent adult.

Mycobacteria chelonae was originally included in group IV of Runyon's classification of atypical mycobacteria. This rapidly growing environmental organism often caused infections in immunocompromised hosts. Candida albicans is a ubiquitous micro-organism and frequently isolated from the gastrointestinal tract. These two micro-organisms seldom cause esophageal diseases in healthy humans. We report a case of a fruit farmer with a submucosa tumor of distal esophagus caused by coexistence of M. chelonae and C. albicans infections, which was successfully treated by surgical resection and following antimicrobial regimens postoperatively.

Adult↗

Total cyclooxygenase-2 mRNA levels correlate with vascular endothelial growth factor mRNA levels, tumor angiogenesis and prognosis in non-small cell lung cancer patients.

Interaction between cancer cells and adjacent stromal cells is important to promote tumor development. Our aim was to study total COX-2 mRNA expression in both cancer cells and surrounding stromal cells and its association with angiogenic factor VEGF mRNA expression, tumor angiogenesis and prognosis in patients with NSCLC. COX-2 mRNA expression in both cancer cells and stromal tissue was analyzed using real-time quantitative (RTQ) RT-PCR in 60 NSCLC surgical specimens. Immunohistochemistry (IHC) was used to localize COX-2 protein in tumor specimens. Correlations between tumoral total COX-2 mRNA expression and VEGF mRNA expression (measured by RTQ RT-PCR), intratumoral microvessel counts (evaluated by IHC), other clinicopathologic variables, survival and relapse were tested. COX-2 protein expression was found in cancer as well as the surrounding stromal cells (including infiltrating inflammatory cells and endothelial cells of tumor-associated microvessels). VEGF protein expression was mainly located in cancer cells. There was a significant association between high tumoral total COX-2 mRNA expression and high VEGF mRNA expression (p = 0.01) or high intratumoral MVC (p < 0.001) but not other clinicopathologic variables, including tumor status and lymph node metastasis. Patients with higher tumoral total COX-2 mRNA expression had a statistically shorter survival time (median 15.0 +/- 2.61 months) and relapse time (median 5.0 +/- 1.37 months) than those with lower tumoral total COX-2 mRNA expression (median 40.0 +/- 3.12 and 34.0 +/- 3.11 months; p < 0.0001 and p < 0.0001, respectively, log-rank test). A significant difference in survival and relapse time was also seen between patients with high and low tumoral VEGF mRNA expression and between those with high and low intratumoral MVC (p = 0.0046 and p = 0.0038, respectively). After stratification by disease stage or histologic subtype, the prognostic significance of high total COX-2 mRNA expression was still apparent in both stage I and stage II-IV and in both squamous cell carcinoma and adenocarcinoma (p < or = 0.01 for all). Multivariate analysis using the Cox regression model with backward elimination showed that tumoral total COX-2 mRNA expression and lymph node status were the 2 most important independent prognostic predictors for survival and disease relapse. We report that total COX-2 mRNA expression in cancer cells and surrounding stromal cells correlates strongly and positively with VEGF mRNA expression, intratumoral MVC and adverse prognosis in NSCLC patients. This implies that COX-2 expression in both cancer cells and stromal cells within the tumor microenvironment may play an important role in upregulating the expression of the angiogenic factor VEGF and tumor angiogenesis in NSCLC and explains, in part, the adverse prognostic effect of COX-2 overexpression in patients with NSCLC.

Adenocarcinoma↗

Association of GSTP1 polymorphism and survival for esophageal cancer.

PURPOSE: Activity of glutathione S-transferase (GST) is associated with detoxification of xenobiotics and the maintenance of cell viability. Genetically variant GSTs produce different enzymatic activities. The clinical significance of this variation is still puzzling. We investigated whether genetic polymorphisms of GST including GSTP1, GSTM1, and GSTT1 affect survival among esophageal cancer patients. EXPERIMENTAL DESIGN: From 1996 to 2002, 233 patients with pathologically proven esophageal cancer were recruited from the Department of Surgery, National Taiwan University Hospital. GST genotypes, including GSTT1, GSTM1, and GSTP1, were determined by PCR or PCR-RFLP. The influence of the genetic polymorphisms on patient survival was estimated using the method of Kaplan-Meier survival function and Cox proportional hazards models. RESULTS: The mean survival times (months) of the GSTP1 Ile/Ile, Ile/Val, and Val/Val were 11, 10, and 7, respectively (P < 0.05). The more the patients carried GSTP1 variant Val alleles, the poorer the survival rate (adjusted hazard ratio, 1.36; 95% confidence interval, 1.01-1.84; Ptrend = 0.045). In contrast, no association of GSTT1 or GSTM1 genotypes with survival rate was noted. CONCLUSION: The presence of the GSTP1 variant allele (Val) is associated with a poorer prognosis of esophageal cancer.

Adult↗