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Using the Serial Analysis of Gene Expression (SAGE) database from the Cancer Genome Anatomy Project, we identified heparin co-factor II (HCII), which is over-expressed in non-small cell lung cancer (NSCLC). Here, we investigated the clinical significance of HCII and provided molecular evidence to support the suggestion that HCII could enhance cancer metastasis in NSCLC. We found that high HCII expression in tumour tissue was associated with increased cancer recurrence and shorter overall survival times in 75 clinically operable NSCLC patients. High pretreatment plasma concentration of HCII was associated with reduced overall survival in 57 consecutive NSCLC patients. We over-expressed and knocked down HCII expression in lung cancer cell lines and confirmed that HCII could promote cell motility, invasion ability and filopodium dynamics in NSCLC cells in vitro and increased metastatic colonization in an in vivo mouse model. Exogenous treatment of HCII promoted cancer cell migration, and this promigratory effect of HCII was independent of thrombin. We further showed that HCII could up-regulate cancer cell migration through the activation of PI3K, which acts upstream of Rac1 and Cdc42, and this effect could be blocked by heparin. We suggest that HCII is a novel metastasis enhancer and may be used as a prognostic predictor for heparin treatment in NSCLC. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd

In order to improve prognostic applications and treatment decisions, we report our experiences of visceral pleural surface invasion (VPSI) in non-small cell lung cancers (NSCLCs) with pleural retraction. A total of 321 NSCLCs with pleural retraction were identified by carefully inspecting surgically resected specimens. The extent of pleural invasion, including the use of elastic stain, was evaluated. Patients with and without VPSI were compared for clinicopathologic parameters and survival. VPSI was identified in 170 (53.0 %) of the stage I–III cases and 98 (43.4 %) of the patients with stage I disease. VPSI was associated with a higher frequency of tumor size greater than 3 cm, moderate/poor differentiation, vascular invasion, mediastinal lymph node metastasis, extranodal involvement, and higher TNM stages. Multivariate analysis revealed VPSI to be a significant independent predictor of unfavorable prognosis. The 5-year survival of patients with and without VPSI was 57.9 and 83.0 %, respectively (P = 0.001), and was 74.3 and 88.5 % (P = 0.005) in stages I–III and stage I disease, respectively. VPSI is an independent factor for poor prognosis in NSCLCs, regardless of lymph node status. Stage IB NSCLCs with PL1 pleural invasion are associated with a survival rate similar to that of stage IA NSCLCs and could be classified as T1 lesions. While surgical treatment is adequate in these patients, stage IB NSCLCs with VPSI have poor prognosis, and these patients should be considered for adjuvant chemotherapy.

Purpose To identify germline polymorphisms to predict concurrent chemoradiation therapy (CCRT) response in esophageal cancer patients. Materials and Methods A total of 139 esophageal cancer patients treated with CCRT (cisplatin-based chemotherapy combined with 40 Gy of irradiation) and subsequent esophagectomy were recruited at the National Taiwan University Hospital between 1997 and 2008. After excluding confounding factors ( i.e ., females and patients aged ≥70 years), 116 patients were enrolled to identify single nucleotide polymorphisms (SNPs) associated with specific CCRT responses. Genotyping arrays and mass spectrometry were used sequentially to determine germline polymorphisms from blood samples. These polymorphisms remain stable throughout disease progression, unlike somatic mutations from tumor tissues. Two-stage design and additive genetic models were adopted in this study. Results From the 26 SNPs identified in the first stage, 2 SNPs were found to be significantly associated with CCRT response in the second stage. Single nucleotide polymorphism rs16863886, located between SGPP2 and FARSB on chromosome 2q36.1, was significantly associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.62–10.30) under additive models. Single nucleotide polymorphism rs4954256, located in ZRANB3 on chromosome 2q21.3, was associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.57–10.87). The predictive accuracy for CCRT response was 71.59% with these two SNPs combined. Conclusions This is the first study to identify germline polymorphisms with a high accuracy for predicting CCRT response in the treatment of esophageal cancer.

Pleomorphic carcinomas of the lung are uncommon malignant tumors composed of carcinomatous and sarcomatous components and are distinguished from other non-small-cell lung carcinomas by a more aggressive clinical course with early distant metastases and far worse survival. Epidermal growth factor receptor (EGFR) and p53 are common genes involved in the pathogenesis of non-small-cell lung carcinomas, but their roles in pleomorphic carcinomas are unclear. The potential clinical activity of EGFR-targeted therapy is also unknown. A total of 42 pleomorphic carcinomas were identified to investigate somatic mutations of EGFR and p53. Genomic DNA was extracted from microdissected cells of paraffin-embedded tumor tissues. Somatic mutations in EGFR (exons 18–21) and p53 (exons 5–8) were examined. EGFR mutations were detected in 10 of 42 cases. Five of these patients had point mutations in exon 21 majorly with L858R; this mutation was found in both adenocarcinomatous and sarcomatous components in 1 case. The other 5 cases harbored 4 deletions and 1 mutation in exon 19. p53 mutations were found in 12 patients. Notably, identical mutation was observed in carcinomatous and sarcomatous components in 3 patients, and this finding strongly supported the theory of monoclonal histogenesis. The occurrence (23.8%) of EGFR mutations, including the exons 19 and 21 mutations observed frequently in our series, suggests that the patients with inoperable pleomorphic carcinomas are likely to benefit from treatment with EGFR tyrosine kinase inhibitors.

The EGFR gene has been demonstrated to be an important factor influencing treatment response for various cancers, and its expression has been shown to be modified by the polymorphic CA repeat length at the 5′-regulatory sequence in intron 1. We investigated whether this EGFR polymorphism is associated with prognosis in patients with esophageal cancer after concurrent chemoradiotherapy (CCRT) and esophagectomy. A cohort of 148 patients with esophageal cancer received cisplatin-based CCRT (concurrently combined with 40 Gy irradiation) and subsequent esophagectomy. Their EGFR genotypes were determined by polymerase chain reaction from leukocyte DNA, which was obtained before treatment and was correlated with patient survival. Patients with the homozygous short allele (

Mediastinal seminomas are uncommon primary mediastinal neoplasms, and most are solid in appearance. Cystic mediastinal seminoma is an unusual type of extragonadal germ cell tumor that has rarely been reported in the literature. Here we describe a 36-year-old man with a 7.5-cm cystic mediastinal seminoma. The tumor was excised successfully by video-assisted thoracoscopic surgery. No recurrence was noted during 28 months of follow-up.

p53 and epidermal growth factor receptor (EGFR) are common genes involved in the pathogenesis of lung cancer, but their roles in lymphoepithelioma-like carcinomas (LELC) are unclear. In this study, we investigate the roles of p53 and EGFR in LELC carcinogenesis. Forty-six pulmonary LELCs were identified to evaluate p53 and EGFR aberrations. p53 mutations were identified in three patients, which all occurred in exon 8. EGFR mutations were detected in 8 of 46 cases with a majority of exon 21 mutations but without L858R. The other cases harbored mutations in exons 20 and 18. Only one case gained a deletion in exon 19. Notably, EGFR mutation was more commonly observed in patients with tumor size ≤ 3 cm (P = 0.014). In addition, there was a trend of more common EGFR overexpression in female (22/30) than in male patients (7/16, P = 0.061). However, there was no correlation between p53/EGFR mutations and protein expressions, suggesting the presence of complex mechanisms. p53 and EGFR mutations are uncommon in LELCs, indicating that these genes are not the important events in carcinogenesis for this tumor subtype. The EGFR mutation in 35% patients with LELC tumors

Fibroblast growth factor (FGF)-9 belongs to the FGF family which modulate cell proliferation, differentiation, and motility. Benzo(a)pyrene is a polycyclic aromatic hydrocarbon (PAH) and ubiquitous environmental carcinogen present in automobile exhaust, cigarette smoke, and foods. The major purposes of this study were to explore the roles of FGF-9 in the benzo(a)pyrene-induced lung cancer invasion in vitro and the metastatic development of lung adenocarcinoma in human. The data of RT-PCR analysis indicated that treatments of human lung adenocarcinoma CL5 cells with benzo(a)pyrene and a PAH mixture motorcycle exhaust particulate (MEP) extracts increased FGF-9 mRNA expression. The increased expression was blocked by cotreatments with a p38 mitogen-activated protein kinase inhibitor SB202190 and an extracellular signal-regulated kinase inhibitor PD98059. The results of immunoblot analysis and Matrigel assay showed that benzo(a)pyrene and MEP extracts produced a concomitant induction of FGF-9 protein and invasive ability of CL5 cells. The benzo(a)pyrene- and MEP-induced invasion was suppressed by FGF-9 neutralizing antibodies. The results of immunohistochemistry analysis of human lung adenocarcinoma specimens showed that FGF-9 protein was detected in the adenocarcinoma cells but not in normal epithelium. FGF-9 staining intensity was positively correlated with status of disease and degree of lymph node metastasis in these lung adenocarcinomas. These present findings suggest that FGF-9 has potential roles in benzo(a)pyrene-induced CL5 cell invasion and human lung adenocarcinoma metastasis.

Proteus syndrome is a very rare, sporadic and congenital condition that is characterized by postnatal mosaic overgrowth. This disorder is thought to be caused by a somatic gene mutation, but the exact etiology is unknown. Commonly involved tissues include connective tissue, bone, skin and the central nervous system. Another less common symptom involves pulmonary emphysematous changes. This report documents a 25-year-old man with Proteus syndrome who presented with progressive exertional dyspnea and asymmetric overgrowth of his extremities. He underwent left pneumonectomy and his postoperative course was uneventful. Lung tissue showed emphysematous changes with multiple bulla formation and scattered calcification. We also review recent literature related to pulmonary manifestations and management of Proteus syndrome.

Collapsin response mediator protein (CRMP) family proteins are cytosolic phosphoproteins involved in semaphorin 3A-mediated neuronal cell growth cone collapse and cancer invasion. We identified a novel human isoform of CRMP family proteins named long form CRMP-1 (LCRMP-1), which was different from the known invasion suppressor, CRMP-1, in its molecular weight and the N-terminal exon-1. This study was aimed to elucidate the clinical significance of LCRMP-1 in non-small cell lung cancer (NSCLC) patients. Full-length human LCRMP-1 was cloned from lung adenocarcinoma based on the Expressed Sequence Tags (EST) database. We generated LCRMP-1 specific antibody and subsequent in vitro and in vivo invasion assays showed positive correlations between LCRMP-1 expression and lung cancer cell invasiveness. We further demonstrated that high LCRMP-1 mRNA expressions were associated with poor overall and disease-free survivals (P=0.004 and 0.006, respectively, log-rank test) in 72 NSCLC patients. The results were confirmed in an independent cohort of 54 NSCLC patients by immunohistochemistry (P=0.032, log-rank test). The metastatic lymph nodes showed higher LCRMP-1 expressions as compared with the paired primary lung tumors (P=0.012, McNemar's test). In conclusion, LCRMP-1 was a cancer invasion enhancer that could be a novel prognostic biomarker in NSCLC.

To investigate the association between clinical/dosimetric factors and postoperative pulmonary complications (PPC) in esophageal cancer patients undergoing neoadjuvant chemotherapy and intensity-modulated radiation therapy (IMRT) followed by thoracic esophagectomy. The data from 52 patients receiving combined modality treatment were analyzed. Chemotherapy was taxane-based in 43 and 5-fluorouracil-based in 9 patients. IMRT (40–45 Gy, median 40 Gy, at 1.8–2 Gy per fraction) was given using a 3–5-beam arrangement. Surgery consisted of open or minimally invasive esophagectomy. The dosimetric parameters were generated from lung dose-volume histogram computed by the treatment planning software. PPC was defined as pneumonia or respiratory insufficiency within 30 days after surgery. Statistical correlations were analyzed between clinical/dosimetric factors and PPC. The incidence of PPC was 34.6%. No patients died of PPC. Two patients (3.8%) became ventilator dependent. In univariate analyses, preoperative forced expiratory volume in 1 s (FEV1) and forced vital capacity before surgery were significantly associated with PPC (P = 0.02 and 0.04, respectively). None of the dosimetric factors predicted development of PPC. For the 51 patients undergoing right transthoracic surgery, higher absolute spared volume of the right lung receiving 15 Gy was significantly associated with PPC (P = 0.03). In multivariate analysis, preoperative FEV1 was the only independent factor associated with PPC (P = 0.002). Preoperative rather than prechemoradiation FEV1 predicts development of PPC. Reducing the absolute volume of the right lung that is irradiated might decrease the risk of PPC for patients receiving right transthoracic surgery.

The evidence concerning open lung biopsy (OLB) for diffuse pulmonary infiltrates in patients with AIDS is limited. This study retrospectively evaluated the diagnostic and therapeutic yields of OLB compared with bronchoscopy for patients with AIDS with diffuse pulmonary infiltrate treated in the National Taiwan University Hospital from 1997 to 2004. There were 15 and 46 patients enrolled in the OLB and bronchoscopic groups in this study, respectively. As compared with the bronchoscopic group, patients from the OLB group had a higher chance of acquiring a specific diagnosis and possible change of therapy (73 vs 32.6% and 60 vs 21.7%, respectively; P < 0.05). There were two (13.3%) patients with prolonged air leak (greater than 7 days) in the OLB group, whereas four patients (8.7%) had procedure-related complications in the bronchoscopic group. There was no procedure-related mortality in the OLB group. This study demonstrated that OLB can be safely performed in select patients and provide a superior diagnostic and therapeutic benefit compared with bronchoscopy for diffuse pulmonary infiltrates in patients with AIDS. This procedure should be performed early in the clinical course to avoid irreversible clinical deterioration of the patients with severe illness.

Claudin (CLDN)-1, a key component of tight junction complexes, was down-regulated in human lung adenocarcinomas.To investigate the clinical significance of CLDN1 expression in patients with lung adenocarcinoma and its role in cancer invasion and metastasis.We examined the CLDN1 mRNA expression in tumor specimens from 64 patients with lung adenocarcinoma and protein expression by immunohistochemistry in an independent cohort of 67 patients with lung adenocarcinoma. CLDN1 functions in cancer cell migration, invasion, and metastatic colonization were studied by overexpression and knockdown of CLDN1. Affymetrix microarrays were performed to identify gene expression changes associated with CLDN1 overexpression.We found that low-CLDN1 mRNA expression had shorter overall survival (P = 0.027, log-rank test) in 64 patients with lung adenocarcinoma, and we confirmed by immunohistochemistry that low CLDN1 expression had shorter overall survival (P = 0.024, log-rank test) in an independent cohort of 67 patients with lung adenocarcinoma. Overexpression of CLDN1 inhibited cancer cell dissociation in time-lapse imaging of wound healing, and suppressed cancer cell migration, invasion, and metastasis. Knockdown CLDN1 expression increased cancer cell invasive and metastatic abilities. Affymetrix microarrays identified a panel of genes altered by CLDN1 overexpression. CLDN1 increased expressions of cancer invasion/metastasis suppressors (e.g., connective tissue growth factor [CTGF], thrombospondin 1 [THBS1], deleted in liver cancer 1 [DLC1], occludin [OCLN], zona occludens 1 [ZO-1]) and suppressed expressions of invasion/metastasis enhancers (e.g., secreted phosphoprotein 1 [SPP1], cut-like homeobox 1 [CUTL1], transforming growth factor alpha [TGF-alpha], solute carrier family 2 [faciliated glucose transporter] member 3 [SLC2A3], placental growth factor [PGF]), supporting a role for CLDN1 as an invasion and metastasis suppressor.CLDN1 is a cancer invasion/metastasis suppressor. CLDN1 is also a useful prognostic predictor and potential drug treatment target for patients with lung adenocarcinoma.

Titanium plate has been widely used in several surgical fields, such as craniofacial reconstruction and orthopedic prosthesis. This prosthesis has been proved not only with good biocompatibility and mechanical strength, but also with light weight and low radiological interference. From October 1991 to May 1995, 6 patients underwent thoracic cage reconstruction with titanium plate in our hospital. They included 5 females and 1 male, with ages ranging from 26 to 62 years. Four of them suffered from primary chest wall tumors (2 desmoid tumors, 1 chondrosarcoma, and 1 hemangioma), one had a recurrent chest wall tumor from breast carcinoma, and one had thoracic hypoplasia. The thoracic cage defect ranged from 5 times 6 cm to 10 times 15 cm, and 1 to 3 titanium plates were used for the reconstruction. No paradoxical movement or other prosthesis-related complications have occurred during the follow-up period. We conclude that titanium plate is a good material for thoracic cage reconstruction.

Objective Early diagnosis and aggressive surgical drainage are very important for successful treatment of descending necrotizing mediastinitis. However, the surgical techniques used for this condition remain controversial. We report our 10-year experience of managing this devastating disease, focusing on the multidisciplinary, minimally invasive operative procedures and the unique bacteriologic factors in Taiwan. Methods Between January 1997 and January 2007, we retrospectively reviewed 18 patients with descending necrotizing mediastinitis who were treated in the National Taiwan University Hospital. Diagnosis and Endo classification were confirmed by computed tomography of the neck and chest. Results Eight women and 10 men were included in this study. The mean age was 57.8 ± 15.2 years. Cervical drainage was performed in the involved area in all patients. The methods for mediastinal drainage included transcervical (n = 10), video-assisted thoracic surgical drainage (n = 6), subxiphoid drainage (n = 1), and mediastinoscopy-assisted drainage (n = 1). We could not rescue 3 patients because of uncontrolled sepsis before surgery, for a mortality rate of 16.7%. Klebsiella pneumoniae uniquely represents the most common pathogen in diabetic patients ( P = .01), leading to more complicated courses in older patients ( P =.04) and requiring more surgical interventions ( P =.05) than other pathogens. Conclusion Transcervical mediastinal drainage is first justified in patients with limited disease in the upper mediastinum. For those with involvement of the lower anterior mediastinum, an additional subxiphoid approach is suggested. Cervicotomy with video-assissted mediastinal drainage is an excellent combination for involvement of the posterior mediastinum and pleural space. Klebsiella pneumoniae uniquely represents the most important and threatening causative pathogen for diabetic patients with descending necrotizing mediastinitis.

Background and Objectives To investigate the impact of using paclitaxel in chemoradiation on locally advanced esophageal squamous cell carcinoma (SCC) treated with or without surgery. Methods Of 127 patients with AJCC stages II–III esophageal SCC undergoing definitive chemoradiation (DefCRT, n = 44) or neoadjuvant chemoradiation plus surgery (NeoCRT + S, n = 83), 57 received chemotherapy with paclitaxel and cisplatin (TP), and 70 received 5-fluorouracil and cisplatin (PF). Three-year local progression-free survival (LPFS), distant metastasis-free survival, overall survival, and prognostic factors were retrospectively analyzed. Results The median survival was 30 months. Pathological complete response rate was 41% and 27% with TP and PF, respectively (P = 0.19). NeoCRT + S achieved significantly higher LPFS than DefCRT (71% vs. 39%, P

This study was to compare 18F-FDG positron emission tomography (PET) with thoracic contrast-enhanced CT (CECT) in the ability of lymph node (LN) staging non-small cell lung cancer (NSCLC) in a tuberculosis-prevalent country. The usefulness of dual time point PET imaging (DTPI) in NSCLC nodal staging was also evaluated. We reviewed 96 NSCLC patients (mean age, 65.3 ± 11.7 years) who had received PET studies before their surgery. DTPI were performed on 37 patients (mean age, 64.8 ± 12.2 years) who received an additional scan of thorax 3 h after tracer injection. The accuracies of nodal staging by CECT and PET were evaluated according to final histopathology of hilar and mediastinal LN resected by surgery. The accuracy for nodal staging by CECT was 65.6% and that by PET was 82.3% (p

Objectives According to our previous study, the concurrent detection of p53 and epidermal growth factor receptor mutations significantly improves the clonality assessment and impact management of patients with multiple primary lung cancer. Nevertheless, the treatment, outcome, and safety of patients with this complex disease remain controversial. This series of cases detail our experiences with surgical resections in 92 patients during the past 16 years. Methods A database of 1651 patients was evaluated for unilateral and bilateral synchronous multiple primary lung cancers. The relationships among the location of tumors, number of tumors, tumor size, tumor histology, vascular invasion, regional lymph node metastasis, extranodal extension, type of surgery, mortality, and survival were analyzed. Results The 5-year survival for all synchronous multiple primary lung cancers was 35.3%. The overall surgical mortality was 1.1%. Notably, lymph node metastasis, extranodal extension, vascular invasion, tumors with adenosquamous carcinoma or different histology, and poor survival were observed. Multivariate analysis showed that only the occurrence of lymph node metastasis remained a statistically significant prognostic factor. The 5-year survivals were 52.5% and 15.5% for patients with and without lymph node metastasis, respectively ( P Conclusion An aggressive surgical approach is safe and justified in patients with synchronous multiple primary lung cancers and node-negative diseases. The status of this particular form of non–small cell lung cancers might be considered in the conventional TNM staging system for more accurate prediction of patient prognosis.

The explosion of microarray studies has promised to shed light on the identification of disease markers. To find novel prognostic factors, we used the expression profile of a poor prognostic factor of lung cancer, survivin (BIRC5), as a template to search for and compare transcriptome expression profiles in a lung adenocarcinoma microarray dataset. Trophinin (TRO) was identified as one of the best-correlated genes. The trophinin expression in lung cancer specimens was examined by immunohistochemical staining. The role of trophinin in cancer metastasis was further investigated by approaches of overexpression and knock down with small interfering RNA (siRNA). For stage I lung adenocarcinoma, the patients without trophinin expression had a better overall and disease-free survival. Overexpression of trophinin increases cell invasion ability and knock down with siRNA inhibits cell invasion. Through a combination of data mining and biochemical assays, we identified trophinin, which could enhance cell invasion, as a novel prognostic factor for early stage lung cancer.

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.

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 100 unit 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.

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.

Objective Estrogen receptor expression in lung cancer has been understudied, particularly in light of its potential biologic importance in the epidemic of lung cancer in women. The expression of estrogen receptors was investigated to better understand the possible role of sex hormones in lung cancer. Methods A total of 301 patients with surgically resected non–small cell lung cancers of stages I to III were explored. Sections of paraffin-embedded tumor samples were stained with estrogen receptor α and estrogen receptor β antibodies. Tumors with moderate-to-strong nuclear staining in at least 50% of the tumor cells were scored as positive for overexpression. Results The overall frequency of overexpression for estrogen receptor β was 45.8% (138/301). It was detected most frequently in female patients (in 54.3% of 127 tumors vs 39.7% of 174 tumors in men, P = .012). However, there was no estrogen receptor α nuclear staining detectable in non–small cell lung cancers. Interestingly, a significant correlation between estrogen receptor β expression, stage of disease, grade of differentiation, smoking status, vascular invasion, and survival in patients with stage II and III disease was found. By using multivariate analysis of survival among patients with stage II and III disease, estrogen receptor β overexpression, stage II tumor, well differentiation, nonsmoking status, and lack of vascular invasion were significantly favorable prognostic factors. Conclusions The results presented here show for the first time that immunohistochemical expression of estrogen receptor β can be used as a prognostic indicator in patients with surgically resected stage II and III non–small cell lung cancers. These observations might offer a possibility for hormonal therapy in patients with lung cancer.

Sclerosing hemangioma (SH) of the lung is an uncommon tumor with a predilection for middle-aged women. This special phenomenon prompted us to examine SH for the expression of ERalpha (human estrogen receptor) and ERbeta (a second isoform of estrogen receptor). To investigate the staining pattern of these tumors, we also stained lung tissues from patients with non-small cell lung carcinomas and nonneoplastic type II pneumocytes for comparison. Thirty-seven pulmonary SHs and 301 non-small cell lung cancers specimens were explored. Expression of ERalpha and ERbeta was immunohistochemically measured. The overall frequency of overexpression for ERbeta was 91.9%. It was detected in both female (in 91.4% of 35 cases) and male (in 100.0% of 2 tumors from men) patients. There was ERbeta overexpression in all 9 tumors of solid pattern, 6 of 7 tumors of papillary pattern, all 4 tumors of sclerotic pattern, 12 of 13 tumors of hemorrhagic pattern, and 3 of 4 tumors of mixed pattern. The staining pattern of the neoplastic cells of the SH was similar to that of type II pneumocytes adjacent to the tumor rather than that of non-small cell lung cancers, in which the frequency of ERbeta overexpression was 45.8%. However, there was no ERalpha detectable in these neoplasms. Estrogen receptor beta overexpression is very frequent in pulmonary SHs, which is similar to that of alveolar cells but quite different from non-small cell carcinoma.

ObjectiveSurgical lung biopsy is considered the final method of diagnostic modality in patients with undiagnosed diffuse pulmonary disease. Nevertheless, the effect of surgical lung biopsy on the diagnosis, treatment, and outcome of the patient still remains controversial. This study reviewed the experiences of surgical lung biopsies in 196 consecutive patients during the past 7 years.MethodsSurgical lung biopsy was performed after achievement of general anesthesia through video-assisted thoracoscopic surgery or a 7-cm minithoracotomy. Biopsy specimens were swabbed for aerobic and anaerobic bacterial, fungal, and mycobacterial cultures. The sections of specimens were routinely stained with hematoxylin and eosin, and acid-fast, Gomori methenamine silver, Gram stain, or other special stains were added if necessary.ResultsThe pathologic diagnosis after surgical lung biopsy included infection (30.6%), interstitial pneumonia or fibrosis (21.9%), diffuse alveolar damage (17.3%), neoplasm (13.3%), autoimmune diseases (8.2%), and others (8.2%). After surgical lung biopsy, 165 (84.2%) patients had changes in their therapy, 124 (63.3%) patients had clinical improvement of their conditions, and 119 (60.7%) patients survived to hospital discharge. Comparison between immunocompromised and immunocompetent patients showed that diagnosis of infection was significantly higher (P < .01) in the former group (41.2% vs 20.2%). In addition, there was no significant difference in the distribution of diagnosis and rate of change in therapy between the respiratory failure and nonrespiratory failure groups. However, the rates of response to therapy and patient survival were significantly lower in the respiratory failure group (51.2% and 41.5%) than in the nonrespiratory failure group (71.9% and 78.1%, P < .05). There was no surgical mortality directly related to the procedure. The surgical morbidity rate was 6.6%.ConclusionSurgical lung biopsy is a safe and accurate diagnostic tool for diffuse pulmonary disease. For a large proportion of the patients, change of therapy and then clinical improvement can be achieved after surgical lung biopsy. Surgical lung biopsy should be considered earlier in patients with undiagnosed diffuse pulmonary disease, especially when the respiratory condition is deteriorating.

Epidemiological studies have demonstrated that areca quid chewing can be an independent risk factor for developing esophageal cancer. However, no studies are available to elucidate the mechanisms of how areca induces carcinogenesis in the esophagus. Since the areca nut in Taiwan contains a high concentration of safrole, a well-known carcinogenic agent, we analyzed safrole-DNA adducts by the 32P-postlabelling method in tissue specimens from esophageal cancer patients. In total, we evaluated 47 patients with esophageal cancer (16 areca chewers and 31 non-chewers) who underwent esophagectomy at the National Taiwan University Hospital between 1996 and 2002. Of the individuals with a history of habitual areca chewing (14 cigarette smokers and two non-smokers), one of the tumor tissue samples and five of the normal esophageal mucosa samples were positive for safrole-DNA adducts. All patients positive for safrole-DNA adducts were also cigarette smokers. Such adducts could not be found in patients who did not chew areca, irrespective of their habits of alcohol consumption or cigarette smoking (p

Background Diffuse pulmonary infiltrates is the major complication and cause of mortality after bone marrow transplantation. We analyzed the etiologies and prognostic factors in bone marrow recipients with diffuse pulmonary infiltrates and assessed the role of open lung biopsy in managing this complication. Methods Medical records of patients with diffuse pulmonary infiltrates after bone marrow transplantation were reviewed. Possible prognostic factors were analyzed by multivariate logistic regression. Results Sixty-eight (20%) of 341 bone marrow recipients had diffuse pulmonary infiltrates and 34 died. Thirty-five underwent open lung biopsy, resulting in therapeutic changes in 22 (63%) and clinical improvement in 16 (46%). The leading diagnoses were idiopathic interstitial pneumonitis (40%) and cytomegalovirus pneumonitis (20%). Cytomegalovirus pneumonitis caused radiographically observable interstitial infiltrates exclusively and was frequently associated with hepatitis. Idiopathic interstitial pneumonitis resulted in either diffuse ground-glass opacity or interstitial infiltrates. Three (9%) patients had miliary tuberculosis. Respiratory failure ( p p = 0.016) were the poor prognostic factors. Conclusions Among bone marrow recipients, we found diffuse pulmonary infiltrates in 20% and a mortality rate of 50%. Idiopathic interstitial pneumonitis and cytomegalovirus pneumonitis were the most common causes and should be suspected in patients with diffuse interstitial infiltrates. In endemic areas, miliary tuberculosis should be suspected in bone marrow recipients with diffuse reticulonodular lesions. Respiratory failure and acute graft-versus-host disease were poor prognostic factors. By establishing a correct diagnosis, open lung biopsy led to treatment changes in about two-thirds of these patients.

Objective: The use of a circular stapler in cervical esophagogastric anastomosis remains controversial. This study was to compare the postoperative and long-term results of manual and mechanical techniques for cervical esophagogastric anastomosis after resection for squamous cell carcinoma. Methods: A prospective randomized controlled trial was undertaken in 63 patients with curatively resectable squamous cell cancer of the thoracic esophagus between 1996 and 1999. Patients were randomized to receive either a hand-sewn (32 patients) or circular stapled (31 patients) cervical esophagogastric anastomosis. Results: The mean operating time was longer when the handsewn method was used (524 vs. 447 min, P , 0:001). Anastomotic leakage was noted in seven patients (22%) in the hand-sewn group and eight patients (26%) in the stapler group (P ¼ NS). Hospital mortality occurred in four patients (13%) of the hand-sewn group and in three patients (10%) of the stapler group (P ¼ NS). After the operation, four patients (14%) in the hand-sewn group and five patients (18%) in the stapler group developed a benign esophageal stricture (P ¼ NS). The mean follow-up time was 24 months, and the rates of freedom from benign stricture and survival were comparable in each group. Conclusions: Performing cervical esophagogastric anastomoses using a circular mechanical stapler had a shorter operating time and a comparable outcome to the hand-sewn method. The circular mechanical stapler could be used as an alternative for cervical esophagogastric anastomosis after resection for esophageal squamous cell cancer. q 2004 Elsevier B.V. All rights reserved.

Minimal invasive surgery using a laparoscopic or thoracoscopic approach for cardiomyotomy (Heller myotomy) has become a widely accepted procedure to treat achalasia of the esophagus. In this study, we evaluated the long-term results of Heller myotomy achieved by performing video-assisted thoracic surgery (VATS). We recruited patients with achalasia who had undergone VATS for Heller myotomy from 1991 to 2000 at the National Taiwan University Hospital. The myotomy was performed 6 cm above and 1 cm below the gastroesophageal junction. No fundoplication was performed during the procedure. The symptom score, which included dysphagia, regurgitation, and chest pain, was evaluated before and after surgery. Body weight was also recorded before and after surgery. The cases of 14 patients (4 men, 10 women) were studied. The mean patient age was 41.8 +/- 4.9 years. No postoperative mortality or morbidity was found in these patients. The follow-up duration was 56 +/- 7.17 months. The dysphasia score improved from 3.0 preoperatively to 0.79 +/- 0.30 postoperatively (p=0.001). The reflux score improved from 2.64 +/- 0.17 preoperatively to 0.50 +/- 0.20 postoperatively (p=0.001). All the improvements were still in place at the time of the most recent follow-up examinations. Heller myotomy to treat achalasia using a thoracoscopic approach can provide satisfactory long-term results.

Objective. To characterize the sonographic patterns of teratomas located within the mediastinum and to correlate them with pathologic findings, because there have been few reports concerning the application of sonography in the diagnosis of mediastinal teratoma. Methods. Over a 9-year period, we carried out an image analysis of the sonographic findings of 28 mediastinal teratomas whose diagnoses were proved surgically. Results. Sonography showed that 18 patients had a complex mass of heterogeneous echogenicity, including regional bright echoes (n = 12), acoustic shadows (n = 8), hyperechoic lines and dots (n = 7), soft tissue septa (n = 9), dermoid plugs (n = 6), and hypoechoic areas (n = 11). This type of mediastinal teratoma revealed, in pathologic findings, varying combinations of fat, sebaceous and mucinous materials, hair, mineralized elements, and multiple compartments. Eight patients had a homogeneous hyperechoic mass, and the 2 remaining patients had floating spherules within a cystic mass. Pathologically, the homogeneous mass mainly contained hair and sebaceous material. The floating spherules were also composed of sebaceous tissue and were above the fluid of the cyst. Conclusions. On the basis of the evaluation of the sonographic and pathologic findings, we described 3 major patterns of mediastinal teratoma: a complex mass of heterogeneous echogenicity, homogeneous high echogenicity within a solid mass, and floating spherules within a cystic mass. Thus, sonography can improve the diagnosis of mediastinal teratoma. However, additional prospective studies are needed to test the sensitivity and specificity of these sonographic patterns in the diagnosis of mediastinal teratoma.

Lymphoepithelioma-like carcinoma, an uncommon epithelial tumor, has been described as being closely associated with Epstein-Barr virus (EBV) infection in many organs, especially the nasopharynx. We experienced 23 cases of lymphoepithelioma-like carcinoma arising in the lung from 2498 lung cancer patients in the Cancer Registry of our hospital. Seven patients were male and 16 were female. All patients were Chinese. Their ages ranged from 42 to 80 years. Six patients were smokers and 17 were nonsmokers. The tumor sizes ranged from 1.2 to 11.0 cm. All tumors showed the typical syncytial growth pattern of undifferentiated epithelial cells with a significant CD8+ T-lymphocyte reaction. EBV serology revealed prior infection in all 15 serum-available patients, all of whom were also found by in situ hybridization to have the virus genome. In addition, the higher the EBV serology titer, the larger the tumor size and the higher the staging would be. EBV viral capsid antigen IgG level remained elevated despite response to therapy. Nearly all cases had bcl-2 oncoprotein expression, but the detection rate of latent membrane protein-1, p53, and c-erb B-2 expression was extremely low. The encouraging chemotherapy response for advanced stage disease is also discussed.

Cardiopulmonary bypass (CPB) is required in some lung transplantation (LTx) operations. However, it increases risks of bleeding and early graft dysfunction. We report our experiences of replacing CPB with heparin-bound extracorporeal membrane oxygenation (ECMO) in LTx operations. If extracorporeal circulation was anticipated for the LTx operations, ECMO support was set up through the femoral venoarterial route after induction of anesthesia; then, LTx was done as usual. Five thousand units of heparin was injected intravenously during the femoral vessels cannulation, but no more was used during the first 24 h of ECMO support. If necessary, as in patients undergoing single LTx for end-stage pulmonary hypertension, the ECMO support was directly extended into the postoperative period until reperfusion edema of the graft lung subsided. Twelve single LTxs and 3 bilateral sequential single LTxs were done under ECMO support. The advantages of using femoral ECMO rather than conventional CPB in LTx operations were the operative field was not disturbed by the bypass cannula, stable cardiopulmonary function and normothermia were maintained throughout the operations, there were less blood loss and transfusion requirements, and the left LTx was as easily performed as the right LTx. Red blood cell transfusion requirements during the operation and the first postoperative day were 4.4 +/- 2.8 and 2.4 +/- 2.0 U, respectively, in 10 adult patients undergoing uncomplicated single LTx with ECMO support, and 4.3 +/- 1.3 and 1.5 +/- 1.5 U in 8 adult patients undergoing single LTx without any extracorporeal circulatory support. The difference was not significant between the 2 groups (p = 0.53 and 0.32 by Mann-Whitney U test). The ECMO did not increase blood transfusion requirements. In comparison, 13 U of red blood cell transfusion was required in 2 patients receiving single LTx under CPB support. The ECMO support made the postoperative critical care easier in recipients with graft lung edema. Except for 2 cases of primary graft failure, the ECMO could be weaned off and removed at bedside within a short period (27.9 +/- 24.6 h, n = 13) with no major complications. In conclusion, the heparin-bound femoral ECMO rather than CPB should be used for LTx operations unless concomitant cardiac repair is planned.

The esophageal stent is used extensively for a malignant stricture, and many complications have been reported. We present a case of esophageal cancer with surgical esophageal stenting. Spinal epidural abscess occurred postoperatively, and we believe that the pathogenesis may be related to the esophageal stent.

Background. Alterations of the P53 or Rb gene are among the most frequently observed genetic changes in primary lung cancer. Nevertheless, there has been no final conclusion on the relationship between P53 or Rb protein expression and clinico-pathological parameters in primary lung cancer. A large-scale study was performed to examine the clinicopathological and prognostic significance of P53 and Rb expressions in 207 surgically resected non-small cell lung cancer (NSCLC) patients. Methods. Tumor specimens were obtained from 207 primary NSCLC surgically resected from January 1990 through December 1994. The avidin-biotin-peroxidase method was used to determine the expression of P53 or Rb of tumor cells using anti-P53 or anti-Rb monoclonal antibodies. The relationships between P53 or Rb protein expression and the clinicopathological parameters were analyzed. Results. Expression of P53 or Rb protein was detected in 115 (55.6%) and 136 (65.7%) of the 207 lung tumors, respectively. P53 had significantly higher positive results in patients with regional lymph node metastasis and advanced tumor stage. Rb expression was significantly lower in lung cancers with a macro- or microscopic picture of tumor necrosis. Additionally, an inverse correlation between the expression of Rb and P53 was found. By multiple variate analysis, P53 expression and pathological stage were independent, significant prognostic factors. Further analysis demonstrated P53 expression was an independent prognostic factor in stage 1, but not in other stages. Conclusions. P53 expression is especially useful as a prognostic factor in stage 1 lung cancer.

Fourteen cases (13 pleural and one intrapulmonary) of solitary fibrous tumors (SFTs) (the so-called fibrous mesothelioma) were studied. The lesions occurred more in females (nine cases) than males (five cases). The age of patients ranged from 44 to 73 years old (median 60 years). The tumors presented as cough with or without blood-tinged sputum, exertional dyspnea, chest pain, nausea, body weight loss, fever, or as asymptomatic masses detected by routine chest radiograph. Two patients with huge (tumor larger than 20 cm) malignant tumors had accompanying pleural effusion and one associated with hypoglycemia. Ten benign tumors measured 2-11 cm (median size 7 cm) while the remaining four histologically malignant ones measured 20-30 cm in size. All of them were well circumscribed and thinly encapsulated. Hemorrhage and necrosis were more frequently seen in the malignant tumors. Histologically, these lesions were characterized by 'patternless pattern' with occasional hemangiopericytic features (three cases). The tumor cells were all immunoreactive for vimentin, CD 34, and focally actin-positive in one case, but not for keratin, desmin, S-100 protein, carcinoembryonic antigen, alpha 1-ACT and F VIII-related antigen, supported a primitive mesenchymal origin. p53 protein was expressed in two of the malignant cases. Proliferating cell nuclear antigen stain was positive with 50 and 80% of the labeling index in the benign and malignant tumors, respectively, but retinoblastoma gene protein was negative in all tumors. This analysis confirmed the relationship between histological malignant SFTs and tumor size, cellularity, mitotic activity, necrosis and tumor suppressor gene expression. However, the clinical behavior was unpredictable. Complete respectability seemed to be the most important indicator of clinical outcome in the less aggressive tumors.

BACKGROUND: Pulmonary aspergilloma has been treated surgically for many years but the mortality rates of larger surgical series, varying from 7% to 23%, is not considered acceptable by today's standards. The authors report their experience in the surgical treatment of pulmonary aspergilloma and present a review of the literature. METHODS: Sixty seven patients who underwent thoracotomy for pulmonary aspergilloma from 1968 to 1995 were studied retrospectively by reviewing their medical records. RESULTS: The most common clinical presentation of pulmonary aspergilloma was haemoptysis which occurred in 61 patients (91.0%). Tuberculosis was the most common pre-existing disease, occurring in 54 patients (80.6%). The plain chest radiograph showed the typical "air-crescent" sign in 36 patients (53.7%). Systemic antifungal therapy neither palliated the clinical symptoms nor eradicated the aspergilloma, and transarterial embolisation was also unsuccessful. Surgery offered the only chance of cure for both unilateral and bilateral disease. Procedures varied from segmentectomy to pneumonectomy with most (61.4%) undergoing lobectomy. There was one death following surgery from pneumonia and 15 postoperative complications occurred in 12 patients-empyema (7), massive bleeding (3), bronchopleural fistula (2), wound infection (2), and Horner's syndrome (1). Postoperatively, most of the patients were symptom-free. CONCLUSIONS: With appropriate preoperative evaluation and judicious surgical technique, surgery is the preferred treatment for pulmonary aspergilloma, both for eradicating the tumour and for curing the underlying disease.

In order to improve arterial oxygenation and venous admixture during one lung ventilation, the effect of selective infusion of prostaglandin E 1 into the pulmonary, artery of the ventilated lung was investigated in 12 adult patients undergoing thoracotomy. Patients' bronchi were intubated with a Mallinckrodt bronchial tube and ventilated with 66% oxygen in air. Cardiopulmonary factors such as systemic and pulmonary arterial pressures, pulmonary vascular resistance, blood gas analyses, cardiac output and airway pressure were measured before and during one lung ventilation ; venous admixture (Qs/Qt) was calculated. Serial blood samples were taken from the pulmonary artery of the ventilated lung for endothelin-1 estimation. One lung ventilation reduced the mean PaO 2 from 42.1 (2.3)kPa to 11.8 (1.4)kPa (p < 0.001) and increased Qs/Qt from 10.8 (3.2)% to 39.2(4.7)% (p < 0.001). Pulmonary vascular resistance also increased from 167 (24) dyne.s.cm -5 to 262 (38) dyne.s.cm -5 (p < 0.05) with a corresponding increase of plasma endothelin-1 (p < 0.05). After 30 min alone lung ventilation, PGE 1 was infused continuously into the pulmonary artery of the ventilated lung at a rate which increased incrementally from 0.04-0.10 μg.kg -1 .min -1 . PaO 2 increased to 20.7 (2.6) kPa (p < 0.01) and Qs/Qt decreased to 30.6 (3.5)% (p < 0.05). During the infusion, pulmonary vascular resistance reduced to 173 (30) dyne.s.cm -5 (p < 0.01). The plasma endothelin-1 concentration reached a plateau between the end of one lung ventilation (before closing the thorax) and 6 h postoperatively. This correlated inversely with the pre-operative forced expiratory volume in one second (r = - 0.68, p < 0.005), declining to normal values 72 after operation. The selective infusion of PGE 1 into the pulmonary artery of the ventilated lung corrected pulmonary vasconstriction and improved both arterial oxygenation and venous admixture during one lung ventilation for thoracotomy.

This study investigated the clinico-pathologic correlation of tumor angiogenesis in non-small-cell lung cancers. Formalin-fixed, paraffin-embedded surgical specimens of 55 consecutive patients with primary non-small-cell lung cancers were examined. Included were 26 squamous cell carcinomas and 29 adenocarcinomas. Twenty-five patients had stage I disease, eight patients had stage II disease, and 22 patients had stage IIIA or IIIB disease. Among them, 28 had nodal metastasis and 27 did not. The microvessel was demonstrated by immunocytochemical staining for factor VIII and platelet endothelial cell adhesion molecules (PECAM-1). The microvessels in the areas of highest neovascularization were counted under light microscopy in 200x field by two independent observers without knowledge of clinical information. At least three separate fields were counted for each specimen. The Mann-Whitney U test was used for statistical analysis. The microvessel counts in adenocarcinoma were significantly higher than in the squamous cell carcinoma (54.4 +/- 35.65 versus 26.16 +/- 20.46 in factor VIII staining and 80.52 +/- 48.42 versus 40.04 +/- 32.33 in PECAM-1 staining; p0.001). The microvessel counts in patients with Stages I-II disease were significantly lower than that of stages IIIA-IIIB disease (23.63 +/- 16.21 versus 65.36 +/- 31.92 in factor VIII staining and 41.85 +/- 36.76 versus 93.00 +/- 43.08 in PECAM-1; p0.001). Patients with nodal metastasis had higher microvessel density than those without nodal metastasis (56.67 +/- 35.55 versus 23.44 +/- 15.77 in factor VIII staining and 86.89 +/- 46.46 versus 36.30 +/- 25.83 in PECAM-1 staining; p0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

The epidemiologic characteristics of lung cancer in Taiwan differ from those in other parts of the world in low male-to-female ratio, the high percentage of adenocarcinoma, and the relatively high percentage of nonsmokers who are victims. To investigate possible correlation between p53 gene alteration and the unique characteristics of lung cancer here, p53 gene status of 36 patients with primary, resected non-small-cell lung cancer (NSCLC) was studied by directly sequencing the cDNA of the p53 gene, then acquiring clinical and pathologic data to correlate p53 gene status with clinical parameters and pathologic staging. Missense mutations were present in 42% (15 of 36) of patients with NSCLC, including 42% (10 of 24) with adenocarcinomas, and 45% (five of 11) with squamous cell carcinomas. The frequency of p53 mutation was 50% in smokers and 29% in nonsmokers (p = 0.355). The mutation occurred most frequently in exon 8 (56%), and G:C to A:T transitions in non-CpG or CpG sites were the most commonly observed base changes (56%). These findings differ from the high prevalence of G to T transversion found in previous reports. The frequency of metastasis in hilar and mediastinal lymph nodes was significantly higher in tumors with p53 mutations. The association with nodal stage was strong for mutations within exon 8, but it was less apparent for mutations in other exons probably because of the small number. This study suggests that p53 gene missense is common in NSCLC in Taiwan, but smoking is probably not the sole contributing factor. More interestingly, p53 gene mutations, especially those in exon 8, may be associated with regional nodal metastasis.

Objective: To evaluate the feasibility and safety of thoracoscopic lobectomy without endotracheal intubation. Summary Background Data: General anesthesia with single-lung ventilation is considered mandatory for thoracoscopic lobectomy for non–small cell lung cancer (NSCLC). Nonintubated thoracoscopic lobectomy has not been reported previously. Methods: From August 2009 through June 2010, some 30 consecutive patients with clinical stage I or II NSCLC were treated by nonintubated thoracoscopic lobectomy using epidural anesthesia, intrathoracic vagal blockade, and sedation. To evaluate the feasibility and safety of this novel technique, they were compared with a control group consisting of 30 consecutive patients with clinical stage I or II NSCLC who underwent thoracoscopic lobectomy using intubated general anesthesia from August 2008 through July 2009. Results: Collapse of the operative lung and inhibition of coughing were satisfactory in the nonintubated patients, induced by spontaneous breathing, and vagal blockade. Three patients in the nonintubated group required conversion to intubated-single lung ventilation because of persistent hypoxemia, poor epidural anesthesia pain control, and bleeding. One patient in each group was converted to thoracotomy because of bleeding. The 2 groups had comparable anesthesia durations, surgical durations, blood loss, and numbers of dissected lymph nodes. Patients who underwent nonintubated surgery had lower rates of sore throat (6.7% vs 40.0%, P = 0.002) and earlier resumption of oral intake (mean, 4.7 hours vs 18.8 hours, P < 0.001). Patients undergoing nonintubated surgery also had a trend toward better noncomplication rates (90% vs 66.7%, P = 0.057) and shorter postoperative hospital stays (mean, 5.9 days vs 7.1 days, P = 0.078). Conclusions: Nonintubated thoracoscopic lobectomy is technically feasible and is as safe as lobectomy performed with intubation in highly selected patients. It can be a valid alternative of single-lung-ventilated thoracoscopic surgery in managing early-stage NSCLC.

Epidermal growth factor receptor (EGFR) is a novel target for therapy in subsets of non-small cell lung cancer, especially adenocarcinoma. Tumors with EGFR mutations showed good response to EGFR tyrosine kinase inhibitors (TKIs). We aimed to identify the discriminating capacity of immunohistochemical (IHC) scoring to detect L858R and E746-A750 deletion mutation in lung adenocarcinoma patients and predict EGFR TKIs response. Patients with surgically resected lung adenocarcinoma were enrolled. EGFR mutation status was genotyped by PCR and direct sequencing. Mutation-specific antibodies for L858R and E746-A750 deletion were used for IHC staining. Receiver operating characteristic (ROC) curves were used to determine the capacity of IHC, including intensity and/or quickscore (Q score), in differentiating L858R and E746-A750 deletion. We enrolled 143 patients during September 2000 to May 2009. Logistic-regression-model-based scoring containing both L858R Q score and total EGFR expression Q score was able to obtain a maximal area under the curve (AUC: 0.891) to differentiate the patients with L858R. Predictive model based on IHC Q score of E746-A750 deletion and IHC intensity of total EGFR expression reached an AUC of 0.969. The predictive model of L858R had a significantly higher AUC than L858R intensity only (p = 0.036). Of the six patients harboring complex EGFR mutations with classical mutation patterns, five had positive IHC staining. For EGFR TKI treated cancer recurrence patients, those with positive mutation-specific antibody IHC staining had better EGFR TKI response (p = 0.008) and longer progression-free survival (p = 0.012) than those without. In conclusion, total EGFR expression should be included in the IHC interpretation of L858R. After adjusting for total EGFR expression, the scoring method decreased the false positive rate and increased diagnostic power. According to the scoring method, the IHC method is useful to predict the clinical outcome and refine personalized therapy.

Purpose: To evaluate the efficacy and patterns of failure of elective nodal irradiation (ENI) in patients with esophageal squamous cell carcinoma (SCC) undergoing preoperative concurrent chemoradiation (CCRT) followed by radical surgery. Methods and Materials: We retrospectively studied 118 patients with AJCC Stage II to III esophageal SCC undergoing preoperative CCRT (median, 36 Gy), followed by radical esophagectomy. Of them, 73 patients (62%) had ENI and 45 patients (38%) had no ENI. Patients with ENI received radiotherapy to either supraclavicular (n = 54) or celiac (n = 19) lymphatics. Fifty-six patients (57%) received chemotherapy with paclitaxel plus cisplatin. The 3-year progression-free survival, overall survival, and patterns of failure were analyzed. Distant nodal recurrence was classified into M1a and M1b regions. A separate analysis using matched cases was conducted. Results: The median follow-up was 38 months. There were no differences in pathological complete response rate (p = 0.12), perioperative mortality rate (p = 0.48), or delayed Grade 3 or greater cardiopulmonary toxicities (p = 0.44), between the groups. More patients in the non-ENI group had M1a failure than in the ENI group, with 3-year rates of 11% and 3%, respectively (p = 0.05). However, the 3-year isolated distant nodal (M1a + M1b) failure rates were not different (ENI, 10%; non-ENI, 14%; p = 0.29). In multivariate analysis, pathological nodal status was the only independent prognostic factor associated with overall survival (hazard ratio = 1.78, p = 0.045). The 3-year overall survival and progression-free survival were 45% and 45%, respectively, in the ENI group, and 52% and 43%, respectively, in the non-ENI group (p = 0.31 and 0.89, respectively). Matched cases analysis did not show a statistical difference in outcomes between the groups. Conclusions: ENI reduced the M1a failure rate but was not associated with improved outcomes in patients undergoing preoperative CCRT for esophageal SCC. Pathological nodal metastasis predicted poor outcome. 2011 Elsevier Inc. Esophageal cancer, Squamous cell carcinoma, Preoperative chemo-radiation, Elective nodal irradiation.

We explored covariates of the quality of life (QOL) in non-small-cell lung cancer (NSCLC) patients and made a comparison with healthy controls. We assessed the QOL of 220 consecutive NSCLC patients at a university hospital. The QOL data were measured by the brief version of the World Health Organization’s Quality of Life and by utility using the standard gamble method. We selected demographically matched healthy controls from the 2001 National Health Interview Survey for comparison. Multiple linear regression models were constructed to explore significant factors of QOL after controlling for covariates. Patients with more advanced stages of NSCLC had poorer scores than did the healthy controls in the physical and psychological domains. Patients with disease duration of longer than 1 year tended to report higher physical and environment QOL than did those with NSCLC diagnosed for less than 1 year. Insight into one’s own illness was associated with a higher utility, better social support, and improved financial resources. QOL was significantly associated with staging and duration of NSCLC. Disease insight appears to be a positive factor for operable NSCLC patients of the Taiwanese culture, which implies that clinicians should respect patient autonomy in diagnosis disclosure.

To obtain insight into the cancer progression and metastatic process, we evaluate p53/epidermal growth factor receptor (EGFR) somatic aberrations in non-small-cell lung cancers to compare accumulated genetic alterations between primary tumors and lymph node metastases. A total of 56 primary lung cancers with corresponding lymph node metastases were identified to investigate somatic mutations and altered expressions of p53 and EGFR for clonality assessment. Genomic DNA was extracted from macrodissected cells of paraffin-embedded primary tumor and metastatic lymph node tissues. Overexpression and somatic mutations in exons of p53 (exons 5–8) and tyrosine kinase domain of EGFR (exons 18–21) were examined by immunohistochemical staining and DNA sequencing, respectively. p53 and EGFR mutation/overexpression status were different between primary tumors and lymph node metastases in 5.4/7.2% and 28.6/33.9%, respectively. In most cases, the p53 and EGFR mutations usually preceded lymph node metastasis, and these gene statuses in the primary cancer and their lymph node metastasis were concordant (92.9 and 69.6%, respectively), which further supported the hypothesis that when these p53 mutations occur before the establishment of lymph node metastasis, they subsequently persist in the metastatic nodes. The expressions of p53 and EGFR showed 7.1 and 33.9% discordance in that order. Our results reveal that p53 and EGFR mutations usually precede lymph node metastasis. The higher prevalence of EGFR heterogeneity existing in the primary tumor is not reflected in all lymph node metastasis and thus might have therapeutic implications when adjuvant therapy is considered.

Two hundred and eighteen patients, with thoracic tumors larger than 3 cm in size, underwent ultrasound-guided percutaneous transthoracic core biopsy with a large-bore Tru-Cut needle. Fifty-five tumors were in the mediastinum, and 122 tumors were located at subpleural area, and 42 tumors were within the lungs. In 122 subpleural tumors, the sensitivity of ultrasound-guided core biopsy for the diagnosis of malignancy was 96.8%, and accuracy was 97.5%. Sensitivity for the diagnosis of malignant tumors located within the lungs was 94.6%, and accuracy was 95.2%. In 54 patients with mediastinal tumors, definite histologic diagnosis could be obtained in 48 patients (88.9%). The sensitivity of ultrasound-guided biopsy for the diagnosis of malignancy in these 48 mediastinal tumors was 97.1%, with an accuracy of 97.9%. Three patients had complications with minimal pneumothorax and one with mild hemoptysis. We conclude that percutaneous transthoracic core biopsy with Tru-Cut needle under ultrasound guidance is a safe and sensitive way to obtain specimens for accurate histologic diagnosis of thoracic tumors. The diagnostic yield is high, and the technique, relatively simple, can also be used for outpatients.

BACKGROUND: Ultrasound has been used to guide percutaneous aspiration biopsy of thoracic tumours with high diagnostic yield. This study assessed the diagnostic value of ultrasound guided percutaneous cutting biopsy for pulmonary consolidation of unknown aetiology. METHODS: Thirty patients with undiagnosed lobar or segmental consolidation underwent ultrasound guided percutaneous needle aspiration and large bore cutting biopsy. The needle aspirates and biopsy specimens were sent for cytological, microbiological, and histopathological examination. RESULTS: Percutaneous needle aspiration provided a diagnosis in nine of 30 patients (30%), whereas cutting biopsy obtained a satisfactory specimen for histological diagnosis in 28 patients (93%) and provided a definite aetiological diagnosis in 17 patients (57%). The combination of needle aspiration with Trucut biopsy provided a diagnostic rate of 63%. The underlying diagnoses were fungal pneumonia (five patients), tuberculosis (five), bacterial pneumonia (one), bronchioloalveolar carcinoma (three), lymphoma (two), adenocarcinoma (one), vasculitis (one), acute pneumonia of unknown aetiology (one), and chronic non-specific pneumonia (nine). Two patients, who had necrotic tissue only in the biopsy specimen, were found at thoracotomy to have an adenocarcinoma and aspergillosis. Two patients had complications from the technique, a small pneumothorax in one and a small haemoptysis in another. CONCLUSIONS: Ultrasound guided percutaneous cutting biopsy is a valuable method for diagnosing pulmonary consolidation of unknown aetiology. The diagnostic yield is high and the procedure appears to be relatively safe.

BACKGROUND: Malignancies located in the upper middle mediastinum usually do not have a sufficiently large acoustic window to permit a conventional ultrasound guided parasternal biopsy. This study was concerned with an alternative approach whereby ultrasound is applied through the supraclavicular paratracheal window to allow percutaneous biopsy of middle mediastinal malignancies. METHODS: Fifteen patients who had upper mediastinal malignancies not in contact with the chest wall underwent real time and Doppler ultrasonographic studies by the supraclavicular approach. None of these tumours could be reached by conventional ultrasound guided parasternal biopsy. The ultrasound was scanned downwards through the supraclavicular fossa, along the acoustic window of the paratracheal soft tissue space. Percutaneous aspiration biopsy was performed with a 22 gauge needle under ultrasound guidance. If fine needle aspiration could not obtain an adequate tissue smear an 18 gauge Trucut biopsy was performed to obtain a histological diagnosis. RESULTS: Twelve of 15 mediastinal malignancies were detected by ultrasound through the supraclavicular approach. These 12 patients underwent percutaneous needle aspiration biopsy under ultrasound guidance. Four of the patients also had a Trucut biopsy because the needle aspirates from the tumours were inadequate. The needle had to pass through the jugular veins in four patients who received fine needle aspiration but in none of the patients who required a Trucut biopsy. Definite histological diagnoses were obtained in all 12 of these patients. Ten of the tumours were malignant and two benign. None of the patients developed any complication. CONCLUSIONS: Ultrasound and ultrasound guided biopsy through the supraclavicular paratracheal window provides a new approach for malignancy located in the upper middle mediastinum, which cannot be reached by conventional ultrasound guided parasternal biopsy. The diagnostic yield of this technique is high and the procedure is relatively safe.

Corrosive tracheobronchitis and lung perforation after caustic aspiration are not very common. We present a case of life-threatening acute respiratory system corrosion after aspiration of caustic alkaline crystals during a suicide attempt. The patient survived the severe burns of the tracheobronchial tract and the liquefaction necrosis of the lung lobe by aggressive airway protection procedures and surgical resection of the destroyed lung. We report this rare, clinical condition and discuss the possible mechanism and its management.