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SummaryWe investigated whether microRNA expression profiles can predict clinical outcome of NSCLC patients. Using real-time RT-PCR, we obtained microRNA expressions in 112 NSCLC patients, which were divided into the training and testing sets. Using Cox regression and risk-score analysis, we identified a five-microRNA signature for the prediction of treatment outcome of NSCLC in the training set. This microRNA signature was validated by the testing set and an independent cohort. Patients with high-risk scores in their microRNA signatures had poor overall and disease-free survivals compared to the low-risk-score patients. This microRNA signature is an independent predictor of the cancer relapse and survival of NSCLC patients.

Background/purposeBronchogenic cysts (BCs) are usually located in the mediastinum and they occur less commonly in the lung parenchyma. This study investigated the findings from computed tomography (CT) images, clinical presentation and histopathologic findings of intrapulmonary BCs.MethodsFrom the last 7 years, the CT images of 20 patients (12 females, 8 males; mean age, 38.8 ± 21.7 year; median age, 34 years) with intrapulmonary BC were available. Contrast-enhanced CT findings were characterized and correlated with clinical presentation and histopathologic findings (using Fisher's exact tests).ResultsThe majority of intrapulmonary BCs were subpleural in location (55%), in the lower lobes (60%), symptomatic (80%), and in adults (90%). Three CT patterns were identified: cyst with content of fluid attenuation (9 patients), cyst with air and fluid content (9 patients), cyst with content of soft tissue attenuation (2 patients). Preoperative diagnosis of intrapulmonary BC was correct in only 20% using the CT criteria of cysts with fluid attenuation and without anomalous blood supply. Cysts with air component were significantly larger than those without air component (p = 0.0452), but cyst size and air component were not correlated with clinical presentation. Surrounding infiltration or thick wall on CT were significantly correlated with the presence of any clinical symptom (p = 0.014) or fever (p = 0.042). CT findings of surrounding consolidation, ground glass opacity or thick wall were significantly correlated with chronic inflammation or pneumonic change on histopathology (p = 0.0008).ConclusionThere is a wide spectrum of intrapulmonary BCs that have CT findings that are correlated with clinical presentations and histopathologic findings. [J Formos Med Assoc 2007;106(1):8-15]

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.

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.

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.

Botryomycosis is an unusual chronic suppurative disease characterized by the histological finding of sulphur granules containing the causative bacteria in an abscess. We describe a previously healthy 14-year-old girl who presented with chronic productive cough. Chest computed tomography (CT) revealed a right lower mass with involvement of the parietal pleura, chest wall, diaphragm, liver and costovertebral junction. Thoracostomy biopsy was performed due to suspicion of low-grade mucosa-associated lymphoid tissue lymphoma. However, histological analysis revealed a pulmonary botryomycosis. The right lower lung mass completely resolved after 3 months of antibiotics treatment. This case emphasizes that primary pulmonary botryomycosis with extensive contiguous involvement may not be distinguishable from lung cancer, lymphoma or fungal infection on chest CT.

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.

Acute traumatic aortic transection is a critical condition in victims of major trauma. How to avoid the complications of surgical repair is still a challenge to trauma and cardiovascular surgeons. A 74-year-old woman was referred to our hospital with multiple fractures and hypotension after a motor vehicle accident. Computed tomography revealed acute traumatic aortic transection at the upper thoracic aorta with periaortic hematoma. She underwent repair of the aortic injury after primary survey. The patient received urgent aortic grafting under heparin-free extracorporeal membrane oxygenation support for lower body perfusion. The postoperative course was smooth. No neurologic or hemorrhagic complication was noted. The results of this case indicate that extracorporeal membrane oxygenation could be used as a heparin-free partial bypass system during surgery for traumatic aortic transection. The risk of spinal cord ischemia during aortic clamp or bleeding due to heparinization during conventional cardiopulmonary bypass could be minimized.

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.

Certain alternatively spliced exons of CD44 gene have been associated with specific functions. However, these functions may have come from inclusion of a central array of alternatively spliced exons, rather than a single one. The goals of this study were to analyze all of the variant exons included by alternative splicing, the entire population of CD44 mRNA transcripts, and the prognostic implications of CD44 mRNA and protein isoforms expressed by non-small cell lung cancer (NSCLC).Using a polymerase chain reaction protocol with short reaction times, we amplified, sequenced and quantified CD44 mRNA transcripts from 52 samples of NSCLC to determine the splicing patterns of alternatively included exons and the proportion of each CD44 mRNA transcript. The expression of CD44 standard form and variant isoforms CD44v3 and CD44v6 were also analyzed by immunohistochemistry (IHC).Normal lung and NSCLC expressed CD44 mRNA transcripts containing variant exons v10, v8-10, v6-10, v3-10 and v2-10. In squamous cell carcinoma, the expression rates of these mRNA transcripts were equal to or higher than those of the normal lung, and the splicing pattern was not associated with disease progression. In adenocarcinoma, the expression rates of CD44v6-10, v3-10 and v2-10 mRNA were lower than in normal lung. The down-regulation of CD44v6-10, CD44v3-10 mRNA and CD44v6 protein paralleled the progression of adenocarcinoma. Recurrence of adenocarcinoma was associated with negative expression of CD44v6-10 or CD44v3-10 mRNA, and with low-level expression of CD44v6 or CD44v3 by IHC. Negative expression of CD44v6-10 mRNA and reduced expression of CD44 v6 protein were associated with a shorter disease-free and overall survival in the univariate but not the multivariate analysis.Our data suggest that CD44 splicing pattern is associated with disease progression in adenocarcinoma.

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.

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.

The diagnostic value and indications for fiberoptic bronchoscopy in the preoperative assessment of patients with esophageal cancer have not been fully studied. We evaluated the role of fiberoptic bronchoscopic examination in the stage work-up of patients with esophageal cancer and correlated the results with survival time analysis.The medical records of 153 patients with an initial diagnosis of esophageal cancer were reviewed. Clinical data, bronchoscopic findings, treatment courses, and survival time of these patients were analyzed.On initial bronchoscopic examinations, distortion/compression of the normal structure and protrusion at the posterior wall of the trachea or bronchus were the most common bronchoscopic findings (35.9%). We stratified patients into 3 subgroups according to bronchoscopic findings of direct invasion, external compression, and negative findings. The symptoms of dyspnea, hoarseness, aspiration and fever were more frequent in patients with direct airway invasion compared with patients with external compression and negative bronchoscopic findings (p0.02). Washing and brushing cytology examinations were all negative in patients with external compression of the airway. There was a significant difference of survival time among these 3 groups of patients (direct invasion: 5.6 +/- 0.6 months; external compression: 12.3 +/- 0.9 months; negative findings: 13.3 +/- 1.1 months, p0.01). Direct airway invasion and original cancer stage were the most important variables for survival in the multivariate analysis, and the hazard ratio for prognosis was 2.5 (95% confidence interval [CI], 1.1-4.6) and 4.2 (95% CI, 1.5-9.3), respectively. Twelve patients (80%) with tracheoesophageal (TE) fistulae died within 3 months after diagnosis due to aspiration pneumonia and septic shock.The role of bronchoscopic examination in patients with esophageal cancer for preoperative evaluation resides in its ability to predict airway invasion and its impact on survival. Advanced cancer stage (stage IV) and direct airway invasion (especially TE fistula) were significantly associated with poor prognosis. These results suggest that patients suffering from dyspnea, hoarseness, aspiration and fever, implicating a high probability of airway invasion, are more likely to benefit from bronchoscopic examination and proper management in order to prevent aspiration or complications.

Background: Pulmonary complications remain the major cause of postoperative mortality in patients with esophageal cancer undergoing esophagectomy. It was unclear whether this dismal complication has a genetic predisposition. We therefore investigated the role of an angiotensin-converting enzyme (ACE) insertion/deletion polymorphism in developing these complications. Methods: We conducted a prospective study including 152 patients with esophageal cancer who underwent esophagectomy in National Taiwan University Hospital between 1996 and 2002. The ACE genotype was determined by polymerase chain reaction amplification of leukocyte DNA obtained before surgery. The serum ACE concentration was determined by enzyme-linked immunosorbent assay. Results: Thirty-five patients (23%) developed pulmonary complications following esophagectomy. As compared with patients with the I/I and I/D genotypes, those with the D/D genotype had a higher risk for pulmonary complications (adjusted odds ratio OR, 3.12; 95% confidence interval CI, 1.01‐9.65). The risk was additively enhanced by combination of the ACE D/D genotype with other clinical risk factors (old age, hypoalbuminemia, and poor pulmonary function). The circulating ACE level was also dose-dependently with the presence of ACE D allele. As compared with the patients with circulating ACE less than 200 ng/mL, the patients with circulating ACE of 200 to 400 ng/mL and over 400 ng/mL had ORs (95% CI) of 2.75 (1.12‐6.67) and 15.00 (4.3‐52.34) to present with ACE D allele, respectively. Conclusions: An ACE insertion/deletion polymorphism might modulate the function of ACE gene and play a role in affecting individual susceptibility to pulmonary injury following esophagectomy in patients of esophageal cancer. (Ann Surg 2005;241: 659‐665)

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 ≤ 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. © 2005 Wiley-Liss, Inc.

doi:10.1016/j.jtcvs.2004.06.004 Primary spontaneous pneumothorax (SP) has a tendency toward bilateral bullous lesions of the lung, with incidence ranging from 7.8% to 20% of the total cases of SP. A previous study demonstrated that bilateral video-assisted thoracoscopic surgery (VATS) in the supine position is feasible in the treatment of bilateral SP. In the past, we have used sequential inflation pneumatic cuffs to simplify these procedures.

Primary pulmonary hypertension (PPH) is a progressive disease for which there is no cure. Continuous intravenous infusion of epoprostenol in selected patients with advanced PPH improves symptoms and survival, but the long-term impact has not been reported in Taiwanese patients. Four patients with advanced PPH treated with epoprostenol therapy were enrolled in this study from July 2000 to September 2001. The basic hemodynamic status, cardiothoracic ratio, 6-minute-walk test results, maximum oxygen consumption, New York Heart Association functional class and survival were re-evaluated before and after 12 months of epoprostenol treatment. One of the patients died after 10 months of epoprostenol therapy due to heart failure, and the other 3 were still alive after a mean of 28 months. The surviving patients had pronounced symptomatic, hemodynamic, functional and survival benefit from epoprostenol therapy. Our results suggest that chronic infusion of epoprostenol can improve functional status and survival of Taiwanese patients with advanced PPH disease.

Tracheoesophageal fistula is an uncommon complication usually associated with chronic usage of ventilator and pressure necrosis of the tracheoesophageal wall. A 56-year-old female patient with severe acute respiratory syndrome (SARS) with tracheoesophageal fistula is reported. She was intubated for ventilatory support 3 days after admission because of progressive respiratory distress. Methylprednisolone pulse therapy followed by a maintenance dosage was given due to persistence of bilateral pulmonary fibrosis. Thirty three days after admission, she underwent tracheostomy because of difficulty in weaning from the ventilator. Ten days after tracheostomy, she developed tracheoesophageal fistula, which was confirmed by bronchoscopy and panendoscopy. Tracheal resection and primary repair for the esophageal defect was performed via a cervical incision combined with partial sternotomy. She was weaned from the ventilator soon after the surgery and discharged 34 days after the operation. In SARS patients with persistent pulmonary fibrosis and under prolonged corticosteroid treatment, special care should be given to avoid intubation-related tracheal injury during the period of ventilatory support. The tracheoesophageal fistula, once developed, can be repaired in a single stage after improvement of the nutritional status.

We present a patient with intermittent pain over the right chest for 2 years. Computed tomograph of the chest disclosed a cystic tumor over the right posterior basal lung. Pathological examinations of the excised tumor disclosed a granulomatous inflammation within the multilocular bronchogenic cysts and microbiological culture of the tissue yielded Mycobacterium avium. This is the first reported case of infected bronchogenic cyst caused by M. avium in humans.

Botryomycosis is a rare chronic suppurative disease characterized by the presence of eosinophilic granules containing the causative bacteria on histological study of an abscess specimen. The majority of cases involve the skin and visceral involvement is rare. A 54-year-old man with primary pulmonary botryomycosis which involved parietal pleura presented with exertional dyspnea for 2 weeks. Echo-guided aspiration of lung mass yielded viridans streptococci and positive Gram stain of the surgical specimen indicated viridians streptococci was the causative pathogen. There was no recurrence during 2 years of follow-up after surgery and antibiotic treatment. Early differentiation of botryomycosis from lung cancer, pulmonary tuberculosis, and actinomycosis is essential.

The RNA-binding motif (RRM) gene on Y chromosome (RBMY), encoding a male germ cell-specific RNA-binding protein associated with spermatogenesis, was found inserted by hepatitis B virus (HBV) DNA in one childhood hepatocellular carcinoma (HCC). This study is aimed to explore the oncogenic potential of the RBMY protein. The RBMY transcripts, expressed exclusively in the testis of normal people, were detected by reverse transcription-polymerase chain reaction in 36% of HCCs from 90 males and in 67% of hepatoblastoma from six boys. The nontumor liver counter parts, cirrhotic liver tissues from children with biliary atresia, and other types of cancers, such as bile duct, colon, stomach, lung, prostate, and kidney, were all negative for RBMY expression. One to four types of RBMY transcripts, including wild type and variants with N-terminal RRM deletion, C-terminal SRGY (serine-arginine-glycine-tyrosine) boxes deletion, or deletion of both domains, were found in the testis and liver cancer tissues. The wild-type RBMY protein was expressed in the nucleus and demonstrated its tumorigenicity by transformation of mouse fibroblast NIH3T3 cells and in vivo tumor formation. The RBMY variant protein with deletion of C-terminal exons 9-12 was trapped in the cytoplasm and showed decreased tumorigenicity. Our results suggest that RBMY is a new candidate oncogene specific for male liver cancer.

The appropriate type of intervention for the treatment of empyema in children remains controversial. This study analyzed whether video-assisted thoracoscopic debridement (VATD) as first-line treatment is effective in the management of pediatric parapneumonic empyema.We retrospectively reviewed the medical and microbiological records of pediatric patients with parapneumonic empyema diagnosed at a medical center from January 1995 to December 2002. The 55 patients included in this study were initially treated with either tube thoracostomy drainage (TTD group [n = 37]) or video-assisted thoracoscopic debridement (VATD group [n = 18]).A comparative analysis found no significant difference in patient characteristics between these 2 groups. Patients in the VATD group had a significantly shorter duration of fever (18.9 +/- 1.7 vs 26.9 +/- 1.3 days), chest tube placement (5.3 +/- 0.7 vs 15.2 +/- 2.0 days), antibiotic therapy after the procedure (12.2 +/- 1.0 vs 26.3 +/- 2.8 days), and hospital stay (21.5 +/- 2.1 vs 33.2 +/- 2.8 days). No additional procedures were required in the VATD group, whereas 65% (24/37) of patients in the TTD group underwent salvage VATD.Primary management using video-assisted thoracoscopic decortication was more effective and reduced the duration of illness in pediatric patients with parapneumonic empyema.

Sialyl Lewis antigens (sLe(x/a)) are cancer-associated carbohydrate determinants, serve as ligands of the selectin family and are associated with hematogenous metastasis of cancer. So far, the clinicopathologic values of sialyl Lewis x (sLe(x)) and sialyl Lewis a (sLe(a)) in lung cancer have remained controversial. Using immunohistochemistry, the expressions of sLe(x) and sLe(a) antigens, and an airway mucin (MUC5AC) protein, which was supposed to be the major carrying protein of sialyl Lewis moieties, were studied in surgically resected tumor tissues of 61 patients with stages I or II NSCLC. Thirty-two (52.5%) of the 61 studied subjects were found to be positive for expression of sLe(a), 40 (65.6%) were positive for expression of sLe(x), and 16 (26.2%) were positive for MUC5AC protein. Both the expression of sLe(x) and MUC5AC were associated with adenocarcinoma subtype. Patients bearing tumors with MUC5AC and/or sLe(x) expression had a higher probability of post-operative distant metastasis. Survival analysis demonstrated that patients bearing tumors with expression of sLe(x) antigen or MUC5AC had shorter overall survival. The multivariate logistic regression showed that age >65 years old (OR = 0.207, 95% CI = 0.075-0.569, P = 0.002), nodal status (OR = 6.575, 95% CI = 2.459-17.583, P < 0.001), and MUC5AC (OR = 5.545, 95% CI = 1.998-15.386, P = 0.001) were independent factors affecting survival. We concluded that the expression of sLe(x) was related to MUC5AC protein, while patients with tumors co-expressing both MUC5AC and sLe(x) antigen had the worst survival.

Thyroid transcription factor-1 (TTF-1) is a tissue-specific transcription factor expressed in the thyroid and lung. The clinical utility and limitation of TTF-1 in primary or metastatic carcinomas of the lung have not been previously studied in detail. We examined TTF-1 expression in 510 primary lung and 107 metastatic neoplasms. TTF-1 was detectable in 4/99 (4%) squamous cell carcinomas, 169/176 (96%) solitary adenocarcinomas, 34/34 (100%) multifocal adenocarcinomas, 1/1 (100%) signet ring cell carcinoma, 16/20 (80%) mucinous adenocarcinomas, 23/23 (100%) nonmucinous bronchioloalveolar carcinomas, 19/36 (53%) small cell carcinomas, and 39/44 (89%) sclerosing hemangioma. TTF-1 was absent in all eight carcinoids, three atypical carcinoids, 23 pleomorphic carcinomas, 25 lymphoepithelioma-like carcinomas, the sarcomatous component of one pseudomesotheliomatous carcinoma, and one mesothelioma. In four combined small cell carcinomas and 12 adenosquamous carcinomas, TTF-1 expression was only demonstrated in the adenocarcinoma component. There were 78 TTF-1 non-immunoreactive metastatic cases from 22 livers, 20 colorectums, 10 breasts, six nasopharynx, four larynx, four ovaries, three salivary glands, three esophagus, two adrenal glands, two kidneys, one bile duct, and one endometrium. TTF-1 was also detected in all 10 cervical lymph nodes, seven brain, and 6/7 (86%) bony tissues of 24 patients with metastatic carcinomas of unknown primary site, but it was absent in 125 patients with metastatic carcinomas other than lung origin in cervical lymph nodes, brain, and bony tissues. These results indicate the clinical usefulness and limitation in certain primary and metastatic lung neoplasms.

J Thorac Cardiovasc Surg 2003;125:191-3

Background Quality of life (QOL) is one of the major outcomes to reflect lung cancer patients' general condition. However, the individually physical and psychological differences may affect and cause different types of QOL trajectories. The aims of this study were to (1) explore the potential types of QOL trajectories in advanced lung cancer patients during the first 6 month of diagnosis, and (2) identify factors related to each type of the QOL trajectories. Methods A prospective longitudinal study was conducted in a medical center in Taiwan. A total of 170 newly diagnosed non-operable lung cancer patients were recruited and completed 4 assessments during pre-treatment and 1, 3, 6 months from receiving treatments (T1-4, respectively). QOL trajectory was measured by the overall QOL item from the EORTC QLQ-C30. Physical function and symptoms, depression, uncertainty (about illness) land self-efficacy (level of confidence) in coping with cancer were assessed and analyzed as potential related factors of each QOL trajectory. We used Latent Class Growth Analysis (LCGA) to identify the types of QOL trajectory and their related factors. Results Three types of QOL trajectories were identified. The first type of QOL type covered 41.8% of patients which represented a “declining form moderate level of QOL to lower QOL and then back to moderate levels of QOL “. The second type of QOL covered 19.6% of patients and represented “the relatively higher level of QOL declined to relatively lower level of QOL and then steadily back to moderate QOL“. The third type of QOL covered 39.6% of patients and represented “steadily moderate level of QOL“. The factors significantly related to the first type of QOL trajectory were physical function, pain, poor appetite, uncertainty, and self efficacy; pain, uncertainty and self-efficacy were related to the second type of QOL trajectory; and depression and uncertainty were related to the third type of QOL trajectory. Conclusion Based on the QOL trajectories and identified factors, the timely and tailoring interventions should be developed, applied to and tested for their clinical effectiveness in enhancing advanced lung cancer patients' QOL during the most distressful first 6 months of having lung cancer. Acknowledge This study is supported by National Health Research Institute (NHRI) in Taiwan. Disclosure All authors have declared no conflicts of interest.

Sulfotransferase (SULT) 1A1 detoxifies and bioactivates a broad spectrum of substrates including xenobiotics. It has been suggested that the SULT1A1 his (histidine) allele, which is caused by a his for arg (arginine) substitution due to a GA transition at codon 213, carries a significantly higher risk for women to develop breast cancer. We investigated the association between the SULT1A1 arg/his genotype and esophageal cancer in men, 187 cases of esophageal squamous cell carcinoma and 308 controls from 3 medical centers in Taiwan. Cigarette smoking, areca chewing and alcohol consumption were the major risks for developing esophageal cancer. The frequencies of arg/his in cases and controls were 27.8% (52/187) and 11.0% (34/308), respectively (p < 0.0001). No subjects carried his/his. After adjusting for substance use and other covariates, individuals with arg/his had a 3.53-fold higher risk (95% CI = 2.12–5.87) of developing esophageal cancer than those with arg/arg. Unexpectedly, this positive association was found to be even stronger (adjusted OR = 4.04–4.80) among non-smokers, non-drinkers or non-chewers. Our findings suggest that the SULT1A1 his213 allele is important in the development of esophageal cancer in men. © 2002 Wiley-Liss, Inc.

Laparoscopic antireflux surgery has recently been introduced as an alternative to laparotomy for the treatment of gastroesophageal reflux disease (GERD) at National Taiwan University Hospital. This study compared the results of traditional open and laparoscopic fundoplication for the treatment of GERD.The surgical records and medical charts of 29 adult patients who were surgically treated for GERD between 1980 and 2001 were retrospectively reviewed. The clinical characteristics, indications for surgery, and surgical findings and procedures were analyzed.Laparotomy and Nissen fundoplication were carried out on 20 of the patients between 1985 and 2000. Laparoscopic Nissen or Toupet fundoplication was performed on nine patients between 1997 and 2001. Patients in the laparoscopic group were younger than those in the laparotomy group (46.7 +/- 15.9 vs 58.3 +/- 18.5 yr). The incidence of associated prominent hiatal hernia was significantly higher in the laparotomy group (60 vs 33%). The mean operation time was 164.5 +/- 25.5 minutes in the laparotomy group and 182.2 +/- 52.2 minutes in the laparoscopy group (p = 0.6129). The mean hospital stay in the laparotomy group was significantly longer than that in the laparoscopy group (8.7 vs 3.4 days). Postoperative complications included three ventral hernias and one ileus in the laparotomy group. Results were good or excellent in 78.9% (15/19) of patients undergoing laparotomy (one patient was lost to follow-up 2 months later), and in 77.7% (7/9) of those undergoing laparoscopy. Symptomatic and endoscopic recurrence was recorded in two patients in the laparotomy group and one in the laparoscopy group.Laparoscopic fundoplication is as effective as traditional laparotomy for treating GERD. More GERD patients in Taiwan, even the young and those without associated hiatal hernia, would rather undergo the less invasive and cosmetically better laparoscopic surgery than require medication throughout their lives.

A 7-year-old boy who presented with cyanosis and exercise intolerance was diagnosed with pulmonary arteriovenous malformations (PAVMs) secondary to a congenital superior-mesenteric-vein-to-left-renal-vein (SMV-LRV) shunt. Resolution of the PAVMs (confirmed by chest computed tomography [CT]) occurred after embolization of this shunt. Although the pathogenesis of his PAVM is not well known, this case demonstrated a close relationship between a congenital SMV-LRV shunt and the development of PAVM.

PURPOSE: To evaluate interactions between expressions of tumor suppressor gene p53 and angiogenic factors vascular endothelial cell growth factor (VEGF) and interleukin-8 (IL-8) and their effect on tumor angiogenesis and patient prognosis in non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: p53, VEGF, IL-8, and the microvessel endothelium were immunostained, and VEGF and IL-8 mRNA expression were quantified using the real-time quantitative reverse-transcription polymerase chain reaction in 65 NSCLC surgical specimens. Aberrant p53 expression was correlated with VEGF and IL-8 mRNA expression, microvessel count (MVC), other clinical-pathologic variables, and patients’ survival. RESULTS: Tumors with high aberrant p53 expression showed significantly higher VEGF and IL-8 mRNA expression and MVC than those with low aberrant p53 expression (P < .001). When tested as a continuous variable, aberrant p53 expression correlated strongly and positively with VEGF and IL-8 mRNA expression and MVC (P < .0001). Tumors with high aberrant p53 expression were associated with mediastinal or distant lymph node metastasis (P = .006). Survival and postoperative relapse time were significantly shorter in patients with high aberrant p53 expression tumors than in those with low aberrant expression tumors (P < .0001). A significant difference in survival was also seen between patients with high and low tumoral VEGF mRNA expression and between those with high and low tumoral IL-8 mRNA expression (P < .0001). CONCLUSION: We report here for the first time that aberrant p53 expression is strongly positively correlated with VEGF mRNA and IL-8 mRNA expression in NSCLC. This result indicates that aberrant p53 expression may play a significant role in regulation of VEGF and IL-8 expression and be involved in controlling angiogenesis and explains the adverse prognosis of cancers with high aberrant p53 expression.

BACKGROUND Numerous genetic changes are associated with metastasis and invasion of cancer cells. To identify differentially expressed invasion-associated genes, we screened a panel of lung cancer cell lines (CL(1-0), CL(1-1), CL(1-5), and CL(1-5)-F(4) in order of increasing invasive activity) for such genes and selected one gene, collapsin response mediator protein-1 (CRMP-1), to characterize. METHODS We used a microarray containing 9600 gene sequences to assess gene expression in the cell panel and selected the differentially expressed CRMP-1 gene for further study. We confirmed the differential expression of CRMP-1 with northern and western blot analyses. After transfecting and overexpressing CRMP-1 in highly invasive CL(1-5) cells, the cells were assessed morphologically and with an in vitro invasion assay. We used enhanced green fluorescent protein-tagged CRMP-1 and fluorescence microscopy to localize CRMP-1 intracellularly. CRMP-1 expression in 80 lung cancer specimens was determined by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). All statistical tests were two-sided. RESULTS Expression of CRMP-1 was inversely associated with invasive activity in the cell panel, an observation confirmed by northern and western blot analyses. CRMP-1-transfected CL(1-5) cells became rounded and had fewer filopodia and statistically significantly lower in vitro invasive activity than untransfected cells (all P< .001). During interphase, CRMP-1 protein was present uniformly throughout the cytoplasm and sometimes in the nucleus; during mitosis, CRMP-1 was associated with mitotic spindles, centrosomes, and the midbody (in late telophase). Real-time RT-PCR of lung cancer specimens showed that reduced expression of CRMP-1 was statistically significantly associated with advanced disease (stage III or IV; P = .010), lymph node metastasis (N1, N2, and N3; P =.043), early postoperative relapse (P = .030), and shorter survival (P = .016). CONCLUSIONS CRMP-1 appears to be involved in cancer invasion and metastasis and may be an invasion-suppressor gene.

Pleomorphic (spindle) cell carcinoma, also known as monophasic sarcomatoid carcinoma, is a rare primary pulmonary malignancy. This type of tumor shows concurrent presence of malignant epithelial and homologous sarcomatoid spindle cell components by co-expressing cytokeratin and vimentin in various degrees. Sixteen cases (four central endobronchial lesions and 12 peripheral parenchymal masses) were studied clinicopathologically. Men were affected far more frequently than women (13:3). The patients were between 56 and 80 years of age. The disease is strongly associated with smoking. Among seven of the patients who underwent surgical resection, four of them had mediastinum, pleura and chest wall invasions, and three of them had regional lymph node metastases. All of the patients succumbed to early distant metastases (range 2 weeks-5 months) in organs including brain, bone, adrenal gland, and unusual sites such as esophagus, jejunum, rectum and kidney. The remaining nine inoperable cases were late stage disease and treated with chemoradiotherapy with little effect. The median duration of survival was 3 months. All parenchymal masses appeared as cavities with marked central necrosis, and only peripheral rim of tumor cells was left. More definite diagnostic results will depend on further tissue sections and can be confirmed by immunohistochemical studies. Significantly fewer Ki-67, p53 and c-erb B-2 oncoprotein expressions were also noted.

PURPOSE: The purpose of this study was to evaluate the correlation between the expression of four different vascular endothelial growth factor (VEGF) mRNA isoforms (VEGF121, VEGF165, VEGF 189, and VEGF206) and the clinicopathologic characteristics, tumor angiogenesis, and outcome of patients with non–small-cell lung cancer. PATIENTS AND METHODS: We examined the expression of four different VEGF mRNA isoforms in 57 non–small-cell lung cancers using reverse transcriptase polymerase chain reaction and the tumor angiogenesis using immunohistochemical staining. RESULTS: All 57 lung cancer samples expressed the VEGF121, VEGF165, and VEGF189 mRNA isoforms, and three expressed the VEGF206 mRNA isoform. A high tumoral VEGF189 mRNA isoform expression ratio was associated with a high intratumoral microvessel count (P = .013), short survival (< 24 months; P = .001), and early postoperative relapse (< 12 months; P = .001). Survival and postoperative relapse time were significantly shorter in patients with a high compared with a low tumor VEGF189 mRNA isoform expression ratio (P = .0001 and P = .0086, respectively, log-rank test). In contrast, the VEGF165 and VEGF 206 mRNA isoform expression ratios showed no statistical correlation with tumor angiogenesis, postoperative relapse time, or survival. A high VEGF121 mRNA isoform expression ratio was associated with short survival (< 24 months) and early relapse (< 12 months). Multivariate analysis showed that VEGF 189 mRNA isoform expression, microvessel count, and nodal status were the most important independent prognostic factors for patient survival and postoperation recurrence. CONCLUSION: The VEGF189 mRNA isoform expression ratio shows a greater correlation with tumor angiogenesis, postoperative relapse time, and survival than do the expression ratios for the VEGF121, VEGF165, and VEGF206 mRNA isoforms and can be used as a prognostic indicator for patients with non–small-cell lung cancers.

Thymomas are thymic epithelial tumors. The term thymoma has been customarily restricted to those neoplasms arising from or exhibiting differentiation toward thymic epithelial cells. Thymomas with capsular or extracapsular invasion were thought to be malignant thymomas. Thymic carcinoma was defined as a malignant epithelial tumor with overt cytologic atypia and without organotypic features. Thymic carcinoma is rare and accounts for 0.06% of all thymic tumors. Thymoma is frequently associated with parathymic autoimmune diseases. In contrast, the association of thymic carcinoma and autoimmune disease is rare. We present an interesting case of thymic carcinoma associated with 2 rare parathymic syndromes.

Many mechanisms have been proposed for hepatic hydrothorax (HH), pleural effusion seen in cirrhotic patients, and the transdiaphragmatic flow of ascitic fluid through the diaphragmatic defects is considered the most probable. There are several methods for diagnosis of HH, including biochemical analysis of ascitic and pleural fluids, conventional radiography, radioisotopic imaging, magnetic resonance imaging, and thoracoscopy. Among these, ultrasonography may be considered the easiest method and has the benefit of real-time diagnosis of anatomic integrity. On the other hand, the magnification offered by the optical system of thoracoscopy allows excellent localization of diaphragmatic defects. This study is the first demonstration of the transdiaphragmatic flow by color Doppler ultrasonography that further directly verifies detected defects by means of video-assisted thoracoscopic surgery.

We report a 73-year-old man who presented with dyspnea that was caused by a huge and single cystic cellular schwannoma in the left chest. He underwent radical tumor excision by a thoracotomy. The patient is doing well, without evidence of recurrence, 8 months after surgical resection.

A new technique of near-total esophageal exclusion was used successfully in the treatment of 2 patients with chronic thoracic esophageal perforation and continuing sepsis. The most striking point of this technique is the use of cervical T-tube esophagostomy with the lower arm of the T tube circumfixed by chromic catgut tie to prevent swallowing of saliva. Whereas most of the previously reported procedures of cervical esophageal diversion require subsequent esophageal reconstruction, this technique is simple and effective and does not require a second operation.

Background. To assess the effects of gabexate mesilate (FOY), a protease inhibitor, on a canine model of pulmonary ischemia–reperfusion injury. FOY has been applied clinically to treat acute pancreatitis and disseminated intravascular coagulation (DIC) and has been found to suppress some leukocyte-mediated tissue injuries in both in vitro and in vivo studies. Materials and methods. Design: Comparison of four experimental groups: group 1 (untreated control, n = 8), unilateral (left) pulmonary ischemia due to perfusion and ventilation obstruction followed by reperfusion, without receiving any specific treatment; group 2 (negative control, sham operation, n = 8), left pulmonary hilar dissection without ischemia; group 3 (FOY posttreatment, n = 8), FOY treatment during the reperfusion stage only; and group 4 (FOY pretreatment, n = 8), FOY treatment before ischemia and then continued during reperfusion. Setting: University animal laboratory. Subjects: Heart-worm-free mongrel dogs (12 to 15 kg body wt) were anesthetized with pentobarbital and mechanically ventilated. Investigations: Lung ischemia was made by snaring the left pulmonary artery and veins and clamping the bronchus with peribronchial tissue for 90 min followed by reperfusion for 18 h. Animals of the two treatment groups received a 1 mg/kg bolus of FOY at the beginning of reperfusion, with infusion of 2 mg/kg/h of FOY continuously starting 30 min before ischemia (group 4) or after reperfusion (group 3). During this study the following were measured: hemodynamics and aerodynamics, blood gas, bronchoalveolar lavage (BAL) fluid neutrophil percentage and protein concentration, lung wet to dry weight ratio (W/D ratio), myeloperoxidase (MPO) activity of the lung tissue, alveolar neutrophil infiltration, and degree of injury. Results. This model of lung ischemia–reperfusion induced significant pulmonary hypertension, increased pulmonary vascular resistance, decreased pulmonary dynamic compliance and arterial hypoxemia, increased BAL fluid total protein amount and neutrophil percentage, and increased alveolar neutrophil infiltration, histological injury score, and lung tissue MPO assay (group 1). Animals of the sham operation (negative control, group 2) showed only minimal changes in the above parameters. Treatment with FOY significantly attenuated the injury by decreasing the lung W/D ratio, alveolar neutrophil infiltration, histological injury score, lung tissue MPO assay, BAL fluid neutrophil percentage, and protein amount. Pretreatment with FOY (group 4) attenuated the injury to a significantly greater degree than it did when administered at the reperfusion stage only (group 3), which was reflected by the above-mentioned parameters, and as well significantly improved gas exchange function. FOY treatment was found to have little effect in altering hemodynamics and aerodynamics at most time points in this model of lung injury. Conclusions. FOY can attenuate the ischemia–reperfusion-induced acute lung injury in dogs by ameliorating the degree of alveolar membrane permeability change, neutrophil aggregation, and activation. FOY treatment starting before ischemia attenuated this injury to a significantly higher degree than its use after ischemia. However, the effect of FOY may be partial because it cannot alter the hemodynamics or aerodynamics as prominently as other parameters in this type of lung injury. Concomitant use of FOY with other agents will have additive or synergic effects in preventing lung ischemia–reperfusion injury.

The clinical courses of 35 tuberculous empyema patients were investigated retrospectively from November 1990 through November 1995. Most patients had nonspecific symptoms and signs but with far-advanced pulmonary parenchymal lesions in their chest roentgenographs. The effusions showed neutrophilic leukocytosis with a 60% positive culture rate for Mycobacterium tuberculosis. Multidrug resistant strains were found in 7 out of 18 cultures. All patients received chemotherapy and eight of them underwent additional surgical management. Twenty-two (62.9%) patients had been treated successfully and one patient is still under treatment. The remaining 12 patients either died during treatment or defaulted; and four (11.4%) of them had died of tuberculosis. We conclude that the treatment outcome of tuberculous empyema is less satisfactory than that of pulmonary tuberculosis, however, modern multidrug chemotherapy with repeated drainage and opportune surgical interventions could be in prospect of successful treatment of tuberculous empyema.

Carcinoid tumors of the gastrointestinal tract are distinctive endocrine neoplasms commonly found in the small bowel and appendix; however, they are exceedingly uncommon in the esophagus. It was first reported in 1974 that esophageal carcinoids arise from the argyrophil endocrine cells, which are amine precursor uptake and decarboxylation cells of the mucosa. 1 The aggressiveness of atypical carcinoid of the esophagus often precludes the use of limited surgical resection and requires adjuvant chemoradiotherapy. 2 Here we report our successful palliative management of an advanced esophageal atypical carcinoid with tracheal invasion using a covered Ultraflex expandable metallic tracheal stent (Boston Scientific, Galway, Ireland) and oral thalidomide. Clinical Summary

This study was carried out in order to investigate the local immune reaction of tumour-infiltrating lymphocytes (TILs) in the primary tumours of non-small cell lung carcinomas. Thirty non-small cell lung cancer (NSCLC) patients were included. The tumour tissue was taken at thoracotomy and monocellular suspension of the tumour was obtained by mechanical disaggregation. Dual-coloured flow cytometric analysis of TILs and their corresponding peripheral blood lymphocytes (PBLs) was performed. Tumour-infiltrating lymphocytes contained significantly higher proportions of CD3(+) T lymphocytes and CD8(+) T lymphocytes than the corresponding PBLs (82.0%+/-13.9% vs 66.3%+/-10.6% for CD3, P

Objective—To develop new electrocardiographic (ECG) criteria for the differentiation between counterclockwise and clockwise atrial flutters. Background—Traditionally, the ECG differentiation between counterclockwise and clockwise atrial flutters is based on the flutter wave polarity in the inferior leads. However, determination of flutter wave polarity is subjective and sometimes difficult, especially in flutter waves of undulating pattern. Patients—The study comprised 37 consecutive patients with drug resistant atrial flutter; 30 had counterclockwise and 17 had clockwise atrial flutter (10 had both forms of atrial flutter). The isthmus dependence was confirmed by entrainment study and catheter ablation. The ECG patterns of both types of atrial flutter were compared and the flutter wave polarity in the inferior leads was determined by four independent cardiologists. Results—The flutter wave polarity in the inferior leads appeared negative in 24, positive in one, and equivocal in five of the counterclockwise atrial flutters; polarity appeared negative in one, positive in 10, and equivocal in six of the clockwise atrial flutters. However, the aVF/lead I flutter wave amplitude ratio was > 2.5 in all counterclockwise but