Heparin co-factor II enhances cell motility and promotes metastasis in non-small cell lung cancer.

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.

MicroRNA signature predicts survival and relapse in lung cancer.

We 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.

Frequent EGFR mutations in nonsmall cell lung cancer presenting with miliary intrapulmonary carcinomatosis.

Nonsmall cell lung cancer (NSCLC) presenting with miliary intrapulmonary carcinomatosis (MIPC) is rare. We investigated the clinical characteristics and epidermal growth factor receptor (EGFR) mutation rate of NSCLC patients with MIPC at initial diagnosis. From June 2004 to December 2008, we screened newly diagnosed NSCLC patients for MIPC using image-based criteria. We recorded clinical data and analysed EGFR mutation status. For comparison, we collected specimens from stage IV NSCLC patients without MIPC tested for EGFR mutations from April 2001 to November 2008. From 3,612 NSCLC patients, 85 patients with MIPC at initial diagnosis were identified; 81 had adenocarcinoma. Of the 85 patients, 60 had specimen sequencing to detect EGFR mutation; 42 (70%) were positive. Compared with 673 stage IV patients without MIPC, patients with MIPC had higher EGFR mutation rate (p=0.036); even male smokers had a high EGFR mutation rate (91%). Multivariate analysis of prognostic factors for overall survival of the 85 patients with MIPC revealed that adenocarcinoma, absence of extrapulmonary metastasis and having EGFR mutation were associated with longer overall survival. NSCLC patients with MIPC at initial diagnosis had higher rates of adenocarcinoma and EGFR mutation. EGFR tyrosine kinase inhibition may be the treatment of choice for NSCLC patients with MIPC at initial diagnosis among Asians.

Human pulmonary dirofilariasis coexisting with intercostal neurilemmoma: a case report and literature review.

Human pulmonary dirofilariasis (HPD) is a rare zoonotic infection caused by Dirofilaria immitis. Dogs are the definite hosts and humans are infected occasionally via a vector, generally a mosquito. Most thoracic neurilemmoma arise in the mediastinum and fewer tumors originate peripherally from the intercostal nerves. Most patients with HPD or thoracic neurilemmoma are asymptomatic and these diseases are often discovered incidentally. We present a 53-year-old female who was found to have a pulmonary nodule and a chest wall nodule during a routine health examination. She underwent a video-assisted thoracoscopic surgery (VATS) with partial lung resection and local excision of the chest wall. The pathological examination revealed a coiled, degenerating Dirofilariasis immitis worm surrounded by granulomatous inflammation with caseous necrosis and a neurilemmoma composed of S-100 protein immunoreactive but smooth muscle actin negative spindle cells. Because these diseases are self-limiting and make further treatment unnecessary, video-assisted thoracoscopic surgery (VATS) is considered preferable and less invasive for definitive diagnosis and management.

Airway obstruction following bronchoscopic photodynamic therapy in early centrally located lung cancer requiring extracorporeal membrane oxygenation.

Photodynamic therapy (PDT) is a treatment modality of early central located non-small-cell lung cancer, and in patients who are unsuitable for surgical intervention. Most complications of PDT reported in the literature are minor and can be easily handled. We report a case presenting with nearly fatal complication: airway obstruction following bronchoscopic photodynamic therapy for early endobronchial lung cancer, requiring extracorporeal membrane oxygenation. An 81-year-old man was admitted to thoracic surgery division due to an early centrally located lung cancer. Due to multiple comorbidity and high surgical risk we performed bronchoscopic PDT instead of aggressive lung resection for the patient. After the procedure, he developed severe airway obstruction by tumor debris and required temporary cardiopulmonary support with extracorporeal membrane oxygenation. The patient recovered smoothly after the episode and was free from tumor recurrence for >2 years without any neurological sequelae.

Lobar torsion after lung transplantation.

Lobar torsion is a rare complication after lung transplantation. Here we report a case of right middle lobe (RML) torsion after bilateral sequential lung transplantation (BLTx). This 30-year-old lady underwent BLTx for bronchiolitis obliterans due to paraneoplastic pemphigus. The right lower lobe of the donor lung was resected due to inflammatory change during procurement. The postoperative chest X-ray showed persisting RML infiltrates. Fever and leukocytosis were noted 1 week later. RML lobectomy was performed after the reconstructed chest computed tomography confirmed the diagnosis of RML torsion. Adult respiratory distress syndrome with unstable vital signs, refractory hypoxemia and respiratory acidosis occurred thereafter. After venoarterial extracorporeal membrane oxygenation support, the patient recovered slowly and was discharged 5 months after BLTx.

The significance of visceral pleural surface invasion in 321 cases of non-small cell lung cancers with pleural retraction.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Unique p53 and epidermal growth factor receptor gene mutation status in 46 pulmonary lymphoepithelioma-like carcinomas.

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 <3 cm in size suggests the potential benefits to EGFR tyrosine kinase inhibitors of inoperable LELCs.

Nonintubated thoracoscopic lobectomy for lung cancer.

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.

Genetic variants in DNA repair predicts the survival of patients with esophageal cancer.

OBJECTIVE: To investigate the association of the genetic variants in excision repair cross-complementation group 2 (ERCC2) R156R and ERCC4 rs3136038 with survival duration for patients with esophageal cancer. BACKGROUND: ERCC2 and ERCC4 are important molecules participating nucleotide excision repair system. The clinical relevance of the genetic variants of these genes is largely unknown currently. PATIENTS AND METHODS: A total of 400 patients with a diagnosis of esophageal cancer were included. The genetic variants in the promoter regions of ERCC2 on R156R and ERCC4 on rs3136038 were analyzed with the TaqMan assay from leukocyte DNA collected before treatment and correlated to survival of the patients. RESULTS: Presence with ERCC2 R156R C/C or ERCC4 rs3136038 C/T genotype of the patients could additively increase risk of death and disease progression. Under multivariate analysis, T, N staging and simultaneous presentation of these unfavorable genotypes were found significant for prognosis (P < 0.05). Accumulation of each unfavorable genotype would associate with adjusted HRs [95% CI] of 1.35 [1.10-1.65] and 1.37 [1.12-1.68] (P ≤ 0.05) for death and disease progression respectively. The prognostic impact of these genotypes were more evident in the subgroup of patients with early disease status including T staging (II or less), free from lymph node metastasis or being able to undergo surgical resection (P < 0.05 for both overall and disease progression-free survival duration, respectively). CONCLUSION: Genetic variants in ERCC2 and ERCC4 may provide further survival prediction in addition to TNM staging system of esophageal cancer, which is more evident in the patients with early disease status.

EGFR and p53 status of pulmonary pleomorphic carcinoma: implications for EGFR tyrosine kinase inhibitors therapy of an aggressive lung malignancy.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Comparison of p53 and epidermal growth factor receptor gene status between primary tumors and lymph node metastases in non-small cell lung cancers.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Polymorphism in epidermal growth factor receptor intron 1 predicts prognosis of patients with esophageal cancer after chemoradiation and surgery.

BACKGROUND: 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. METHODS: 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. RESULTS: Patients with the homozygous short allele (<20 CA) of the EGFR gene in intron 1 were more likely to have a shorter duration of survival after CCRT and surgery than those with the homozygous long allele [adjusted hazard ratio (HR) (95% confidence interval [CI]) of death: 1.88 (1.02-3.49); P = 0.045]. This unfavorable prognostic effect of EGFR homozygous short CA repeat was mainly manifested in patients with good response to CCRT [adjusted HR (95% CI) of death 3.40 (1.06-10.89); P = 0.039]; it was less evident in those with poor response to CCRT [adjusted HR (95% CI) 1.40 (0.65-3.02); P = 0.384]. CONCLUSIONS: The EGFR CA repeat genetic polymorphism may act as a valuable molecular predictor of clinical outcome of esophageal cancer after CCRT and esophagectomy, especially in those with good response to CCRT.

Is there any benefit to incorporating a laparoscopic procedure into minimally invasive esophagectomy? The impact on perioperative results in patients with esophageal cancer.

BACKGROUND: The benefit of using the laparoscopic approach in minimally invasive esophagectomy (MIE) has not been established. We therefore compared the outcome of esophagectomy for patients with esophageal cancer performed with open surgery, video-assisted thoracic surgery (VATS)/laparotomy (hybrid MIE), and VATS/ laparoscopy (total MIE). METHODS: Patients with esophageal cancer undergoing tri-incisional esophagectomy with three different approaches between 2005 and 2009 were analyzed from a prospective database. RESULTS: Three groups of patients underwent esophagectomy by open surgery (n = 64), hybrid MIE (n = 44), and total MIE (n = 30). The total MIE group had significantly longer operative times but had shorter postoperative ventilator usage times postoperative hospital stay, and they began jejunostomy feeding sooner (P < 0.05, compared with the other groups). There was a significant trend toward a decrease in postoperative pulmonary complications and anastomotic leakage in parallel to the proportion of minimally invasive procedures for esophagectomy (P < 0.05 for the trend test), with a significant difference between the open surgery and total MIE groups (30% vs. 6.7%, and 28% vs. 6.7%, respectively; P < 0.05). CONCLUSIONS: Use of a laparoscopic procedure in MIE for patients with esophageal cancer might provide benefit by facilitating postoperative recovery and reducing the rates of post-esophagectomy pulmonary complications and anastomotic leakage.

Comparison of the quality of life between patients with non-small-cell lung cancer and healthy controls.

PURPOSE: We explored covariates of the quality of life (QOL) in non-small-cell lung cancer (NSCLC) patients and made a comparison with healthy controls. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Quality of life of patients with oesophageal cancer in Taiwan: validation and application of the Taiwan Chinese (Mandarin) version of the EORTC QLQ-OES18: a brief communication.

PURPOSE: The aim of this study was to examine the reliability and validity, and the application of the Taiwan Chinese Version of the EORTC QLQ-OES18. METHODS: The authors translated the questionnaire according to the guideline of the EORTC. Ninety-five patients with oesophageal cancer in National Taiwan University Hospital were interviewed using the questionnaire and the EORTC QLQ-C30 between October 2002 and September 2007. Answer distribution and psychometric properties of the EORTC QLQ-OES18 were examined. RESULTS: The mean age of the patients was 60 years (SD 12 years). Most of the patients were in advanced stages of disease, with two-thirds off-treatment. The Cronbach's alpha coefficients were satisfactory (0.77-0.82) or near-satisfactory (pain: 0.67). The item-to-own and item-to-other scale correlations showed satisfactory results. Patients who were on-treatment versus off-treatment had significantly poorer quality of life scores in dysphagia, dry mouth, and taste, and a borderline poorer score in cough. Opposite situations were seen in the scales of reflux and choking. CONCLUSIONS: The EORTC QLQ-OES18 is a valid instrument to assess quality of life issues in patients with oesophageal cancer in Taiwan.

Potential roles of fibroblast growth factor-9 in the benzo(a)pyrene-induced invasion in vitro and the metastasis of human lung adenocarcinoma.

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.

Claudin-1 is a metastasis suppressor and correlates with clinical outcome in lung adenocarcinoma.

RATIONALE: Claudin (CLDN)-1, a key component of tight junction complexes, was down-regulated in human lung adenocarcinomas. OBJECTIVES: To investigate the clinical significance of CLDN1 expression in patients with lung adenocarcinoma and its role in cancer invasion and metastasis. METHODS: 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. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: CLDN1 is a cancer invasion/metastasis suppressor. CLDN1 is also a useful prognostic predictor and potential drug treatment target for patients with lung adenocarcinoma.

Rescue a drowning patient by prolonged extracorporeal membrane oxygenation support for 117 days.

Drowning is one of the most common causes of accidental events. Here we report a drowning patient who experienced acute respiratory distress syndrome after hospitalization. Although the compliance of lung was as poor less as 5 mL/cm H2O, this patient was eventually rescued and recovered by extraprolonged extracorporeal membrane oxygenation support for 117 days.

Pulmonary manifestations and management of proteus syndrome.

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.