Pathway cross-talk network strategy reveals key pathways in non-small cell lung cancer.

PURPOSE: The purpose of this study was to explore the pathway cross-talks and key pathways in non-small cell lung cancer (NSCLC) to better understand the underlying pathological mechanism. METHODS: Integrated gene expression data, pathway data and protein-protein interaction (PPI) data were assessed to identify the pathway regulatory interactions in NSCLC, and constructed the background and disease pathway crosstalk networks, respectively. In this work, the attractor method was implemented to identified the differential pathways, and the rank product (RP) algorithm was used to determine the importance of pathways. RESULTS: Based on 787,896 PPI interactions from STRING database and 300 human pathways from KEGG, we constructed the back pathway cross-talk network with 300 nodes and 42239 edges. Integrating with expression data of NSCLC, each pathway cross-talk endowed with a weight value, and disease pathway cross-talks were identified. By RP algorithm and topology analysis of network, we selected 5 key pathways, including Alanine, DNA replication, Fanconi anemia pathway, Cell cycle and MicroRNAs in cancer under the pre-set thresholds. CONCLUSION: We successfully revealed the disease pathway cross-talks and explored 5 key pathways in NSCLC, which may be the underlying therapeutic targets for lung cancer.

MiRNA-155 and miRNA-132 as potential diagnostic biomarkers for pulmonary tuberculosis: A preliminary study.

In our study, we aimed to profile a panel microRNAs (miRNAs) as potential biomarkers for the early diagnosis of pulmonary tuberculosis (PTB) and to illuminate the molecular mechanisms in the development of PTB. Firstly, gene expression profile of E-GEOD-49951 was downloaded from ArrayExpress database, and quantile-adjusted conditional maximum likelihood method was utilized to identify statistical difference between miRNAs of Mycobacterium tuberculosis (MTB)-infected individuals and healthy subjects. Furthermore, in order to assess the performance of our methodology, random forest (RF) classification model was utilized to identify the top 10 miRNAs with better Area Under The Curve (AUC) using 10-fold cross-validation method. Additionally, Monte Carlo Cross-Validation was repeated 50 times to explore the best miRNAs. In order to learn more about the differentially-expressed miRNAs, the target genes of differentially-expressed miRNAs were retrieved from TargetScan database and Ingenuity Pathways Analysis (IPA) was used to screen out biological pathways where target genes were involved. After normalization, a total of 478 miRNAs with higher than 0.25-fold quantile average across all samples were required. Based on the differential expression analysis, 38 differentially expressed miRNAs were identified when the significance was set as false discovery rate (FDR) < 0.01. Among the top 10 differentially expressed miRNAs, miRNA-155 obtained a highest AUC value 0.976, showing a good performance between PTB and control groups. Similarly, miRNA-449a, miRNA-212 and miRNA-132 revealed also a good performance with AUC values 0.947, 0.931 and 0.930, respectively. Moreover, miRNA-155, miRNA-449a, miRNA-29b-1* and miRNA-132 appeared in 50, 49, 49 and 48 bootstraps. Thus, miRNA-155 and miRNA-132 might be important in the progression of PTB and thereby, might present potential signatures for diagnosis of PTB.

Integrating differential pathway analysis with Monte Carlo cross-validation reveals seed cross-talks in non-small cell lung carcinoma.

PURPOSE: The objective of this study was to identify seed pathway cross-talks in non-small cell lung carcinoma (NSCLC), and to reveal potential pathological mechanism at molecular level systematically. METHODS: Differentially expressed genes (DEGs) between NSCLC and normal controls were identified using quantile- adjusted conditional maximum likelihood (QCML) method. Subsequently, differential pathways (DPs) enriched by DEGs were determined according to the Ingenuity Pathways Analysis )IPA) pathways and Fisher's exact test. A discriminating score )DS) was computed for each pair of DPs also called as cross-talk, and random forest )RF) algorithm was implemented to investigated hub cross-talks. Finally, global cross-talks with repeated times > 5 were calculated by Monte Carlo Cross-Validation )MCCV). By taking intersections between hub cross-talks and global crosstalks, we obtained seed cross-talks. RESULTS: We obtained 122 DEGs and 5 DPs between NSCLC samples and normal controls. Based on DS and RF algorithm, 5 hub cross-talks with best area under the curve )AUC) were identified, of which Agranulocyte Adhesion and Diapedesis, and IL-17A Signaling in Fibroblasts were the best with AUC=0.996. After intersected with global cross-talks, we gained 2 seed cross-talks (Agranulocyte Adhesion and Diapedesis, Granulocyte Adhesion and Diapedesis and Agranulocyte Adhesion and Diapedesis, Glutathione Redox Reactions I). CONCLUSIONS: Two seed cross-talks were identified and validated by MCCV, which may give insights for revealing pathological mechanism and potential biomarkers for target therapy in NSCLC.

Real-World Survival Outcomes Based on EGFR Mutation Status in Chinese Patients With Lung Adenocarcinoma After Complete Resection: Results From the ICAN Study.

INTRODUCTION: The adjuvant treatment of patients with resected lung adenocarcinoma (LUAD) remains unstandardized. We analyzed the survival outcomes of these patients based on EGFR mutation status and adjuvant chemotherapy treatment. METHODS: This noninterventional real-world study (ICAN) enrolled Chinese patients with resected stages I to III LUAD from April 8, 2010, to December 31, 2010. Tumor EGFR mutation status and 3-year disease-free survival (DFS) were determined. The extension phase provided long-term follow-up with overall survival (OS) as the primary end point. Secondary end points included DFS and prognostic factors of survival. Survival outcomes based on adjuvant chemotherapy treatment, EGFR mutation status, and postoperative stage were analyzed post hoc. RESULTS: Among 568 patients in the ICAN cohort, 472 continued to the extension phase and remained eligible. The 3-year DFS rate was 58.8%. In the extension cohort, 260 patients (55.1%) had EGFR-mutant disease and 207 (43.9%) received adjuvant chemotherapy. At a median follow-up of 109.0 (95% confidence interval [CI]: 106.6-111.4) months, median OS and DFS were 103.3 (95% CI: 101.7-104.9) and 67.4 (95% CI: 49.7-85.2) months, respectively. The 5-year OS and DFS rates were 68.9% (95% CI: 64.3-73.6) and 52.9% (95% CI: 48.2-57.7), respectively. EGFR wild-type disease was a significant independent predictor of worse OS (HR = 1.24, 95% CI: 1.07-1.44, p= 0.004) based on the Cox regression analysis of common factors. Post hoc subgroup analysis revealed that survival outcomes were not significantly different with adjuvant chemotherapy regardless of EGFR mutation status across all postoperative stages. CONCLUSIONS: EGFR mutations are common in operable LUAD, and recurrence and mortality after resection were considerable. Adjuvant chemotherapy did not improve survival outcomes, regardless of EGFR mutation status and postoperative stage.

[Diagnosis and surgical treatment for mediastinal hemangioma and lymphangioma].

OBJECTIVE: To review the experience of diagnosis and surgical treatment of the primary mediastinal hemangioma and lymphangioma. METHODS: We summarized the medical records of patients with primary mediastinal hemangioma or lymphangioma at our hospital from January 1998 to January 2009, then extracted relevant clinical data and carried out the retrospective analysis. RESULTS: There were 11 patients in the whole group. The age range was 4 - 78 years old (average: 38.9). Six patients were symptom-free and most patients had not an accurate preoperative diagnosis. All patients underwent surgical procedures. The radical excision was accomplished in 10 cases and incomplete excision in 1 case. Two cases of surgically related complications were observed. All the cases were diagnosed by postoperative histopathological examination. There were hemangioma (n = 5), lymphangioma (n = 3) and hematolymphangioma (n = 3). CONCLUSIONS: The operation should be performed once the diagnosis of hemangioma or lymphangioma is made. Radical excision should be performed to prevent a post-operative recurrence.

[Therapeutic effect of 125I-103Pd hybrid radioactive seeds on pulmonary carcinomas in BALB/c-nu mice].

OBJECTIVE: To prepared (125)I-(103)Pd hybrid radioactive seeds and to explore their therapeutic effect on pulmonary carcinomas. METHODS: The (125)I-(103)Pd hybrid radioactive seeds were prepared by a chemical method of step-by-step coat plating. Pulmonary adenocarcinoma of GLC-82 cells and pulmonary large cell carcinoma of H460 cells were cultured in vitro and then were exposed directly to (125)I, (103)Pd and (125)I-(103)Pd seeds for 48 hours to observe the killing effects of radiation. GLC-82 and H460 tumor models were established and 20 mice chosen randomly for each model. For each tumor model, there were 4 groups (n = 5 each). Then (125)I-(103)Pd, (125)I, (103)Pd and nonradioactive seeds were implanted into the tumors. Tumor sizes and weights of mice were measured and recorded every 5 days for a 2-month observation. RESULTS: The (125)I-(103)Pd hybrid radioactive seeds were prepared successfully. After a 48-hour radiation from radioactive seeds, the GLC-82 cells within one particulate around (125)I, (103)Pd or (125)I-(103)Pd seeds were inhibited so as to become swollen and transfiguring. The H460 cells around (125)I seeds showed no obvious abnormality while those within one particulate around (103)Pd or (125)I-(103)Pd seeds were much fewer. No mouse died during the observation period. The radioactive seeds could inhibit the tumors. The radiotherapeutic effects were similar in two tumor modes: (125)I-(103)Pd seeds > (103)Pd seeds ≈ (125)I seeds > non-radioactive seeds. H460 tumors grew much faster than GLC-82 tumors. Meanwhile the seeds with the same nuclide were much more effective for GLC-82 tumors than for H460 tumors. CONCLUSION: The (125)I-(103)Pd hybrid radioactive seeds are clinically applicable due to their effective inhibitions of tumor growth.

[Diagnosis and surgical treatment of congenital bronchoesophageal fistula in adult].

OBJECTIVE: To explore the clinical characteristics, diagnosis and surgical treatment of adult congenital bronchoesophageal fistula. METHODS: Eleven cases of adult congenital bronchoesophageal fistula that were diagnosed and surgically treated between May 1990 and August 2010 had been reviewed. There were 7 male and 4 female patients, ranging in age from 28 to 66 years (mean 48.7 years). The chief clinical presentation included coughing and sputum in 10 cases, recurrent bouts of coughing after drinking liquid food in 6 cases, hemoptysis in 6 cases, low fever in 4 cases, chest pain in 3 cases. The duration of symptoms before diagnosis ranged from 5 to 36 years (mean 16.8 years). The diagnosis of bronchoesophageal fistula was confirmed most by esophagography. Associated diseased lung was resected in all patients (lobectomy in 10 cases and pneumonectomy in 1 case). The operation included right thoracotomy in 7 cases and left thoracotomy in 4 cases. The fistula was completely resected in 10 cases. The tract was simply divided and the end was sutured in 1 case. RESULTS: The postoperative course was uneventful in 10 patients who were discharged from hospital 10 to 18 d after operation. One patient suffered from esophageal fistula and received second operation. Regular follow-up was conducted on all 11 patients, proving that 3-year survival rate was 11/11 and 5-year survival rate was 9/11. CONCLUSION: Persistence of congenital bronchoesophageal fistula into adulthood is rare. The main symptom is nonspecific coughing and bouts of coughing after drinking liquid food. The most useful diagnostic method is the esophagography. Even though it is benign disease, life-threatening complications might occur and it must be treated surgically as soon as the diagnosis is established.

[Comparison of the biodistribution and PET imaging with (11)C-PDT and (18)F-FDG in the mouse model of lung adenocarcinoma].

OBJECTIVE: The objective of this study was to compare the biodistribution and PET imaging of (11)C-PDT and (18)F-FDG in a mouse model of lung adenocarcinoma, and to evaluate the value of (11)C-PDT as a new tracer for PET imaging of lung cancer. METHODS: Twenty four lung adenocarcinoma-bearing mice were randomly divided into two groups, 12 each. The mice received (11)C-PDT or (18)F-FDG injection i.v. respectively. The biodistribution of (11)C-PDT or (18)F-FDG in the mice was measured with a well-gamma detector at 60 min after injection. The PET imagings of mice were performed using either of the two tracers. RESULTS: Considerable uptake of the both radioactive tracers in the tumors was observed. The tumor uptake of (11)C-PDT [(0.65 +/- 0.20)%ID/g] was significantly lower than that of (18)F-FDG [(7.44 +/- 1.56)%ID/g, P < 0.01]. In the (11)C-PDT group, the highest uptake was observed in the liver, kidney and blood in a successively declining order, while the highest uptake of (18)F-FDG was seen in a order of heart, tumor and kidneys. The tumor/muscle ratio of (11)C-PDT uptake was relatively high (2.02 +/- 0.56), but still lower than that of (18)F-FDG (2.95 +/- 0.49, P < 0.01). All values of other tumor/organ ratios (T/NT) of (11)C-PDT uptake were < 2. High radioactive uptake was showed in the tumor and abdominal organs on PET images in the tumor-bearing mice injected with (11)C-PDT, and (18)F-FDG uptake was showed in the heart, tumor and abdominal organs. The tumor PET images with (11)C-PDT and (18)F-FDG were all clear. CONCLUSION: The uptake of (11)C-PDT in lung cancer is higher than that in muscle tissues, and pulmonary cancers can be detected by PET imaging. (11)C-PDT may be a promising PET tracer for lung cancers.

[Expression of EYA2 in non-small cell lang cancer].

OBJECTIVE: To identify the expression of Drosophila Eyes Absent Homologue 2 (EYA2) in non-small cell lung cancer (NSCLC) and to investigate its correlation with clinical parameters. METHODS: 59 fresh specimens of lung cancer and paired normal lung tissue were obtained from 59 NSCLC cases treated in the department of thoracic surgery in our hospital from June 2006 to October 2007. Western blotting and immunohistochemistry were used to assay the specimens with goat anti-human EYA2 polyclone antibody. Clinicopathological parameters were collected and the correlation with EYA2 expression was subsequently analyzed. RESULTS: The expression of EYA2 was detected in cytoplasm and nucleus of the cancer cells, but mostly in cytoplasm. Western blotting and immunohistochemistry showed the expression of EYA2 in NSCLC was increased and correlated with pathological type, but not with gender, age, pTNM stage, histological differentiation and lymph node metastasis. EYA2 expression was significantly up-regulated in adenocarcinoma, while not changed in lung squamous cell carcinoma. CONCLUSION: The results of this study suggest that expression of EYA2 in lung adenocarcinoma is augmented. EYA2 is likely participating in the development of lung adenocarcinoma as a transcriptional activator.

[Effect of non-restrictive external stent on the expression of platelet-derived growth factor in vein grafts of rabbits].

OBJECTIVE: To investigate the potential mechanism of non-restrictive external stent in preventing re-stenosis of vein grafts. METHODS: Thirty-six rabbits underwent reversed bypass grafting of autologous external jugular vein into common carotid artery and then were randomly divided into two equal groups, stenting group (Group S), with an external stent 6 mm in diameter (Dacron vascular prosthesis) surrounding the vein graft, and control group (Group NS) , without stenting. The vein grafts were harvested 7, 14, and 28 days after the operation respectively. Immunocytochemistry was used to detect the platelet-derived growth factor B (PDGF-B) positive cells. The mRNA expression of PDGF-B was detected with RT-PCR. RESULTS: The PDGF-B positive cell percentages in the intima of Group S 7 and 14 days later were both significantly lower than those of Group NS (15.2% +/- 3.6% vs 21.6% +/- 4.6%, and 6.5% +/- 2.6% vs 12.5% +/- 4.4%, both P < 0.05) . The PDGF-B positive cell percentages in media 7, 14 and 28 days later of Group S were all significantly lower than those of Group NS (13.8% +/- 4.6% vs 25.4% +/- 6.2%, 21.3% +/- 4.4% vs 35.7% +/- 7.3%, and 7.2% +/- 3.2% vs 19.2% +/- 5.4%, all P < 0.01). The PDGF-B positive cell percentage in adventitia peaked 28 days later in Group S and 14 days later in Group NS, and the PDGF-B positive cell percentage in adventitia 28 days later of Group S was significantly higher than that of Group NS (42.5% +/- 8.6% vs 31.9% +/- 4.6%, P < 0.01). RT-PCR analysis revealed that PDGF-B amplification products (457 bp) appeared in both group S and NS from 7 to 28 days, and the PDGF-B mRNA expression levels 7, 14, and 28 days later of Group S were all significantly lower than those of Group NS (31.2% +/- 6.5% vs 45.4% +/- 8.4%, P < 0.05; 42.3% +/- 6.2% vs 65.2% +/- 11.5%, P < 0.01; and 21.3% +/- 5.6% vs 36.2% +/- 9.4%, P < 0.01). CONCLUSION: Non-restrictive external stenting can inhibit the synthesis of PDGF and change its distribution, which may be one of the mechanisms of external stent in preventing re-stenosis of vein grafts.

[Biodistribution and positron emission tomography imaging of 11C-acetate in murine model of lung carcinoma].

OBJECTIVE: To investigate the biodistribution and positron emission tomography (PET) imaging of 11C-acetate (11C-AC) in a murine model of pulmonary carcinoma, and to evaluate the use of 11C-AC for diagnosis of malignant tumor. METHODS: A total of 30 T739 mice underwent subcutaneous injection of mouse pulmonary adenocarcinoma cells of the line LA-795 to establish adenocarcinoma models and then were randomly divided into five equal groups. Four groups underwent intravenous injection of 11C-acetate through the caudal vein, killed 5, 10, 20, and 30 minutes later respectively, underwent PET, and then their organs and tumors were isolated. The mice in the control group underwent injection of 11F-fluorodeoxyglucose (18F-FDG) and were killed 60 min later. The biodistribution of 11C-AC and that of 18F-FDG were measured with well-gamma detector. The ratios of the levels of percentage activity of injection dose per gram of tissue between the tumor and normal tissues (T/NT ratios), were calculated. RESULTS: In the biodistribution study of 11C-AC, considerable radioactive uptake of tumor was observed, and much radioactivity was showed in kidney, liver, and spleen. The ratios of tumor/blood, tumor/muscle, and tumor/lung were all above 2. 0. The tumor PET images with 11C-AC as tracer were as clear as that with 18F-FDGas tracer. The 11C-AC standard uptake value (SUV) of the tumors was 2.8 +/- 0.8, significantly lower than that of 18F-FDG (5.3 +/- 1.6, P <0.01). CONCLUSION: 11C-AC can be used in PET imaging of pulmonary malignancy. The optimized imaging acquisition time point is 20 min after injection. It may become a complementary tracer in the cases with unsatisfying 18F-FDG images.

Utilizing multiple pathway cross-talk networks reveals hub pathways in primary mediastinal B-cell lymphoma.

OBJECTIVE: The objective of this paper was to reveal hub pathways in primary mediastinal B-cell lymphoma (PMBL) based on multiple pathway crosstalk networks (PCNs) and give insight for its pathological mechanism. MATERIALS AND METHODS: Based on gene expression data, pathway data and protein-protein interaction data, background PCN (BPCN) and tumor PCN (TPCN) of PMBL were constructed. The rank product algorithm was implemented to identify hub pathways of BPCN and TPCN. Finally, topological properties (degree, closeness, betweenness, and transitivity) of hub pathways were analyzed. RESULTS: For BPCN, there were three hundred nodes and 42,239 edges, and the pathway pairs had great overlaps. TPCN was composed of 281 nodes and 12,700 cross-talks. A total of five hub pathways were identified, nonalcoholic fatty liver disease (NAFLD), tuberculosis, human T-lymphotropic virus type-I (HTLV-I) infection, hepatitis B, and Epstein-Barr virus infection. The topological properties for them were different from each other, further between PMBL and normal controls. CONCLUSION: We have identified five hub pathways for PMBL, such as NAFLD, HTLV-I infection, and Hepatitis B, which might be potential biomarkers for target therapy for PMBL.

Tracking significant modules and key genes for esophageal squamous cell carcinoma based on differential modules.

BACKGROUND: The exact molecular mechanism of esophageal squamous cell carcinoma (ESCC) is still unknown, and the prognosis of ESCC has not been significantly improved. OBJECTIVE: To understand the molecular mechanism of ESCC, differential modules (DMs) and key genes were identified through conducting analysis on the differential co-expression network (DCN) based on the gene expression profiles of ESCC and protein-protein interaction (PPI) data. MATERIALS AND METHODS: First, gene expression profiles of ESCC and PPI data recruiting and preprocessing were conducted; then, a DCN was constructed based on the gene co-expression and gene differential expression in ESCC; in the following, candidate DMs were mined from DCN through a systemic module searching strategy, and significance analysis was performed on candidate DMs to identify DMs; moreover, significant genes contained in the DMs were analyzed to identify the underlying biomarkers for ESCC. Finally, pathway enrichment analysis was conducted to disclose the function of these DMs. RESULTS: A total of 10,975 genes were obtained after comprehensively preprocessing on the gene expression profiles and PPI data. Then, a DCN with 915 nodes (1164 interactions) was built, and 45 seed genes were identified. In the following, four DMs that separately enriched in phenylalanine metabolism, nicotine addiction, phenylalanine metabolism, and B-cell receptor signaling pathway were identified, where module 1 and module 3 were all enriched in phenylalanine metabolism pathway. Furthermore, the most significant seed gene myeloperoxidase (MPO) was contained in all of the DMs. CONCLUSIONS: In this study, we successfully identified 4 DMs, three significant pathways, and a key gene MPO in ESCC, which might play key roles during the occurrence and development of ESCC and could be chosen as good indicators and therapeutic schedule for ESCC.

[Diagnosis and surgical treatment of mediastinal tumors and cysts: analysis of 343 cases].

OBJECTIVE: To review the experience of diagnosis and surgical treatment of mediastinal tumors and cysts. METHODS: The clinical data of 343 cases with mediastinal tumors and cysts who underwent operation from March 1996 to April 2005, 208 males and 135 females, aged 40.5 +/- 16.1, were analyzed. RESULTS: No specific symptom and sign was found among the patients. Tumor of Thymus accounted for 42.24%. 300 of the 343 patients were subjected to radical excision, and 25 patients to partial excision. The diagnosis of all the patients was confirmed by postoperative histopathological examination. Surgically related complications were observed in 9 cases. CONCLUSION: Tumor of thymus is the commonest mediastinal tumors. Early operation is necessary provided there is no contraindication thereto.

[Diagnosis and surgical treatment of the primary mediastinal teratoma].

OBJECTIVE: To review the experience of diagnosis and surgical treatment of the primary mediastinal teratomas. METHODS: The clinical data of forty-nine cases with teratoma were retrospectively analysed from March 1996 to March 2006. RESULTS: Based on history, physical examination, chest X-ray, CT scan and magnetic resonance, the diagnosis of forty-eight cases were confirmed before surgery. Surgical procedures were performed in all cases. Forty-six patients were subjected to radical excision, two patients to partial excision and one patient to exploratory operation. Among all the cases, Wedge resection of the lung was performed in eight cases, partial pericardium excision in six cases. There was no surgically related mortality or complications in any patients. The diagnosis of teratoma was confirmed by postoperative histopathological examination. No relapse occurred during follow-up. CONCLUSIONS: History, physical examination and radiological imaging are the main diagnostic means for the primary mediastinal teratoma. Surgical resection is an effective therapy. Early diagnosis and correct selection of operation according to the characteristic of the tumor are important to therapy.

[The application of stapling device in surgery of carcinoma of the esophagus and cardia].

OBJECTIVE: To evaluate the application of circular stapler in upper digestive tract reconstruction. METHODS: We present a retrospective review of 3322 patients with Carcinoma of esophagus and cardia undergoing a stapled esophagogastric anastomosis from August 1980 to September 2004. There were 2642 males and 680 females with age ranged from 28 to 83 years old. Carcinoma of esophagus was present in 2312 patients and carcinoma of gastric cardia in 1010 patients. The anastomosis was performed in the cervical region in 102 cases, thoracic apex in 147 cases, up aortic in 1838 cases and below aortic in 1235 cases. RESULTS: Anastomotic leakage occurred in 18 patients with an overall incidence of 0.54%, including thoracic leakage in 11 cases and cervical leakage in 7 cases. nine patients were dead because of the thoracic leakage, and the mortality of thoracic leakage was 81.8%. Benign anastomotic stricture was found in 66 patients with a rate of 2.0%, and instrumental failure occurred in 36 patients with a rate of 1.1%. CONCLUSION: Circular stapler can be used safely and reliably in upper digestive tract surgery, and the stapled anastomosis is an effective technique to reduce the incidence of anastomotic leakage.

Pleuropneumonectomy for diffuse pleural metastasis in primary lung cancer.

OBJECTIVE: The purpose of this study is to analyze a single institution experience with pleuropneumonectomy for pleural metastasis and malignant pleural effusion in primary lung cancer. MATERIALS AND METHODS: From August 1978 to August 2011, 66 consecutive patients with lung cancer underwent pleuropneumonectomy. Patients were followed-up after the operation. The quality-of-life and the survival time were recorded. RESULTS: All the 66 patients were successfully operated on, including 38 patients in early years (1978-1993) and 28 patients in recent years (1994-2011). Two patients in early years died after the operation. Post-operative complications occurred including heart arrhythmia, respiratory insufficiency and bacterial infection of residual lung, chylothoraxin and mental disorder. A total of 61 patients have been successfully followed-up and three patients in early years were lost in 1 year after the operation. Local recurrence was found in seven cases (4 in early years, 3 in recent years) and distant metastasis was found in 48 cases (29 in early years, 19 in recent years). A total of 54 patients died from tumors, seven patients survived. The actuarial 1, 2 and 3-year survival rates are 72.7%, 27.2% and 6.1% of 36 in patients of early years and 85.7%, 46.4% and 21.4% in 28 patients of recent years. The mean survival and the median survival of the total 64 patients were 20.0 ± 10.9 months and 17 months respectively. Further analysis showed that the mean survival and the median survival of the 36 patients in early years were 17.2 ± 9.7 months and 15 months, in contrast to 23.4 ± 11.3 months and 18 months of the 28 patients in recent years. CONCLUSION: Pleuropneumonectomy is an option of patients with advanced-stage lung cancer associated with uncontrolled malignant pleural fluid by conservative therapies. Strict selection of patient to be operated, careful procedures to eradicate obvious tumors and metastasis and enhanced post-operative combined therapy are beneficial to patients' long-term survival.

Congenital bronchoesophageal fistula in adults.

AIM: To study the clinical characteristics, diagnosis and surgical treatment of congenital bronchoesophageal fistulae in adults. METHODS: Eleven adult cases of congenital bronchoesophageal fistula diagnosed and treated in our hospital between May 1990 and August 2010 were reviewed. Its clinical presentations, diagnostic methods, anatomic type, treatment, and follow-up were recorded. RESULTS: Of the chief clinical presentations, nonspecific cough and sputum were found in 10 (90.9%), recurrent bouts of cough after drinking liquid food in 6 (54.6%), hemoptysis in 6 (54.6%), low fever in 4 (36.4%), and chest pain in 3 (27.3%) of the 11 cases, respectively. The duration of symptoms before diagnosis ranged 5-36.5 years. The diagnosis of congenital bronchoesophageal fistulae was established in 9 patients by barium esophagography, in 1 patient by esophagoscopy and in 1 patient by bronchoscopy, respectively. The congenital bronchoesophageal fistulae communicated with a segmental bronchus, a main bronchus, and an intermediate bronchus in 8, 2 and 1 patients, respectively. The treatment of congenital bronchoesophageal fistulae involved excision of the fistula in 10 patients or division and suturing in 1 patient. The associated lung lesion was removed in all patients. No long-term sequelae were found during the postoperative follow-up except in 1 patient with bronchial fistula who accepted reoperation before recovery. CONCLUSION: Congenital bronchoesophageal fistula is rare in adults. Its most useful diagnostic method is esophagography. It must be treated surgically as soon as the diagnosis is established.

[Expression of dopamine receptor D2 in pulmonary carcinoma cells and effects of dopamine on the cell apoptosis].

OBJECTIVE: To detect the expression of dopamine receptor D2 in different pulmonary carcinoma cells and investigate the effect of dopamine in inducing apoptosis of A549 cells. METHODS: Western blotting and RT-PCR were employed to detect the expression of dopamine receptor D2 in different pulmonary carcinoma cells (95D, H460, GLC-82, A549 and H446 cells). The apoptosis of A549 cells after a 6-hour exposure to 0.02%, 0.04%, 0.08% and 0.1% dopamine was analyzed by flow cytometry. The apoptosis-inducing effect of dopamine in vivo was also tested by intratumoral injection of 1% dopamine in 2 BALB/c-nu mice bearing A549 tumor xenograft using flow cytometry. RESULTS: The presence of dopamine receptor D2 expression was detected by Western blotting and RT-PCR in 95D, H460, GLC-82, A549 and H446 cells. Flow cytometry detected obvious apoptosis of A549 cells following dopamine exposure in vitro in positive correlation to dopamine concentration. In the tumor-bearing mice, dopamine also showed an obvious apoptosis-inducing effect on A549 cells. CONCLUSION: Dopamine receptor D2 exists extensively in different pulmonary carcinoma cells. Dopamine may promote the apoptosis of pulmonary carcinoma cells through dopamine receptor D2.

Utility of squamous cell carcinoma antigen, carcinoembryonic antigen, Cyfra 21-1 and neuron specific enolase in lung cancer diagnosis: a prospective study from China.

BACKGROUND: Early detection and diagnosis is urgent for the sake of effective treatment strategy for lung cancer. However, a convenient, economical and relatively precise method is not available. We here report a prospective study to find the possible value of the combined use of four popular tumor markers in the early diagnosis of lung cancer among patients with suspicious nodules in the lung. METHODS: Six hundred and sixty inpatients with suspicious nodules in the lung were divided into a lung cancer group and a benign pulmonary tumor group according to post-operative histological examinations. Serum levels of four tumor markers including squamous cell carcinoma antigen (SCC), carcinoembryonic antigen (CEA), Cyfra 21-1 and neuron specific enolase (NSE) were assayed for each patient. Receiver operating characteristic (ROC) curves were constructed for each tumor marker. The power of lung cancer diagnosis of each tumor marker, as well as a combination of them were analyzed and compared. RESULTS: The serum levels (median, range) of SCC, CEA, Cyfra 21-1 and NSE were 0.44 (0.01 - 35.70) ng/ml, 2.49 (0.30 - 26.78) ng/ml, 2.30 (0.82 - 73.33) ng/ml and 10.54 (0.10 - 56.41) ng/ml respectively in lung cancer group, and were 0.32 (0.01 - 0.90) ng/ml, 1.60 (0.20 - 8.93) ng/ml, 1.41 (0.72 - 4.82) ng/ml and 9.36 (6.56 - 24.24) ng/ml respectively in the benign pulmonary tumor group. The difference in each tumor marker between the two groups was significant (P < 0.05). The ROCs of SCC, CEA, Cyfra 21-1 and NSE were 0.702 (95%CI, 0.654 - 0.751), 0.611 (95%CI, 0.563 - 0.659), 0.650 (95%CI, 0.601 - 0.700) and 0.598 (95%CI, 0.542 - 0.654) respectively, indicating very low power of these four tumor markers. When a combination of SCC, CEA, Cyfra 21-1 and NSE were employed, the diagnosis power was strengthened. CONCLUSION: SCC, CEA, Cyfra 21-1 and NSE are valuable in the early diagnosis of lung cancer among suspicious nodules in the lung, especially when they were assayed together for one patient.