Cardiorespiratory impact of transesophageal endoscopic mediastinoscopy compared with cervical mediastinoscopy: a randomized experimental study.

BACKGROUND: Transesophageal natural-orifice transluminal endoscopic surgery (NOTES) mediastinoscopy has been described as a feasible, less-invasive alternative to video-assisted mediastinoscopy (VAM). We aimed to investigate hemodynamic and respiratory effects during transesophageal NOTES mediastinoscopy compared with VAM. PATIENTS AND METHODS: This was a short-survival experiment in 20 female pigs randomized to NOTES (n = 10) or VAM (n = 10) mediastinoscopy. In the NOTES group, an endoscopist accessed the mediastinum through a 5-cm submucosal tunnel in the esophageal wall, and CO2 was used to create the pneumomediastinum. Conventional VAM was carried out by thoracic surgeons. A 30-minute systematic exploration of the mediastinum was then performed, including invasive monitoring for hemodynamic and respiratory data. Blood samples were drawn for gas analyses. RESULTS: All experiments except 2 in the NOTES group (one because of technical difficulties, the other because of thoracic lymphatic duct lesion) were completed as planned, and animals survived 24 hours. Also, 3 animals in the NOTES group presented a tension pneumothorax that was immediately recognized and percutaneously drained. VAM and NOTES animals showed similar pulmonary and systemic hemodynamic behavior during mediastinoscopy. Pulmonary gas exchange pattern was mildly impaired during the NOTES procedure, showing lower partial arterial oxygen pressure associated with higher airway pressures (more important in animals that presented with pneumothorax). CONCLUSIONS: NOTES mediastinoscopy induces minimal deleterious respiratory effects and hemodynamic changes similar to conventional cervical VAM and could be feasible when performed under strict hemodynamic and respiratory surveillance. Notably, serious complications caused by the injury of pleura are more frequent in NOTES, which mandates an improvement in technique and suitable equipment.

Low miR-145 and high miR-367 are associated with unfavourable prognosis in resected nonsmall cell lung cancer.

The transcription factors SRY-related HMG box (SOX)2 and octamer-binding transcription factor (OCT)4 regulate the expression of the miR-302-367 cluster. miR-145 regulates SOX2 and OCT4 translation and p53 regulates miR-145 expression. We analysed the expression of the miR-302-367 cluster and miR-145 and the mutational status of p53 in resected nonsmall cell lung cancer (NSCLC) patients and correlated results with time to relapse (TTR). Tumour and paired normal tissue samples were obtained from 70 NSCLC patients. MicroRNA expression was assessed with TaqMan MicroRNA Assays. p53 exons 5 to 8 were sequenced. miR-145 was downregulated (p<0.0001) and miR-367 was upregulated (p<0.0001) in tumour compared with normal tissue. Mean TTR was 18.4 months for patients with low miR-145 levels and 28.2 months for those with high levels (p=0.015). Mean TTR was 29.1 months for patients with low miR-367 levels and 23.4 months for those with high levels (p=0.048). TTR was shorter for patients with both unfavourable variables (p=0.009). Low miR-145 expression (p=0.049), the combination of unfavourable microRNA levels (p=0.02) and the combination of low miR-145 with p53 mutations (p=0.011) were independent markers of shorter TTR. In conclusion, miR-145 and miR-367 expression could be novel markers for relapse in surgically treated NSCLC. p53 may play a role in modulating miR-145 expression in NSCLC.

Adverse events of NOTES mediastinoscopy compared to conventional video-assisted mediastinoscopy: a randomized survival study in a porcine model.

BACKGROUND: Safety is a concern in natural orifice transluminal endoscopic surgery (NOTES) mediastinoscopy. The objective of this study was to compare the safety of NOTES mediastinoscopy with video-assisted mediastinoscopy (VAM). METHODS: Twenty-four pigs were randomly assigned to NOTES or VAM. Thirty-minute mediastinoscopies were performed with the identification of seven predetermined structures. The animals were euthanized after 7 days and necropsy was performed. RESULTS: Mediastinoscopy was not possible in one animal in each group. There were more intraoperative adverse events with NOTES than VAM (7 vs. 2, P = 0.04); hemorrhage was the most frequent adverse event (4 and 1, respectively). At necropsy, pathological findings were observed in 13 animals (9 NOTES and 4 VAM; P = 0.03). Inflammatory parameters were not different between groups and were not related to adverse events. CONCLUSION: Systematic NOTES mediastinoscopy is possible and comparable to VAM in terms of number of organs identified and inflammatory impact. However, the safety profile of NOTES mediastinoscopy has to be improved before it can be adopted in a clinical setting.

Video-assisted direct closure of bronchial fistula.

Video-assisted thoracoscopic surgery is a well-established method for managing persistent air leak in spontaneous pneumothorax. We describe a case of complicated spontaneous secondary pneumothorax in a patient with bullous emphysema that was treated by video-assisted manual suture of the bronchial fistula at the end of the right upper bronchus.

[Cyclooxigenase-2 levels are increased in the lung tissue and bronchial tumors of patients with chronic obstructive pulmonary disease]. / La ciclooxigenasa-2 está regulada al alza en el pulmón y en los tumores bronquiales de pacientes con enfermedad pulmonar obstructiva crónica.

INTRODUCTION: The expression of cyclooxygenase 2 (COX-2) is usually increased in inflammation and cancer. This study examines the expression of COX-2 in the lung of chronic obstructive pulmonary disease (COPD) patients with lung cancer. METHODS: We studied 44 male patients with bronchial cancer (27 squamous carcinoma and 17 adenocarcinoma). Samples were obtained from the pulmonary parenchyma, from the bronchial mucosa adjacent to the tumor and from the tumor itself. Lung tissue specimens from 14 patients with pneumothorax were used as control. The mRNA and the COX-1 and COX-2 proteins were assessed by RT-PCR and Western blot, respectively. RESULTS: COX-1 and COX-2 mRNA levels were significantly higher in the lung parenchyma of COPD patients than in the control subjects. COX-2 mRNA levels were also higher in the lung parenchyma than in both tumor and airway tissue samples procured from COPD patients. There were no differences in the COX-2 mRNA levels between squamous carcinoma and adenocarcinoma. In contrast, COX-2 protein levels were significantly higher in tumors than in lung parenchyma and airways. COX-2 protein levels were higher in adenocarcinoma compared with squamous carcinoma. CONCLUSION: This study shows that in COPD, the pathway of cyclooxygenase is activated and associated with an increase in the expression of COX-2 in lung tumors. These observations suggest that COX-2 is possibly involved in the association between COPD and cancer.

A dual role for KRT81: a miR-SNP associated with recurrence in non-small-cell lung cancer and a novel marker of squamous cell lung carcinoma.

MicroRNAs (miRNAs) play an important role in carcinogenesis through the regulation of their target genes. miRNA-related single nucleotide polymorphisms (miR-SNPs) can affect miRNA biogenesis and target sites and can alter microRNA expression and functions. We examined 11 miR-SNPs, including 5 in microRNA genes, 3 in microRNA binding sites and 3 in microRNA-processing machinery components, and evaluated time to recurrence (TTR) according to miR-SNP genotypes in 175 surgically resected non-small-cell lung cancer (NSCLC) patients. Significant differences in TTR were found according to KRT81 rs3660 (median TTR: 20.3 months for the CC genotype versus 86.8 months for the CG or GG genotype; P = 0.003) and XPO5 rs11077 (median TTR: 24.7 months for the AA genotype versus 73.1 months for the AC or CC genotypes; P = 0.029). Moreover, when patients were divided according to stage, these differences were maintained for stage I patients (P = 0.002 for KRT81 rs3660; P<0.001 for XPO5 rs11077). When patients were divided into sub-groups according to histology, the effect of the KRT81 rs3660 genotype on TTR was significant in patients with squamous cell carcinoma (P = 0.004) but not in those with adenocarcinoma. In the multivariate analyses, the KRT81 rs3660 CC genotype (OR = 1.8; P = 0.023) and the XPO5 rs11077 AA genotype (OR = 1.77; P = 0.026) emerged as independent variables influencing TTR. Immunohistochemical analyses in 80 lung specimens showed that 95% of squamous cell carcinomas were positive for KRT81, compared to only 19% of adenocarcinomas (P<0.0001). In conclusion, miR-SNPs are a novel class of SNPs that can add useful prognostic information on the clinical outcome of resected NSCLC patients and may be a potential key tool for selecting high-risk stage I patients. Moreover, KRT81 has emerged as a promising immunohistochemical marker for the identification of squamous cell lung carcinoma.

Incidence of occult mediastinal node involvement in cN0 non-small-cell lung cancer patients after negative uptake of positron emission tomography/computer tomography scan.

OBJECTIVE: This study sought to assess the real incidence of pN2 among patients with non-small-cell lung cancer (NSCLC) (cN0) with negative mediastinal uptake of 2-deoxy-2-(18F)-fluoro-o-glucose (FDG). METHODS: During 30 consecutive months (January 2007-May 2009), all patients with NSCLC scheduled for surgery in our unit had a preoperative FDG-positron emission tomography (PET)/computed tomography (CT) in our institution, after a dedicated chest CT (n=259). Only patients with both FDG-PET/CT and negative dedicated chest CT scan (N1 and N2 nodes <1cm) were prospectively included (n=125). Patients with cN1/cN2/cN3 and patients who had undergone preoperative chemo-radiotherapy were excluded. No invasive surgical staging was carried out in this group and curative resection plus systematic mediastinal dissection was performed except in the event of unexpected oncological contraindication. All variables were collected prospectively and, when pathological information was obtained, all the cases were carefully reviewed. RESULTS: Mediastinal assessment by FDG-PET/CT, negative predictive value (NPV) was 85.6%, confidence interval (CI): [77-91]; false negatives (FNs) for mediastinal lymph nodes involvement was 14.4% (18 cases). The pN2 stations most frequently involved were: 4R (six cases), seven (six cases) and five (five cases). Multiple-level pN2 occurred in six (4.8%) cases. Occult (pN2) lymph nodes were more frequent in women (p<0.01), adenocarcinoma (p<0.05) and pN1 (p<0.05). Pathological N2 prevalence for pN1 was 34 (27.7%). Considering pathological staging as the gold standard, the agreement was 70% and 47.5% for stage IA and IB (Kappa's index: 0.72 and 0.76) and, in all patients, 47% (Kappa's index: 0.27). In general, down-staging is more frequent than up-staging. CONCLUSIONS: Mediastinal staging of NSCLC by FDG-PET/CT showed a considerable incidence of FNs. NPV is lower than previously reported and the preoperative mediastinal staging by 18FDG-PET/CT may jeopardise the accurate treatment for early stage NSCLC patients.

La ciclooxigenasa-2 está regulada al alza en el pulmón y en los tumores bronquiales de pacientes con enfermedad pulmonar obstructiva crónica / Cyclooxigenase-2 Levels are Increased in the Lung Tissue and Bronchial Tumors of Patients with Chronic Obstructive Pulmonary Disease

IntroducciónLa ciclooxigenasa 2 (COX-2) está aumentada en la inflamación y en el cáncer. En este estudio se evaluó la expresión de la COX-2 en el pulmón y en el cáncer bronquial de pacientes con EPOC.MétodosSe estudiaron 44 pacientes varones con cáncer bronquial (27 escamosos y 17 adenocarcinomas). Se obtuvieron muestras del parénquima pulmonar, de la mucosa bronquial adyacente al tumor y del tumor mismo. El tejido pulmonar de 14 pacientes con neumotórax se empleó como control. El ARNm y la proteína de la COX-1 y de la COX-2 se midieron mediante RT-PCR y western blot, respectivamente.ResultadosLos niveles de ARNm de la COX-1 y de la COX -2 en el parénquima de los pacientes con EPOC fueron superiores a los de los controles. Los niveles del ARNm de la COX-2 en pacientes con EPOC fueron más altos en el parénquima pulmonar que en las vías aéreas y los tumores. No hubo diferencias en los niveles del ARNm de la COX-2 entre escamosos y adenocarcinomas. En contraste, la proteína de COX-2 mostró niveles más altos en los tumores que en el parénquima y las vías aéreas. Los niveles de la proteína de COX-2 fueron más altos en los adenocarcinomas que en los carcinomas escamosos.ConclusiónEste estudio muestra que en la EPOC la vía de la ciclooxigenasa está activada y asociada a un aumento en la expresión de la COX-2 en los tumores. Cabe la posibilidad de que la COX-2 esté involucrada en la asociación de EPOC y cáncer(AU)

IntroductionThe expression of cyclooxygenase 2 (COX-2) is usually increased in inflammation and cancer. This study examines the expression of COX-2 in the lung of chronic obstructive pulmonary disease (COPD) patients with lung cancer.MethodsWe studied 44 male patients with bronchial cancer (27 squamous carcinoma and 17 adenocarcinoma). Samples were obtained from the pulmonary parenchyma, from the bronchial mucosa adjacent to the tumor and from the tumor itself. Lung tissue specimens from 14 patients with pneumothorax were used as control. The mRNA and the COX-1 and COX-2 proteins were assessed by RT-PCR and Western blot, respectively.ResultsCOX-1 and COX-2 mRNA levels were significantly higher in the lung parenchyma of COPD patients than in the control subjects. COX-2 mRNA levels were also higher in the lung parenchyma than in both tumor and airway tissue samples procured from COPD patients. There were no differences in the COX-2 mRNA levels between squamous carcinoma and adenocarcinoma. In contrast, COX-2 protein levels were significantly higher in tumors than in lung parenchyma and airways. COX-2 protein levels were higher in adenocarcinoma compared with squamous carcinoma.ConclusionThis study shows that in COPD, the pathway of cyclooxygenase is activated and associated with an increase in the expression of COX-2 in lung tumors. These observations suggest that COX-2 is possibly involved in the association between COPD and cancer(AU)