Airway and Esophageal Stenting in Patients with Advanced Esophageal Cancer and Pulmonary Involvement

BACKGROUND: Most inoperable patients with esophageal-advanced cancer (EGC) have a poor prognosis. Esophageal stenting, as part of a palliative therapy management has dramatically improved the quality of live of EGC patients. Airway stenting is generally proposed in case of esophageal stent complication, with a high failure rate. The study was conducted to assess the efficacy and safety of scheduled and non-scheduled airway stenting in case of indicated esophageal stenting for EGC. METHODS AND FINDINGS: The study is an observational study conducted in pulmonary and gastroenterology endoscopy units. Consecutive patients with EGC were referred to endoscopy units. We analyzed the outcome of airway stenting in patients with esophageal stent indication admitted in emergency or with a scheduled intervention. Forty-four patients (58+/-\-8 years of age) with esophageal stenting indication were investigated. Seven patients (group 1) were admitted in emergency due to esophageal stent complication in the airway (4 fistulas, 3 cases with malignant infiltration and compression). Airway stenting failed for 5 patients. Thirty-seven remaining patients had a scheduled stenting procedure (group 2): stent was inserted for 13 patients with tracheal or bronchial malignant infiltration, 12 patients with fistulas, and 12 patients with airway extrinsic compression (preventive indication). Stenting the airway was well tolerated. Life-threatening complications were related to group 1. Overall mean survival was 26+/-10 weeks and was significantly shorter in group 1 (6+/-7.6 weeks) than in group 2 (28+/-11 weeks), p<0.001). Scheduled double stenting significantly improved symptoms (95% at day 7) with a low complication rate (13%), and achieved a specific cancer treatment (84%) in most cases. CONCLUSION: Stenting the airway should always be considered in case of esophageal stent indication. A multidisciplinary approach with initial airway evaluation improved prognosis and decreased airways complications related to esophageal stent. Emergency procedures were rarely efficient in our experience

Diverse Roles and Interactions of the SWI/SNF Chromatin Remodeling Complex Revealed Using Global Approaches

A systems understanding of nuclear organization and events is critical for determining how cells divide, differentiate, and respond to stimuli and for identifying the causes of diseases. Chromatin remodeling complexes such as SWI/SNF have been implicated in a wide variety of cellular processes including gene expression, nuclear organization, centromere function, and chromosomal stability, and mutations in SWI/SNF components have been linked to several types of cancer. To better understand the biological processes in which chromatin remodeling proteins participate, we globally mapped binding regions for several components of the SWI/SNF complex throughout the human genome using ChIP-Seq. SWI/SNF components were found to lie near regulatory elements integral to transcription (e.g. 5′ ends, RNA Polymerases II and III, and enhancers) as well as regions critical for chromosome organization (e.g. CTCF, lamins, and DNA replication origins). Interestingly we also find that certain configurations of SWI/SNF subunits are associated with transcripts that have higher levels of expression, whereas other configurations of SWI/SNF factors are associated with transcripts that have lower levels of expression. To further elucidate the association of SWI/SNF subunits with each other as well as with other nuclear proteins, we also analyzed SWI/SNF immunoprecipitated complexes by mass spectrometry. Individual SWI/SNF factors are associated with their own family members, as well as with cellular constituents such as nuclear matrix proteins, key transcription factors, and centromere components, implying a ubiquitous role in gene regulation and nuclear function. We find an overrepresentation of both SWI/SNF-associated regions and proteins in cell cycle and chromosome organization. Taken together the results from our ChIP and immunoprecipitation experiments suggest that SWI/SNF facilitates gene regulation and genome function more broadly and through a greater diversity of interactions than previously appreciated

Free radical production in the esophago-gastro-duodenal mucosa in response to acid and bile

Several studies have demonstrated the role of free radicals in causing esophagus-gastro-duodenal mucosal injury. The present study has been designed to investigate: whether acid, bile salts and a combination of bile + acid could determine the production of O-2-derived free radicals by oesophageal, gastric and duodenal mucosa; which agent is capable of producing more free radicals and if O-2-derived free radicals production depends on the duration of contact with acid, bile salts and their combination. Wistar rats' gastro-intestinal mucosa were perfused with bile, acid and a combination of bile + acid at pH4 and pH2 for 1 hour and 2 hours. Free radical production (FRP) was assessed by chemoluminescence. After 1 hour, the increase in FRP in comparison with control reached statistical significance (P < 0.05) at all tested pH levels in the duodenum, at pH1, 2 and 3 in the esophagus, and at pH1 in the stomach. Comparing different segments, both the esophagus and duodenum behaved similarly, producing more free radicals than the stomach at all pH values. However, this difference reached statistical significance at pH1 and 2 only. In comparison to control, FRP was increased by bile (pH7) infusion after 1 and 2 hours. There was increased FRP in all segments after the infusion of bile at pH2 and 4 in comparison to control. Infusion of bile at pH2 stimulates more FRP than infusion of bile at pH4 in all segments. This increased FRP reaches statistical significance in the esophagus after 2 hours of infusion, in the stomach after 1 and 2 hours of infusion, but in the duodenum it does not reach statistical significance. Acid, bile and bile + acid at pH2 and 4 can cause free radical production in esophageal, gastric and duodenal mucosa. Their role in producing free radicals is different according to the segment and the chemical composition of the solution