Systemic chemotherapy for treatment of advanced small bowel adenocarcinoma with prognostic factor analysis: retrospective study

<p>Abstract</p> <p>Background</p> <p>We sought to evaluate prognostic factors affecting overall survival (OS), and to investigate the role of palliative chemotherapy using propensity score-based weighting, in patients with advanced small bowel adenocarcinoma (SBA).</p> <p>Methods</p> <p>Data from a total of 91 patients diagnosed with advanced SBA at the Asan Medical Center between January 1989 and December 2009 were retrospectively analyzed. Patients were split into two groups, those who did and did not receive palliative chemotherapy.</p> <p>Results</p> <p>Overall, 81 patients (89.0%) died, at a median survival time of 6.6 months (95% confidence interval [CI], 5.5 - 7.5 months). The 40 patients receiving chemotherapy showed overall response and disease control rates of 11.1% and 37.0%, respectively, with OS and progression-free survival (PFS) of 11.8 months (95% CI, 4.6 - 19.0 months) and 5.7 months (95% CI, 3.5 - 8.0 months), respectively. The 41 patients who did not receive chemotherapy had an OS of 4.1 months (95% CI, 3.1 - 5.1 months) and a PFS of 1.3 months (95% CI, 0.8 - 1.7 months). Multivariate analysis showed that lack of tumor resection, non-prescription of chemotherapy, liver metastasis, and intra-abdominal lymph node metastasis, were all independently associated with poor survival outcomes. After inverse probability of treatment weighting (IPTW) adjustment, the group that did not receive chemotherapy was at a significantly higher risk of mortality (HR 3.44, 95% CI 2.03 - 5.83, p < 0.001) than were patients receiving chemotherapy.</p> <p>Conclusion</p> <p>Palliative chemotherapy may improve survival outcomes in patients with advanced SBA.</p

Could Fractional Exhaled Nitric Oxide Test be Useful in Predicting Inhaled Corticosteroid Responsiveness in Chronic Cough? A Systematic Review

© 2016 Background Fractional exhaled nitric oxide (FENO) is a safe and convenient test for assessing T H 2 airway inflammation, which is potentially useful in the management of patients with chronic cough. Objective To summarize the current evidence on the diagnostic usefulness of FENO for predicting inhaled corticosteroid (ICS) responsiveness in patients with chronic cough. Methods A systematic literature review was conducted to identify articles published in peer-reviewed journals up to February 2015, without language restriction. We included studies that reported the usefulness of FENO (index test) for predicting ICS responsiveness (reference standard) in patients with chronic cough (target condition). The data were extracted to construct a 2 × 2 accuracy table. Study quality was assessed with Quality Assessment of Diagnostic Accuracy Studies 2. Results We identified 5 original studies (2 prospective and 3 retrospective studies). We identified considerable heterogeneities in study design and outcome definitions, and thus were unable to perform a meta-analysis. The proportion of ICS responders ranged from 44% to 59%. Sensitivity and specificity ranged from 53% to 90%, and from 63% to 97%, respectively. The reported area under the curve ranged from abou t 0.60 to 0.87; however, studies with a prospective design and a lower prevalence of asthma had lower area under the curve values. None measured placebo effects or objective cough frequency. Conclusions We did not find strong evidence to support the use of FENO tests for predicting ICS responsiveness in chronic cough. Further studies need to have a randomized, placebo-controlled design, and should use validated measurement tools for cough. Standardization would facilitate the development of clinical evidence

The Effect of Doxycycline on PMA-Induced MUC5B Expression via MMP-9 and p38 in NCI-H292 Cells

ObjectivesDoxycycline is commonly used in medicine for its bacteriostatic antimicrobial properties. Recent studies have reported that doxycycline also has anti-inflammatory effects. Matrix metalloproteinase (MMP)-9 has been found to be involved in the physiological and pathological process of inflammatory airway disease. Phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, is known to stimulate the expression of MMP and mucin genes in the airway and intestinal epithelial cells. Therefore, the effects and signal pathways of doxycycline on PMA-induced MUC5B expression dependent MMP-9 in human airway epithelial cells were investigated.MethodsIn human NCI-H292 airway epithelial cells, MUC5B and MMP-9 mRNA expression, MUC5B protein expression, and MMP-9 protein activity after the treatment with PMA, MMP-9 or doxycycline were determined by reverse transcriptase-polymerase chain reaction, enzyme immunoassay, gelatin zymography, and Western blot analysis.ResultsPMA increased MMP-9 and MUC5B expression. MMP-9 increased MUC5B expression. Doxycycline inhibited PMA-induced MUC5B expression, and PMA-induced MMP-9 mRNA expression and protein activity. Doxycycline inhibited phosphorylation of p38 induced by PMA and MMP-9.ConclusionThe results of this study suggest that doxycycline inhibited PMA-induced MUC5B mRNA expression and protein production through the MMP-9 and p38 pathways in human NCI-H292 airway epithelial cells