Nitrous oxide may not increase the risk of cancer recurrence after colorectal surgery: a follow-up of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Even the best cancer surgery is usually associated with minimal residual disease. Whether these remaining malignant cells develop into clinical recurrence is at least partially determined by adequacy of host defense, especially natural killer cell function. Anesthetics impair immune defenses to varying degrees, but nitrous oxide appears to be especially problematic. We therefore tested the hypothesis that colorectal-cancer recurrence risk is augmented by nitrous oxide administration during colorectal surgery.</p> <p>Methods</p> <p>We conducted a 4- to 8-year follow-up of 204 patients with colorectal cancer who were randomly assigned to 65% nitrous oxide (n = 97) or nitrogen (n = 107), balanced with isoflurane and remifentanil. The primary outcome was the time to cancer recurrence. Our primary analysis was a multivariable Cox-proportional-hazards regression model that included relevant baseline variables. In addition to treatment group, the model considered patient age, tumor grade, dissemination, adjacent organ invasion, vessel invasion, and the number of nodes involved. The study had 80% power to detect a 56% or greater reduction in recurrence rates (i.e., hazard ratio of 0.44 or less) at the 0.05 significance level.</p> <p>Results</p> <p>After adjusting for significant baseline covariables, risk of recurrence did not differ significantly for nitrous oxide and nitrogen, with a hazard ratio estimate (95% CI) of 1.10 (0.66, 1.83), <it>P </it>= 0.72. No two-way interactions with the treatment were statistically significant.</p> <p>Conclusion</p> <p>Colorectal-cancer recurrence risks were not greatly different in patients who were randomly assigned to 65% nitrous oxide or nitrogen during surgery. Our results may not support avoiding nitrous oxide use to prevent recurrence of colorectal cancer.</p> <p>Implications Statement</p> <p>The risk of colorectal cancer recurrence was similar in patients who were randomly assigned to 65% nitrous oxide or nitrogen during colorectal surgery.</p> <p>Trial Registration</p> <p>Current Controlled Clinical Trials NCT00781352 <url>http://www.clinicaltrials.gov</url></p

Estragole quantity optimization from fennel seeds by supercritical fluid extraction (carbon dioxide–methanol) using a Box–Behnken design : characterization of fennel extracts

Oleoresin extraction from fennel seeds using a supercritical fluid extraction (SFE) was carried out. Box–Behnken experimental design was used to optimize the SFE variables: pressure (10, 17.5, and 25 MPa), temperature (313.15, 323.15, and 333.15 K) and time of extraction (1, 2.5, and 4 h). Different percentages of methanol (0, 3, and 6%) were also evaluated to improve the extraction of the corresponding volatile compounds. Besides volatile profile characterization of fennel seeds, the amount of estragole was determined (by gas chromatography-flame ionization detector (GC-FID)) due to its recent concern in being considered a potential carcinogen agent. The optimal values of SFE variables for methanol extracts were high levels of pressure (24 MPa), 333.15 K of temperature, 3.41 h of extraction time, and an intermediate value of methanol percentage (3%), obtaining an optimal value of 1320 ± 260 mg of estragole/kg dry plant. The volatile profile of the methanol extracts was evaluated by gas chromatography–mass spectrometry (GC–MS) obtaining mainly, terpenes, phenyl derivatives, and fatty acids.We are grateful for the financial support of this work to the Spanish Ministry of Science and Innovation (project CTQ2011-28967), which has partial financial support from the FEDER funds of the European Union. Jose Manuel Salgado acknowledge the financial support from "Fundacao para a Ciencia e Tecnologia (FCT)" of Portugal through grant SFRH/BD/87953/2012