Traditional invasive vs. minimally invasive esophagectomy: a multi-center, randomized trial (TIME-trial)

<p>Abstract</p> <p>Background</p> <p>There is a rise in incidence of esophageal carcinoma due to increasing incidence of adenocarcinoma. Probably the only curative option to date is the use of neoadjuvant therapy followed by surgical resection. Traditional open esophageal resection is associated with a high morbidity and mortality rate. Furthermore, this approach involves long intensive care unit stay, in-hospital stay and long recovery period. Minimally invasive esophagectomy could reduce the morbidity and accelerate the post-operative recovery.</p> <p>Methods/Design</p> <p>Comparison between traditional open and minimally invasive esophagectomy in a multi-center, randomized trial. Patients with a resectable intrathoracic esophageal carcinoma, including the gastro-esophageal junction tumors (Siewert I) are eligible for inclusion. Prior thoracic surgery and cervical esophageal carcinoma are indications for exclusion. The surgical technique involves a right thoracotomy with lung blockade and laparotomy either with a cervical or thoracic anastomosis for the traditional group. The minimally invasive procedure involves a right thoracoscopy in prone position with a single lumen tube and laparoscopy either with a cervical or thoracic anastomosis. All patients in both groups will undergo identical pre-operative and post-operative protocol. Primary endpoint of this study are post-operative respiratory complications within the first two post-operative weeks confirmed by clinical, radiological and sputum culture data. Secondary endpoints are the operative data, the post-operative data and oncological data such as quality of the specimen and survival. Operative data include duration of the operation, blood loss and conversion to open procedure. Post-operative data include morbidity (major and minor), quality of life tests and hospital stay.</p> <p>Based on current literature and the experience of all participating centers, an incidence of pulmonary complications for 57% in the traditional arm and 29% in the minimally invasive arm, it is estimated that per arm 48 patients are needed. This is based on a two-sided significance level (alpha) of 0.05 and a power of 0.80. Knowing that approximately 20% of the patients will be excluded, we will randomize 60 patients per arm.</p> <p>Discussion</p> <p>The TIME-trial is a prospective, multi-center, randomized study to define the role of minimally invasive esophageal resection in patients with resectable intrathoracic and junction esophageal cancer.</p> <p>Trial registration (Netherlands Trial Register)</p> <p><a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2040">NTR2452</a></p

Invasive Plants and Enemy Release: Evolution of Trait Means and Trait Correlations in Ulex europaeus

Several hypotheses that attempt to explain invasive processes are based on the fact that plants have been introduced without their natural enemies. Among them, the EICA (Evolution of Increased Competitive Ability) hypothesis is the most influential. It states that, due to enemy release, exotic plants evolve a shift in resource allocation from defence to reproduction or growth. In the native range of the invasive species Ulex europaeus, traits involved in reproduction and growth have been shown to be highly variable and genetically correlated. Thus, in order to explore the joint evolution of life history traits and susceptibility to seed predation in this species, we investigated changes in both trait means and trait correlations. To do so, we compared plants from native and invaded regions grown in a common garden. According to the expectations of the EICA hypothesis, we observed an increase in seedling height. However, there was little change in other trait means. By contrast, correlations exhibited a clear pattern: the correlations between life history traits and infestation rate by seed predators were always weaker in the invaded range than in the native range. In U. europaeus, the role of enemy release in shaping life history traits thus appeared to imply trait correlations rather than trait means. In the invaded regions studied, the correlations involving infestation rates and key life history traits such as flowering phenology, growth and pod density were reduced, enabling more independent evolution of these key traits and potentially facilitating local adaptation to a wide range of environments. These results led us to hypothesise that a relaxation of genetic correlations may be implied in the expansion of invasive species

The Effects of Arbuscular Mycorrhizal Fungi on Direct and Indirect Defense Metabolites of Plantago lanceolata L.

Arbuscular mycorrhizal fungi can strongly influence the metabolism of their host plant, but their effect on plant defense mechanisms has not yet been thoroughly investigated. We studied how the principal direct defenses (iridoid glycosides) and indirect defenses (volatile organic compounds) of Plantago lanceolata L. are affected by insect herbivory and mechanical wounding. Volatile compounds were collected and quantified from mycorrhizal and non-mycorrhizal P. lanceolata plants that underwent three different treatments: 1) insect herbivory, 2) mechanical wounding, or 3) no damage. The iridoids aucubin and catalpol were extracted and quantified from the same plants. Emission of terpenoid volatiles was significantly higher after insect herbivory than after the other treatments. However, herbivore-damaged mycorrhizal plants emitted lower amounts of sesquiterpenes, but not monoterpenes, than herbivore-damaged non-mycorrhizal plants. In contrast, mycorrhizal infection increased the emission of the green leaf volatile (Z)-3-hexenyl acetate in untreated control plants, making it comparable to emission from mechanically wounded or herbivore-damaged plants whether or not they had mycorrhizal associates. Neither mycorrhization nor treatment had any influence on the levels of iridoid glycosides. Thus, mycorrhizal infection did not have any effect on the levels of direct defense compounds measured in P. lanceolata. However, the large decline in herbivore-induced sesquiterpene emission may have important implications for the indirect defense potential of this species

Heritability of seed weight in Maritime pine, a relevant trait in the transmission of environmental maternal effects

Quantitative seed provisioning is an important life-history trait with strong effects on offspring phenotype and fitness. As for any other trait, heritability estimates are vital for understanding its evolutionary dynamics. However, being a trait in between two generations, estimating additive genetic variation of seed provisioning requires complex quantitative genetic approaches for distinguishing between true genetic and environmental maternal effects. Here, using Maritime pine as a long-lived plant model, we quantified additive genetic variation of cone and seed weight (SW) mean and SW within-individual variation. We used a powerful approach combining both half-sib analysis and parent-offspring regression using several common garden tests established in contrasting environments to separate G, E and G x E effects. Both cone weight and SW mean showed significant genetic variation but were also influenced by the maternal environment. Most of the large variation in SW mean was attributable to additive genetic effects (h(2) = 0.55-0.74). SW showed no apparent G x E interaction, particularly when accounting for cone weight covariation, suggesting that the maternal genotypes actively control the SW mean irrespective of the amount of resources allocated to cones. Within-individual variation in SW was low (12%) relative to between-individual variation (88%), and showed no genetic variation but was largely affected by the maternal environment, with greater variation in the less favourable sites for pine growth. In summary, results were very consistent between the parental and the offspring common garden tests, and clearly indicated heritable genetic variation for SW mean but not for within-individual variation in SW.This study was financed by the Spanish National Research Grants RTA2007-100 and AGL2012-40151 (FENOPIN), both co-financed by EU-FEDER. The progeny trials and the clonal seed orchards are part of the experimental set up of the Maritime pine breeding programme developed by the Centro de Investigacion Forestal de Lourizan, Xunta de Galicia.Spanish National Research Grant RTA2007-100Spanish National Research Grant AGL2012-40151 (FENOPIN)EU-FEDERPeer reviewe

Curative treatment of oesophageal carcinoma: current options and future developments

Since the 1980s major advances in surgery, radiotherapy and chemotherapy have established multimodal approaches as curative treatment options for oesophageal cancer. In addition the introduction of functional imaging modalities such as PET-CT created new opportunities for a more adequate patient selection and therapy response assessment