Background For patients with esophageal adenocarcinoma or cancer of the gastroesophageal junction, radical esophagectomy with 2-field lymphadenectomy is the cornerstone of the multimodality treatment ...with curative intent. Both conventional minimally invasive esophagectomy (MIE) and robot assisted minimally invasive esophagectomy (RAMIE) were shown to be superior compared to open transthoracic esophagectomy considering postoperative complications. However, no randomized comparison exists between MIE and RAMIE in the Western World for patients with esophageal adenocarcinoma. Methods This is an investigator-initiated and investigator-driven multicenter randomized controlled parallel-group superiority trial. All adult patients (age greater than or equai to 18 and less than or equai to 90 years) with histologically proven, surgically resectable (cT1-4a, N0-3, M0) esophageal adenocarcinoma of the intrathoracic esophagus or adenocarcinoma of the gastroesophageal junction and with European Clinical Oncology Group performance status 0, 1 or 2 will be assessed for eligibility and included after obtaining informed consent. Patients (n = 218) with resectable esophageal adenocarcinoma of the intrathoracic esophagus or adenocarcinoma of the gastroesophageal junction are randomized to either RAMIE (n = 109) or MIE (n = 109). The primary outcome of this study is the total number of resected abdominal and mediastinal lymph nodes specified per lymph node station. Conclusion This is the first randomized controlled trial designed to compare RAMIE to MIE as surgical treatment for resectable esophageal adenocarcinoma or adenocarcinoma of the gastroesophageal junction in the Western World. The hypothesis of the proposed study is that RAMIE will result in a higher abdominal and mediastinal lymph node yield specified per station compared to conventional MIE. Short-term results and the primary endpoint (total number of resected abdominal and mediastinal lymph nodes per lymph node station) will be analyzed and published after discharge of the last randomized patient within this trial. Trial registration ClinicalTrials.gov Identifier: NCT04306458. Registered 13th March 2020, Keywords: MIE, RAMIE, Ivor-Lewis, Esophageal adenocarcinoma, Lymphadenectomy
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Implementation of the Nitrates Directive (NiD) and its environmental impacts were compared for member states in the northwest of the European Union (Ireland, United Kingdom, Denmark, the Netherlands, ...Belgium, Northern France and Germany). The main sources of data were national reports for the third reporting period for the NiD (2004–2007) and results of the MITERRA-EUROPE model. Implementation of the NiD in the considered member states is fairly comparable regarding restrictions for where and when to apply fertilizer and manure, but very different regarding application limits for N fertilization. Issues of concern and improvement of the implementation of the NiD are accounting for the fertilizer value of nitrogen in manure, and relating application limits for total nitrogen (N) to potential crop yield and N removal. The most significant environmental effect of the implementation of the NiD since 1995 is a major contribution to the decrease of the soil N balance (N surplus), particularly in Belgium, Denmark, Ireland, the Netherlands and the United Kingdom. This decrease is accompanied by a modest decrease of nitrate concentrations since 2000 in fresh surface waters in most countries. This decrease is less prominent for groundwater in view of delayed response of nitrate in deep aquifers. In spite of improved fertilization practices, the southeast of the Netherlands, the Flemish Region and Brittany remain to be regions of major concern in view of a combination of a high nitrogen surplus, high leaching fractions to groundwater and tenacious exceedance of the water quality standards. On average the gross N balance in 2008 for the seven member states in EUROSTAT and in national reports was about 20 kg N ha−1 yr−1 lower than by MITERRA. The major cause is higher estimates of N removal in national reports which can amount to more than 50 kg N ha−1 yr−1. Differences between procedures in member states to assess nitrogen balances and water quality and a lack of cross-boundary policy evaluations are handicaps when benchmarking the effectiveness of the NiD. This provides a challenge for the European Commission and its member states, as the NiD remains an important piece of legislation for protecting drinking water quality in regions with many private or small public production facilities and controlling aquatic eutrophication from agricultural sources.
The traditional view of the planktonic food web describes consumption of inorganic nutrients by photoautotrophic phytoplankton, which in turn supports zooplankton and ultimately higher trophic ...levels. Pathways centred on bacteria provide mechanisms for nutrient recycling. This structure lies at the foundation of most models used to explore biogeochemical cycling, functioning of the biological pump, and the impact of climate change on these processes. We suggest an alternative new paradigm, which sees the bulk of the base of this food web supported by protist plankton communities that are mixotrophic - combining phototrophy and phagotrophy within a single cell. The photoautotrophic eukaryotic plankton and their heterotrophic microzooplankton grazers dominate only during the developmental phases of ecosystems (e.g. spring bloom in temperate systems). With their flexible nutrition, mixotrophic protists dominate in more-mature systems (e.g. temperate summer, established eutrophic systems and oligotrophic systems); the more-stable water columns suggested under climate change may also be expected to favour these mixotrophs. We explore how such a predominantly mixotrophic structure affects microbial trophic dynamics and the biological pump. The mixotroph-dominated structure differs fundamentally in its flow of energy and nutrients, with a shortened and potentially more efficient chain from nutrient regeneration to primary production. Furthermore, mixotrophy enables a direct conduit for the support of primary production from bacterial production. We show how the exclusion of an explicit mixotrophic component in studies of the pelagic microbial communities leads to a failure to capture the true dynamics of the carbon flow. In order to prevent a misinterpretation of the full implications of climate change upon biogeochemical cycling and the functioning of the biological pump, we recommend inclusion of multi-nutrient mixotroph models within ecosystem studies.
A single dose of the anti‐CD20 monoclonal antibody rituximab induces a nearly complete B cell depletion in peripheral blood, but not in secondary lymphoid organs. Modulation of this remaining B cell ...population due to rituximab treatment may contribute to the therapeutic effects of rituximab. To assess the in vivo effects of rituximab we used lymph nodes (LNs) collected during renal transplant surgery in patients who had received rituximab 4 weeks earlier in preparation for an ABO‐incompatible transplantation. Rituximab treatment resulted in a lower percentage of naïve (IgD+CD27−) and a higher percentage of switched memory (IgD−CD27+) B cells. Remarkably, transitional (CD24++CD38++) B cells were virtually lacking in the LNs of rituximab‐treated patients. Moreover, LN‐derived B cells from rituximab‐treated patients produced different amounts of various Ig‐subclasses after anti‐CD40/IL‐21 stimulation ex vivo. Finally, after stimulation of allogeneic T cells with LN‐derived B cells from rituximab‐treated patients, the proliferated T cells showed a decreased production of IL‐17. In conclusion, after treatment with rituximab there remains a B cell population with different functional capacities. Consequently, the effect of rituximab on the immune response will not only be determined by the extent of B cell depletion, but also by the functional properties of the remaining B cells.
The authors report that although a single dose of rituximab results in a nearly complete B cell depletion in the peripheral blood of renal transplant recipients, there is a relative increase of B cells with a switched memory phenotype in lymph nodes of these patients that may result in an altered immune response.
The Meteorological Synthesizing Centre-West (MSC-W) of the European Monitoring and Evaluation Programme (EMEP) has been performing model calculations in support of the Convention on Long Range ...Transboundary Air Pollution (CLRTAP) for more than 30 years. The EMEP MSC-W chemical transport model is still one of the key tools within European air pollution policy assessments. Traditionally, the model has covered all of Europe with a resolution of about 50 km × 50 km, and extending vertically from ground level to the tropopause (100 hPa). The model has changed extensively over the last ten years, however, with flexible processing of chemical schemes, meteorological inputs, and with nesting capability: the code is now applied on scales ranging from local (ca. 5 km grid size) to global (with 1 degree resolution). The model is used to simulate photo-oxidants and both inorganic and organic aerosols. In 2008 the EMEP model was released for the first time as public domain code, along with all required input data for model runs for one year. The second release of the EMEP MSC-W model became available in mid 2011, and a new release is targeted for summer 2012. This publication is intended to document this third release of the EMEP MSC-W model. The model formulations are given, along with details of input data-sets which are used, and a brief background on some of the choices made in the formulation is presented. The model code itself is available at www.emep.int, along with the data required to run for a full year over Europe.
Background
Studies comparing the anastomotic leak rate in patients with an intrathoracic versus a cervical anastomosis after oesophagectomy are equivocal. The aim of this study was to compare ...clinical outcome after oesophagectomy in patients with an intrathoracic or cervical anastomosis, and to identify predictors of anastomotic leakage in a nationwide audit.
Methods
Between January 2011 and December 2015, all consecutive patients who underwent oesophagectomy for cancer were identified from the Dutch Upper Gastrointestinal Cancer Audit. For the comparison between an intrathoracic and cervical anastomosis, propensity score matching was used to adjust for potential confounders. Multivariable logistic regression modelling with backward stepwise selection was used to determine independent predictors of anastomotic leakage.
Results
Some 3348 patients were included. After propensity score matching, 654 patients were included in both the cervical and intrathoracic anastomosis groups. An intrathoracic anastomosis was associated with a lower leak rate than a cervical anastomosis (17·0 versus 21·9 per cent; P = 0·025). The percentage of patients with recurrent nerve paresis was also lower (0·6 versus 7·0 per cent; P < 0·001) and an intrathoracic anastomosis was associated with a shorter median hospital stay (12 versus 14 days; P = 0·001). Multivariable analysis revealed that ASA fitness grade III or higher, chronic obstructive pulmonary disease, cardiac arrhythmia, diabetes mellitus and proximal oesophageal tumours were independent predictors of anastomotic leakage.
Conclusion
An intrathoracic oesophagogastric anastomosis was associated with a lower anastomotic leak rate, lower rate of recurrent nerve paresis and a shorter hospital stay. Risk factors for anastomotic leak were co‐morbidities and proximal tumours.
Lower leak rates after intrathoracic anastomosis
This study investigated whether a supervised exercise programme improves quality of life (QoL), fatigue and cardiorespiratory fitness in patients in the first year after oesophagectomy.
The ...multicentre PERFECT trial randomly assigned patients to an exercise intervention (EX) or usual care (UC) group. EX patients participated in a 12-week moderate- to high-intensity aerobic and resistance exercise programme supervised by a physiotherapist. Primary (global QoL, QoL summary score) and secondary (QoL subscales, fatigue and cardiorespiratory fitness) outcomes were assessed at baseline, 12 and 24 weeks and analysed as between-group differences using either linear mixed effects models or ANCOVA.
A total of 120 patients (mean(s.d.) age 64(8) years) were included and randomized to EX (61 patients) or UC (59 patients). Patients in the EX group participated in 96 per cent (i.q.r. 92-100 per cent) of the exercise sessions and the relative exercise dose intensity was high (92 per cent). At 12 weeks, beneficial EX effects were found for QoL summary score (3.5, 95 per cent c.i. 0.2 to 6.8) and QoL role functioning (9.4, 95 per cent c.i. 1.3 to 17.5). Global QoL was not statistically significant different between groups (3.0, 95 per cent c.i. -2.2 to 8.2). Physical fatigue was lower in the EX group (-1.2, 95 per cent c.i. -2.6 to 0.1), albeit not significantly. There was statistically significant improvement in cardiorespiratory fitness following EX compared with UC (peak oxygen uptake (1.8 ml/min/kg, 95 per cent c.i. 0.6 to 3.0)). After 24 weeks, all EX effects were attenuated.
A supervised exercise programme improved cardiorespiratory fitness and aspects of QoL.
Dutch Trial Register NTR 5045 (www.trialregister.nl/trial/4942).
* Cobalt carbide (Co2C) was monitored using novel in situ magnetometer. * The formation of cobalt carbide was confirmed by means of in situ XRD and synchrotron XRD measurements. * Cobalt carbide, ...once formed, is very stable at realistic Fischer-Tropsch conditions. * The formation of cobalt carbide is inversely proportional to H2/CO ratio and FT reaction temperature. * The carbide formation is thermodynamically feasible, but only small amounts form at realistic FT conditions. While carbides are always present in iron-based Fischer-Tropsch synthesis, very little is known about the presence and the role of carbides in cobalt-based CO hydrogenation. Cobalt carbide, Co2C, has been reported in catalysts where operational upsets occurred and it is associated with low catalyst activity and increased methane selectivity. In this study, a novel in situ magnetometer was used to study the formation and the stability of cobalt carbide during the Fischer-Tropsch synthesis at fully relevant conditions. The formation of cobalt carbide was confirmed by means of in situ XRD and synchrotron XRD measurements. Cobalt carbide is relatively stable at typical reaction conditions, but a rapid decomposition into hcp cobalt occurs in hydrogen above 150°C. Cobalt carbide formation is inversely proportional to the H2/CO ratio and the reaction temperature. However, the amounts of cobalt carbide formed are small and the impact on deactivation at realistic Fischer-Tropsch conditions should generally be negligible.
In renal transplantation, use of calcineurin inhibitors (CNIs) is associated with nephrotoxicity and immunosuppression with malignancies and infections. This trial aimed to minimize CNI exposure and ...total immunosuppression while maintaining efficacy. We performed a randomized controlled, open‐label multicenter trial with early cyclosporine A (CsA) elimination. Patients started with basiliximab, prednisolone (P), mycophenolate sodium (MPS), and CsA. At 6 months, immunosuppression was tapered to P/CsA, P/MPS, or P/everolimus (EVL). Primary outcomes were renal fibrosis and inflammation. Secondary outcomes were estimated glomerular filtration rate (eGFR) and incidence of rejection at 24 months. The P/MPS arm was prematurely halted. The trial continued with P/CsA (N = 89) and P/EVL (N = 96). Interstitial fibrosis and inflammation were significantly decreased and the eGFR was significantly higher in the P/EVL arm. Cumulative rejection rates were 13% (P/EVL) and 19% (P/CsA), (p = 0.08). A post hoc analysis of HLA and donor‐specific antibodies at 1 year after transplantation revealed no differences. An individualized immunosuppressive strategy of early CNI elimination to dual therapy with everolimus was associated with decreased allograft fibrosis, preserved allograft function, and good efficacy, but also with more serious adverse events and discontinuation. This can be a valuable alternative regimen in patients suffering from CNI toxicity.
This randomized trial in renal transplant recipients shows that with tight monitoring of drug levels, a triple calcineurin inhibitor–containing drug maintenance regimen can be tapered to a double calcineurin‐free drug regimen, and that this regimen is associated with better renal function and less interstitial fibrosis and inflammation.
Background
Studies investigating the association between hospital volume and quality of gastric cancer surgery are lacking. In the present study, the effect of hospital volume on quality of gastric ...cancer surgery was evaluated by analysing data from the CRITICS (ChemoRadiotherapy after Induction chemotherapy In Cancer of the Stomach) trial.
Methods
Patients who underwent gastrectomy with curative intent in the Netherlands were selected from the CRITICS trial database. Annual hospital volume of participating centres was derived from the Netherlands Cancer Registry. Hospital volume was categorized into very low (1–10 gastrectomies per year per institution), low (11–20), medium (21–30) and high (31 or more), and linked to the CRITICS database. Quality of surgery was analysed by surgicopathological compliance (removal of at least 15 lymph nodes), surgical compliance (removal of indicated lymph node stations) and the Maruyama Index. Postoperative morbidity and mortality were also compared between hospital categories.
Results
Between 2007 and 2015, 788 patients were included in the CRITICS study, of whom 494 were analysed. Surgicopathological compliance was higher (86·7 versus 50·4 per cent; P < 0·001), surgical compliance was greater (52·9 versus 19·8 per cent; P < 0·001) and median Maruyama Index was lower (0 versus 6; P = 0·006) in high‐volume hospitals compared with very low‐volume hospitals. There was no statistically significant difference in postoperative complications or mortality between the hospital volume categories.
Conclusion
Surgery performed in high‐volume hospitals was associated with better surgical quality than surgery carried out in lower‐volume hospitals.
High volume better quality
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