Control of Antarctic phytoplankton community composition and standing stock by light availability

Southern Ocean phytoplankton are especially subjected to pronounced seasonal and interannual changes in light availability. Although previous studies have examined the role of light in these environments, very few combined pigment-based taxonomy with flow cytometry to better discriminate the light response of various phytoplankton groups. In particular the different populations within the diverse and important taxonomic group of diatoms require further investigation. Six incubation experiments (9–10 days) were performed during the main productive period with natural seawater collected at the Western Antarctic Peninsula. Standing stock of Phaeocystis spp. cells displayed relatively fast accumulation under all levels of light (low, medium, high; 4–7, 30–50 and 150–200 µmol quanta m−2 s−1), whilst the small- and larger-sized diatom populations (4.5 and 20 µm diameter) exhibited faster accumulation in medium and high light. In contrast, intermediate-sized diatoms (11.5 µm diameter) displayed fastest net growth under low light, subsequently dominating the phytoplankton community. Low light was a key factor limiting accumulation and peak phytoplankton biomass, except one incubation displaying relatively high accumulation rates under low light. The 3-week low-light period prior to experimentation likely allowed adaptation to maximize achievable growth and seems a strong determinant of whether the different natural Antarctic phytoplankton populations sustain, thrive or decline. Our study provides improved insight into how light intensity modulates the net response of key Antarctic phytoplankton, both between and within taxonomic groups

Antarctic phytoplankton community composition and size structure: importance of ice type and temperature as regulatory factors

Climate change at the Western Antarctic Peninsula (WAP) is predicted to cause major changes in phytoplankton community composition, however, detailed seasonal field data remain limited and it is largely unknown how (changes in) environmental factors influence cell size and ecosystem function. Physicochemical drivers of phytoplankton community abundance, taxonomic composition and size class were studied over two productive austral seasons in the coastal waters of the climatically sensitive WAP. Ice type (fast, grease, pack or brash ice) was important in structuring the pre-bloom phytoplankton community as well as cell size of the summer phytoplankton bloom. Maximum biomass accumulation was regulated by light and nutrient availability, which in turn were regulated by wind-driven mixing events. The proportion of larger-sized (> 20 µm) diatoms increased under prolonged summer stratification in combination with frequent and moderate-strength wind-induced mixing. Canonical correspondence analysis showed that relatively high temperature was correlated with nano-sized cryptophytes, whereas prymnesiophytes (Phaeocystis antarctica) increased in association with high irradiance and low salinities. During autumn of Season 1, a large bloom of 4.5-µm-sized diatoms occurred under conditions of seawater temperature > 0 °C and relatively high light and phosphate concentrations. This bloom was followed by a succession of larger nano-sized diatoms (11.4 µm) related to reductions in phosphate and light availability. Our results demonstrate that flow cytometry in combination with chemotaxonomy and size fractionation provides a powerful approach to monitor phytoplankton community dynamics in the rapidly warming Antarctic coastal waters

Short-Course External Beam Radiotherapy Versus Brachytherapy for Palliation of Dysphagia in Esophageal Cancer: A Matched Comparison of Two Prospective Trials

Introduction: Short-course external beam radiotherapy (EBRT) and intraluminal brachytherapy are both accepted treatments for the palliation of dysphagia in patients with incurable esophageal cancer. We compared the effects of both treatments from two prospective studies. Methods: We performed a multicenter prospective cohort study of patients with metastasized or otherwise incurable esophageal cancer requiring palliation of dysphagia from September 2016 to March 2019. Patients were treated with EBRT in five fractions of 4 Gy. Data were compared with all patients treated with a single brachytherapy dose of 12 Gy in the SIREC (Stent or Intraluminal Radiotherapy for inoperable Esophageal Cancer) trial, both between the original cohorts and between 1:1 propensity score–matched cohorts. The primary end point was an improvement of dysphagia at 3 months without reintervention. The secondary end points included toxicit

Variability and Change in the West Antarctic Peninsula Marine System: Research Priorities and Opportunities

The west Antarctic Peninsula (WAP) region has undergone significant changes in temperature and seasonal ice dynamics since the mid-twentieth century, with strong impacts on the regional ecosystem, ocean chemistry and hydrographic properties. Changes to these long-term trends of warming and sea ice decline have been observed in the 21st century, but their consequences for ocean physics, chemistry and the ecology of the high-productivity shelf ecosystem are yet to be fully established. The WAP shelf is important for regional krill stocks and higher trophic levels, whilst the degree of variability and change in the physical environment and documented biological and biogeochemical responses make this a model system for how climate and sea ice changes might restructure high-latitude ecosystems. Although this region is arguably the best-measured and best-understood shelf region around Antarctica, significant gaps remain in spatial and temporal data capable of resolving the atmosphere-ice-ocean-ecosystem feedbacks that control the dynamics and evolution of this complex polar system. Here we summarise the current state of knowledge regarding the key mechanisms and interactions regulating the physical, biogeochemical and biological processes at work, the ways in which the shelf environment is changing, and the ecosystem response to the changes underway. We outline the overarching cross-disciplinary priorities for future research, as well as the most important discipline-specific objectives. Underpinning these priorities and objectives is the need to better define the causes, magnitude and timescales of variability and change at all levels of the system. A combination of traditional and innovative approaches will be critical to addressing these priorities and developing a co-ordinated observing system for the WAP shelf, which is required to detect and elucidate change into the future

Changes in hospital variation in the probability of receiving treatment with curative intent for esophageal and gastric cancer

Background: Previous studies describe a large variation in the proportion of patients undergoing treatment with curative intent for esophageal (EC) and gastric cancer (GC). Since centralization of surgical care was initiated and more awareness regarding hospital practice variation was potentially present, we hypothesized that hospital practice variation for potentially curable EC and GC patients changed over time. Methods: Patients with potentially curable EC (n = 10,115) or GC (n = 3988) diagnosed between 2012–2017 were selected from the Netherlands Cancer Registry. Multilevel multivariable logistic regression was used to analyze the differences in the probability of treatment with curative intent between hospitals of diagnosis over time, comparing 2012−2014 with 2015−2017. Relative survival (RS) between hospitals with different probabilities of treatment with curative intent were compared. Results: The range of proportions of patients undergoing treatment with curative intent per hospital of diagnosis for EC was 45–95 % in 2012−2014 and 54–89 % in 2015−2017, and for GC 52–100 % and 45–100 %. The adjusted variation declined for EC with Odds Ratios ranging from 0.50 to 1.72 between centers in the first period to 0.70–1.44 in the second period (p < 0.001) and did not change for GC (O

Nationwide comprehensive gastro-intestinal cancer cohorts: the 3P initiative

Background: The increasing sub-classification of cancer patients due to more detailed molecular classification of tumors, and limitations of current trial designs, require innovative research designs. We present the design, governance and current standing of three comprehensive nationwide cohorts including pancreatic, esophageal/gastric, and colorectal cancer patients (NCT02070146). Multidisciplinary collection of clinical data, tumor tissue, blood samples, and patient-reported outcome (PRO) measures with a nationwide coverage, provides the infrastructure for future and novel trial designs and facilitates research to improve outcomes of gastrointestinal cancer patients. Material and methods: All patients aged ≥18 years with pancreatic, esophageal/gastric or colorectal cancer are eligible. Patients provide informed consent for: (1) reuse of clinical data; (2) biobanking of primary tumor tissue; (3) collection of blood samples; (4) to be informed about relevant newly identified genomic aberrations; (5) collection of longitudinal PROs; and (6) to receive information on new interventional studies and possible participation in cohort multiple randomized controlled trials (cmRCT) in the future. Results: In 2015, clinical data of 21,758 newly diagnosed patients were collected in the Netherlands Cancer Registry. Additional clinical data on the surgical procedures were registered in surgical audits for 13,845 patients. Within the first two years, tumor tissue and blood samples were obtained from 1507 patients; during this period, 1180 patients were included in the PRO registry. Response rate for PROs was 90%. The consent rate to receive information on new interventional studies and possible participation in cmRCTs in the future was >85%. The number of hospitals participating in the cohorts is steadily increasing. Conclusion: A comprehensive nationwide multidisciplinary gastrointestinal cancer cohort is feasible and surpasses the limitations of classical study designs. With this initiative, novel and innovative studies can be performed in an efficient, safe, and comprehensive setting

Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: A stepped-wedge cluster randomised trial

Background: Neoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard treatment for locally advanced oesophageal cancer. With this treatment, 29% of patients have a pathologically complete response in the resection specimen. This provides the rationale for investigating an active surveillance approach. The aim of this study is to assess the (cost-)effectiveness of active surveillance vs. standard oesophagectomy after nCRT for oesophageal cancer. Methods: This is a phase-III multi-centre, stepped-wedge cluster randomised controlled trial. A total of 300 patients with clinically complete response (cCR, i.e. no local or disseminated disease proven by histology) after nCRT will be randomised to show non-inferiority of active surveillance to standard oesophagectomy (non-inferiority margin 15%, intra-correlation coefficient 0.02, power 80%, 2-sided α 0.05, 12% drop-out). Patients will undergo a first clinical response evaluation (CRE-I) 4-6 weeks after nCRT, consisting of endoscopy with bite-on-bite biopsies of the primary tumour site and other suspected lesions. Clinically complete responders will undergo a second CRE (CRE-II), 6-8 weeks after CRE-I. CRE-II will include 18F-FDG-PET-CT, followed by endoscopy with bite-on-bite biopsies and ultra-endosonography plus fine needle aspiration of suspected lymph nodes and/or PET- positive lesions. Patients with cCR at CRE-II will be assigned to oesophagectomy (first phase) or active surveillance (second phase of the study). The duration of the first phase is determined randomly over the 12 centres, i.e., stepped-wedge cluster design. Patients in the active surveillance arm will undergo diagnostic evaluations similar to CRE-II at 6/9/12/16/20/24/30/36/48 and 60 months after nCRT. In this arm, oesophagectomy will be offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant dissemination. The main study parameter is overall survival; secondary endpoints include percentage of patients who do not undergo surgery, quality of life, clinical irresectability (cT4b) rate, radical resection rate, postoperative complications, progression-free survival, distant dissemination rate, and cost-effectiveness. We hypothesise that active surveillance leads to non-inferior survival, improved quality of life and a reduction in costs, compared to standard oesophagectomy. Discussion: If active surveillance and surgery as needed after nCRT leads to non-inferior survival compared to standard oesophagectomy, this organ-sparing approach can be implemented as a standard of care

Nationwide comprehensive gastro-intestinal cancer cohorts: the 3P initiative

Background: The increasing sub-classification of cancer patients due to more detailed molecular classification of tumors, and limitations of current trial designs, require innovative research designs. We present the design, governance and current standing of three comprehensive nationwide cohorts including pancreatic, esophageal/gastric, and colorectal cancer patients (NCT02070146). Multidisciplinary collection of clinical data, tumor tissue, blood samples, and patient-reported outcome (PRO) measures with a nationwide coverage, provides the infrastructure for future and novel trial designs and facilitates research to improve outcomes of gastrointestinal cancer patients. Material and methods: All patients aged ≥18 years with pancreatic, esophageal/gastric or colorectal cancer are eligible. Patients provide informed consent for: (1) reuse of clinical data; (2) biobanking of primary tumor tissue; (3) collection of blood samples; (4) to be informed about relevant newly identified genomic aberrations; (5) collection of longitudinal PROs; and (6) to receive information on new interventional studies and possible participation in cohort multiple randomized controlled trials (cmRCT) in the future. Results: In 2015, clinical data of 21,758 newly diagnosed patients were collected in the Netherlands Cancer Registry. Additional clinical data on the surgical procedures were registered in surgical audits for 13,845 patients. Within the first two years, tumor tissue and blood samples were obtained from 1507 patients; during this period, 1180 patients were included in the PRO registry. Response rate for PROs was 90%. The consent rate to receive information on new interventional studies and possible participation in cmRCTs in the future was >85%. The number of hospitals participating in the cohorts is steadily increasing. Conclusion: A comprehensive nationwide multidisciplinary gastrointestinal cancer cohort is feasible and surpasses the limitations of classical study designs. With this initiative, novel and innovative studies can be performed in an efficient, safe, and comprehensive setting