Endoscopic mucosal resection (EMR) versus endoscopic submucosal dissection (ESD) for resection of large distal non-pedunculated colorectal adenomas (MATILDA-trial): Rationale and design of a multicenter randomized clinical trial

Background: Endoscopic mucosal resection (EMR) is currently the most used technique for resection of large distal colorectal polyps. However, in large lesions EMR can often only be performed in a piecemeal fashion resulting in relatively low radical (R0)-resection rates and high recurrence rates. Endoscopic submucosal dissection (ESD) is a newer procedure that is more difficult resulting in a longer procedural time, but is promising due to the high en-bloc resection rates and the very low recurrence rates. We aim to evaluate the (cost-)effectiveness of ESD against EMR on both short (i.e. 6 months) and long-term (i.e. 36 months). We hypothesize that in the short-run ESD is more time consuming resulting in higher healthcare costs, but is (cost-) effective on the long-term due to lower patients burden, a higher number of R0-resections and lower recurrence rates with less need for repeated procedures. Methods: This is a multicenter randomized clinical trial in patients with a non-pedunculated polyp larger than 20 mm in the rectum, sigmoid, or descending colon suspected to be an adenoma by means of endoscopic assessment. Primary endpoint is recurrence rate at follow-up colonoscopy at 6 months. Secondary endpoints are R0-resection rate, perceived burden and quality of life, healthcare resources utilization and costs, surgical referral rate, complication rate and recurrence rate at 36 months. Quality-adjusted-life-year (QALY) will be estimated taking an area under the curve approach and using EQ-5D-indexes. Healthcare costs will be calculated by multiplying used healthcare services with unit prices. The cost-effectiveness of ESD against EMR will be expressed as incremental cost-effectiveness ratios (ICER) showing additional costs per recurrence free patient and as ICER showing additional costs per QALY. Discussion: If this trial confirms ESD to be favorable on the long-term, the burden of extra colonoscopies and repeated procedures can be prevented for future patients. Trial registration:NCT02657044(Clinicaltrials.gov), registered January 8, 2016

Individual variability in cardiac biomarker release after 30 min of high-intensity rowing in elite and amateur athletes

This study had two objectives: (i) to examine individual variation in the pattern of cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) release in response to high-intensity rowing exercise, and (ii) to establish whether individual heterogeneity in biomarker appearance was influenced by athletic status (elite vs. amateur). We examined cTnI and NT-proBNP in 18 elite and 14 amateur rowers before and 5 min, 1, 3, 6, 12, and 24 h after a 30-min maximal rowing test. Compared with pre-exercise levels, peak postexercise cTnI (pre: 0.014 ± 0.030 μg·L–1; peak post: 0.058 ± 0.091 μg·L–1; p = 0.000) and NT-proBNP (pre: 15 ± 11 ng·L–1; peak post: 31 ± 19 ng·L–1; p = 0.000) were elevated. Substantial individual heterogeneity in peak and time-course data was noted for cTnI. Peak cTnI exceeded the upper reference limit (URL) in 9 elite and 3 amateur rowers. No rower exceeded the URL for NT-proBNP. Elite rowers had higher baseline (0.019 ± 0.038 vs. 0.008 ± 0.015 μg·L–1; p = 0.003) and peak postexercise cTnI (0.080 ± 0.115 vs. 0.030 ± 0.029 μg·L–1; p = 0.022) than amateur rowers, but the change with exercise was similar between groups. There were no significant differences in baseline and peak postexercise NT-proBNP between groups. In summary, marked individuality in the cTnI response to a short but high-intensity rowing bout was observed. Athletic status did not seem to affect the change in cardiac biomarkers in response to high-intensity exercise

Pedunculated Morphology of T1 Colorectal Tumors Associates With Reduced Risk of Adverse Outcome

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Full-thickness scar resection after R1/Rx excised T1 colorectal cancers as an alternative to completion surgery

INTRODUCTION: Local full-thickness resections of the scar (FTRS) after local excision of a T1 colorectal cancer (CRC) with uncertain resection margins is proposed as an alternative strategy to completion surgery (CS), provided that no local intramural residual cancer (LIRC) is found. However, a comparison on long-term oncological outcome between both strategies is missing.METHODS: A large cohort of patients with consecutive T1 CRC between 2000 and 2017 was used. Patients were selected if they underwent a macroscopically complete local excision of a T1 CRC but positive or unassessable (R1/Rx) resection margins at histology and without lymphovascular invasion or poor differentiation. Patients treated with CS or FTRS were compared on the presence of CRC recurrence, a 5-year overall survival, disease-free survival, and metastasis-free survival.RESULTS: Of 3,697 patients with a T1 CRC, 434 met the inclusion criteria (mean age 66 years, 61% men). Three hundred thirty-four patients underwent CS, and 100 patients underwent FTRS. The median follow-up period was 64 months. CRC recurrence was seen in 7 patients who underwent CS (2.2%, 95% CI 0.9%-4.6%) and in 8 patients who underwent FTRS (9.0%, 95% CI 3.9%-17.7%). Disease-free survival was lower in FTRS strategy (96.8% vs 89.9%, P=0.019), but 5 of the 8 FTRS recurrences could be treated with salvage surgery. The metastasis-free survival (CS 96.8% vs FTRS 92.1%, P=0.10) and overall survival (CS 95.6% vs FTRS 94.4%, P=0.55) did not differ significantly between both strategies.DISCUSSION: FTRS after local excision of a T1 CRC with R1/Rx resection margins as a sole risk factor, followed by surveillance and salvage surgery in case of CRC recurrence, could be a valid alternative strategy to CS.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Tectonic model for development of the Byrd Glacier discontinuity and surrounding regions of the Transantarctic Mountains during Neoproterozoic-Early Paleozoic

The Byrd Glacier discontinuity us a major boundary crossing the Ross Orogen, with crystalline rocks to the north and primarily sedimentary rocks to the south. Most models for the tectonic development of the Ross Orogen in the central Transantarctic Mountains consits of two-dimensional transects across the belt, but do not adress the major longitudinal contrast at Byrd Glacier. This paper presents a tectonic model centering on the Byrd Glacier discontinuity. Rifting in the Neoproterozoic producede a crustal promontory in the craton margin to the north of Byrd Glacier. Oblique convergence of the terrane (Beardmore microcontinent) during the latest Neroproterozoic and Early Cambrian was accompanied by subduction along the craton margin of East Antarctica. New data presented herein in the support of this hypothesis are U-Pb dates of 545.7 ± 6.8 Ma and 531.0 ± 7.5 Ma on plutonic rocks from the Britannia Range, subduction stepped out, and Byrd Glacier. After docking of the terrane, subduction stepped out, and Byrd Group was deposited during the Atdabanian-Botomian across the inner margin of the terrane. Beginning in the upper Botomian, reactivation of the sutured boundaries of the terrane resulted in an outpouring of clastic sediment and folding and faulting of the Byrd Group

Multiresolution elastic registration of head magnetic resonance images

A non-rigid body registration algorithm was proposed by Kovalev and Petrou [1] where the image grid was deformed by localised deformation operators in order to optimise a global cost function. In this paper, we propose to implement this non-rigid body registration over a multiresolution pyramid in order to obtain large-scale deformations at the coarse levels and fine-detail deformations at the finer levels, resulting in faster convergence

Effects of grazing method and fertiliser inputs on the productivity and sustainability of phalaris-based pastures in Western Victoria

The effects of combinations of different fertiliser rates and grazing methods applied to phalaris-based pastures on an acid, saline, yellow sodosol on the Dundas Tablelands of western Victoria (mean annual rainfall 623 mm) were measured from 1997 to 2000. The objective was to help identify management systems that improve phalaris growth and persistence, water use, and animal production, and thereby the productivity and sustainability of grazing systems. Pastures were either set stocked with low [mean 6.4 kg phosphorus (P)/ha.year] or high (mean 25 kg P/ha.year) fertiliser rates, or rotationally grazed with high fertiliser (mean 25 kg P/ha.year). Rotational grazing was implemented as either a simple '4-paddock' system (fixed rotation length), or a more intensive system where rotation length varied with pasture growth rate. Unreplicated paddocks of volunteer pasture (dominated by onion grass and annual grass weeds) receiving an average of 8 kg P/ha.year were also monitored. All treatments were stocked with spring-lambing Merino ewes. Stocking rate was an emergent property of each treatment, and was driven by pasture quality and availability. Total pasture herbage accumulation ranged from 7150 to 9750 kg DM/ha.year and was significantly lower on the set-stocked, low-fertility treatment than on all other treatments. A significant treatment.day effect in the spline analysis of herbage mass was explained by a trend toward higher pasture mass in the rotationally grazed treatments than set-stocked treatments from the break of season until mid-spring. Rotational grazing led to significantly higher phalaris herbage accumulation than set stocking (mean 3680 v. 2120 kg DM/ha.year), but significantly lower subterranean clover herbage accumulation (1440 v. 2490 kg DM/ha.year). Despite the stronger growth of deep-rooted phalaris in the rotationally grazed treatments, maximum soil water deficits at the end of summer differed only slightly between treatments, with the difference between driest and wettest treatments amounting to only 14 mm. Summer growth of phalaris was apparently insufficient to generate significant differences in soil water extraction at depth, even when phalaris content was increased by rotational grazing, and re-wetting of the soil profile occurred at a similar rate for all treatments. Rotationally grazed treatments supported higher stocking rates than set-stocked treatments at high fertiliser rates (mean 14.9 v. 13.7 ewes/ha), but apparent losses in pasture feeding value due to lower legume content under rotational grazing meant that there were few significant differences between treatments in lamb production per hectare. The experiment showed that grazing method can have a substantial and rapid effect on pasture botanical composition. There are clear opportunities for producers to use temporal and spatial combinations of set stocking and rotational grazing to manipulate herbage mass and pasture composition within broad target ranges for achieving both animal production (e.g. high per-head animal performance) and sustainability (e.g. persistence of perennial grasses) objectives. Rigid application of either set stocking or rotational grazing imposes limitations on both pasture and animal production, and neither grazing method will optimise system performance under all conditions. The experiment also demonstrated that management and land-use changes that have much greater potential to increase water use than those examined here will be needed to ensure the sustainability of pasture systems in the high rainfall zone of western Victoria