A multi-centred randomised trial of radical surgery versus adjuvant chemoradiotherapy after local excision for early rectal cancer

Background: Rectal cancer surgery is accompanied with high morbidity and poor long term functional outcome. Screening programs have shown a shift towards more early staged cancers. Patients with early rectal cancer can potentially benefit significantly from rectal preserving therapy. For the earliest stage cancers, local excision is sufficient when the risk of lymph node disease and subsequent recurrence is below 5 %. However, the majority of early cancers are associated with an intermediate risk of lymph node involvement (5-20 %) suggesting that local excision alone is not sufficient, while completion radical surgery, which is currently standard of care, could be a substantial overtreatment for this group of patients. Methods/Study design: In this multicentre randomised trial, patients with an intermediate risk T1-2 rectal cancer, that has been locally excised using an endoluminal technique, will be randomized between adjuvant chemo-radiotherapylimited to the mesorectum and standard completion total mesorectal excision (TME). To strictly monitor the risk of locoregional recurrence in the experimental arm and enable early salvage surgery, there will be additional follow up with frequent MRI and endoscopy. The primary outcome of the study is three-year local recurrence rate. Secondary outcomes are morbidity, disease free and overall survival, stoma rate, functional outcomes, health related quality of life and costs. The design is a non inferiority study with a total sample size of 302 patients. Discussion: The results of the TESAR trial will potentially demonstrate that adjuvant chemoradiotherapy is an oncological safe treatment option in patients who are confronted with the difficult clinical dilemma of a radically removed intermediate risk early rectal cancer by polypectomy or transanal surgery that is conventionally treated with subsequent radical surgery. Preserving the rectum using adjuvant radiotherapy is expected to significantly improve morbidity, function and quality of life if compared to completion TME surgery. Trial registration:NCT02371304, registration date: February 2015

Search for Nova Presolar Grains: γ -Ray Spectroscopy of Ar 34 and its Relevance for the Astrophysical Cl 33 (p,γ) Reaction

The discovery of presolar grains in primitive meteorites has initiated a new era of research in the study of stellar nucleosynthesis. However, the accurate classification of presolar grains as being of specific stellar origins is particularly challenging. Recently, it has been suggested that sulfur isotopic abundances may hold the key to definitively identifying presolar grains with being of nova origins and, in this regard, the astrophysical Cl33(p,γ)Ar34 reaction is expected to play a decisive role. As such, we have performed a detailed γ-ray spectroscopy study of Ar34. Excitation energies have been measured with high precision and spin-parity assignments for resonant states, located above the proton threshold in Ar34, have been made for the first time. Uncertainties in the Cl33(p,γ) reaction have been dramatically reduced and the results indicate that a newly identified ℓ =0 resonance at Er=396.9(13) keV dominates the entire rate for T=0.25-0.40 GK. Furthermore, nova hydrodynamic simulations based on the present work indicate an ejected S32/S33 abundance ratio distinctive from type-II supernovae and potentially compatible with recent measurements of a presolar grain

Level structure of the Tz=-1 nucleus Ar 34 and its relevance for nucleosynthesis in ONe novae

The Mg24+C12 fusion reaction was used to perform a detailed γ-ray spectroscopy study of the astrophysically important nucleus Ar34. In particular, an experimental setup, coupling the advanced γ-ray tracking array GRETINA with the well-established Argonne fragment mass analyzer (FMA), was employed to obtain excitation energies and spin-parity assignments for excited states in Ar34, both above and below the proton separation energy. For the first time, an angular distribution analysis of in-beam γ rays from fusion-evaporation reactions, using a tracking array, has been performed and Coulomb energy differences of analog states in the T=1, A=34 mirror system, explored from 0 to 6 MeV. Furthermore, we present a comprehensive discussion of the astrophysical Cl33(p,γ) stellar reaction rate, together with implications for the identification of nova presolar grains from sulfur isotopic abundances

Mathematical Models of Incompressible Fluids as Singular Limits of Complete Fluid Systems

A rigorous justification of several well-known mathematical models of incompressible fluid flows can be given in terms of singular limits of the scaled Navier-Stokes-Fourier system, where some of the characteristic numbers become small or large enough. We discuss the problem in the framework of global-in-time solutions for both the primitive and the target system. © 2010 Springer Basel AG

Psycho-social correlates of medication serum levels in patients with seizures: implications for education of patients

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67536/2/10.1177_001789697002900301.pd

Assessment of Clinical Complete Response After Chemoradiation for Rectal Cancer with Digital Rectal Examination, Endoscopy, and MRI: Selection for Organ-Saving Treatment

BACKGROUND: The response to chemoradiotherapy (CRT) for rectal cancer can be assessed by clinical examination, consisting of digital rectal examination (DRE) and endoscopy, and by MRI. A high accuracy is required to select complete response (CR) for organ-preserving treatment. The aim of this study was to evaluate the value of clinical examination (endoscopy with or without biopsy and DRE), T2W-MRI, and diffusion-weighted MRI (DWI) for the detection of CR after CRT. METHODS: This prospective cohort study in a university hospital recruited 50 patients who underwent clinical assessment (DRE, endoscopy with or without biopsy), T2W-MRI, and DWI at 6-8 weeks after CRT. Confidence levels were used to score the likelihood of CR. The reference standard was histopathology or recurrence-free interval of >12 months in cases of wait-and-see approaches. Diagnostic performance was calculated by area under the receiver operator characteristics curve, with corresponding sensitivities and specificities. Strategies were assessed and compared by use of likelihood ratios. RESULTS: Seventeen (34 %) of 50 patients had a CR. Areas under the curve were 0.88 (0.78-1.00) for clinical assessment and 0.79 (0.66-0.92) for T2W-MRI and DWI. Combining the modalities led to a posttest probability for predicting a CR of 98 %. Conversely, when all modalities indicated residual tumor, 15 % of patients still experienced CR. CONCLUSIONS: Clinical assessment after CRT is the single most accurate modality for identification of CR after CRT. Addition of MRI with DWI further improves the diagnostic performance, and the combination can be recommended as the optimal strategy for a safe and accurate selection of CR after CRT