Colorectal liver metastases: Surgery versus thermal ablation (COLLISION) - a phase III single-blind prospective randomized controlled trial

Background: Radiofrequency ablation (RFA) and microwave ablation (MWA) are widely accepted techniques to eliminate small unresectable colorectal liver metastases (CRLM). Although previous studies labelled thermal ablation inferior to surgical resection, the apparent selection bias when comparing patients with unresectable disease to surgical candidates, the superior safety profile, and the competitive overall survival results for the more recent reports mandate the setup of a randomized controlled trial. The objective of the COLLISION trial is to prove non-inferiority of thermal ablation compared to hepatic resection in patients with at least one resectable and ablatable CRLM and no extrahepatic disease. Methods: In this two-arm, single-blind multi-center phase-III clinical trial, six hundred and eighteen patients with at least one CRLM (≤3cm) will be included to undergo either surgical resection or thermal ablation of appointed target lesion(s) (≤3cm). Primary endpoint is OS (overall survival, intention-to-treat analysis). Main secondary endpoints are overall disease-free survival (DFS), time to progression (TTP), time to local progression (TTLP), primary and assisted technique efficacy (PTE, ATE), procedural morbidity and mortality, length of hospital stay, assessment of pain and quality of life (QoL), cost-effectiveness ratio (ICER) and quality-adjusted life years (QALY). Discussion: If thermal ablation proves to be non-inferior in treating lesions ≤3cm, a switch in treatment-method may lead to a reduction of the post-procedural morbidity and mortality, length of hospital stay and incremental costs without compromising oncological outcome for patients with CRLM. Trial registration:NCT03088150 , January 11th 2017

Influence of the platform in multicoordinate ligands for actinide partitioning

Multicoordinate ligands based on the trityl, C-pivot, and CTV platforms and the ligating groups CMPO, DGA, PICO, and MPMA were synthesized and studied for their extraction properties. The extraction efficiencies of these multicoordinate ligands are largely influenced by the properties of the platform. The DAm values follow the order CTV6 > trityl ≈ C-pivot > CTV3 > CTV0 with a maximum for CTV6CMPO of DAm = 30 (SAm/Eu = 1.4, cL = 10–4 M, 3 M HNO3). There is a strong relationship between the DAm values, increasing in the order of CTV0CMPO < CTV3CMPO < CTV6CMPO, and the ‘mobility’ of their CMPO groups. The SAm/Eu values are less influenced by the platform and range between 0.2 and 2.0, though they can reverse under the influence of the HNO3 concentration (CTV6PICOSAm/Eu = 0.7 at 0.001 M HNO3 to 1.2 at 0.01 M HNO3) or by changing the platform (CTV(0, 3 or 6)MPMA from SAm/Eu = 0.4 to 1.6 for tritMPMA both at 0.001 M HNO3). For the CMPO derivatives the SAm/Eu values are most consistent, ranging from 1.4 to 1.8

Multicoordinate ligands for actinide/lanthanide separtations

In nuclear waste treatment processes there is a need for improved ligands for the separation of actinides (An(III)) and lanthanides (Ln(III)). Several research groups are involved in the design and synthesis of new An(III) ligands and in the confinement of these and existing An(III) ligands onto molecular platforms giving multicoordinate ligands. The preorganization of ligands considerably improves the An(III) extraction properties, which are largely dependent on the solubility and rigidity of the platform. This tutorial review summarizes the most important An(III) ligands with emphasis on the preorganization strategy using (macrocyclic) platforms

Modular Click Assembly of Degradable Capsules Using Polyrotaxanes

A modular approach for the formation of degradable capsules using polyrotaxanes (PRXs) is described. The PRXs consist of α-cyclodextrin (αCD) and poly(ethylene glycol) (PEG), which are both biologically benign and the main degradation products of the capsules. The PRXs were equipped with three alkyne groups at their ends and could be successfully grafted to azide-functionalized silica particles (2.76 μm diameter) using azide–alkyne click chemistry. The assembled PRXs were then cross-linked using a degradable linker. The cross-linked structure was sufficiently robust to allow the formation of capsules after dissolving the template silica particles. The formation of capsules of <i>ca</i>. 2 μm diameter was verified by optical microscopy, TEM, and AFM imaging. The capsules were loaded with the chemotherapy drug doxorubicin (DOX) by conjugating it to the threaded αCDs <i>via</i> their free OH groups, while maintaining degradability of the capsules. Alkyne moieties at the surface of the cross-linked PRX architecture were available for further functionalization of the capsules, as is demonstrated by clicking on fluorescent PEG moieties. The DOX-loaded capsules were degraded within 90 min at 37 °C upon exposure to a 5 mM solution of glutathione in water

Influence of the platform in multicoordinate ligands for actinide partitioning

Multicoordinate ligands based on the trityl, C-pivot, and CTV platforms and the ligating groups CMPO, DGA, PICO, and MPMA were synthesized and studied for their extraction properties. The extraction efficiencies of these multicoordinate ligands are largely influenced by the properties of the platform. The DAm values follow the order CTV6 > trityl ≈ C-pivot > CTV3 > CTV0 with a maximum for CTV6CMPO of DAm = 30 (SAm/Eu = 1.4, cL = 10–4 M, 3 M HNO3). There is a strong relationship between the DAm values, increasing in the order of CTV0CMPO < CTV3CMPO < CTV6CMPO, and the ‘mobility’ of their CMPO groups. The SAm/Eu values are less influenced by the platform and range between 0.2 and 2.0, though they can reverse under the influence of the HNO3 concentration (CTV6PICOSAm/Eu = 0.7 at 0.001 M HNO3 to 1.2 at 0.01 M HNO3) or by changing the platform (CTV(0, 3 or 6)MPMA from SAm/Eu = 0.4 to 1.6 for tritMPMA both at 0.001 M HNO3). For the CMPO derivatives the SAm/Eu values are most consistent, ranging from 1.4 to 1.8.\ud \ud \u

Formation and Degradation of Layer-by-Layer-Assembled Polyelectrolyte Polyrotaxane Capsules

We report the preparation of degradable capsules via layer-by-layer assembly using polyelectrolyte (PE) polyrotaxanes (PRXs). The PRX capsules were prepared by the sequential deposition of PRXs onto silica particles followed by the dissolution of the silica cores. The colloidal stability of the PRX capsules that are formed depends on the salt/buffer solution used in the assembly process. Various salt/buffer combinations were examined to avoid aggregation of the core–shell particles during PRX assembly and core dissolution. Using appropriate assembly conditions, we prepared colloidally stable, robust capsules. PRX capsules consisting of eight layers of PE PRXs had a wall thickness of ∼15 nm. The degradation of the PRX capsules was demonstrated through the disassembly of the PE PRXs using glutathione, which cleaves the disulfide bonds linking the end-capping groups of the PE PRXs. Given the supramolecular noncovalent structure of PRXs and their adjustable properties, it is expected that PRXs will be used as building blocks for assembling advanced capsules with unique and tailored properties

UV Photoelectron Spectra of Some Bent Bis(η5-cyclopentadienyl)Niobium and Tantalum Complexes

He(I) and He(II) photoelectron spectra are reported for (η5-C5H5)2MLX (M = Nb, Ta; L = H, CO; X = propene, 1-butene, propyl) and some methylcyclopentadienyl derivatives. Also the spectra of some π-allyl and dihalide complexes are reported. Unambiguous assignments could be made of the metal d a1 orbital, the Cp orbitals, the olefin π ionization and the M-hydride and π-allyl orbitals. Very regular trends are observed in the ionization energies upon substitution of the ligands. The olefin π ionization is found at very low energy indicating that the π backbonding to the olefin is very important. He(I)/He(II) cross section differences show clearly differences in metal character of the various M. O.’s.

Methodology for the qualitative screening of parallel arrays of potential Am3+ ligands using a photographic film

A screening method for parallel Am3+ ligand libraries is presented. The method makes use of α-radiation in combination with a photographic film to detect the complexed Am3+. After screening and development of the film spots of varying intensities are obtained. The intensities of the spots correspond with the amount of complexed Am3+. This allows a fast discrimination between the Am3+ complexation efficiencies of ligands from large libraries. Depending on the exposure time of the film, activities as small as 5 Bq 241Am can be detected. Using internal standards a semi-quantitative assessment can be performed