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

Redundancy of mammalian Y family DNA polymerases in cellular responses to genomic DNA lesions induced by ultraviolet light

Toxicogenetic

Prediction of time of death after withdrawal of life-sustaining treatment in potential donors after cardiac death*

OBJECTIVE: Organ donation after cardiac death increases the number of donor organs. In controlled donation after cardiac death donors, the period between withdrawal of life-sustaining treatment and cardiac arrest is one of the parameters used to assess whether organs are suitable for transplantation. The objective of this study was to identify donation after cardiac death donor characteristics that affect the interval between withdrawal of life-sustaining treatment and cardiac death. DESIGN: Prospective multicenter study of observational data. PATIENTS: All potential donation after cardiac death donors in The Netherlands between May 2007 and June 2009 were identified. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 242 potential donation after cardiac death donors, 211 entered analysis, 76% of them died within 60 mins, and 83% died within 120 mins after withdrawal of life-sustaining treatment. The median time to death was 20 mins (range 1 min to 3.8 days). Controlled mechanical ventilation, use of norepinephrine, absence of reflexes, neurologic deficit as cause of death, and absence of cardiovascular comorbidity were associated with death within 60 and 120 mins. The use of analgesics, sedatives, or extubation did not significantly influence the moment of death. In the multivariable logistic regression analysis, controlled mechanical ventilation remained a risk factor for death within 60 mins, and norepinephrine administration and absence of cardiovascular comorbidity remained risk factors for death within 120 mins. The clinical judgment of the intensivist predicted death within 60 and 120 mins with a sensitivity of 73% and 89%, respectively, and a specificity of 56% and 25%, respectively. CONCLUSION: Despite the identification of risk factors for early death and the additional value of the clinical judgment by the intensivist, it is not possible to reliably identify potential donation after cardiac death donors who will die within 1 or 2 hrs after life-sustaining treatment has been withdrawn. Consequently, a donation procedure should be initiated in every potential donor

PCNA ubiquitination-independent activation of polymerase eta during somatic hypermutation and DNA damage tolerance

Replication associated mutagenesi