Dragon 1 Protocol Manuscript: Training, Accreditation, Implementation and Safety Evaluation of Portal and Hepatic Vein Embolization (PVE/HVE) to Accelerate Future Liver Remnant (FLR) Hypertrophy.

STUDY PURPOSE: The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) to accelerate future liver remnant (FLR) hypertrophy in patients with borderline resectable colorectal cancer liver metastases. METHODS: The DRAGON 1 trial is a worldwide multicenter prospective single arm trial. The primary endpoint is a composite of the safety of PVE/HVE, 90-day mortality, and one year accrual monitoring of each participating center. Secondary endpoints include: feasibility of resection, the used PVE and HVE techniques, FLR-hypertrophy, liver function (subset of centers), overall survival, and disease-free survival. All complications after the PVE/HVE procedure are documented. Liver volumes will be measured at week 1 and if applicable at week 3 and 6 after PVE/HVE and follow-up visits will be held at 1, 3, 6, and 12 months after the resection. RESULTS: Not applicable. CONCLUSION: DRAGON 1 is a prospective trial to assess the safety and feasibility of PVE/HVE. Participating study centers will be trained, and procedures standardized using Work Instructions (WI) to prepare for the DRAGON 2 randomized controlled trial. Outcomes should reveal the accrual potential of centers, safety profile of combined PVE/HVE and the effect of FLR-hypertrophy induction by PVE/HVE in patients with CRLM and a small FLR. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04272931 (February 17, 2020). Toestingonline.nl: NL71535.068.19 (September 20, 2019).

Bone healing and mannose-binding lectin.

Non-union of a fracture is a phenomenon that may complicate bone healing. Consolidation of a fracture can be divided into three phases: inflammation, reconstruction, and remodeling. Both the complement system and the coagulation cascade interact at various steps throughout these phases. Several complement components are specifically associated with the inflammation phase of bone healing. However, in which way complement components influence the remodeling phase has not been established yet. Mannose-Binding Lectin (MBL) and its associated serine protease MASP-2 (Mannanbinding lectin serine protease-2) are important initiating proteins of the complement system and have also been implicated in coagulation. With respect to the characteristics and interactions of MBL, it is likely to assume a considerable influence of MBL in the remodeling phase of bone healing. A deficiency in MBL then, caused by a genetic variation, may disturb this particular process during bone healing, due to either an accumulation of apoptotic cells or to a diminished scaffold of fibrin molecules. The next step would be early identification of patients with a deficiency of MBL, allowing for early therapeutic intervention or even non-union preventive measures. This review aims to discuss the true and hypothesized role of MBL in bone healing and the consequences of a depletion of the protein in the etiology of fracture non-union.