Contemporary management of patients with synchronous colorectal cancer and liver metastases is complex. The aim of this project was to provide a practical framework for care of patients with ...synchronous colorectal cancer and liver metastases with a focus on terminology, diagnosis and management.
This project was a multi-organisational, multidisciplinary consensus. The consensus group produced statements which focused on terminology, diagnosis and management. Statements were refined during an online Delphi process and those with 70% agreement or above were reviewed at a final meeting. Iterations of the report were shared by electronic mail to arrive at a final agreed document comprising twelve key statements.
Synchronous liver metastases are those detected at the time of presentation of the primary tumour. The term “early metachronous metastases” applies to those absent at presentation but detected within 12 months of diagnosis of the primary tumour with “late metachronous metastases” applied to those detected after 12 months. Disappearing metastases applies to lesions which are no longer detectable on MR scan after systemic chemotherapy. Guidance was provided on the recommended composition of tumour boards and clinical assessment in emergency and elective settings. The consensus focused on treatment pathways including systemic chemotherapy, synchronous surgery and the staged approach with either colorectal or liver-directed surgery as first step. Management of pulmonary metastases and the role of minimally invasive surgery was discussed.
The recommendations of this contemporary consensus provide information of practical value to clinicians managing patients with synchronous colorectal cancer and liver metastases.
Dithiatopazine, a 1,2-dithietane, is a recently isolated compound in the Nicolaou laboratories. Its synthesis, chemistry and stability is examined. Theoretical studies of this novel system are also ...included. The synthesis of dithiatopazine was achieved via carefully controlled photoirradiation of its pregenitor, a 12-membered dithionolactone. Further photolysis of dithiatopazine resulted in formation of the corresponding enol ether, a transformation that can be carried out by a variety of reagents. Some other reactions of dithiatopazine are also described. In a few cases some skeletal rearrangements took place. The kinetics of its conversion to the enol ether have been studied revealing an activation energy of 26.3 Kcal/mol. Molecular and quantum mechanical calculations were performed on dithiatopazine and a related episulfide to shine light on their stability and conformation. (12S,5Z,8E,10E)-12-Hydroxyheptadeca-5,8,10-trienoic acid (HHT) is a major oxygenated metabolite of arachidonic acid (AA) formed by incubation of AA with washed human platelets in the presence of molecular oxygen. The first stereocontrolled total synthesis of HHT methyl ester was achieved in 21 steps and 0.14% overall yield via a Pd$\sp{\rm 0}$-TIOH catalyzed coupling reaction of a vinyliodide and a vinylborane according to Kishi's procedure. Calichemicin $\gamma\sp{\rm I}\sb{1 \alpha}$ is a naturally occuring substance with potent biological activity. The total synthesis of the glycon fragment was recently reported by the Nicolaou group. Here, the construction of the CD ring system is described. The D ring is a sugar derivative of L-rhamnose, whilst the C ring is a fully substituted phenol derivative of 3,4,5-trimethoxytoluene. This phenol was coupled to the fluoride of a rhamnose derivative under the Mukaiyama conditions employing AgClO$\sb4$ and SnCl$\sb2$. This coupling furnished the skeleton of the CD ring system. The phenol derivative mentioned above was crystallographically studied because of the existence of two pure enantiomers in the crystal state even though there is no quaternary carbon. This phenomenon is known as spontaneous resolution.
