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Full NameProfessor Donal Buggy
Department:Anaesthesiology Perioperative Medicine
Organisation:University College Dublin
Other Research Fields:
patient outcomes after major surgery
Postgrad Medical Specialties
- Clinical Trials
Can anaesthesia or analgesic technique during cancer surgery influence the risk of recurrence or metastasis? Our unit is a global leader in clinical and translational research around this question. In addition, we contribute to international clinical trials evaluating reduction in other adverse outcomes after complex surgery.
Addressing the hypothesis that anaesthetic-analgesic technique during cancer surgery might influence long term recurrence or metastasis has become a research priority. Experimental data from cell culture models suggests that amide local anaesthetic agents (prototype lidocaine) have multiple cellular effects which inhibit metastasis. Propofol and high dose steroids have also been hypothesized, based on cell culture and clinical observational studies, to reduce metastatic risk in cancer. Lidocaine may have chemotherapy-enhancing effects in existing laboratory models. However, there is little quality pre-clinical data, which is an essential bridge to obtaining large grants necessary to fund a prospective, randomised controlled clinical trial (RCT) to prove a causal link between anaesthetic technique and oncologic outcomes.
We will test the hypotheses that perioperative lidocaine, propofol and steroids reduce metastasis compared with sevoflurane inhalation anaesthesia. Also, whether these routinely used anaesthetic and perioperative drugs enhance or inhibit the action of cisplatin, a chemotherapeutic agent.
We propose this programme of essential pre-clinical studies, using the 4T1 syngeneic, murine breast cancer model, which is an authentic model of human breast cancer metastasis, after breast tumour resection surgery of curative intent. This model is established and working in our laboratory, with a publication track record. Murine breast cancer cells will be inoculated into the mammary area of immunocompetent mice. Seven days later, or when tumour diameter >5mm, it will be excised after randomization to one of ten different general anaesthesiology and perioperative intervention techniques listed. Mice will be monitored postoperatively and sacrificed Day 14 after surgery. The primary outcome measure will be the number of discrete lung metastasis colonies. This data will support our application for an RCT, with international collaborators. If the results support our hypothesis, individual patient benefit and societal cost savings will be significant from reduced cancer recurrence.