Hepatobiliary and Pancreatic Surgery
Colorectal Liver Metastases
The main focus of our research work is on the treatment of colorectal liver metastases. A highly reproducible animal model of liver metastases, using intrasplenic injection of DMH induced colon cancer cells in male CBA mice, has been developed in our department. The following techniques are available for assessing the impact of various treatment modalities.
- Histopathology with light microscopy
- Tumour volume assessment by digital stereology.
- Laser doppler flowmetry for in-vivo measurement of tumour and liver blood flow
- Corrosion casting with Mercox / Methacrylate polymer for Scanning Electron Microscopy of tumour and liver microvasculature.
- Technique for using Optiscan laser in-vivo microscopy for the assessment of tumour vasculature is currently being evaluated.
- Technique for in-vivo stereological assessment of tumour growth using MRI scanning is also currently being evaluated.
Research projects
Role of adhesion Molecules and Angiogenesis in the Pathogenesis of Colorectal Liver Metastases
Anti-Vascular Drug Therapy in Colorectal Liver Metastases
Combretastatin A4 Prodrug (CA4P) Study of effect on the growth and microvasculature of colorectal liver metastases in a murine model.
Combretastatin A4 Prodrug (CA4P) is an agent, which has been found to preferentially damage blood vessels of tumours. It is a tubulin binding inhibitor, which has shown promising effects in animal models. Our studies of CA4P on tumour microvasculature have provided direct evidence of a significant decrease in the density of patent vessels, as well as thinning and tapering of tumour microvessels. We have also shown that a single dose of CA4P produces a decrease in tumour blood flow, and an increases tumour cell necrosis in a time dependent manner. A continuous low dose infusion of CA4P produced a significant decrease in tumour growth. We have found CA4P to be an effective anti-vascular agent. Further study to identify the most effective dosage, and schedule, to define the most appropriate regimen for clinical use are essential for this potential anti-cancer agent.
Figure 1.
Scanning Electron micrographs of corrosion casts of colorectal liver metastases after single dose of CA4P. Note the marked reduction in density of patent tumor blood vessels at the tumor-host interface, resulting in a halo zone.
Figure 2.
Haematoxylin and Eosin stained histological section (3m m) of a colorectal liver metastases treated with CA4P. Note widespread central necrosis and viable cells at the periphery of the tumor.
Anti-Angiogenic Drug Therapy in Colorectal Liver Metastases
Thalidomide: Study of effect on the growth and microvasculature of colorectal liver metastases in a murine model.
.Interstitial Laser Hyperthermia (ILH) in Colorectal Liver Metastases
Interstitial laser hyperthermia is an in-situ ablative technique used in the treatment of unresectable, but localised colorectal liver metastases. It has the potential for development as an alternative to liver resection. Its present limitations include the size of tissue necrosis achieved by a single fibre.
Characterisation of the effect of ILH in liver and tumour tissue
- Histopathological study of the nature and pattern of thermal injury
- Dose response relationship of power and energy on the size of tissue necrosis
Identifying methods of increasing the size of tissue necrosis
- Blood flow modulation by mechanical occlusion
- Blood flow modulation by CA4P
- Thermal sensitisation with Metronidazole
- Assess the efficacy of cylindrical diffusing tip fibre
Establish the oncologic safety of the ILH
- Effect of ILH on establishment of metastases
- Effect of ILH on the growth of established metastases
Define the host immune response to thermal ablation of tumour tissue
Figure 3. Effect of laser on the mouse liver metastases.
Research Groups
- Mr Chris Christophi
- Mr Vijayaragavan Muralidharan
- Dr Darshini Kuruppu
- Prof. Paul E O¹Brien
- Mrs Cathy Malcontenti-Wilson
Related Research
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