Alternative Insufflation Gases For Laparoscopic Surgery
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
It is now recognised that laparoscopic (keyhole) surgery for cancer can be associated with the spread of tumour to surgical wounds, i.e. port sites. However, whether this is more likely following laparoscopy than conventional open surgery is controversial. Isolated case reports and the recent results of experimental studies suggest that the problem is important. Previous studies suggest that carbon dioxide gas used to inflate the abdomen during laparoscopy may be the specific cause of this probl ....It is now recognised that laparoscopic (keyhole) surgery for cancer can be associated with the spread of tumour to surgical wounds, i.e. port sites. However, whether this is more likely following laparoscopy than conventional open surgery is controversial. Isolated case reports and the recent results of experimental studies suggest that the problem is important. Previous studies suggest that carbon dioxide gas used to inflate the abdomen during laparoscopy may be the specific cause of this problem. A four to fivefold increase in the rate of cancer spread has been shown in previous experiments, and this can be reduced by using an inert gas such as helium. We propose to further investigate this issue using a combination of small and large animal models, and will also commence clinical trials of helium during clinical surgery. These studies aim will determine the gas of choice during laparoscopic surgery. They will also clarify advantages demonstrated for the use of helium in previous animal studies, and better investigate the safety of helium use. If our preliminary findings are supported by these studies, helium (or other inert gases) should be considered for routine use during clinical laparoscopy.Read moreRead less
Reevaluation Of The Anatomy Of The Human Lymphatic Vessel Network
Funder
National Health and Medical Research Council
Funding Amount
$539,750.00
Summary
The mode of spread of cancer cells from a primary tumour to other parts of the body is still not completely understood, although the lymphatic system is known to be important in this process. Lymph vessels are tiny transparent channels that form a network over the entire body. They transport tissue fluid to regional lymph glands in the neck, armpits, groin, chest and abdomen where the immune response maybe initiated to combat foreign agents such as bacteria and cancer cells. Current knowledge of ....The mode of spread of cancer cells from a primary tumour to other parts of the body is still not completely understood, although the lymphatic system is known to be important in this process. Lymph vessels are tiny transparent channels that form a network over the entire body. They transport tissue fluid to regional lymph glands in the neck, armpits, groin, chest and abdomen where the immune response maybe initiated to combat foreign agents such as bacteria and cancer cells. Current knowledge of the anatomy of these tiny vessels is based on work done by Sappey more than a century ago. There is an urgent need to update this work as many of his conclusions have been found to be inaccurate. We will use our pioneering methods of microsurgical tissue transfer- now being used worldwide - and our extensive experience in delineating fine channels, to address some of the basic questions about the anatomical pathways of spread of cancer. We hope to discover for example: why cancer on one side of the back can spread to glands in the opposite groin or armpit, thought by Sappey to be impossible; why cancer on one side of the tongue can spread to lymph glands on the opposite side of the neck; and why there is sometimes swelling of the limbs following lymph gland ablation by surgery or radiotherapy of glands in the groin or armpit. Currently it is thought that the only major connections with the venous system are at the base of the neck. Our initial work has shown unexpected connections with blood vessels in the periphery and unreported lymphatic vessel pathways between the skin and deep tissues. The results of this research will give information that will aid in localizing and treating the spread of malignancies and will underlie future treatment of obstructed lymph vessels that are the cause of painful, disabling swelling (lymphoedema) of the limbs.Read moreRead less
Childhood Lymphatic Malformations: The Mechanism Of Rapamycin In Controlling Growth
Funder
National Health and Medical Research Council
Funding Amount
$456,579.00
Summary
Lymphatic malformations (also known as cystic hygromas or lymphangiomas) cause deformity and pain which can last lifelong. Current treatments help but do not fix all the symptoms. Rapamycin, a drug used for many years in children and adults with kidney transplants, may be useful for treating children with lymphatic malformations. We aim to understand how the drug works on the cells of lymphatic malformations in culture and in an animal model, to develop new and more effective treatments.
Until recently, cancer of the oesophagus was a very uncommon tumour in Australia and other western populations. However during the past three decades, there have been very large increases in the incidence of this disease. Indeed, rates of oesophageal cancer have risen faster than any other cancer in the United Statesand similar dramatic increases in incidence have been observed in Europe and Australia. With increasing population prevalence of the causes of cancer of the oesophagus in western soc ....Until recently, cancer of the oesophagus was a very uncommon tumour in Australia and other western populations. However during the past three decades, there have been very large increases in the incidence of this disease. Indeed, rates of oesophageal cancer have risen faster than any other cancer in the United Statesand similar dramatic increases in incidence have been observed in Europe and Australia. With increasing population prevalence of the causes of cancer of the oesophagus in western societies (namely acid reflux, obesity and poor diet), there are strong grounds for predicting that incidence will continue to rise, and that oesophageal cancer will constitute an increasingly large burden on society. Unfortunately, treatment options are limited, survival is often short, and there is no way of identifying which tumours will respond to therapy. This proposal will collect treatment and health outcomes data for a population-based cohort of patients with oesophageal cancer. The goal is to identify prognostic and predictive markers to aid patients and clinicians when making treatment decisions, as now exist for breast cancer. Such markers may also serve as novel targets for therapy. The proposed study builds upon the platform of the Australian Cancer Study [ACS], one of the world's largest studies of oesophageal cancer. This represents a unique opportunity to investigate a pressing clinical problem by building upon a study of acknowledged international importance.Read moreRead less
A Novel Tumour-targeting Nanoliposome Drug Delivery System For The Treatment Of Malignant Gliomas
Funder
National Health and Medical Research Council
Funding Amount
$445,097.00
Summary
Most patients with malignant brain tumours die within a year after diagnosis due to the difficulty in effectively delivering drugs to the tumour cells. We aim to develop a safe and novel drug delivery system to effectively deliver anticancer drugs and novel anticancer agents to brain tumour cells that remain in normal brain after surgery. The success of this project will bring us a step forward in our efforts to significantly improve the survival rate and quality of life of such patients.
Selective Therapies Targeting Tumour Vasculature Of Colorectal Liver Metastases
Funder
National Health and Medical Research Council
Funding Amount
$519,279.00
Summary
Cancer of the bowel is the second highest cause of cancer related deaths in Australia. Over 70% of these deaths are due to bowel cancer spread to the liver or liver metastases. Treatment options for the majority of patients with liver spread are limited. Although chemotherapies are a standard treatment option, they cause significant side-effects as they are small in size and thereby distributed to both cancer and normal tissue. Given the limitations of chemotherapy, our objective is to investiga ....Cancer of the bowel is the second highest cause of cancer related deaths in Australia. Over 70% of these deaths are due to bowel cancer spread to the liver or liver metastases. Treatment options for the majority of patients with liver spread are limited. Although chemotherapies are a standard treatment option, they cause significant side-effects as they are small in size and thereby distributed to both cancer and normal tissue. Given the limitations of chemotherapy, our objective is to investigate two new strategies which selectively destruct tumours with minimal effect to normal tissues. Cancer growth is dependent on an efficient blood supply. One strategy uses drug delivery systems (DDS) to selectively target cancers by exploiting the unique properties of tumour blood vessels. The second strategy uses vascular targeting agents (VTA's) which act on tumour vessels to reduce blood flow and starve the tumour of oxygen, leading to its destruction. We will be testing two agents: SMA-Pirarubicin, a DDS and an innovative VTA, Oxi4503, in an animal model of colorectal cancer liver metastases. Although these drugs are successful in destroying the majority of tumour cells, they have a patchy effect and do not completely destroy the cancerous growth. The varied effects of these agents may be due to variations in tissue hypoxia, tumour vessel structure or factors which trigger blood vessel formation and breakdown. These features will be investigated using techniques established within our laboratory. We will also investigate the combined effect of other novel agents and hyperbaric oxygen administration to improve the effectiveness of these drugs. A successful outcome will result in the development of an improved treatment method which targets tumours, producing maximum destruction with minimum side-effects. This has the potential to replace standard chemotherapies as the preferred treatment for patients with bowel cancer spread, with overall significant patient benefits.Read moreRead less