An investigation of the detection and treatment of colorectal liver metastases

In the United Kingdom, colorectal cancer creates a significant health burden, with over 34 000 new cases diagnosed each year and over 16 000 deaths per year. Almost 50% of patients with colorectal cancer will develop liver metastases: up to 25% will have liver metastases at time of initial presentation with the remaining 25% developing liver metastases during the course of their disease. Death from hepatic metastases accounts for a large percentage of colorectal cancer mortalities and if left untreated the prognosis is poor, with median survival from 5 to 21 months with almost none alive at 5 years. Surgical resection offers the only potential curative treatment for colorectal liver metastases with the five year survival rate varying in the literature from 25% to 51%. Hepatic surgery was associated with high morbidity and mortality and it is only since the 1990s that an evidence base has been published showing improved long term outcomes. Radiological imaging plays an essential role in the detection and characterisation of colorectal liver metastases. Accurate staging of the disease allows patient selection for hepatic surgery. Despite recent and significant technological advances in radiological imaging, up to 50% of patients that have undergone curative partial hepatectomy will develop hepatic recurrence in the first two years after surgery. Evidence from growth rate studies has shown that colorectal liver metastases are slow growing and that these recurrences were present at the time of initial staging. Therefore, the problem of occult liver metastases remains. This thesis has assessed the potential clinical role of a new imaging modality in the detection of colorectal liver metastases: contrast enhanced ultrasound (CE-US). Initially a prospective trial using percutaneous CE-US with intravenous administration of an ultrasound contrast agent that has been used primarily in cardiac imaging was performed. The results of this study found that CE-US enhanced late phase vascular imaging. This is an important finding as the persistence of a hypoechoic liver lesion in to the late phase of CE-US imaging is typical of a colorectal liver metastasis and an agent that optimises the late phase would allow improved characterisation of colorectal liver metastases. As a result, CE-US was then compared to percutaneous unenhanced ultrasound and found to have improved sensitivity and accuracy in the detection of colorectal liver metastases (sensitivity 100%, accuracy 90.8% versus 64.4% and 64.4% respectively). Furthermore, the optimal late phase imaging was achieved by the lowest dose of agent (0.4mL) that would allow repeated injections if incorporated into routine clinical practice. These findings support the growing evidence base for percutaneous CE-US and it is likely that CE-US will replace unenhanced ultrasound in routine clinical practice. (Abstract shortened by ProQuest.)