**2. Current diagnostic tools**

Imaging of the liver of CRC patients requires high sensitivity and reliable characterization of the lesions, allowing differentiation of malignant from benign tumours. Accurate and timely detection of hepatic metastases has long-range therapeutic and prognostic implications, since untreated liver metastases have a poor prognosis (5-year survival rate of 0–3%) while the resection with curative intent offers a much better one (5-year survival rate from 35% to 58%) (El Khodary et al. 2011). An understanding of the segmental anatomy of the liver is imperative for localization and appropriate management of hepatic neoplasms. The classification proposed by Couinaud (Couinaud 1957 ) and later modified by Bismuth (Bismuth 1982) provides the surgically relevant information and is easily applicable to crosssectional imaging techniques, such as computed tomography (CT), magnetic resonance imaging (MRI) and ultrasonography (US).

avoided. These were factors related to the patient, the primary tumour and the liver metastases (Fong et al. 1999; Nordlinger et al. 1996). However, some authors do not contraindicate surgery in patients with poor prognostic criteria provided a R0 resection may be obtained, as a number of prognostic factors are known only after resection (Marín et al. 2009). These factors include the histological study (number, resection margin size, microsatellites, type of growth, presence of tumour pseudocapsule, tumour differentiation grade, histological type, nuclear grade and number of mitoses/mm2) and the immunohistochemical study of the resected specimen. The latter may combine the markers of cell proliferation and cell cycle control, p53 and Ki67. There is increasing evidence supporting the concept that in human cancer, a minority of cells (tumour stem cells) has acquired characteristics of uncontrolled growth and the ability to form metastases (Reya et al. 2001; Dalerba et al. 2007; Jordan et al. 2006). This hypothesis is supported by different experimental observations made initially in acute myeloid leukaemia (Bonnet D & Dick J 1997) and subsequently in human solid tumours, such as breast (Al-Hajj 2003), brain (Singh et al. 2004; Galli et al. 2004), colorectal (O' Brien et al. 2004; Ricci-Vitiani et al. 2007), head and neck (Prince et al. 2007) and pancreatic cancer (Li et al. 2007). However, this concept continues to be highly controversial and data reported on colorectal cancer are not yet

It is therefore interesting to know both the qualitative and quantitative stem cell population in the tumour using markers, such as CD44, CD133, and CD166. The tissue microarray (TMA) technique allows for monitoring and simultaneous evaluation of a great number of samples or tumour series in a single experiment, ensuring homogeneity of the techniques between specimens and validation of the results obtained with various histological, immunohistochemical and in-situ hybridization (FISH) techniques (Battifora 1986; Kononen

In addition, over the last decade, a revolution in the approach to CRC liver metastases has occurred. Firstly, there was the advent of new chemotherapy drugs that have allowed better control of the disease, higher response rates and longer survival rates. Secondly, this has opened up a greater possibility of surgical rescue in more patients. Aggressive surgical management is called extreme liver surgery: ante-situ, in-situ and ex-situ liver resections are

Imaging of the liver of CRC patients requires high sensitivity and reliable characterization of the lesions, allowing differentiation of malignant from benign tumours. Accurate and timely detection of hepatic metastases has long-range therapeutic and prognostic implications, since untreated liver metastases have a poor prognosis (5-year survival rate of 0–3%) while the resection with curative intent offers a much better one (5-year survival rate from 35% to 58%) (El Khodary et al. 2011). An understanding of the segmental anatomy of the liver is imperative for localization and appropriate management of hepatic neoplasms. The classification proposed by Couinaud (Couinaud 1957 ) and later modified by Bismuth (Bismuth 1982) provides the surgically relevant information and is easily applicable to crosssectional imaging techniques, such as computed tomography (CT), magnetic resonance

included (Mehrabi et al. 2011; Hoti et al. 2011; Oldhafer et al. 2001).

conclusive (Ricci-Vitiani et al. 2007; Hill 2006).

et al 1998; Milanes-Yearsley et al 2002).

**2. Current diagnostic tools** 

imaging (MRI) and ultrasonography (US).

The imaging assessment of potentially resectable CRC liver metastases, needed for a careful pre-operative selection of patients, should address the following five critical issues:


Imaging techniques used nowadays for diagnosis of these lesions include US, multi-detector CT (MDCT), MRI and fluorine-18-fluorodeoxyglucose positron emission tomography (FDG PET). FDG PET and CT can be combined in order to provide fused images, allowing high spatial resolution and functional information in the same examination (FDG PET/CT). In studies with specificity higher than 85%, the sensitivity for detection of liver metastases is progressively increasing from US to CT, MRI and FDG PET (Kinkel et al. 2002). The extensive literature regarding the benefits and constraints of each of these modalities for detecting liver metastases shows several limitations: inadequate definition of inclusion and exclusion criteria, incomplete reporting of methods, lack of uniform references, etc. The best standard of reference is laparotomy with bimanual palpation and intraoperative ultrasonography (IOUS), but this was used in only a few studies (Valls et al 2001). When a suboptimal standard is used, underreporting of lesions and overestimation of detection rate are the results (van Erkel et al 2002). Another confounding factor is the different methods for reporting sensitivity: per patient (detection of at least one lesion per patient) and per lesion (detection of all lesions per patient). Therefore, it is important to inquire into the results of the current studies, also because improving technology can make results of prior studies superfluous (Lucey et al. 2006).
