**1. Introduction**

144 Liver Tumors

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recurrent hepatocellular carcinoma: a local experience and a systematic review.

Colorectal cancer (CRC) is the third most frequent in men in developed countries (after lung and prostate tumours) and second among women (after breast cancer), with approximately one million new cases per year throughout the world (550,000 men and 470,000 women), representing 14.6% and 15.2% respectively of all malignant tumours diagnosed. The role of colonoscopy in the screening of this pathology is crucial. CRC affecting the intestine has a high rate of cure (45-50%) with radical surgery. The most frequent metastatic involvement in CRC, after lymph nodes invasion, is seen in the liver.

Several studies have analyzed the pre-operative prognostic factors in patients undergoing liver resection for liver metastases of CRC in order to select patients for surgical treatment. However, intraoperative and post-operative factors have been poorly studied and that could report on the aggressiveness of the tumour and the curative efficacy of the surgery performed. The purpose of surgery is resection of all liver lesions with a tumour-free margin, provided R0 resection (complete resection with no microscopic residual tumour) may be achieved with low morbidity and mortality (Choti et al. 2002; Marin et al. 2009; Lordan & Karanjia 2007) without endangering the life of the patient due to either liver insufficiency or post-operative complications. According to most authors, it should be noted that surgery, however extensive it is, does not prolong survival if residual microscopic or gross tumour is left (Harmantas et al. 1996; Kronawitter et al. 1999).

Since Woodington and Waugh reported the first favourable results of surgical treatment for CRC liver metastases (Woodington & Waugh, 1964), a disease previously considered incurable, to date, a 5- and 10-year survival rates of 35-58% and 20-25% respectively have been achieved, while survival without treatment is less than 2% (Ohlsson et al. 1998; Fong et al. 1999).

The key for indicating the most adequate treatment is the study conducted by a multidisciplinary team (Söreide et al. 2008; Artigas et al. 2007). The difficulty for assessing the indication stems from the fact that the presence of extrahepatic tumour, the possibility of achieving a tumour-free margin and the actual number of liver metastases are frequently known during the laparotomy. Different studies have analyzed the traditional pre-operative factors predicting survival in order to select patients in whom unnecessary surgery could be 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 conclusive (Ricci-Vitiani et al. 2007; Hill 2006).

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

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