Hepatic Metastases Features

The presence of symptoms caused by secondary metastases and alteration of hepatic function represent variables correlated with a worse prognosis after an R0 hepatic resection.

Carcinoembryonic antigen (CEA) pre-operative level may be considered as an aggressive behaviour of the tumour with a higher risk of recurrence, both in the primitive rectal tumour and in the secondary hepatic metastases. Nordlinger reports a 5-year survival of 30% in patients with a CEA pre-operative value lower than 5 ng/ml and 18% in patients having a value higher than 30 ng/dl [28].

It is still under discussion whether there is a significant difference in terms of survival between the synchronous and metachronous metastases. Some Authors report a higher survival rate among patients with metachronous metastases, but only if it appears later than 12 months after resection of primary tumour. Hughes et al. [4] report a 5-year survival rate of 42% in patients with a disease-free period longer than one year, and 24% for patients with diagnosis of liver metastases within 12 months after primary rectal surgery. More recently, other Authors showed no differences in terms of survival between patients submitted to radical liver resection with synchronous or metachronous metastases [5].

Size and number represent considerable prognosis factors. The number of metastases significantly influences survival and the best results in terms of survival have been observed in patients with less than 4 metastases. The number of metastases influence the likelihood of removing all lesions, more so if lesions are localised in both lobes. A higher rate of radical resections should explain the better results in patients with less than 4 nodules reported in the literature [29]. Fong et al. [18] report a 5-year survival of 47% in patients with single hepatic metastasis, 31% in patients with 2 or 3 metastases and 24% in patients with more than 4 metastases. Nowadays more than 4 metastases does not represent a contraindication to hepatic resection, as long as a radical resection can be performed.

Satellite nodules are found in 14-24% of patients and must be distinct from multifocal hepatic metastases [31]. Satellite nodules develop through local diffusion via the portal vein system and indicate an aggressive behaviour of the tumour, characterised by an early vascular invasion. Satellite nodules are defined as the presence of two or more nodules located less than 2 cm from the main lesion and with a diameter lower than 50% of the primitive hepatic metastasis.

Satellite nodules increase the risk of developing metachronous lung metastases that in these patients are twofold higher than in patients without satellite nodules. Five-year survival is 11-17% for patients with satellite nodules and 30-47% for patients without satellite nodules [15].

The extension of the hepatic involvement represents an important prognostic element, even if the techniques used to measure the hepatic parenchyma have not been standardised. Five-year survival is 22% for patients with hepatic replacement less than 25% of the whole liver, compared with 9% of survival for patients with a hepatic replacement of 25-50% of the liver.

Lymph node involvement of the hepatic hilum represents one of the most important elements affecting the prognosis after radical resection. Nowadays it is clear that involvement of hilar lymph nodes, through the lymphatic drainage coming from the liver, is a sign of tumour progression in patients with liver metastases. Lymph node involvement of the hepatic hilum, of the hepatoduodenal ligament and of the coeliac tripod represents an element for an unfavourable prognosis. Laurent and Rullier [30] report lymph node involvement in 15% of cases, associated with 0% 5-year survival, after radical resection and hilar lymphadenectomy. The 3- and 5-year survivals were 0% and 3% for patients with N+ lymph nodes at the hepatoduodenal ligament, in comparison with 48 and 22% in patients with N-[31]. Nakamura et al. [32] proposed an extended lymphadenectomy of the hepatic pedicle in selected patients. This Author performed this procedure without an increase in morbidity. Lymph node involvement was observed in 14% of patients and 5-year survival with N+ reaching 40%, even if they underwent reiterated resections due to hepatic recurrence. These data support the theory that an aggressive surgical attitude, in carefully selected patients, may lead to good results in terms of survival, even though it is not yet a standardised procedure.

Extra-hepatic metastases represent the most negative prognostic element and contraindicate hepatic resection. It is important to distinguish distant metastasis from metastases of structures adjacent to the liver, such as diaphragm, retrohepatic vena cava, vascular structures of the hepatic hilum, extra-hepatic biliary tract, omentum, right colonic flexure, stomach and transverse colon. In these situations radical resection of hepatic metastases and of the infiltrated organs may, in rare and selected cases, have good results, with a 5-year survival of 33%.

Isolated lung metastases are discovered in only 2% of patients, whereas associations between liver and lung metastases are observed in 25% of patients. In carefully selected cases, resection of both lung and liver metastases has acceptable results: Headrick and Miller [3] report combined resection of hepatic and lung metastases with a morbidity of 12% and a 5-year survival of 30%. The presence of metastatic lung lymph nodes and high levels of CEA are associated with a reduction of the survival. In 2003, Elias and Ouellet [33] reports a 5-year survival of 33% for patients who underwent hepatic resection, hepatic hilum lymphadenectomy and a resection of 1 or 2 lung metastases.

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