**7. Surgical treatment of the liver metastasis of colorectal cancer**

The prognosis of metastatic colorectal cancer is serious. The 5-year survival of patients receiving chemotherapy is low. In contrast, hepatic metastasectomy is an accepted procedure with low perioperative mortality (2.3–2.8%) ensuring 5-year survival 28–58% and 10-year survival 22-36% [15, 18, 78, 79]. The median survival of surgically treated patients is 42.5 months [4].

The CRC metastases can be treated surgically if all metastases can be completely resected, at least 2 adjacent liver segments can be spared and sufficient liver function is expected [1].

The liver is composed of segments defined by vascular branching. As described by the International Hepato-Pancreato-Biliary Association, the liver segments are unified in four sections: left lateral and medial, right lateral and medial. Thus, segmentectomy, singular sectionectomy, hemihepatectomy involving two sections and trisectionectomy can be per‐ formed [4]. Nonanatomic liver resection shows no differences from anatomic resection regarding morbidity, mortality, recurrence rate or survival. In addition, it has the benefit of parenchymal sparing providing more opportunities for repeated resections that are usually limited by insufficient remnant liver. Nonanatomic resections can be carried out during shorter operation time and are associated with less blood loss [80].

Extrahepatic vascular anatomy must be carefully considered before the operation as only 55% of persons have typical arterial anatomy. Aberrant right hepatic arteries can arise from superior mesenteric artery and from left gastric artery. The trifurcation of portal vein can be observed. Computed tomography is the method of choice for vascular imaging [4].

Liver resection necessitates parenchymal dissection and haemostasis. The liver parenchyma can be divided by finger-fracture or crush-clamp technique, by scissors using scratch or sharp dissection technique, or by ultrasound or radiofrequency knives. Small vessels must be occluded by bipolar coagulation, titan clipping or ligation. Bipolar or ultrasound coagulation devices can be used for dissection and closure of small vessels. Larger vessels must be ligated. Liver resection with staplers involves tissue dissection and automatic vessel clamping [4].

To limit the bleeding, total inflow occlusion can be used but can result in ischemia/reperfusion injury if prolonged. Intermittent occlusion (15 min, alternating with 5 min of perfusion) better preserves liver function. Bleeding from hepatic veins can be decreased by low central venous pressure (less than 4 mm Hg) or total vascular occlusion of the liver with or without in-situ cooling of the liver [4].

lular carcinoma, and especially fibrolamellar variant, can arise in the absence of cirrhosis. In contrast, colorectal cancer metastasis can be surrounded by liver tissue that is damaged by

The tissue analysis of cardinal tumour features and cancer microenvironment, production of cytokinesand growth factors in the metastasis, evaluation of circulating neoplastic cells, analysis of tumour hypoxia and angiogenesis atprotein, gene and miRNA levels can also bring prognostic and predictive information [72–77]. Besides the tumour characteristics, hepatic lymphatic anatomy and its involvement by tumour can be evaluated to predict the recurrence

The prognosis of metastatic colorectal cancer is serious. The 5-year survival of patients receiving chemotherapy is low. In contrast, hepatic metastasectomy is an accepted procedure with low perioperative mortality (2.3–2.8%) ensuring 5-year survival 28–58% and 10-year survival 22-36% [15, 18, 78, 79]. The median survival of surgically treated patients is 42.5

The CRC metastases can be treated surgically if all metastases can be completely resected, at least 2 adjacent liver segments can be spared and sufficient liver function is expected [1].

The liver is composed of segments defined by vascular branching. As described by the International Hepato-Pancreato-Biliary Association, the liver segments are unified in four sections: left lateral and medial, right lateral and medial. Thus, segmentectomy, singular sectionectomy, hemihepatectomy involving two sections and trisectionectomy can be per‐ formed [4]. Nonanatomic liver resection shows no differences from anatomic resection regarding morbidity, mortality, recurrence rate or survival. In addition, it has the benefit of parenchymal sparing providing more opportunities for repeated resections that are usually limited by insufficient remnant liver. Nonanatomic resections can be carried out during shorter

Extrahepatic vascular anatomy must be carefully considered before the operation as only 55% of persons have typical arterial anatomy. Aberrant right hepatic arteries can arise from superior mesenteric artery and from left gastric artery. The trifurcation of portal vein can be observed.

Liver resection necessitates parenchymal dissection and haemostasis. The liver parenchyma can be divided by finger-fracture or crush-clamp technique, by scissors using scratch or sharp dissection technique, or by ultrasound or radiofrequency knives. Small vessels must be occluded by bipolar coagulation, titan clipping or ligation. Bipolar or ultrasound coagulation devices can be used for dissection and closure of small vessels. Larger vessels must be ligated. Liver resection with staplers involves tissue dissection and automatic vessel clamping [4]. To limit the bleeding, total inflow occlusion can be used but can result in ischemia/reperfusion injury if prolonged. Intermittent occlusion (15 min, alternating with 5 min of perfusion) better

peritumoural or treatment-related cell damage, fibrosis and inflammation [71].

**7. Surgical treatment of the liver metastasis of colorectal cancer**

operation time and are associated with less blood loss [80].

Computed tomography is the method of choice for vascular imaging [4].

[15].

182 Recent Advances in Liver Diseases and Surgery

months [4].

Laparoscopic approach sincreasinglyapplied for liver resections, including even hemihepatec‐ tomy [4, 81]. The best indications for laparoscopic resection are single metastases, not exceed‐ ing 5 cm in diameter, in readily accessible segments 2–6. In contrast, segments 1, 7 and 8 are considered difficult to access except for skilled professionals. Single incision laparoscopic surgery has been used for liver resection but faces technical difficulties in spatial manoeuvres withthe instruments.Ashumanergonomics is limited,robotic surgeryhas beendevelopedand applied for liver resections facilitating the manipulations with the instruments and improv‐ ing the overview of operating field at the expense of remote contact with tissues and patient. The lack of tactile feedback compromises the estimation of interaction strength and pressure applied on the tissues. The conversion to open operation necessitates reorganisation of the operation team [82]. Despite these shortcomings, in a recent review, robotic liver resection was found to be a safe procedure [83]. Robotic malfunction is rare (2.4–4.5%). Major hepatecto‐ mies have been performed by robotic surgery [82]. However, the greatest advance of robotic surgery can be the possibility to remove small, but hardly accessible lesions by small sectoral, segmental or subsegmental resections instead of extensive routine liver resection [82, 84].

The surgical treatment can be precluded by involvement of portal vein, hepatic artery or common bile duct. The goal of surgery is to resect all malignant tissue. If this would lead to insufficient remnant liver, as in case of multiple bilobar metastases or deep metastases close to hilum or major vessels, the surgery also is contraindicated [18]. To increase the size of liver remnant, two-stage hepatectomy [85] or portal vein embolisation or ligation can be applied. Both procedures take advantage of the regenerative capacity of the liver [4]. Portal vein embolisation increases the resectability rate [86]. The portal vein occlusion can be performed as intraoperative ligation of portal vein branches, transileocolic embolisation or percutaneous transhepatic ipsilateral or contralateral embolisation. The spectrum of applied embolisation materials includes polyvinyl alcohol particles, coils, gelatine sponge, fibrin glue, lipoiodol or butyl cyanoacrylate. In a recent review, authors showed that preoperative portal vein embo‐ lisation has a high technical and clinical success rate. Liver cirrhosis impaired the regeneration. However, cirrhosis is rarely encountered in association with metastatic cancers. Cholestasis and preceding chemotherapy had no negative impact [87]. The resectability can also be improved by chemotherapy-induced downstaging [86, 88, 89]. By chemotherapy, resectability can be achieved in up to 40% of patients [90]. If the downstaging is successful and followed by the resection, the 5-year survival reaches 33% that is comparable with the results in patients with initially resectable metastases [86]. Preoperative chemotherapy is not indicated for resectable lesions [89] and should not be excessively extended (9 cycles or more) to avoid marked hepatotoxicity without improving the pathologic response [91]. Among the chemo‐ therapy-related liver damage, steatosis can be induced by 5-fluorouracil, nonalcoholic steatohepatitis by irinotecan and sinusoidal obstruction syndrome by oxaliplatin [92]. For successful downstaging, the type of chemotherapy is more important than the number of cycles. Thus, the inclusion of bevacizumab in the chemotherapy schedule in addition to FOLFOX improves the outcome in terms of achieving resectability [91].

The planning of liver surgery can be challenging in patients presenting with colorectal cancer and synchronous liver metastases. Simultaneous resection of primary tumours and liver metastases can be performed in selected patients. Liver resection can safely be performed as the first operation followed by the large bowel operation [93]. The safety of liver-first approach has been confirmed in a recent review [94].

The risk factors of cancer recurrence include the presence of lymph node or extrahepatic metastases, high CEA (above 200 ng/mL), multiple and large (above 5 cm) metastases, short disease-free survival [18], high tumour grade and positive resection lines [4]. Regarding the resection line, the minimal requirements are under discussion regarding R0 resection with distance between tumour and resection line less than 1 cm. In the recent literature, lack of 1 cm margin is not considered a contraindication for liver resection [80], and generally the requirement for tumour-free tissue border has decreased from 10 to 2 mm or even 0 mm [95– 98]. The presence of hilar lymph node metastases is an adverse prognostic factor in comparison to metastases affecting only liver but can be less hazardous in prognostic terms than metastases in lymph nodes adjacent to truncus coeliacus or aorta [4].

After resection, MRI or CT should be used for surveillance. The examinations must be repeated every 3–6 months for 2 years after resection and every 6 months for 3–5 years after the surgery [1]. Perioperative chemotherapy, including adjuvant treatment, increases recurrence-free survival [99].
