Resection for Colorectal Liver Metastases

Colorectal cancer is the third most frequent cancer in the Western world. About half of the patients develop synchronous or metachronous metastases. The liver is the most common site of such metastases and thus hepatic metastatic disease is a significant socio-medical problem. If it is not treated, the median patient survival is only some months. Surgical resection is the treatment of choice for patients with isolated colorectal liver metastases when feasible. For patients with four or fewer isolated hepatic lesions, five year relapse-free survival rates range from 24 to 58 percent and ten year survival rates vary between 17 and 33 percent. There is a convincing socio-epidemiological evidence of the dramatic unfavourable influence on population wealth of untimely diagnosis and inadequate treatment of the patients with advanced and metastatic colorectal cancer worldwide (Hata et al., 2010; Kostov & Kobakov, 2006a; Stillwell et al., 2011; Tsoulfas et al., 2011).


Introduction
Colorectal cancer is the third most frequent cancer in the Western world. About half of the patients develop synchronous or metachronous metastases. The liver is the most common site of such metastases and thus hepatic metastatic disease is a significant socio-medical problem. If it is not treated, the median patient survival is only some months. Surgical resection is the treatment of choice for patients with isolated colorectal liver metastases when feasible. For patients with four or fewer isolated hepatic lesions, five year relapse-free survival rates range from 24 to 58 percent and ten year survival rates vary between 17 and 33 percent. There is a convincing socio-epidemiological evidence of the dramatic unfavourable influence on population wealth of untimely diagnosis and inadequate treatment of the patients with advanced and metastatic colorectal cancer worldwide (Hata et al., 2010;Kostov & Kobakov, 2006a;Stillwell et al., 2011;Tsoulfas et al., 2011).

Purposes of the study
The purposes of the present paper are to define the variety of liver resections as an important component of the modern treatment of colorectal liver metastases, to describe their operative techniques and postoperative results, to illustrate some peculiar resection patterns from our own patients' contingent and, based on our own experience with the complex preoperative diagnostic algorithm and the individualized indications and contraindications for surgery and multimodal therapy, to outline the advantages of different types of hepatic resections in properly selected cases with colorectal liver metastases as manifested by improved patient's quality of life and survival.

Material
types of surgical interventions and conservative therapy as well as metastatic tumour localization, volume, number and staging were systematized. Only some of our data could be presented in the present paper. Number and mean age of male and female patients can be seen on

Methods
The algorithm for contemporary diagnostic evaluation comprised total colonoscopy, conventional chest radiography, conventional blood tests, serum levels of some tumour markers such as carcinoembryonic antigen (CEA), carbohydrate antigen CA 19.9 and carbohydrate antigen CA 242, abdominal preoperative and intraoperative ultrasonography (for estimation of the type and volume of liver resection), intraoperative cholangiography (for pre-and postoperative bile drainage evaluation in remnant hepatic parenchyma), methyene-blue injection through the portal vein (for assessment of afferent and efferent blood flow in remnant hepatic parenchyma), contrast-enhanced and spiral computed abdominal tomography, MRI in case of contradictory computer tomographic data and histopathology of enlarged hilar lymph nodes. The volume of the liver resection was determined not only by the number, size and localization of the metastases but also by the degree of compensatory hypertrophy of the intact hepatic volume. The presentation of all the types of surgical interventions included the following: i. types of surgical access, liver mobilization, hilar dissection, and hepatic-vein control, ii. operative approaches, and iii. operative volumes. Patients' distribution according to the volume of liver resection is demonstrated on Table 2. During the last 8 years, a total of 14 patients underwent repeated liver resections. A third resection was done in three of these patients, and a fourth resection was done in two of these patients. Table 3 indicates the consecutive number and volume of primary and repeated liver resections. Some essential parameters of colorectal liver metastases in these repeated resections of different consecutive number are summarized on Table 4. Additionally, multimodal treatment of all the patients with colorectal liver metastases included a variety of chemotherapeutic protocols as aneoadjuvant and/or adjuvant chemotherapy along with radiofrequent ablation, portal vein embolization, and two-stage resection of bilobar colorectal liver metastases (Kostov & Kobakov, 2006). The effect of neoadjuvant chemotherapy was assessed according to the Response Evaluation Criteria in Solid Tumours (Eisenhauer et al., 2009  One-and three-year survival data were retrospectively recorded up to December, 2010. Memorial Sloan-Kettering Cancer Center Clinical Risk Score (MSKCC-CRS) was used to evaluate the postoperative prognosis of the patients (Arru et al., 2008). Kaplan-Meier estimates outlined differences with Kaplan-Meier curves. Comparisons of sex and age between segmentectomy and major hepatectomy patients applied chi-square and ttest. The t-test compared mean blood loss, diameter of colorectal liver metastases, duration of surgery, length of hospital stay, and resection margins. The postoperative complications were compared by means of Fisher's exact test. Patients' homogeneity was comparatively assessed by means of the log rank and Wilcoxon tests.

Types of surgical access
The following types of surgical access for liver mobilization, hilar dissection, and hepaticvein control can be used (Kostov & Kobakov, 2010) Usually, both left and middle hepatic veins present with a common trunk as their bifurcation is intraparenchymally located (Fig. 2). Clamping the three hepatic veins enables a complete vascular exclusion with blood flow preservation through vena cava inferior. With single 'hanging'-maneuver, a rubber tape passes cranially between the right and middle hepatic veins but caudally -between hilar vessels for the right and left hemiliver (Fig. 3). This method is applied in right/left hemihepatectomy or right segmentectomy. With double 'hanging'-maneuver, a second rubber tape is additionally used which passes cranially between the middle and left hepatic veins but caudally -between hilar vessels for the right and left hemiliver (Fig. 4). This method is applied in mesohepatectomy or proximal segmentectomy. With complete vascular exclusion and blood flow interruption through vena cava inferior the latter is clamped over the three hepatic veins and over the inflow of renal veins. For that purpose, vena cava inferior is mobilized at two sites -below the diaphragm and over the inflow of renal veins ( Fig. 5). Right suprarenal vein is obligatorily interrupted.

Operative approaches
The following operative approaches can be made use of (Kostov & Kobakov, 2010): i. extrahepatic approach to the hepatic inflow pedicles for ligation of a portal triad to the Sg 1 and 4, right anterior section, right posterior section, left hemiliver and right hemiliver, ii. intrahepatic anterior approach to the hepatic inflow pedicles for ligation of a portal triad to an individual Sg (2, 3, 5, 6, 7 and 8), iii. intrahepatic posterior approach to the hepatic pedicles by using Glissonian sheaths, and iv. combined extrahepatic and intrahepatic approaches for ligation of a portal triad were used in some bisegmentectomies, right trisectionectomies, and left trisectionectomies.

Operative volumes
According to the localization and expansion of the pathologic process, one of the following operative volumes should be selected by liver surgeons (Kostov & Kobakov, 2010):

Segmentectomies
Stages of the following monosegmentectomies -segmentectomy 1 ( Sg 1), Sg 2, Sg 3, Sg 4, Sg 5, Sg 6, Sg 7, Sg 8, and wedge resection: Segmentectomy 1 passes through five stages: i) devascularization of proc. caudatus, ii) devascularization of Spiegel's lobe, iii) interruption of short retrohepatic veins which enter directly vena cava inferior, iv) mobilization of right, middle and left hepatic veins and v) parenchymal transection at the borderline between Sg1 and Sg4. Resection to the right ends at the borderline to Sg7. www.intechopen.com The extrahepatic approach requires interruption of the afferent and efferent blood supply to the hepatic part outside the liver which is subject to removal. Among monosegmentectomies, only Sg1 devascularization can be entirely done through such an approach. With isolated segmentectomy 1, the line of parenchymal transsection passing behind the three hepatic veins is of interest (Fig. 6 through Fig. 8).  Both segmentectomy 2 and segmentectomy 3 pass through three stages each: i) definition of borderlines of Sg2 and Sg3 ii) parenchymal transection with intraparenchymal interruption of portal triad vessels for Sg2 and Sg3 ( Fig. 9) and iii) interruption of branches of left hepatic vein for Sg2 and Sg3 through anterior intrahepatic access (Fig. 10). Segmentectomy 4 passes through five stages: i) extrahepatic interruption of the artery for lobus quadratus which, normally, is left hepatic artery branch, ii) ligation of some ascendent www.intechopen.com portal veins through extrahepatic access, iii) interruption of descendent portal veins during parenchymal transection along lig. falciforme hepatis (Fig. 11 one hand, and between left and right hemiliver, on the other hand. Transversal resection borderline between Sg8 and Sg5 is established by means of intraoperative echography while the left borderline passes along lig. falciforme hepatis, iii) parenchymal transection along Rex-Cantlie line and consecutive interruption of the veins draining blood from Sg5,8 into middle hepatic vein and portal triad vessels for Sg8. Sg8 devascularization results in ischaemic demarcation line at the borderline to Sg5 and iv) parenchymal transection along this line continuing in a sagittal plane between Sg7 and Sg8 and reaching cranially up to the borderline between the right and the middle hepatic vein. Next follows parenchymal transection along lig. falciforme hepatis in order to liberate Sg4a ending, cranially, at the borderline between the left and the middle hepatic vein. Finally, both Sg8 and Sg4a are entirely mobilized around middle hepatic vein which is interrupted at its basis.

Multisegmentectomies
i. Stages of the following multisegmentectomies -mesohepatectomy with preservation of Sg1; mesohepatectomy together with Sg1; resection of Sg4b,5,6 and Spiegel's lobe; resection of Sg3,4b,5; resection of Sg3,5-7; resection of parts of Sg3,4b,5,6,8; resection of Sg4b,6,7, and resection of Sg6-8: Mesohepatectomy (Sg4,5,8) consists in removal of three segments both of which (Sg5 and Sg8) belong anatomically to the right hemiliver while Sg4 belongs to the left hemiliver. This operation is applied in centrally located liver metastases enabling R0 (Fig. 17). Mesohepatectomy with preservation of Sg1 passes through six stages: i) mobilization of left and right hemiliver as double 'hanging'-maneuver lifting on a holder of the right and left hepatic veins facilitates hepatic resection, ii) definition of right resection borderline by consecutive interruption of the artery and portal vein for Sg5,8 (Fig. 18). Parenchymal transection visualizes right resection borderline between Sg5,8 and Sg6,7, iii) interruption of the artery and ascendant portal veins for Sg4 through extrahepatic access. To the left, resection line passes along lig. falciforme hepatis. Sg4,5,8 devascularization enables mesohepatectomy at minimal blood loss, iv) parenchymal transection along lig. falciforme hepatis ending at the borderline between the middle and the left hepatic vein. Consecutive interruption of descendent portal veins, the bile duct for Sg4 and the vein draining blood from lobus quadratus in left hepatic vein, v) parenchymal transection at the borderline between Sg5,8 and Sg6,7 and consecutive interruption of the vein draining blood from Sg5 into right hepatic vein anterior branch and portal triad vessels for Sg5,8. To the right, parenchymal transection ends at the borderline between the right and the middle hepatic vein and vi) interruption of middle hepatic vein around which these already liberated Sg5,8 and Sg4 are located (Fig. 19). Residual liver volume after removal of Sg4,5,8 is shown on Fig. 20.  Mesohepatectomy with segmentectomy 1 is indicated in tumours of central location and passes through seven stages already described in detail in single segmentectomy chapters: i) mobilization of left and right hemiliver by means of double 'hanging'-maneuver, ii) Sg5,8 devascularization through extrahepatic access, iii) Sg4 devascularization through extrahepatic access for the artery and ascendant portal veins, iv) Sg1 devascularization with liberation of the retrohepatic part of vena cava inferior, v) parenchymal transection along lig. falciforme hepatis ending at the borderline between the middle and the left hepatic vein. Caudally, identification and interruption of descendent portal veins for Sg4 enabling the opening of Rex recessus. Interruption of bile ducts for Sg4 located in Rex recessus, vi) parenchymal transection at the borderline between Sg5,8 and Sg6,7 and vii) middle hepatic vein interruption at the end of parenchymal transection and obligatory intraoperative cholangiography after resection of Sg1,4,5,8 for control of bile drainage from the remnant liver parenchyma. Resection of Sg4b,5,6 and Spiegel's lobe combines the already described stages in resections of Sg1,4-6. Portal triad vessels for Sg7,8 are obligatorily preserved. Resection of Sg3,4b,5 combines the already described stages in resections of Sg3,4b,5. Portal triad vessels for Sg6,8 are obligatorily preserved. Resection of Sg3,5-7 combines the already described stages in resections of Sg3,5-7. Portal triad vessels for Sg8 are obligatorily preserved. Resection of parts of Sg3,4b,5,6,8 combines the already described stages in resections of Sg3,4b,5,6,8. Resection of Sg4b,6,7 combines the already described stages in resections of Sg4b,6,7. Resection of Sg6-8 combines the already described stages in resections of Sg6-8. Portal triad vessels for Sg5 are obligatorily preserved. ii. Stages of the following hemihepatectomies -left hemihepatectomy (Sg2-4) iii. Stages of the following trisectionectomies -left trisectionectomy (Sg2-5,8), and right trisectionectomy (Sg4-8): Left trisectionectomy is used in tumours affecting left hemiliver and Sg5,8. No preoperative embolization of portal vein left branch is needed as preserved Sg7 and Sg 6 amount to 30-35% of standard liver volume. Left trisectionectomy passes through five stages: i) mobilization of left hemiliver through consecutive interruption of lig. triangulare sinistrum and lig. coronarium hepatis sinistrum. 'Hanging'-maneuver application facilitates resection, ii) devascularization of left hemiliver with ligation of left hepatic artery and portal vein left branch, iii) Sg5,8 devascularization through extrahepatic access . Sg5,8 ischaemia causes demarcation line at the borderline to Sg6,7 along which parenchymal transection is performed, iv) consecutive interruption of the vein draining blood from Sg5 into middle hepatic vein and intraparenchymal portal triad vessels for Sg5,8. Parenchymal transection ends at the borderline between the right and the middle hepatic vein. Right hepatic vein is lifted on a rubber holder in order to prevent its injury and v) finally, the trunk of the middle and the left hepatic vein is interrupted. Portal triad vessels for Sg6,7 are obligatorily preserved. Right trisectionectomy is used in tumours affecting right hemiliver and Sg4. In most cases, preoperative embolization of portal vein right branch is needed in order to achieve hypertrophy of the left hemiliver and, in particular, of Sg2 and Sg3. Right trisectionectomy passes through five stages: i) mobilization of right hemiliver through consecutive interruption of lig. triangulare dextrum and lig. coronarium hepatis dextrum and short retrohepatic veins; ii) devascularization of right hemiliver with ligation of the right and middle hepatic arteries and the right branch of the portal vein (Fig. 21); iii) devascularization of lobus quadratus by means of interruption of the artery and ascendent portal veins for Sg4 through extrahepatic access (Fig. 22).  The interruption of the right hepatic duct is presented on Fig. 23. A preserved left hepatic vein (single 'hanging'-maneuver) is indicated on Fig. 24, iv) parenchymal transection along lig. falciforme hepatis and consecutive interruption of descendent portal veins for Sg 4. Entering Rex recessus with interruption of the bile ducts for Sg4 (Fig. 25), and v) cranial ligation of the middle and the right hepatic veins (Fig. 26).  In case of damaged blood supply to common hepatic duct, these vessels should be removed with subsequent biliodigestive anastomosis between left hepatic duct and intestinal loop isolated after Roux. Fig. 27 shows residual liver volume following right trisectionectomy.

Results
The results concerning various clinical and laboratory characteristics of the patients having undergone different types of segmentectomies and major liver resections were comparatively demonstrated. The main attention was paid to the following basic parameters: number, diameter, and localization of colorectal liver metastases; postoperative mortality rate; complications; blood loss and required blood transfusions; operative duration; length of hospital stay; resection margins, one-, two and three-year disease-free and overall survival rates. Some of them are shown in the present paper. Postoperative complications following monosegmentectomies and bisegmentectomies, on the one hand, and multisegmentectomies, on the other hand, are comparatively presented on Table 5. It is evident that, as a whole, liver damage caused by the surgical intervention itself occurs statistically significantly more commonly in the patients who have undergone multisegmentectomies. Some surgical characteristics of monosegmentectomies and bisegmentectomies, on the one hand, and multisegmentectomies, on the other hand, are comparatively presented on Table 6. Obviously, several surgical patterns of undoubted medical and socio-economic importance such as total blood loss, necessity of blood transfusions and of application of Pringlemaneuver are statistically significantly more unfavourable in the patients who have undergone multisegmentectomies. Besides, these patients require statistically significantly more often the performance of repeated surgical interventions on the occasion of colorectal liver metastases than those who have undergone mono-or bisegmentectomies. We identify a small number of prognostic criteria which could be considered statistically significant in the patients with colorectal liver metastases. Here belong the increased levels of CEA, the higher number of colorectal liver metastases (more than three), the negative resection areas, the presence of negative lymph nodes in lig. hepatogastroduodenale, the implementation of multisegmentectomy as a less sparing surgical intervention, the presence of at least 3 factors of MSKCC-CRS and the absence of extrahepatic dissemination of the pathological process. Thus our investigations should be enlarged in future in order to more comprehensively explain the dynamic interactions between the single risk factors for the relatively poor prognosis of this contingent of patients.

Discussion
Our own results demonstrate the substantial advantages of segmental resection for colorectal liver metastases over major liver resection (Kobakov & Kostov, 2006;Kostov & Kobakov, 2006b;Kostov & Kobakov, 2009). They are the following: conservation of a sufficient liver volume, achievement of lower perioperative morbidity and mortality rates as well as warranting the similar disease-free and overall survival rates. Liver conservation is essential in normal and damaged liver. It reduces the risk of postoperative liver insufficiency from a small liver remnant and in the patients at advanced age or with cirrhosis.
The following prognostic factors exert a statistically significant effect on short-and longterm survival rates after liver resections for colorectal liver metastases: CEA level, presence of metastatic nodes along lig. hepatoduodenale, number of metastases, extension of liver resection, resection volume, number of prognostic factors according to MSKCC, and extrahepatic dissemination of primary colorectal cancer.
The following therapeutic strategy should be recommended: i) liver resection for resectable colorectal metastases (at stages IVA and IVB); ii) neoadjuvant chemotherapy for primarily non-resectable colorectal metastases (at stage IVC) when downstaging is feasible to allow radical surgery, and iii) only chemotherapy for colorectal metastases in stage IVD patients. Recent literature data convincingly indicate the uninterrupted progress in the interdisciplinary field of oncologic liver surgery. Along with original investigations, a lot of review papers, meta-analyses, multicentre reports and randomized controlled trials are currently published by authors from all over the world. In this respect, multimodal therapy deserves a special attention. It increases the number of resections and improves long-term survival rate (currently more than 40% at 5 years) (Neumann et al., 2010). Advances in staging, surgical technique, perioperative care and systemic chemotherapy contribute to improvement in oncologic outcomes of stage IV colorectal cancer patients (Abdalla, 2011). The limits of resection expand to include cases with more, larger and bilateral colorectal liver metastases as 5-year overall survival exceeds 50% following resection. Tailored, patient-centered treatment includes a variety of liver resections, liver volumetry, and portal vein embolization for preoperative enhancement of the volume and function of the planned future remnant liver (Abdalla, 2011). Multimodality approach of laparoscopic liver resection is feasible and safe in selected patients. It is associated with a low complications rate (Isoniemi et al., 2011, Lai et al., 2011. Intraoperative ablation extends the limits of hepatectomy in the patients not amenable to complete resection (Brown et al., 2011;Govindarajan et al., 2011;Hammill et al., 2011; www.intechopen.com Hompes et al., 2011). Portal vein embolization, radiofrequency ablation, two-stage hepatectomy, conversion therapy and reverse treatment strategy along with hepatectomy are used in the presence of extrahepatic disease (Coimbra et al. 2011;Narita et al., 2011, Tsim et al., 2011. Resection of advanced colorectal liver metastases after a second-line chemotherapy regimen is safe and promising in certain cases. The addition of neoadjuvant chemotherapy should, however, be cost-effective. Positron emission tomography/computed tomography have a higher accuracy for detection of extra-hepatic and colorectal liver metastases than computed tomography alone (Patel et al., 2011). In patients treated with neoadjuvant chemotherapy, magnetic resonance imaging measurements of steatosis show the highest correlation coefficient and the best diagnostic accuracy, as compared to computed tomography ones (Marsman et al., 2011). Intraoperative ultrasound and preoperative imaging significantly increase the diagnostic accuracy of patients undergoing liver resection for colorectal liver metastases (Lordan et al., 2011). Metachronous resections have a better outcome than synchronous. Iterative resection is very encouraging and justifies an aggressive surgical approach (Tonelli et al., 2010). Simultaneous resection is safe and efficient in the treatment of patients with synchronous colorectal liver metastases while avoiding a second major operation (Chen et al., 2011). In patients with bilobar synchronous colorectal liver metastases who are candidates for twostage hepatectomy, combined resection of the primary tumour and first-stage he patectomy reduces the number of procedures, optimizes chemotherapy administration and may improve outcome (Karoui et al., 2010). The two-stage strategy for colorectal liver metastases can be performed with acceptable morbidity and mortality. The second stage is not feasible in 20-25% of patients. Patients completing the two-stage approach may have long-term survival comparable to those treated with a planned single-stage hepatectomy (Tsai et al., 2010). Concomitant extrahepatic disease in a patient with colorectal liver metastases should not be a contraindication to their resection. As there is no significant difference in morbidity, mortality, recurrence rate, or survival in anatomical and nonanatomical liver resections, the latter can be used as a save procedure to preserve liver parenchyma (Lalmahomed et al., 2011). The Pringle maneuver does not seem to affect the survival of patients with liver metastases . Ultrasoundguided finger compression of sectional portal pedicle feeding the right posterior section is a feasible, safe, and effective method for performing anatomical right posterior sectionectomy (Torzilli et al., 2011). Prognostic factors and score systems occupy an important place in oncologic liver surgery (de Haas et al., 2011;Peng et al., 2011;Pulitanò et al., 2011). Although twelve prognostic scoring systems have been identified from 1996 to 2009, there is no 'ideal' system for the clinical management of patients with colorectal liver metastases (Gomez et al., 2010). A predicted positive surgical margin (R1 resection) is not any absolute contraindication to surgery for aggressive or advanced colorectal liver metastases (Tanaka et al., 2011). Liver resection has superior long-term survival which is, however, significantly reduced by the occurrence of post-surgical complications (Schepers et al., 2010). Superior overall healthrelated quality of life merits an aggressive surgical approach and intensive follow-up to detect recurrence early (Wiering et al., 2011).

Conclusion
Based on our own results and reliable scientific evidence available worldwide up-to-date, it can be concluded that the patient presenting with colorectal liver metastases deserves a The projections for future growth in the number of new patients with colorectal cancer in most parts of the world remain unfavorable. When we consider the substantial morbidity and mortality that accompanies the disease, the acute need for improvements and better solutions in patient care becomes evident. This volume, organized in five sections, represents a synopsis of the significant efforts from scientists, clinicians and investigators towards finding improvements in different patient care aspects including nutrition, diagnostic approaches, treatment strategies with the addition of some novel therapeutic approaches, and prevention. For scientists involved in investigations that explore fundamental cellular events in colorectal cancer, this volume provides a framework for translational integration of cell biological and clinical information. Clinicians as well as other healthcare professionals involved in patient management for colorectal cancer will find this volume useful.