**5. Surgery for CRLM**

Primary colon cancer is classified IV in patients presenting CRLM [2]. Most CRLM patients develop liver metastases after initial CRC treatment, while about 20–34% present liver nodules at initial diagnosis [59]. When CRLM are confined to the liver, the intent should be cure, and surgical resection is actually the standard of care, presenting the best survival rates [59, 93]. Neoadjuvant and adjuvant systemic therapy are recommended in most patients prior to surgical resection, as it can improve instances of recurrence [1, 59]. The response to neoadjuvant chemotherapy has shown to be a strong prognostic factor for outcomes after hepatic resection [94]. The aim of liver resection is to remove all macroscopic disease with clear (negative) margins and leave sufficient functioning liver, with proper vascular and biliary flow [95]. An inadequate future liver remnant volume (FLRV) can lead to post-hepatectomy liver failure, a major cause of morbidity and mortality. Typically, FLRV is intended to be more than 30% of the native tissue and 30% future liver remnant, or more than 350 grams of liver remaining per 70 kg body weight [1]. The anatomic description of functional segments, which is based on the organ's blood supply via the hepatic artery and portal vein, its venous drainage via the hepatic veins, and lastly its biliary drainage, is the foundation of liver surgery. Historically, up to six Couinaud segments can be removed in healthy individuals, returning to original size in about three weeks, with restored liver function in about six weeks [29, 96]. An illustration of the liver segments are given in **Figure 2**.

Typical resection complications occur in 20–50% of patients, although the mortality rate is only 1–3% in high volume centers [29, 97]. Most common complications include pleural effusion or pulmonary atelectasis, venous catheter infection, site-incisional infection, ascites, subphrenic infection, intraperitoneal bleeding, biliary tract hemorrhage, coagulation disorders, and bile leakage [98]. Additionally, inadequate post-operative liver response can result from pre-operative liver dysfunction, prolonged vascular occlusion, and inadequate resid-ual liver volume; leading to hepatic insufficiency that results in ascites, mental impairment, hyperbilirubinaemia, and possible sepsis [98]. Post-operative liver function can be evaluated by dynamic functional testing such as indocyanine green (ICG) clearance rate, or by aminopyrine breath tests for cytochrome P-450 function, and post-treatment monitoring with blood serum tests for analytes including coagulation products and albumin [98].

Surgical resection for synchronous CRLM is an extremely complex scenario and surgery remains one of the major curative treatment options available.

Consideration for surgical resection must be given to: the anatomical distribution of the disease; FRLV; management of the primary disease (in the setting of synchronous CRLM); the timing and role of (neo)adjuvant chemotherapy, and whether all disease can be resected successfully at one sitting. Patients are often administered chemotherapy and chosen to undergo a conventional colon-first procedure, a liver-first procedure, or simultaneous resection [99]. Even for patients presenting multifocal bilateral CRLM, the goal should be a full tumor excision with sufficient remaining functional parenchyma. Though, for multifocal bilateral CRLM, resection and ablation often yield survival rates only faintly superior to chemotherapy alone [99]. The traditional colon-first approach involves complete primary CRC tumor resection, along with systemic chemotherapy, then hepatectomy is performed later if resectable [100]. A "liver-first" approach involves

**Figure 2.** *Illustration identifying locations of individual Couinaud segments. Olga Bolbot/shutterstock.com.*

### *Magnetic Resonance-Guided Focused Ultrasound in the Treatment of Colorectal Cancer Liver… DOI: http://dx.doi.org/10.5772/intechopen.105906*

initial systemic chemotherapy, liver tumor removal, then CRC resection [100]. The concept is that the liver tumor is most likely to create further metastasis and the CRC is quite sensitive to systemic chemotherapy [101]. With either approach, approximately only 10–20% of patients are surgical candidates [2, 8, 102]. Reasons include late-stage cancer diagnosis, secondary tumor sites outside the liver, and existing comorbidity ineligibility [2, 8]. Although surgical resections report long-term survival rates, about half of the patients develop widespread metastases within three years [1]. Recurrence after primary liver resection occurs at about a 43% rate in the liver and about a 31% rate in the lungs [8].

Anatomic resections usually involve two or more hepatic segments, while non-anatomic resection involves resection of the metastases with a margin of uninvolved tissue (segmentectomy). Various approaches in liver resection include: right hepatectomy, right lobectomy, left hepatectomy left lobectomy, extended right hepatectomy, and extended left hepatectomy [103]. By performing a segment-based resection, intraoperative hemorrhage and remaining post-treatment ischemic tissue can be avoided, helping to prevent infection and bile duct fistula. Additionally, the segment-based approach allows predetermined calculation of tumor margins and remaining viable parenchyma. Moreover, intrahepatic metastases tend to arise in the same Couinaud segments, allowing better chances to remove small satellite metastatic sites [103, 104].

Modern surgery resection is based on the report of the first successful proce-dure for a right hepatectomy [103, 105]. An illustration of the basic liver anatomy is shown in **Figure 3**. Each Couinaud segment is functionally independent, receiving blood supply from the portal vein and from the hepatic artery; at the same time the outflows is guaranteed by various branches of the hepatic vein. The right hepatic lobe is composed of Couinaud segments 5–8, with the blood supply to the right lobe provided by the right portal vein and right hepatic artery. First, the falciform ligament, coronary ligament, and right triangular ligament are cut to allow increased liver movement. Next, the right hepatic artery, right portal vein, right hepatic duct, and cystic duct are clamped, cut, and ligated. The blood supply to the left lobe is kept intact. This is followed by dissection of the right lobe from the inferior vena cava. Venous outflow from the main and short hepatic veins are divided and ligated. This devascularization creates a line of demarcation due to a color change in the right liver lobe. Then,

### **Figure 3.**

*Overview of the liver anatomy. Olga Bolbot/shutterstock.com.*

transection of the liver parenchyma occurs, dividing the right and left lobes along the middle hepatic vein. This is followed by ligation of the middle hepatic vein blood supply. Parenchyma transection can result in large blood loss that can be lessened using a reduced central venous pressure and Pringle's manoeuvre [103, 104, 106]. Three major complications for the procedure include the introduction of an air embolism into the hepatic veins, hemorrhagic bleeding from the hepatic veins, and biliary leakage into the abdominal cavity [107].

The concept of the "two-staged hepatectomy" has been introduced by Adam et al. [108], as a surgical strategy that could be applied to patients with conventionally irresectable metastases to make them eligible for liver resection. This approach involved a combination of systemic chemotherapy to downstage tumors, with or without portal vein embolization (PVE), with subsequent planned staged operations that permitted curative resection of large tumor burden that would otherwise have been considered unresectable. The interval between operations enabled hypertrophy of the remnant liver to theoretically reduce the chance of liver insufficiency and patients would receive chemotherapy during the interval between operations in an effort to control tumor growth.

More recently, the technique known as ALPPS (Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy) allows removal of extensive tumor load by increasing future liver remnant, allowing increased surgical eligibility, and extended survivability of CRLM patients [109, 110]. Early research included right PVE, which was shown to induce hypertrophy in the left lobe, subsequently allowing increased amounts of liver tissue to be removed in the right lobe [108, 110–112]. This was later applied in two-stage hepatectomies to allow increased amounts of cancerous liver tissue to be removed from both liver lobes, by permitting liver regrowth between procedures [110]. Early two-stage hepatectomies required months for liver regrowth, with tumor progression frequently occurring during this time; however, development of ALPPS allowed the two surgical procedures to be performed within 7–14 days [109, 110]. ALPPS is indicated in case of extensive multifocal CRLM, failure after portal vein embolization, and expected small amounts of FLRV [14].

A generic procedure for two-stage hepatectomy of left lobe wedge resection combined with right lobe hepatectomy includes in situ liver splitting in addition to portal vein ligation [113]. First, the falciform ligament is cut, then tumors locations are confirmed and marked by intraoperative ultrasound. The transection line(s) is identified. Then, the right cystic duct and artery are ligated, followed by dissection and ligation of the right portal vein at the portal bifurcation. The right and middle hepatic veins are isolated, the space between is dissected, and umbilical tape is placed for the hanging maneuver. Then, transection of the parenchyma is performed at the site previously marked with/without Pringle maneuver. The liver is patched, drains placed, abdomen closed, ending the first stage. At this stage the liver is separated but not removed. Then, functional liver testing and weekly volumetry measurements are performed with CT or MRI until the future liver remnant volume surpasses 30%. In the second stage, the incision is reopened, and the hepatic artery and bile duct are ligated on the right lobe that previously underwent portal vein ligation. Then, transection of the right hepatic vein is followed by removal of the right liver lobe and closure of the abdomen.

In the last decade, it has been conceptualized that liver transplantation could offer the theoretical advantage of a real R0 resection, removing also all potentially undetected metastases. Earlier studies in American and European populations showed that transplant after non-neuroendocrine liver metastases from various primary

*Magnetic Resonance-Guided Focused Ultrasound in the Treatment of Colorectal Cancer Liver… DOI: http://dx.doi.org/10.5772/intechopen.105906*

sites yielded one-year survival rates of only 5%, which is compounded by the lack of available donors [33]. More recent studies with tightened inclusion criteria have shown more favorable outcomes and resulted in a large increase in CRLM transplants worldwide [30, 31, 114]. The studies have suggested much longer survival rates after liver transplant for CRLM, when the inclusion criteria included adequate response to chemotherapy, excised primary tumor sites, more than one year between diagnosis and transplant, and liver only metastases [31, 32, 115]. Additional exclusion criteria exist based upon molecular profiling; for instance, exclusion is recommended due to V600 BRAF mutations and MSI from DNA mismatch repair (MMR) mutations [116]. These results have suggested liver transplant possibly provides the best overall survivability compared to other treatment modalities for surgical ineligibility. The drawbacks are smaller study size, the limited availability of liver donors and more specialized training is required across multiple disciplines to conduct the operation [30].
