Colorectal Liver Metastases

5 Colorectal cancer is the second-leading cause of cancer-related deaths in the United States. About 20%

to 25% of colorectal cancer patients are found to have synchronous CLM,103,104 and 35% to 55%

develop CLM during the course of the disease.105 The 5-year survival rate after curative resection of

CLM has been reported to be up to 58%,106–108 while the median survival duration for patients with

CLM without any treatment is approximately 6 months.104 Therefore, adequate assessment and

preoperative management are important in selecting patients with resectable or potentially resectable

CLM who are candidates for liver resection.

CLMs are classified as stage IV colorectal cancer. However, with recent advancements in

chemotherapy and surgical management, the resectability of CLM has dramatically increased and longterm survival after resection of CLM has significantly improved.109 The practical keys to the initial

management of CLM include precise assessment of the extension of disease and the proper selection of

the initial therapeutic options. Although surgical resection is potentially the most curative strategy for

CLM, a multidisciplinary approach by surgeons, medical oncologists, radiologists, and pathologists is

essential for selecting the patients who would benefit from surgery and to determine the optimal timing

of surgery (Algorithm 60-3).110

Table 60-2 Published Results of Expanded Liver Transplant Eligibility Criteria for

Hepatocellular Carcinoma

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In imaging evaluation, the choice of imaging technique for pretreatment assessment of CLM depends

on the local expertise and the availability of imaging modalities. However, at least CT of the chest,

abdomen (including three-phase liver protocol CT), and pelvis should be performed routinely to

evaluate patients with CLM, with selective use of MRI and PET to further evaluate small hepatic

nodules or extrahepatic disease.

Algorithm 60-3. Multidisciplinary treatment approach for colorectal liver metastasis. (Adapted from Kopetz S, Vauthey JN.

Perioperative chemotherapy for resectable hepatic metastases. Lancet 2008;371:964–965 with permission.)

The surgical indication for CLM should be considered from two standpoints: oncologic resectability

and technical resectability. From an oncologic standpoint, complete resection of all viable disease is

crucial if the patient is to derive the most benefit from surgery. The presence of extrahepatic disease

does not necessarily represent an absolute contraindication for surgery. Isolated lung metastases have

reportedly been associated with a high 5-year survival rate (30% to 40%) when complete resection is

feasible. Localized peritoneal disease correlates with an intermediate 5-year survival rate (15% to 30%),

whereas para-aortic adenopathy and evidence of multiple sites of extrahepatic disease are rarely

associated with favorable survival after resection of CLM (5-year survival rate <15%).111 These data

suggest that patients harboring limited extrahepatic disease are amenable to surgical resection with a

reasonable expectation for long-term control with adjuvant therapies.112 However, when the

extrahepatic disease is unresectable or uncontrollable with systemic chemotherapy, hepatic resection for

CLM is contraindicated.

Another oncologically important factor in determining resectability is response to chemotherapy.

With modern effective chemotherapy, disease progression during neoadjuvant systemic therapy is

relatively rare. However, some patients present with tumor progression during preoperative systemic

therapy. Growth of pre-existing intrahepatic metastases does not seem to be associated with poor

outcomes. However, development of a new lesion is reportedly associated with a poor prognosis after

resection of CLM.113 Therefore, the oncologic behavior of the tumor during preoperative chemotherapy

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offers useful information to adequately stratify patients who would benefit from surgical resection.

From a technical standpoint, the resectability of CLM relies on anatomic considerations and

underlying hepatic function. Because a safety limit for the extent of liver resection exists according to

individual hepatic functional reserve, assessment of hepatic function and systematic volumetry of FLR

are mandatory to estimate the risk of postoperative hepatic insufficiency and preoperative intervention

to reduce the risk of surgery, as described later in this chapter. When the estimated FLR volume is

smaller than the minimal FLR volume, to avoid postoperative hepatic insufficiency PVE or another

approach, including two-stage resection, is considered.

Neuroendocrine Liver Metastases

Neuroendocrine tumors grow indolently and metastasize primarily to the liver. In the majority of the

cases, these tumors are nonfunctioning and patients with a significant tumor burden can remain

asymptomatic for years, while patients with minimal lesions can suffer various symptoms caused by

excessive production of hormones by the tumor. Although the best treatment strategy has not yet been

established, resection of functioning NETs reduces symptoms and prolongs survival. The survival rate of

patients undergoing liver resection is relatively high, reaching 91% at 3 years

114 and 61% at 5

years,115,116 even though the curative resection rate is relatively low. NETs are basically incurable in

most advanced-stage cases. However, cytoreduction of >90% of the tumor volume is reportedly

superior to other treatment options, such as transarterial embolization or systemic therapy.117,118 To

maximize the treatment outcomes, a multidisciplinary approach that includes surgery, transarterial

embolization, systemic chemotherapy, and radiation is needed.

PREOPERATIVE SURGICAL MANAGEMENT

When surgical resection is selected as an initial treatment for hepatic malignancy, secondary

assessments for surgical planning and preoperative management are required.

Review of Vascular Anatomy

6 For surgical planning, precise anatomic interpretations of the intrahepatic vascular structures are

needed. This step specifies the ramification pattern of each vascular structure based on the imaging

studies and knowledge of anatomic variations.

Important variations in the portal venous system include its ramification patterns at the hepatic

hilum. In approximately 80% of patients, the main portal vein bifurcates into the left and right portal

branches at the hepatic hilum (bifurcation type). However, trifurcation into the left paramedian, right

paramedian, and right lateral portal trunks at the hilum (10%) or early branching of the right lateral

pedicle (10%) (trifurcation type) is frequently encountered in major hepatectomy. In addition,

anomalies such as right-sided ligamentum teres (0.6% to 1.2%), lack of left portal trunk (0.9%), or lack

of intrahepatic portal vein (<0.1%) are sometimes encountered. Because the portal ramification pattern

defines the segmental anatomy of an individual liver, precise confirmation of the anatomy in the portal

venous system is of primary importance.

As for the hepatic veins, attention should be paid to the drainage pattern of the right lateral sector

(i.e., Segments VI + VII) because thick accessory right hepatic veins, such as the middle right hepatic

vein or the inferior right hepatic vein,119 are observed in nearly 70% of cases. Care must be taken when

these veins are thick and drain a large portion of Segment VI or VII because ligation of these veins may

cause congestion of the right lateral sector and because careless handling of the right hemiliver during

mobilization may cause incidental injury of these veins, resulting in massive bleeding (Fig. 60-11).

Regarding the hepatic arteries, the presence or lack of a “replaced” or “accessory” hepatic artery is

important. Typically, both right and left hepatic arteries are derived from the proper hepatic artery.

However, there are two frequent variations in the ramification patterns of the left and right hepatic

arteries: the left hepatic artery sometimes branches from the left gastric artery, running in the lesser

omentum and feeding Segments II and III, and the right hepatic artery sometimes originates from the

superior mesenteric artery, running behind the portal vein and reaching the right hemiliver on the right

side of the hepatic hilum. When the total arterial supply for the left lateral section (Segments II + III)

or right hemiliver comes from these aberrant arteries, these arteries are called “replaced” arteries, while

they are called “accessory” arteries when the other arterial flow from the proper hepatic artery is also

present. Because of the presence of a typical arterial route derived from the proper hepatic artery,

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accessory arteries can be ligated. In contrast, due to a lack of compensatory arterial supply from the

proper hepatic artery, the replaced arteries should be preserved when the corresponding part of the

liver is not resected. Therefore, preoperative review of the arterial anomalies in the early arterial phase

in dynamic CT is essential, and a routine clamp test with Doppler ultrasound is needed before these

aberrant arteries are ligated.

Figure 60-11. Multiple accessory right hepatic veins during liver mobilization. Intraoperative photo of the exposed right wall of

the inferior vena cava during mobilization of the right lobe of the liver. IVC, inferior vena cava; RHV, right hepatic vein; MRHV,

middle right hepatic vein; IRHV, inferior right hepatic vein. (Adapted from Shindoh J, Aoki T, Hasegawa K, et al. Donor

hepatectomy using hanging maneuvers: Tokyo University experiences in 300 donors. Hepatogastroenterology 2012;59:1939–1943

with permission.)

Aside from the blood vessels, precise preoperative assessment of the biliary anatomy is difficult.

There are considerable variations in the ramification pattern of the right-side biliary branches, while the

anatomy of the left hepatic duct is rather simple and constant. Thus, right or extended right

hepatectomy can be performed safely without any unnecessary injury to the biliary branches to be

preserved. However, when left-side major hepatectomy is being performed, care should be paid not to

injure the biliary branches for the right side. Magnetic resonance cholangiopancreatography may clarify

the ramification pattern of the biliary tree. However, its imaging quality is not always satisfactory

unless the intrahepatic bile duct is obstructed or dilated.

Based on this anatomic information and the tumor distribution, oncologically adequate types of

resection can be planned and a safe vascular handling approach adopted. Conventionally, the quality of

such meticulous anatomic assessments was highly dependent on the surgeon’s knowledge or experience.

However, with recent advancements in imaging modalities, three-dimensional reconstruction of CT

images is easy and the three-dimensional liver simulation technique has provided ready access to the

information on a patient’s precise individual vascular anatomy (Fig. 60-12).120

Assessment of the Minimal Requirement of FLR and CT Volumetry

The functional reserve of the liver depends on the quality of the liver parenchyma. The volume of the

FLR4,14,121–123 and the regenerative capacity of the liver124,125 are important predictors of postoperative

morbidity and mortality after extended hepatectomy. The minimal requirement of the FLR volume is

determined by the balance between the hepatic functional capacity per volume and the actual volume of

the FLR. The ICG clearance test is widely used to measure the hepatic functional reserve and to

determine an adequate extent of surgery, especially for patients with cirrhosis. The landmark criteria

for the maximum extent of resection proposed by Makuuchi et al.82 offer a simple algorithm to safely

perform hepatic resection according to the ICG retention rate at 15 minutes (ICG-R15) (Algorithm 60-

2), and the clinical relevance of this algorithm was validated in a large prospective cohort treated under

the constant resection policy.1 However, ICG-R15 has several limitations. First, it is used mainly to

determine the extent of minor resection for patients with cirrhotic livers, and it does not offer a safety

limit for major hepatectomy. Second, ICG-R15 is influenced by hepatic blood flow and measures

performed after a meal, after exercise, or with patients with portosystemic shunts are not reliable.

Third, because ICG is exclusively excreted in bile, the ICG test cannot be used for patients with

obstructive jaundice or inherited hyperbilirubinemia. 99mTc-GSA, a scintigraphy agent that binds

specifically to asialoglycoprotein receptors on hepatocytes, can be used to evaluate hepatic functional

reserve. Because 99mTc-GSA scintigraphy is not influenced by the hepatic blood flow or biliary

obstruction, it can be used to evaluate the hepatic functional reserve when the ICG clearance test is not

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appropriate.

Figure 60-12. Three-dimensional evaluation of venous drainage areas. Three-dimensional volume assessment of venous drainage

area predicts venous congestion area after deprivation of the corresponding hepatic venous branches or hepatic veins at surgery.

Evaluating the volume of the FLR is the most reliable approach to predicting outcome in patients who

are candidates for major liver resection. Several methods have been described to evaluate the volume of

the FLR. At The University of Texas MD Anderson Cancer Center, the standard liver volume (SLV) is

estimated with a formula that relies on the linear correlation between the SLV and body surface area

(BSA), as follows:

SLV (cm3) = −794.41 + 1,267.28 × BSA (m2)

The standardized FLR (sFLR) is calculated as the ratio of the FLR volume divided by the SLV. In a

series of 301 patients without chronic liver disease or hepatic injury who were undergoing extended

right hepatectomy, an sFLR of <20% was a risk factor for postoperative liver insufficiency and 90-day

postoperative mortality.4 Patients with chemotherapy-induced liver injury require an sFLR of

approximately 30% and those with cirrhosis require at least 40% residual volume.13,14,121

Of note, these volume criteria are based on the volume of the fully functioning hepatic parenchyma;

in other words, the hepatic parenchyma with patent blood flow and intact biliary drainage. If combined

resection of a hepatic vein is needed, the area with deprived venous drainage develops venous

congestion and represents impaired hepatic function,126,127 resulting in atrophy of the corresponding

area.128,129

Portal Flow Modulation to Expand the Surgical Indication

7 PVE is a safe and minimally invasive procedure for inducing ipsilateral atrophy and compensatory

contralateral hypertrophy of the FLR.130–133 When the sFLR volume is considered insufficient according

to the baseline status of the underlying liver, PVE is considered to expand the surgical indication and to

improve the safety of major hepatectomy (Fig. 60-13).

Several studies have demonstrated the efficacy of PVE in terms of hepatic functional shift from the

embolized liver to the FLR and reduced surgical risk. First, a dynamic functional shift from the

embolized liver to the FLR after PVE was confirmed in three studies using the ICG excretion rate,134

99mTc-GSA scintigraphy,135 or bile clearance.136 All of those studies indicated that PVE produced a clear

functional shift from the embolized liver to the nonembolized FLR with a concomitant increase in FLR

volume. Another study showed that when a patient achieved sufficient growth of the FLR to meet the

minimum criteria for FLR volume, the operative risk was significantly reduced compared to the risk for

patients who did not meet the minimum FLR volume criteria after PVE.4

sFLR after PVE sensitively predicts the risk of postoperative hepatic insufficiency. However, recent

studies have indicated that the regeneration capacity or speed of regeneration independently predicts

short-term surgical outcomes in patients undergoing PVE for a small FLR. Ribero et al.124 reported that

the degree of hypertrophy in sFLR volume after PVE is significantly associated with surgical outcomes.

A degree of hypertrophy >5% after PVE along with sFLR >20% predicted good postoperative

outcomes with high specificity and sensitivity in patients with normal liver function. The kinetic growth

rate (defined as the degree of hypertrophy at initial volume assessment divided by the number of weeks

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