Hepatic resection for colorectal cancer liver metastasis

INTRODUCTION — Approximately 153,000 patients are newly diagnosed with colorectal cancer (CRC) in the United States annually [1]. Among those who develop liver metastases, approximately 20 percent will be candidates for potentially curative liver resection. Long-term survival after surgery for colorectal liver metastases (CRLMs) has improved dramatically, with five-year overall survival (OS) rates doubling from approximately 30 percent in the 1980s to 1990s to almost 60 percent in the last two decades.

An overview of how to manage potentially resectable CRLMs can be found here. (See "Potentially resectable colorectal cancer liver metastases: Integration of surgery and chemotherapy".)

This topic will focus specifically on surgical aspects of liver resection for CRLMs and perioperative considerations. Other related topics include:

●Hepatic resection techniques (see "Overview of hepatic resection" and "Open hepatic resection techniques")

●Portal vein embolization (see "Preoperative portal vein embolization")

●Nonsurgical locoregional therapies for CRLMs (eg, tumor ablation, hepatic intra-arterial chemotherapy, radiation) (see "Nonsurgical local treatment strategies for colorectal cancer liver metastases")

●Integration of chemotherapy with resection for CRLMs (see "Potentially resectable colorectal cancer liver metastases: Integration of surgery and chemotherapy")

●Palliation of patients with stage IV CRC (see "Locoregional methods for management and palliation in patients who present with stage IV colorectal cancer")

PATIENT SELECTION — Surgical resection of colorectal liver metastases (CRLMs) provides the greatest chance for cure and long-term survival and therefore is the treatment of choice for resectable CRLMs [2].

Appropriate patient selection is key to ensuring the best perioperative and long-term oncologic outcomes. Essential components in determining if a patient is a candidate for resection involve considering the following factors:

Patient factors — Liver resection subjects patients to substantial physiologic stress. In patients with significant medical comorbidities (eg, significant underlying liver disease, extensive cardiopulmonary disease, advanced age), although a CRLM may be resectable, the perioperative risks may be prohibitive. Preoperative risk assessment is critical prior to surgery, as is allowing sufficient time for medical optimization. The details of risk assessment are discussed in other topics. (See "Assessing surgical risk in patients with liver disease" and "Evaluation of cardiac risk prior to noncardiac surgery" and "Evaluation of perioperative pulmonary risk" and "Preoperative medical evaluation of the healthy adult patient".)

Tumor factors — Tumor biology is one of the most important factors that predict recurrence and survival. Prognostic tools based on clinicopathologic features have been developed to determine the risk of recurrence after resection, help guide whether surgery is an appropriate treatment, and determine if the patient might benefit from neoadjuvant chemotherapy [3-6]. This is imperative in the modern era, in which patients typically receive chemotherapy before and/or after resection.

Four separate clinical risk scores are currently in use to stratify patients based on their likelihood of recurrence (table 1). High-risk patients may be considered for initial chemotherapy in order to assess the biology of the tumor prior to resection (ie, patients who develop rapidly progressive metastases beyond the liver during this trial period will have been spared an unnecessary operation). In one study, in patients who did not receive initial chemotherapy prior to resection, all but the Konopke score correlated with the disease-free survival (DFS), but only the Nagashima score was predictive of overall survival (OS). Among patients who received chemotherapy followed by resection, all but the Konopke score were predictive of DFS and OS [7]. Unfortunately, none of the scoring systems are able to predict disease-specific survival, particularly beyond five years. In clinical practice, these instruments are most often used to discuss outcomes and decision making when planning therapy with patients [8].

The embryonic origin of the primary colon cancer also appears to affect the prognosis of patients who develop liver metastases. In a study of 727 patients who underwent chemotherapy followed by resection, CRLMs from midgut origin (ie, right colon tumors) were associated with worse pathologic response to chemotherapy and worse survival after resection compared with CRLMs from hindgut origin (ie, left/sigmoid colon tumors). This effect was independent of the RAS mutation status [9]. The adverse impact of right- versus left-sided primary tumor location has been noted in other colorectal cancer (CRC) populations, including those with unresectable metastatic disease and localized nonmetastatic disease. (See "Pathology and prognostic determinants of colorectal cancer", section on 'Tumor location'.)

Anatomic factors — While previous guidelines for resection of CRLMs placed limits based on the number of lesions, tumor size, and margins, modern multidisciplinary consensus defines resectable CRC liver metastases simply as tumors that can be resected completely while leaving an adequate liver remnant (table 2) [10]. In other words, if resection can be accomplished to achieve an R0 resection and maintain a functional residual liver volume, other negative prognostic factors should not preclude surgery.

We agree with guidelines developed from a consensus conference held by the American Hepato-Pancreato-Biliary Association, the Society for Surgery of the Alimentary Tract, and the Society of Surgical Oncology in 2006, which state [11]:

●In patients undergoing liver resection for hepatic colorectal metastases, a positive surgical margin is associated with a higher local recurrence and worse OS and should be avoided whenever possible.

●While a wide (>1 cm) resection margin should remain the goal when performing a liver resection, an anticipated margin of <1 cm should not be used as an exclusion criterion for resection. (See 'Wide versus narrow margin' below.)

●Assessment of resectability of hepatic colorectal metastases should focus on the ability to obtain a complete resection (negative margins).

●The feasibility of hepatic resection should also be based on three criteria related to the remaining liver following resection: (1) the ability to preserve two contiguous hepatic segments, (2) preservation of adequate vascular inflow and outflow as well as biliary drainage, and (3) the ability to preserve adequate future liver remnant (>20 percent in a healthy liver; >30 percent after chemotherapy). (See "Overview of hepatic resection", section on 'Contraindications'.)

●The presence of extrahepatic disease should no longer be considered an absolute contraindication to hepatic resection provided the patient is carefully selected and a complete (margin-negative) resection of both intra- and extrahepatic disease is feasible.

Specific to the last point, portohepatic lymph node metastases associated with CRLMs are no longer considered an absolute contraindication to surgery [12-16]. Outcomes are more favorable when nodal involvement is limited to the porta hepatis nodes, as opposed to the common hepatic artery or paraaortic nodes [13].

PREOPERATIVE EVALUATION

Imaging — Preoperative imaging is used to determine the number and extent of liver metastases as well as their anatomic distribution to aid in surgical planning. It should also be used to identify extrahepatic disease spread. Either high-quality contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) can be used. In our practice, we prefer MRI because it is most sensitive in detecting additional lesions that might preclude resection. However, availability and the expertise of both the radiologist and surgeon in interpreting the findings should dictate local practices. (See "Overview of hepatic resection", section on 'Preoperative imaging'.)

Computed tomography — High-quality contrast-enhanced helical CT has a sensitivity between 70 to 95 percent and specificity of 96 percent for detecting liver metastases [17-19]. CT is readily available at most centers with a relatively low cost. Despite the widespread use of CT, it is limited in the ability to identify lesions smaller than 1 cm and can have false negative rates as high as 10 percent. Furthermore, CT has low sensitivity in detecting extrahepatic metastases, such as those on serosal surfaces of both the liver and peritoneum and within the porta hepatis [11].

CT can be used to estimate liver volume prior to resection. This is particularly important in patients undergoing portal vein embolization in order to increase the future liver remnant volume. (See "Preoperative portal vein embolization", section on 'Liver volumetry'.)

Magnetic resonance imaging — MRI images have a better contrast-to-noise ratio than CT images, particularly in livers with high fat content. When used with contrast enhancement, MRI has a sensitivity and specificity of 81 and 97 percent, respectively, for detecting colorectal liver metastases (CRLMs) [11,19,20]. Compared with CT, contrast-enhanced MRI is better at detecting subcentimeter lesions and CRLMs in patients with hepatic steatosis, a common occurrence after neoadjuvant chemotherapy [21,22]. However, MRI is generally less accessible than CT and may be difficult to perform in patients with claustrophobia and metal implants [23].

Positron emission tomography — The role of integrated positron emission tomography (PET)/CT in selecting optimal surgical candidates is uncertain. However, until additional data are available, including long-term follow-up of the Canadian trial [24], we agree with the guidelines from the NCCN, which recommend a staging PET scan for patients who appear to have potentially surgically curable metastatic CRC.

At least in theory, whole body PET scans have the potential to identify radiographically occult extrahepatic disease and optimize the selection of appropriate candidates for hepatic resection, mainly by reducing nontherapeutic laparotomy rates [25-28]. However, the data supporting a benefit for PET in this setting are mixed:

●The benefit of adding PET to the staging strategy was subsequently shown in a randomized trial in which 150 patients with CRC liver metastases selected for hepatic resection by CT were randomly assigned to triple-phase contrast-enhanced CT imaging only or CT plus a separate PET scan [28]. The primary outcome measure was the number of futile laparotomies (any laparotomy that did not result in complete tumor treatment or that did not result in a disease-free survival period of at least six months). The addition of PET significantly reduced the number of futile surgeries (28 versus 45 percent) and prevented unnecessary surgery in one of every six patients.

Two caveats must be considered when interpreting these results. First, this study used separate contrast-enhanced CT and PET images and not the increasingly popular integrated PET/CT imaging, in which both PET and CT are performed sequentially during a single visit on a hybrid PET/CT scanner. The CT component of integrated PET/CT imaging is performed in most institutions without the use of intravenous contrast material, which compromises the detection of small metastases both within and outside of the liver. At some institutions, PET/CT is carried out with intravenous contrast, but this practice is not widespread.

●A benefit for integrated PET/CT could not be confirmed in a later randomized trial in which 404 patients with potentially resectable isolated CRC liver metastases (as established by contrast-enhanced CT of the chest, abdomen, and pelvis within 30 days of randomization) were randomly assigned to preoperative integrated PET/CT or no PET/CT [24]. Of the 263 patients who underwent preoperative PET/CT, only 21 (8 percent) had a change in surgical management; these included seven (2.7 percent) who did not undergo laparotomy, four who had more extensive hepatic surgery, and nine (3.4 percent) who had additional organ surgery. Liver resection was performed in a similar proportion of both groups (91 versus 92 percent of the control group), and at a median follow-up of 36 months, survival did not differ between the groups (two-year survival 80 percent in both groups).

●The superiority of PET over CT alone for detection of extrahepatic disease was also suggested in a systematic overview of retrospective data that utilized a scoring system to weigh the individual studies according to the quality of the data and the clinical impact of the radiographic findings [26]. For the six articles judged to be of the highest quality [29-34], the pooled sensitivity and specificity for PET were 80 and 92 percent, respectively, for hepatic disease, and 91 and 98 percent, respectively, for extrahepatic disease [26]. The corresponding values for CT were 83 and 84 percent, respectively, for hepatic metastases, and 61 and 91 percent, respectively, for extrahepatic metastases. The percent change in clinical management from the performance of PET ranged from 20 to 32 percent (average 25 percent).

The results of restaging PET scans (particularly if negative) must be interpreted in the context of recent therapy. Chemotherapy may reduce the sensitivity of PET for the detection of liver metastases, thought due to decreased cellular metabolic activity following chemotherapy [35-37]. In one study, the false negative rate for hepatic metastases of a PET scan performed within four weeks of chemotherapy was 87 percent [36]. Thus, surgical decisions should not be based on PET scan results in the liver.

PET/CT scans are nearly always performed without intravenous contrast and therefore cannot substitute for contrast-enhanced CT scans.

Diagnostic laparoscopy — With improved sensitivity of cross-sectional imaging modalities, diagnostic laparoscopy is no longer standard for evaluating patients with CRLMs. Instead, we only use it in patients with a suspicion of small-volume carcinomatosis on radiographic imaging studies (ie, CT, MRI, or PET) or who are at particularly high risk for harboring unresectable diseases (eg, a metachronous presentation with several liver metastases that do not respond to chemotherapy).

NEOADJUVANT CHEMOTHERAPY — The availability of increasingly effective systemic chemotherapy for metastatic colorectal cancer (CRC) has prompted interest in preoperative or neoadjuvant systemic chemotherapy prior to liver resection.

Initial systemic chemotherapy is often undertaken as a means of assessing the natural history of metastatic disease prior to embarking on metastasectomy, particularly in those with a synchronous presentation of metastatic disease. Patients whose disease progresses while on chemotherapy or who develop extrahepatic disease have biologically aggressive tumors that would not benefit from resection. (See 'Synchronous colorectal liver metastases' below.)

Neoadjuvant systemic chemotherapy also has the potential to convert some patients with initially unresectable large or critically located liver metastases to resectable disease, although the true frequency with which this occurs is probably low. (See "Potentially resectable colorectal cancer liver metastases: Integration of surgery and chemotherapy", section on 'Patients with initially unresectable metastases'.)

The optimal selection criteria, specific regimen and duration of neoadjuvant chemotherapy, and the best way in which chemotherapy should be integrated with surgery in patients who present with synchronous metastatic disease have not been defined. Thus, the decision to proceed with or omit preoperative systemic chemotherapy should be made with multidisciplinary input, which is further discussed elsewhere. (See "Potentially resectable colorectal cancer liver metastases: Integration of surgery and chemotherapy".)

Morphologic response — After neoadjuvant therapy, standard criteria such as RECIST (Response Evaluation Criteria in Solid Tumors (table 3)) are used to evaluate tumor response to cytotoxic agents; they may not be applicable to biologic agents such as bevacizumab, which have a cytostatic mechanism of action [38-41]. Novel computed tomography (CT)-based morphologic criteria have been proposed that may more accurately predict pathologic response and prolonged survival in patients receiving preoperative chemotherapy, both with and without bevacizumab [40,42]. However, these require external confirmation and validation.

Fiducial placement — The introduction of modern chemotherapeutic agents has resulted in dramatic tumor responses for colorectal liver metastases (CRLMs), reaching almost 60 percent, some of which are complete. Disappearing liver metastases, which are no longer visible on cross-sectional imaging after neoadjuvant chemotherapy, can occur in 5 to 24 percent of patients [43-46]. Lesions at the greatest risk of disappearing are those <2 cm in diameter and >1 cm deep in the liver parenchyma [47]. Unfortunately, resection is still required because a true pathologic complete response or durable clinical response is rare (17 percent) after chemotherapy alone [43].

To locate lesions at the time of resection, those at risk of disappearing after chemotherapy can be marked with a fiducial marker (eg, coil) before initiation of neoadjuvant chemotherapy [48]. In a cohort of 32 patients with 41 CRLMs, 46 percent of lesions disappeared after neoadjuvant treatment. All such lesions in which a fiducial marker had been placed were successfully identified and either resected or ablated [47]. Fiducial placement should be considered for all lesions <2 cm in size, those that are located deeper than 1 cm in the liver parenchyma, and lesions outside of the proposed resection field [47].

Chemotherapy-related liver toxicity — The advent of more effective systemic chemotherapies has increased the number of patients who are candidates for resection of CRLMs. However, chemotherapy-associated liver injury can result in impaired liver function and should be taken into account during operative planning. In general, a future liver remnant volume of >30 percent is needed for livers that have undergone chemotherapy-associated changes.

Longer durations of preoperative chemotherapy are associated with a greater potential for liver toxicity and postoperative complications. Many advocate limiting chemotherapy to four cycles (16 weeks) if a subsequent liver resection is planned. (See "Potentially resectable colorectal cancer liver metastases: Integration of surgery and chemotherapy", section on 'Post-treatment assessment and duration of neoadjuvant therapy'.)

RESECTION OF COLORECTAL LIVER METASTASES — Liver metastases presenting at the same time with the primary colorectal cancer (CRC) or shortly thereafter are referred to as synchronous colorectal liver metastases (CRLMs). Metachronous CRLMs have a more delayed presentation, often after the primary CRC has been treated. There is no precise definition of synchronic versus metachronous disease; various studies have defined synchronous metastases as those occurring within 3, 6, or 12 months of the primary disease [49]. The approach to resecting synchronous CRLMs is typically more complex than resecting metachronous CRLMs as the former often involve two lesions, the primary CRC and the CRLMs.

Metachronous colorectal liver metastases — Metachronous CRLMs typically develop after the primary CRC has been removed. Thus, surgical treatment of these lesions is not different from surgery for any other liver lesions (eg, hepatocellular carcinoma). Detailed descriptions of liver resection techniques can be found elsewhere. (See "Overview of hepatic resection" and "Open hepatic resection techniques".)

Extensive bilobar metastases — Although patients who have significant CRLMs in both lobes of the liver cannot be cured with a single operation, curative resection can still be performed in two stages [50,51]. In the first stage, as many metastases are removed as possible. Systemic therapy is then administered to control the remaining disease while the patient recovers and the remnant liver hypertrophies. Portal vein embolization can be performed after the first operation to promote the extent of liver hypertrophy [52] (see "Preoperative portal vein embolization"). If there is sufficient hypertrophy to prevent liver failure at four to six weeks, a second-stage operation is performed to remove the remaining CRLMs. Unfortunately, up to one-quarter of patients fail to undergo the second-stage operation due to disease progression [53].

Synchronous colorectal liver metastases — The surgical approach to resecting synchronous CRLMs is more varied. Patients with both a primary CRC and CRLMs have the options of undergoing simultaneous resection of the primary tumor and CRLMs or a staged resection, which can be colorectal first (classic) or liver first (reverse approach). Systematic reviews and meta-analyses show no difference in outcomes regardless of which approach is taken [54-56]. (See "Potentially resectable colorectal cancer liver metastases: Integration of surgery and chemotherapy" and "Locoregional methods for management and palliation in patients who present with stage IV colorectal cancer", section on 'Management of the primary cancer'.)

In the METASYNC trial, 39 and 46 patients with initially resectable CRLMs were randomly assigned to simultaneous and delayed liver resection, respectively [57]. While rates of intraoperative and postoperative complications were similar between the two groups, simultaneous resection resulted in superior two-year overall survival (87.2 versus 69.6 percent) and disease-free survival (35.9 versus 17.4 percent). However, there are several concerns about whether the two groups were perfectly matched: there were more patients with rectal primaries or >3 liver metastases in the delayed resection group, adverse mutations that could influence survival were not tested or balanced, and the limited sample size did not allow for the complexity of either colorectal or liver surgery to be factored into the randomization process either.

Thus, despite findings from the METASYNC trial, the decision to perform a staged or simultaneous resection should be individualized to each patient. At high-volume centers, patients with limited colorectal and extensive liver diseases or extensive colorectal and limited liver diseases can frequently be candidates for synchronous resections. Studies have shown that simultaneous resection even with major hepatectomies (>3 segment resection) can be performed safely with this approach [58]. However, patients requiring major colon and major hepatic surgery are best served by staged operations because of the greater risk of postoperative morbidity and compromises in the delivery of systemic treatment [59]. The decision of which approach is used should be evaluated on a case-by-case basis and depends on surgeon expertise.

Selecting a surgical approach — Treatment of the primary and metastatic lesions in patients with synchronous CRLM is often multidisciplinary and multimodal, involving chemotherapy, chemoradiation therapy, surgery, and locoregional therapy. The timing and sequence of surgical resection remain controversial but mostly depend on the acuity of symptoms and disease burden:

●Patients who present with symptoms from the primary CRC, such as bleeding, obstruction, or perforation, should undergo resection of the colorectal primary tumor first. Utilizing the liver-first approach can delay resection of the primary and increase the risk of developing complications related to the primary colorectal tumor. Studies have found rates of bleeding, obstruction, and perforation to be as high as 20 percent [60,61].

●Patients who are asymptomatic from the primary CRC may undergo a simultaneous or staged resection, depending on the extent of their liver involvement:

•Patients with a colorectal primary lesion in a favorable location (eg, right colon) and limited liver metastases may undergo simultaneous resection.

•Patients with extensive bilobar disease would benefit from the classic (colorectal-first) two-staged approach. Complete resection of such extensive CRLMs often requires an anatomic resection combined with multiple partial hepatectomies. This typically cannot be accomplished in a single operation, because of a high risk of liver failure. With the classic approach, at the time of colorectal primary resection, the CRLMs on the future liver remnant are resected with partial hepatectomies, leaving tumors behind on the portion of the liver that can be treated with a future anatomic resection. The patient then undergoes embolization of the portal vein on the side with the remaining tumors. After an adequate hypertrophy of the future liver remnant, a formal anatomic resection of the remaining diseases can be performed as the second-stage operation (figure 1).

•Some patients who are treated with neoadjuvant chemotherapy may benefit from a two-staged liver-first approach. In one example, patients with locally advanced rectal cancer (T4 and/or bulky tumor, or extensive nodal disease) may benefit from intensification of preoperative therapy using induction chemotherapy followed by chemoradiotherapy instead of chemoradiotherapy alone. If such patients have synchronous, potentially resectable liver metastases, they would be candidates for the reverse (liver-first) two-staged approach to resection: after four months of induction chemotherapy, hepatic resection typically takes place first; colorectal resection then follows in another two to four months upon completion of two additional months of chemotherapy and chemoradiotherapy to enhance local control (minimize the risk of a positive margin). Further delaying hepatic resection until a simultaneous resection can be carried out (at six to eight months) may worsen chemotherapy-induced liver changes and increase the risk of postoperative liver failure. (See "Neoadjuvant therapy for rectal adenocarcinoma", section on 'Total neoadjuvant therapy for locally advanced tumors' and 'Chemotherapy-related liver toxicity' above.)

Simultaneous resection — When simultaneous resection is performed, the liver resection is performed first. Intravenous fluids are minimized, and low central venous pressure is maintained until parenchymal transection is complete in order to minimize blood loss. Once the hepatic resection is completed, the patient can be hydrated and colorectal resection performed. After colorectal resection, the liver should be reexamined for bile leak and hemostasis. The details of liver parenchymal transection techniques can be found elsewhere. (See "Open hepatic resection techniques", section on 'Division of the liver tissue and hemostasis'.)

If the hepatic resection is more extensive than anticipated, or there is greater blood loss than anticipated, and/or the patient is not tolerating the procedure, the colorectal portion should be postponed and a staged approach utilized. This is critical because the remnant liver may not be able to withstand the stress of additional surgery and blood loss, resulting in acidosis and potential liver failure.

Typical incisions used for simultaneous resection are midline laparotomy, a modified Makuuchi incision [62], or an L-shaped incision, based on the location of the colorectal primary. Subcostal incisions can be used but may make access to portions of the colon and rectum challenging.

Several studies have shown that length of stay and perioperative mortality are similar between simultaneous and staged CRLM resection, but patients who underwent simultaneous resection in these studies had higher numbers of right-sided colon primaries, smaller and fewer CRLMs, and less extensive liver resection [63-66]. When a major hepatectomy was performed (resection of >3 segments), simultaneous resection carried higher morbidity (36.1 versus 15.1 percent) and mortality (8.3 versus 1.4 percent) than staged resection [66].

The indications for a simultaneous resection have been discussed above. (See 'Selecting a surgical approach' above.)

Staged resection — Traditionally, patients were treated with initial resection of the colorectal primary followed by administration of systemic chemotherapy and CRLM resection two to three months later as long as there was no disease progression [67,68]. Advocates for the classic approach cite higher perioperative morbidity using the simultaneous approach. However, with advances in perioperative management and surgical technology, this viewpoint has been challenged [11]. The contemporary approaches to staged resection can be either colorectal first (classic) or liver first (reverse).

Classic (colorectal-first) approach — The classic colorectal-first approach involves resection of the colorectal primary tumor first, postoperative recovery, and two to three months of systemic chemotherapy. If the patient has stable disease or good response to chemotherapy, resection of the CRLMs is performed.

As mentioned above, response to neoadjuvant chemotherapy is prognostic of improved overall survival (OS). A study examining patients with synchronous CRLMs who underwent staged, colorectal-first resection found that absence of progression after chemotherapy was associated with improved five-year OS (85 versus 35 percent) [69]. The interval from resection of the primary tumor to CRLMs allows for identification of tumors with aggressive biology that will progress, and thereby excluding those patients from a second major operation with doubtful benefit [70].

The indications for a classic approach have been discussed above. (See 'Selecting a surgical approach' above.)

Reverse (liver-first) approach — The liver-first or reverse approach has emerged as a viable option in the management of CRLMs. Proponents of this approach often cite that delaying resection of the colorectal primary to allow hepatic metastasectomy with or without systemic chemotherapy to be performed first rarely reduces resectability of the primary, while delaying resection of the hepatic metastases so that the colorectal primary can be resected first may result in progression of the liver metastases beyond resectability. Therefore, they argue liver resection should precede colorectal primary tumor resection [71]. Furthermore, significant postoperative complications with a colorectal-first surgery can preclude both resection of the CRLM and systemic chemotherapy, which can also result in CRLM progression.

The liver-first approach terminology is misleading as patients typically receive neoadjuvant therapy before surgery. The efficacy of this approach has been shown in the following studies:

●A systematic review of the liver-first approach found that the overall morbidity and mortality after CRLM resection were 20 and 1 percent, respectively [72]. Ultimately, 74 percent of patients had resection of their colorectal primary, and the rates of perioperative morbidity and mortality were 50 and 6 percent, respectively. The median overall survival was 40 months, and 52 percent of patients recurred. This analysis is limited in that only four studies were included, each with heterogeneous patient selection.

●In a network meta-analysis comparing the classic, simultaneous, and liver-first surgical strategies, the authors found that five-year OS, 30 day mortality, and postoperative complications were comparable among all of the groups [73]. However, there was a trend toward better outcomes with the liver-first approach and a nonsignificant increase in the rate of intra-abdominal collections/abscesses in the simultaneous group.

The liver-first approach to a staged resection is often selected by surgeon preference. One sample scenario that calls for this approach has been discussed above. (See 'Selecting a surgical approach' above.)

SURGICAL TECHNIQUES — This section will focus on operative considerations specific to resecting colorectal liver metastases (CRLMs). Detailed but generic descriptions of hepatic resection techniques can be found elsewhere. (See "Open hepatic resection techniques".)

Parenchymal-sparing versus anatomic resection — CRLMs can be resected with an anatomic resection or a nonanatomic, parenchymal-sparing resection (PSR). Anatomic resections are based upon the segmental anatomy of the liver according to Couinaud (figure 2), while the extent of a PSR is determined by the location and size of the CRLMs. (See "Overview of hepatic resection", section on 'Type and extent of resection'.)

The optimal extent of liver resection for CRLMs is subject to debate, but current trends are moving toward nonanatomic PSRs.

The type of resection (anatomic versus PSR) has not been associated with significant differences in rates of positive margin, recurrence, or survival [74]. A 2017 systematic review of PSR versus anatomic resection found that liver preservation did not compromise such oncologic outcomes [75]. Furthermore, there were no differences in estimated blood loss, length of hospital stay, perioperative morbidity, incidence of R0 resection, and mortality. However, anatomic resection was associated with a higher rate of post-hepatic liver insufficiency (8 versus 2 percent). A 2019 systematic review associated PSR with shorter operative time, less blood loss, lower transfusion requirement, and fewer postoperative complications, while the overall survival and recurrence-free survival were not different between the PSR and non-PSR groups [76].

PSR preserves greater hepatic reserve, particularly when chemotherapy-induced liver injury is a concern, and potentially increases salvageability in case of hepatic recurrence. In a retrospective study of solitary CRLMs <3 cm, patients who underwent PSRs and anatomic resections had similar rates of liver recurrences (14 versus 17 percent), but those who underwent PSRs were more likely to undergo repeat hepatectomy when they did develop a recurrence in the liver remnant (68 versus 24 percent) [77]. As a result, PSR was associated with a higher five-year overall survival (OS) than anatomic resection in a subgroup analysis of liver-only recurrences.

Margins — Obtaining a negative resection margin (R0) is one of the key tenets of oncologic surgery and, even in the era of modern chemotherapy, remains an important determinant of survival [78]. For CRLMs, traditionally the standard resection margin is >10 mm [79,80]. However, that view has been challenged by several groups [81,82]. (See "Overview of hepatic resection", section on 'Resection margins'.)

Wide versus narrow margin — There are no prospective randomized clinical trials examining the impact of positive or close margin on survival for CRLMs, and such a study may never occur [83].

We suggest that resection margins of >10 mm for CRLMs should be targeted when anatomically feasible. A 2017 meta-analysis of 34 cohort studies including 11,000 patients found that resection margins >10 mm were associated with improved five-year overall survival compared with margins ≤10 mm (relative risk 0.91, 95% CI 0.85-0.97) [84].

However, we also believe surgery should still be offered when such a wide margin is not feasible but, at minimum, a 1 mm resection margin can be achieved. Several large retrospective studies have examined margin status and found that a margin that is <10 mm but negative is not associated with worse survival:

●In a retrospective study of 378 patients who underwent resection for CRLMs after neoadjuvant therapy at the MD Anderson Cancer Center, those with an R0 resection, defined as tumor-free margin ≥1 mm, had better five-year OS compared with those with a margin <1 mm (55 versus 26 percent) [78]. The impact of positive margin is most pronounced in patients with suboptimal response to systemic therapy. (See 'Morphologic response' above.)

●In a multicenter study of 551 patients undergoing liver resection for CRLMs, surgical margins were categorized as positive or negative with 1 to 4 mm, 5 to 9 mm, and >10 mm of tumor-free margins [81]. Although positive margins were associated with a greater risk of surgical margin recurrence, the width of negative margins did not affect survival, recurrence, or the site of recurrences.

●In a study of 4915 patients who underwent resection for CRLM at the Memorial Sloan Kettering Cancer Institute, the median OS was 32, 40, 53, and 56 months for patients with 0 mm (R1), 0.1 to 0.9 mm, 1 to 9 mm, and >10 mm margins, respectively [85]. Compared with R1 resection, all margin widths, including submillimeter margins, correlated with prolonged OS, and there was no statistically significant difference in survival between the 1 to 9 mm and >10 mm groups. These data suggest that wider margins should be attempted, but even a narrow margin should not preclude resection as long as it is negative.

●In a study of 227 patients undergoing resection for CRLM after neoadjuvant therapy at Massachusetts General Hospital, positive margins (<1 mm) significantly increased the risk of death without, but not with, post-liver-resection chemotherapy. Negative margin sizes of ≥1 to <5 mm, ≥5 to <10 mm, and ≥10 mm were not a significant predictor of OS [86].

●In a study of 633 patients who underwent surgery for CRLMs, having a >1 mm margin was associated with an improved OS of 65 versus 36 months in those with a <1 mm margin [87].

At a molecular level, pathologic examination and deoxyribonucleic acid (DNA) analysis of normal liver tissue surrounding resected CRLMs revealed that almost all micrometastases and viable cancer cells were found within 4 mm of the tumor border [88,89]. This was true even in patients who had reduction in tumor size secondary to neoadjuvant therapy [89].

RAS mutational status — Signaling through the RAS oncogene is an important regulator of cellular signal transduction, and mutations in RAS represent an early step in colorectal tumorigenesis. In addition, RAS mutations portend a more aggressive tumor biology of CRLMs and have been associated with more positive margins and worse survival after resection. Consequently, anatomic resection and/or a wider surgical margin (eg, >10 mm) may be indicated for patients with RAS-mutated CRLMs.

In a retrospective study of 633 patients who underwent curative-intent resection for CRLM at the MD Anderson Cancer Center, 36.2 percent had a RAS mutation [90]. Patients with a RAS mutated tumor were twice as likely to have a positive resection margin (<1 mm) compared with those without a RAS mutation (11 versus 5 percent). RAS mutation (hazard ratio 1.6) and positive margin (hazard ratio 3.4) were independent predictors of poor overall survival by multivariate analysis. The authors proposed aiming for a 1 cm resection margin for RAS-mutated CRLMs.

Others reported that even a wider resection margin may not be sufficient to overcome the aggressive tumor biology associated with a RAS mutation. In study of 411 patients who underwent resection for CRLMs at Johns Hopkins, a 1 to 4 mm margin was associated with improved survival compared with a positive margin (<1 mm or R1) for wild-type KRAS tumors, with which a wider resection margin did not further improve survival. In KRAS-mutated tumors, however, negative margin status, which included a 1 cm margin, did not improve survival [91].

Consequently, other investigators studied whether anatomical resections would benefit RAS-mutated CRLMs [92]. In one such study, 389 patients underwent either an anatomic or nonanatomic CRLM resection. Patients with wild-type RAS tumors had no difference in disease-free survival (DFS) based on the type of resection. By contrast, patients with RAS mutations had worse DFS with nonanatomic compared with anatomic resection (10.5 versus 33.8 months). The authors of the study suggested that the more aggressive anatomic resections may be warranted in patients with RAS-mutated tumors.

The prognostic influence of RAS and other mutations is also discussed below. (See 'Oncologic' below.)

Intraoperative reresection to obtain negative margins — The impact of intraoperative reresection to obtain negative margins has been examined. Data suggest that additional margin >1 cm obtained by intraoperative reresection does not confer the same survival benefit as an initial negative margin of >1 cm [93] and that a negative margin achieved at reresection was not associated with better survival or fewer recurrences compared with R1 resections. This is probably because a narrow or positive margin is reflective of aggressive tumor biology, which is a more important prognostic factor than surgical techniques [94]. Despite that, every effort should be made during resection to obtain an initially negative margin.

Air cholangiogram — Postoperative bile leak is a major complication that occurs after liver resection in approximately 1 in 10 patients. We routinely perform an air cholangiogram to minimize it.

After liver parenchymal transection and hemostasis, a catheter is inserted into the cystic duct stump (assuming cholecystectomy has been performed) and secured with a silk suture [95].

In the first portion of the air cholangiogram test, liver ultrasonography is performed while air is injected into the catheter and digital pressure is applied to occlude the distal common bile duct. Pneumobilia visible on ultrasound indicates patency of the duct. Absence of pneumobilia could be due to bile duct obstruction, massive air leak via a large open bile duct, or, most commonly, incomplete manual occlusion of the distal common bile duct (with air escaping into the duodenum).

In the second portion, the right upper quadrant is filled with sterile water or saline to submerge the liver. Air is again injected via the cholangiogram catheter. The presence of bubbles indicates air leaking through one or more open bile ducts. Each open duct that is identified can be suture ligated, and the procedure is repeated until no more leaks are identified. In one study using this method, 62 percent of the bile duct leaks were identified, which reduced the bile leak rate to 1.9 percent [95].

Drains — Routine placement of intra-abdominal drains after hepatectomy has no clear benefit [96,97]. Thus, we do not routinely use drains in our practice.

In a large multi-institutional study of 1041 patients who underwent a major hepatectomy (>3 segments) without a biliary anastomosis, approximately one-half had drains placed intraoperatively at the surgeon's discretion. Primary drain placement was associated with increased risk of bile leak and 30 day readmission rate but no reduction in the need for secondary drainage procedures [98].

Open versus minimally invasive resection — Hepatic resection for colorectal cancer liver metastasis can be performed open or minimally invasively. Since 2015, the number and complexity of minimally invasive liver resections have both increased dramatically. In experienced centers, an estimated 60 to 70 percent of patients with CRLMs are candidates for minimally invasive resection [99]. Minimally invasive resection, in carefully selected patients, has been shown to have superior short-term outcomes and superior or at least comparable long-term (oncologic) outcomes to its open counterpart [100]. The techniques and outcomes of minimally invasive liver surgery are discussed elsewhere. (See "Minimally invasive liver resection (MILR)".)

UNRESECTABLE COLORECTAL LIVER METASTASES — Approximately 80 percent of patients with metastatic colorectal cancer (CRC) are not candidates for resection at diagnosis [101]. Initial treatment options include chemotherapy and/or locoregional therapies such as ablation.

The term "conversion therapy" has been proposed to designate the use of induction chemotherapy in such patients [102]. It is reported that between 12 and 33 percent of patients with "initially unresectable" hepatic metastases have a sufficient objective response to conversion therapy to permit a subsequent complete (R0) resection (table 4) [103-110].

Ablation is a parenchymal-sparing strategy that is increasingly used for management of small or unresectable tumors. (See "Nonsurgical local treatment strategies for colorectal cancer liver metastases".)

For patients with borderline resectable disease or inadequate future liver remnant for resection, a combined ablation/resection approach can be used for colorectal liver metastasis (CRLM) treatment:

●In a multicenter study of 288 patients who underwent combined intraoperative ablation and resection of CRLMs, the five-year overall survival was 37 percent, and local recurrence-free survival from ablated lesions was 78 percent. Postoperative mortality was 1 percent, and the overall complication rate was 35 percent [111].

●Another study compared combined ablation and resection with two-stage hepatectomy for bilobar CRLMs. The combined ablation/resection strategy achieved a better median overall survival (46 versus 36 months) and cost savings of >$25,000 [112].

Management of initially unresectable CRLMs and locoregional therapies for categorically unresectable CRLMs are further discussed in other topics. (See "Potentially resectable colorectal cancer liver metastases: Integration of surgery and chemotherapy" and "Nonsurgical local treatment strategies for colorectal cancer liver metastases".)

REPEAT RESECTION FOR COLORECTAL LIVER METASTASES — Recurrences following initial resection of colorectal liver metastases (CRLMs) can occur in up to 57 percent of patients, with the liver being the most common location of recurrences [113]. Reresection for recurrence of CRLM is a safe and feasible option in properly selected patients. Sufficient future liver reserve is paramount in order to prevent post-hepatectomy liver failure.

Although randomized trials have not been conducted to prove benefit, repeat hepatic resection may be considered in selected patients who recur in the liver with no evidence of extrahepatic disease and a good performance status. In several reported series, perioperative mortality rates were less than 5 percent, and overall survival rates ranged from 20 to 43 percent at two to five years (table 5) [14,114-128].

Patients with a relapse-free interval of longer than one year appear to have a more favorable outcome from reresection. Other factors associated with a poor outcome include synchronous resection for the first liver metastases and the presence of multiple lesions at second hepatectomy [116-118,122,129].

Interestingly, recurrences at the margin are uncommon [81,130,131]. Repeat hepatectomy is a safe and feasible option, with studies reporting five-year overall survival rates after reresection of 33 to 73 percent with no perioperative mortality [116,132,133]. Evaluation of prognostic factors has identified an initial largest CRLM >5 cm and positive margins at initial resection to be associated with worse survival [132].

Recurrence after two-stage hepatectomy — Disease is thought to recur more frequently after two-stage hepatectomies than after single-stage liver resections because of a more extensive tumor load. (See 'Extensive bilobar metastases' above.)

Nevertheless, long-term survival is still possible with repeat surgery for recurrence even in this cohort of patients:

●In 81 patients who completed two-stage liver resection for extensive CRLM, 62 (77 percent) had recurrence [134]. Repeat surgery was performed in 38 patients, of which 31 were potentially curative. For these 31 patients, the disease-free survival rates at one, three, and five years were 33.0, 14.1, and 12.1 percent after the repeat surgery and 54.7, 30.8, and 22.5 percent after the initial two-stage hepatectomy.

●In another 111 patients who completed two-stage hepatectomy for CRLM, 83 (75 percent) developed recurrence [135]. Thirty-one patients (37 percent) underwent resection for recurrence, and 11 (13 percent) underwent multiple resections for recurrence. The median overall survival among patients with recurrence was much longer with than without resection (143 versus 49 months).

POSTOPERATIVE CARE — Postoperative care following liver resection is described in another topic. (See "Overview of hepatic resection", section on 'Postoperative care'.)

OUTCOMES

Perioperative — In the modern era, perioperative mortality associated with colorectal liver metastasis (CRLM) resection is <5 percent, and around 1 percent in high-volume centers, regardless of whether a simultaneous, classic, or reverse approach is used. (See 'Selecting a surgical approach' above.)

Individual retrospective studies for simultaneous resection reported varying rates of perioperative morbidity ranging from 5 to 48 percent for minor hepatectomy to 33 to 55 percent for major hepatectomy. With staged procedures, morbidity rates ranged from 16 to 67 percent [136].

A systematic review and meta-analysis of 41 studies (over 12,000 patients) undergoing resection of CRLM associated the occurrence of postoperative complication with reduced overall survival (hazard ratio 1.43, 95% CI 1.3-1.57) and reduced disease-free survival (hazard ratio 1.38, 95% CI 1.27-1.49) [137].

Postoperative complications of liver resection, which include bile leak, ascites, liver failure, and pulmonary and thrombotic complications, are discussed elsewhere. (See "Overview of hepatic resection", section on 'Complications'.)

Oncologic — Five-year overall survival (OS) rates for patients with CRLMs receiving systemic chemotherapy alone, even with modern agents, are less than 11 percent, with only 2 percent having a durable response [138]. (See "Systemic therapy for metastatic colorectal cancer: General principles", section on 'Systemic therapy versus supportive care'.)

Resection for CRLMs is possible in approximately 25 percent of patients with liver-only disease. However, in the subset of patients who undergo liver surgery, five-year OS rates have improved from 30 to nearly 60 percent [139-141]. In studies with long-term follow-up, 10 year OS rates of up to 24 percent have been reported, and there are even reports of >20 year survivors [3,142].

Resection offers the greatest likelihood of cure for patients with liver-isolated colorectal cancer (CRC). In surgical case series, five-year survival rates after resection range from 24 to 58 percent, averaging 40 percent (table 6), and surgical mortality rates are generally <5 percent [3,4,25,114,139,140,143-151].

RAS mutation — As discussed above, signaling through the RAS oncogene is an important regulator of cellular signal transduction, and mutations in RAS represent an early step in colorectal tumorigenesis. Consequently, RAS mutations are associated with poor prognosis; patients with RAS-mutated tumors have higher levels of recurrence and poorer OS after resection of CRLMs and a greater chance of positive margins. The influence of RAS mutations on the width of the surgical margin in patients undergoing metastasectomy is addressed above. (See 'Margins' above.)

As an example, in a retrospective study of 421 patients who underwent hepatic resection for CRLM, 44 percent had a RAS mutation [152]. Having a RAS mutation was a risk factor for worse overall survival (hazard ratio [HR] 1.67, p = 0.0031) and disease-free survival (HR 1.70, p = 0.0024).

While RAS mutations have generally been associated with more aggressive tumor biology and hence worse survival [153], their prognostic significance appears to differ by the specific site of metastases. In one study of 193 patients who underwent CRLM resection after chemotherapy, RAS mutations were associated with early lung but not liver recurrence [153]. In another study, 720 patients underwent resection of liver, lung, or peritoneal colorectal metastases. Patients whose tumors contained a RAS mutation had significantly worse OS after resection of liver, but not lung or peritoneal, metastases [154].

Finally, the impact of RAS mutations may also differ by the specific mutation within the RAS gene. A study evaluating KRAS and NRAS mutations in 165 patients undergoing resection of CRLMs found that exon 4 mutations were associated with large, solitary metastases occurring after long disease-free intervals, while exon 3 mutations presented with small, numerous lesions [155]. Furthermore, patients with exon 4 mutations recurred infrequently and had longer OS compared to those with wild-type RAS or other RAS mutations (eg, in exon 2).

The implications of RAS mutations on treatment of colorectal cancer are further discussed elsewhere. (See "Pathology and prognostic determinants of colorectal cancer", section on 'RAS and BRAF' and "Systemic therapy for metastatic colorectal cancer: General principles", section on 'RAS'.)

BRAF mutation — Mutations in the BRAF gene have also been linked to poor prognosis after resection of CRLMs [156-158]. BRAF mutations affect the same signaling pathway as RAS mutations, with BRAF acting downstream from RAS. The incidence of BRAF mutations in resected CRLMs is lower than that of RAS mutations (2 to 4 percent versus 30 to 40 percent). Most mutations of BRAF occur in codon 600 (V600E). (See "Pathology and prognostic determinants of colorectal cancer", section on 'RAS and BRAF'.)

In a multicenter retrospective study of 853 patients undergoing hepatectomy for CRLM, 5, 38, and 57 percent had a mutation in BRAF, RAS, and neither gene, respectively [159]. A V600E mutation, but not non-V600E mutations of BRAF, is associated with worse overall survival (HR 2.76, 95% CI 1.74-4.37) and disease-free survival (HR 2.04, 95% CI 1.3-3.2). The V600E BRAF mutation was more strongly associated with overall and disease-free survivals than RAS mutations.

In another large multi-institutional study, 1497 patients with known BRAF mutation status underwent hepatectomy for CRLM [160], of whom 2 percent had a BRAF mutation (71 percent of which were specifically V600E). Having a BRAF mutation was associated with poorer overall (median 40 versus 81 months, p <0.001) and recurrence-free (median 10 versus 22 months, p <0.001) survival. Despite the poor prognosis, patients with BRAF-mutated tumors who had node-negative primary tumors, a carcinoembryonic antigen (CEA) level <200 mg/L, and clinical risk score (CRS) <4 were able to achieve long-term survival.

These data show that only a small percentage of patients with potentially resectable colorectal liver metastases present with a BRAF mutation. Even though prognosis is poor in this group, some patients are able to achieve long-term survival and may be cured using this approach. Therefore, it is difficult to justify denying a patient an attempted resection based solely on BRAF mutation status. However, that information can be used to help counsel the patient about the likelihood of recurrence and may dissuade surgery if the risks from a resection exceed the benefit when taking into account tumor biology based upon mutation status.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Colorectal cancer" and "Society guideline links: Colorectal surgery for cancer" and "Society guideline links: Liver resection and ablation".)

SUMMARY AND RECOMMENDATIONS

●Hepatic resection is the only curative option for patients with colorectal liver metastases (CRLMs). Survival after resection has doubled, reaching almost 60 percent in the modern era. Perioperative mortality is typically <5 percent, and it is <1 percent in high-volume centers. (See 'Introduction' above and 'Perioperative' above.)

●Operative planning should be based on maintaining inflow (hepatic artery and portal vein), outflow (hepatic veins), biliary drainage, and adequate future liver reserve to prevent post-hepatectomy liver failure. Anatomically speaking, if an R0 resection can be accomplished and a functional residual liver volume preserved, other negative prognostic factors should not preclude surgery. However, patient-related factors (eg, comorbidities) can prohibit surgery. (See 'Patient selection' above.)

●Either high-quality computed tomography (CT) or magnetic resonance imaging (MRI) can be used to determine the quantity and location of CRLMs and their resectability. The quality of the liver should also be assessed as preoperative chemotherapy can cause liver injury. In general, a healthy liver requires a future liver remnant volume of >20 percent, and >30 percent is needed for livers that have undergone chemotherapy-associated changes. (See 'Preoperative evaluation' above and 'Chemotherapy-related liver toxicity' above.)

●Clinical risk scores can be used to counsel patients by determining the risk of recurrence and overall survival. Response to neoadjuvant chemotherapy is one of the strongest predictors of long-term survival and recurrence. Morphologic changes in response to chemotherapy rather than size can provide prognostic data. (See 'Tumor factors' above and 'Morphologic response' above.)

●CRLMs smaller than 2 cm and >1 cm deep in the liver are at greatest risk of disappearing (radiographically) after systemic chemotherapy. They should still be resected because complete pathologic response is rare. Fiducial placement prior to systemic therapy can facilitate identification of these lesions at the time of resection. (See 'Fiducial placement' above.)

●Synchronous CRLMs can be resected using simultaneous, classic (colorectal-first), or reverse (liver-first) approaches. The timing and sequence of resections mostly depend on the acuity of symptoms and disease burden (see 'Synchronous colorectal liver metastases' above):

•Patients who present with symptoms from the primary colorectal cancer (CRC), such as bleeding, obstruction, or perforation, should undergo resection of the colorectal primary tumor first. Following postoperative recovery and two to three months of systemic chemotherapy, resection of the CRLMs is performed if there is no disease progression. (See 'Classic (colorectal-first) approach' above.)

•Patients with extensive bilobar diseases would benefit from the classic (colorectal-first), two-staged approach: at the time of colorectal primary resection, some CRLMs are resected with partial hepatectomies, leaving tumors behind on the portion of the liver that will be treated with a future anatomic resection. The patient then undergoes embolization of the portal vein on the side with the remaining tumors. After an adequate increase in the future liver remnant, a formal anatomic resection of the remaining diseases can be performed at the second-stage operation (figure 1).

•Patients with a colorectal primary lesion in a favorable location (eg, right colon) and limited liver metastases may undergo simultaneous resection. Simultaneous resection should be used cautiously when both the liver and colorectal tumors require an extensive resection. When simultaneous resection is performed, the liver resection is performed first. If the hepatic resection is more extensive than anticipated, or there is greater blood loss than anticipated, and/or the patient is not tolerating the procedure, the colorectal portion should be postponed and a staged approach utilized. (See 'Simultaneous resection' above.)

●Parenchymal-sparing resections achieve similar oncologic outcomes to those of anatomic resections while preserving greater hepatic reserve, which potentially increases salvageability in case of hepatic recurrence. While still debated, current trends are moving toward nonanatomic parenchymal-sparing resections for CRLMs. (See 'Parenchymal-sparing versus anatomic resection' above.)

●The goal of CRLM resection should be to obtain negative margins. When anatomically feasible, we suggest obtaining resection margins of >10 mm (Grade 2C). However, resection should still be offered if a minimal margin of >1 mm can be achieved. Every effort should be made to achieve a negative initial margin as intraoperative reresection of the margin based on frozen section results has not been associated with the same survival advantage as the initial margin. (See 'Wide versus narrow margin' above and 'Intraoperative reresection to obtain negative margins' above.)

●Special consideration should be given to patients with RAS-mutated and BRAF-mutated (V600E) tumors as they have poorer survival and more positive margins when using standard surgical techniques. Wider negative margins (eg, >1 cm) and/or anatomic resection may benefit this population, although narrow margins are likely reflective of aggressive tumor biology rather than poor technique. (See 'RAS mutational status' above and 'RAS mutation' above and 'BRAF mutation' above.)

●We routinely perform an air cholangiogram after anatomic or multiple nonanatomic liver resections to minimize the risk of bile leak. We do not routinely place abdominal drains intraoperatively. (See 'Air cholangiogram' above and 'Drains' above.)

●CRLM recurrence after resection is common, and reresection is a safe and feasible option in properly selected patients with adequate future liver reserve and good performance status. (See 'Repeat resection for colorectal liver metastases' above.)