CME: Liver Resection for Hepatic Colorectal Metastases

Continuing Medical Education
from Clinical Update, Winter 2004

Liver Resection for Hepatic Colorectal Metastases
Perry Shen, M.D., Assistant Professor of Surgical Oncology
Department of General Surgery, Surgical Oncology

Disclosure: Dr. Shen has been involved in research activities with Celgene and Vivant Medical.

Abstract: Colon cancer is the second leading cause of cancer death in the United States. Liver metastases occur in up to 60% of patients. Hepatic resection provides the best chance for long-term survival. New developments in diagnosis and surgical technique have increased the safety of liver surgery and have the potential to improve clinical outcomes.

Introduction
Approximately 150,000 cases of colorectal cancer occur each year in the United States, with 63,000 deaths annually (1). Because the venous drainage of the colon and upper rectum is through the portal vein which then drains directly into the liver, hepatic metastases will occur in up to 60% of these patients, half of which will have only liver disease. Though primary colorectal cancer has a good prognosis when resected with clear margins and negative lymph nodes, the diagnosis of liver metastases portends a poor outcome. The recent addition of new chemotherapeutic regimens such as irinotecan and oxaliplatin, and targeted drug therapy such as bevacizumab and cetuximab have demonstrated median survivals of up to 20 months for patients with stage 4 colon cancer, but they rarely provide a long-term cure (2).

Outcomes for Hepatic Resection
Surgery provides the best chance for cure in patients with hepatic colorectal metastases. Five-year survival rates following resection range between 25% and 39%, with a median survival between 28 and 40 months in large series. Ten-year survival results have been documented in the 20% to 26% range (3). In sharp contrast, the median survival for non-resected colorectal liver metastases is 5-10 months.

Various factors are important in the selection process for surgical candidates. In order to identify which subset of patients will benefit most from resection, various prognostic factors have been identified. The variables most commonly associated with recurrence are a positive resection margin and extrahepatic disease. Thus, inability to completely remove all tumors or the presence of extrahepatic disease are considered contraindications for surgery. Other factors associated with an increased risk of recurrence after hepatic resection include synchronous presentation of liver metastases with the primary tumor, more than 1 lesion in the liver, extent of liver involvement greater than 50%, a margin of resection less than 1 cm, CEA level > 200 ng/ml, and intraoperative blood transfusions. However none of these prognostic variables are an absolute contraindication to surgery. They were mainly formulated to assist in patient selection (4).

Preoperative Evaluation
Diagnostic imaging is important in staging potential candidates for liver resection of their colorectal metastases. The most commonly used modalities are computed tomography (CT) and magnetic resonance imaging (MRI). High quality imaging of the liver is crucial for delineating anatomy and surgical planning. In addition, accurate assessment of the chest, abdomen, and pelvis is important to rule out extrahepatic disease. Contrast-enhanced helical CT has been suggested as the primary imaging modality in the preoperative work-up of patients with colorectal liver metastases because it provides an excellent assessment of the liver anatomy as well as the extrahepatic structures. A sensitivity of 85%, a positive predictive value of 96%, and a false-positive rate of 3.9% have been reported (5). Contrast-enhanced MRI of the liver with gadolinium or ferumoxides also provides excellent characterization of hepatic colorectal metastases. MRI with superparamagnetic iron oxide was found to have a sensitivity of 80.6% in the detection of hepatic colorectal metastases, and this increased to 99% when only tumors larger than 10 mm were analyzed. All the false-negatives were lesions smaller than 10 mm and half of them were located on or close to the liver surface. Both location and size are recognized limitations common to all imaging modalities, as small and superficial lesions are commonly missed by both CT and MRI (6).

18F-fluorodeoxyglucose whole-body positron emission tomography (FDG-PET) has been evaluated in the staging of patients with hepatic colorectal metastases. FDG-PET exploits the natural ability of malignant cells to utilize glucose at greater rates than normal tissue. When administered to a patient with cancer, 18FDG is taken in to tumor cells by hexose transporters and undergoes phosphorylation to FDG-6-phosphate, which is then selectively retained, since it is not subject to any further metabolism in most tumor cells. A prospective study by Ruers et al. (7) examined the impact of FDG-PET in the preoperative evaluation of 51 patients with hepatic colorectal metastases who had already undergone imaging with either CT scan or MRI. FDG-PET changed the clinical management of 20% of patients by detecting unsuspected additional metastatic lesions in 6 patients and ruling out additional disease in 4 patients. When the results of FDG-PET were regarded as decisive in a retrospective analysis, potential change of management was 29% (15 patients). Another study examined the outcome of 100 patients preoperatively screened with FDG-PET and reported a 5-year overall survival of 58%, which is markedly improved from multiple prior studies of surgery for hepatic colorectal metastases (8). The data suggests that FDG-PET may complement CT scan in establishing the presence of extrahepatic disease and may add relevant accuracy to conventional staging.

All patients being considered for resection of hepatic colorectal metastases must have a negative colonoscopy within 1 year of surgery date to rule out local recurrence or a second primary lesion. Complete cardiopulmonary evaluation is selectively employed for patients based on medical history and symptoms. Providing the patient is fit, chronological age by itself should not be regarded as a contraindication for surgery. A study from the Sloan-Kettering Memorial Hospital demonstrated no difference in perioperative morbidity and mortality or in long-term outcome in patients undergoing liver resection who were over 70 in comparison to younger patients, though clearly the older patients in this study were carefully selected (9). Preoperative biopsy of liver lesions is not necessary in this clinical situation.

Advances in Liver Surgery and Preoperative Care
Increased knowledge of segmental liver anatomy has led to the development of segmental-based surgery. The liver can be divided into 8 segments: segment 1 is the caudate lobe, segments 2 through 4 form the anatomic left lobe and segments 5–8 form the anatomic right lobe. Segmental anatomy of the liver is based on the direction of the hepatic veins in relation to the intrahepatic distribution of the portal vein (10). It is possible to resect up to 6 segments out of 8 in one stage, but usually one lobe or part of it is removed. When lesions are located peripherally, hepatic wedge resection or anatomic segmentectomy are indicated. If a tumor is adjacent to or involving major intrahepatic vessels, resection of the entire segment or lobe is necessary. Lobectomy is indicated when multiple lesions are located in different areas of one lobe, whereas wedge resection is universally accepted for small superficial lesions. Classical extrahepatic control of the inflow and outflow vessels for a left or right hepatic lobectomy has changed little since its original description by Lortat-Jacob & Robert in 1952 (11). However, the advent of endovascular linear staplers has improved the ability to transect the main branches of the portal and hepatic veins, which previously had to be laboriously oversewn with non-absorbable vascular sutures with increased risk for blood loss.

Multiple techniques for liver parenchyma transaction have been described and include traditional methods such as finger fracture, cavitronic ultrasonic surgical dissection, and Kelly crush-clamp. The use of low CVP anesthesia with the patient in trendelenberg position reduces bleeding from the hepatic veins during resection, and intermittent occlusion of the inflow vessels—Pringle maneuver—reduces bleeding from the inflow vessels (12). The combination of the Kelly crush-clamp technique, in which a clamp is used to crush the hepatic parenchyma and expose vessels and bile ducts, with low CVP anesthesia and the Pringle maneuver is an effective method to transect the liver parenchyma with minimal blood loss and avoid perioperative transfusion, which has been associated with a worse clinical outcome (13).

Recently a new device for hepatic resection was introduced which is a water-cooled, high-density, monopolar device, the sealing cone-tip. It uses a focused delivery of radiofrequency energy in the tip of a handheld probe that provides coagulation of the hepatic tissue that extends beyond the cut resection edge. Over-coagulation with the production of charred tissue is prevented by a water infusion that keeps the tip of the probe at the appropriate temperature. Small vessels are sealed while larger vessels can be dissected out and subsequently tied, clipped, or stapled (14). There is no clearly superior technique between the traditional and new methods, but they merely give the surgeon more options in deciding how to perform hepatic resection. The effectiveness of any given method in reducing blood loss and operating time depends on the surgeon’s training, experience, and familiarity with each approach.

At centers with experience in liver surgery, the perioperative mortality rate is uniformly less than 5% (3), with a complication rate of approximately 30%. This is in contrast to a report from 1977 of 621 hepatic resections which reported an operative mortality of over 20% for major liver resections, with 20% of the deaths resulting from hemorrhage (15). A review of over 1,800 consecutive hepatic resections (16) found that blood loss and number of segments resected were the only 2 variables both significantly associated with morbidity and mortality on multivariate analysis. Increased utilization of parenchyma-sparing hepatic wedge or segmental resections, along with improved surgical and anesthetic techniques have contributed to the overall improved outcomes associated with modern day hepatic surgery.

Conclusion
Multiple large retrospective series with long-term follow-up have clearly demonstrated the efficacy of resection for liver metastases from colorectal cancer. Increased knowledge of tumor biology and advances in diagnostic and functional imaging have improved patient selection. When these factors are combined with current anesthetic and surgical technique, hepatic resection has become a procedure with acceptable morbidity and low mortality with at least a third of patients achieving long-term survival. Interestingly, a study from the United Kingdom also found that surgery for hepatic colorectal metastases was highly cost-effective compared to nonsurgical treatments (17). However, further research on neo-adjuvant or adjuvant therapies is necessary to increase survival rates.

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