A review of liver resection for colorectal cancer metastasis

This review provided information on surgical resection for liver metastasis in colorectal cancer.

Colorectal cancer patients can often present initially with metastasis (spread of the cancer), with many more developing metastasis during the course of the disease. The most common site of metastasis is the liver, which is present in approximately 80% of patients with stage IV (advanced) disease. It is estimated that up to 20% of these patients have resectable (surgically removable) liver metastasis. Medical advances have led to the belief that hepatectomy (resection of the liver) can lead to disease control that is superior to chemotherapy and, more importantly, long-term cure. The goal of hepatectomy is to achieve negative surgical margins while preserving as much of the liver tissue as possible.

The authors of this article conducted a review of hepatic resection for colorectal metastasis.

Patient selection for hepatectomy is very important. Parameters to be assessed include resectability of the tumor, fitness of the patient to undergo a major surgery and ability to achieve a margin negative resection (absence of cancer cells in the margin of healthy tissue surrounding the removed tumor). Many predictive models have been created to better select patients most likely to benefit from a potentially morbid operation. Patient selection can be more important than technical considerations for metastatic operations.

One study reviewed results from 1,001 patients undergoing liver resection for colorectal metastasis over a 13-year period. Analysis revealed that factors associated with poor overall survival included positive margins (presence of cancer cells in the margin of healthy tissue surrounding the removed tumor), disease outside the liver, number and size of tumors, high pre-operative carcinoembryonic antigen (protein found in the blood of some cancer patients), lymph node positive cancer and short disease-free interval (time spent after treatment without disease). These factors were used to score patients as a measure of mortality risk. Low scoring patients survived an average of 74 months compared to 22 months for those patients with higher scores.  Similar models have found 2-year survival rates of 79% for patients scoring low compared to 43% for patients scoring high.

It has become increasingly recognized that much of the progress made in decreasing the morbidity (being in a disease state), mortality (death), and blood loss associated with hepatic resection is due to maintenance of low central venous pressure during surgery. Central venous pressure is the pressure in the vena cava, the vein that supplies the right side of the heart. One study of 496 patients undergoing liver resection under low venous pressure identified a dramatic decrease in blood loss, morbidity and mortality when liver resection was performed under low central venous pressure conditions. There were no deaths during the operation and an in-hospital mortality rate of 3.8% was seen. 67% of the patients did not require any blood transfusions during surgery or the 12 hours immediately after surgery. Importantly, this study did not reveal any insufficient blood supply to the liver post-operatively.

In the immediate post-operative period, the patient is monitored for evidence of bleeding and adequate pain control. This is monitored using international normalized ratio (the clotting ability of the blood) and the liver’s clearance of bilirubin (the breakdown product of hemoglobin, the body’s oxygen-carrying protein). A trend of increased international normalized ratio and bilirubin over the first few post-operative days should trigger suspicion of post-operative liver failure and supportive measures should be taken, such as phosphorous repletion (replenishing phosphorous levels) and avoidance of hypotension (low blood pressure). One potential actionable cause of post-operative liver failure is prevention and early recognition of infection. The inflammatory response of the body to infection can impair the liver’s ability to regenerate and cause liver failure.

Considerable controversy exists regarding the role of adjuvant (applied after initial surgery) chemotherapy for metastatic colon cancer. A combined study of 278 patients comparing surgery alone versus surgery and chemotherapy showed a 9 month improvement in progression-free survival (survival without worsening of the disease) and a 15 month improvement in overall survival. However, the study failed to achieve statistical significance, leaving questions over the benefit of adjuvant chemotherapy.

 Indeed, another study of 364 patients randomized to receive surgery plus perioperative (pre- and post-operative) chemotherapy with 5-flurouracil, leucovorin and oxaliplatin (Eloxatin) or surgery alone revealed that there was a significant increase in post-operative complications in those receiving chemotherapy. This included 7% of chemotherapy plus surgery patients experiencing intra-abdominal infection compared to 2% of patients receiving surgery alone and 8% of chemotherapy plus surgery patients experiencing biliary fistula (bile leaking from the bile ducts) compared to 4% of patients receiving surgery alone.

This review concluded that though the outcomes of liver surgery have improved, there are still many risks invloved, including bleeding, infection, and liver failure, and these surgeries should be done in experienced centers with appropriate support.