An educational tool to assist in the management of hepatic metastases in patients with colorectal cancer

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Case 23:

Discussant: RENE ADAM, MD

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Case Description:

A 69-year-old patient presented with colon cancer and a solitary, but poorly located isolated hepatic metastasis in segment VIII of the right hemiliver, abutting the junction of the IVC, median and right hepatic veins. She underwent a right colectomy at her primary institution, followed by FOLFOX. She was subsequently seen at a tertiary center for surgical consultation, showing some evidence of liver toxicity and small disease progression while on chemotherapy. She was switched to a chronomodulated FOLFOX regimen, which resulted in normalization of transaminase levels and a decrease in the size of her liver lesion. She then underwent an R1 resection of her hepatic metastasis (1-mm margin) and continued chronomodulated FOLFOX for six additional cycles postoperatively. Two years after surgery, she experienced nonlocal liver only recurrence, treated with chemotherapy and rehepatectomy. She fared well for an additional two years and then succumbed to extrahepatic metastases.

Case Discussion:

This 69-year-old woman presented with a colon tumor and a synchronous deep, hepatic metastasis abutting two hepatic veins and the vena cava. The position of the tumor was deep and the location troublesome. She initially underwent a right colectomy and received adjuvant chemotherapy with two courses of FOLFOX in September of 2003 but developed liver toxicity with increased transaminase. This patient also had increased tumor markers, and the tumor size had increased during chemotherapy. Therefore, the debate was whether or not to operate, based on her risk of developing unresectable disease, or to change the chemotherapy regimen in a way that would allow us to perform surgery during a phase of tumor control to promote a better outcome. We decided to change her chemotherapy.

To decrease the toxicity of FOLFOX, she received four courses of FOLFOX chronotherapy. FOLFOX chronotherapy is defined as delivering FOLFOX at a time, over the 24-hour circadian rhythm scale, when the risk of toxicity is reduced. Many experimental and clinical studies demonstrate that administering a drug like oxaliplatin at selected times over the 24-hour scale can prevent toxicity.

In this patient, the chronoregulated administration of the same regimen of FOLFOX caused the CA-99 to decrease. A decrease in the transaminase occurred in addition to a decrease in the hepatic metastasis. We decide to operate but debated about the type of hepatectomy to perform. Whereas some surgeons prefer to perform an extensive hepatectomy, others prefer a more limited approach to prevent the loss of more than half of all the liver for a small lesion measuring one centimeter. We decided to avoid extensive hepatectomy by performing a local resection of the tumor, probably R1 rather than R0 resection.

Our experience with R1 versus R0 resection was recently described in the October issue of Annals of Surgery. Briefly, the overall survival is comparable between R1 and R0 resection, despite the fact that more recurrences were seen in the R1 group compared to the R0 group but the benefit in survival between the groups was the same.

The patient underwent resection of a 12-millimeter nodule, close to the vena cava and the junction between the right hepatic vein and median hepatic vein. The resection margin was small (1 mm). She then received another six courses of FOLFOX postoperatively and remained without recurrence up until January 2006. Two years after surgery, nonlocal recurrence was observed in the form of four nodules, five to six millimeters in size, all localized in the other segment of the liver.

The patient was newly treated with chemotherapy and another hepatectomy was performed in June 2006. Although the postoperative course went well, the patient died in 2008. Extrahepatic disease was found in the liver and in the lungs. The patient died approximately five years after the initial diagnosis.

It is difficult to estimate the average survival of a patient with a single metastasis — some patients may be cured. Having a single metastasis is a good prognostic factor. Approximately 60 percent of these patients are alive at five years, depending on how aggressive the disease is and the biology of the tumor.


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