A 54-year-old woman with a history of Stage III colon cancer treated with hemicolectomy and six months of adjuvant FOLFOX presents 20 months postresection with elevated CEA levels and PET/CT evidence of four hepatic metastases involving liver segments IV, V, VII and VIII. Importantly, there appeared to be involvement of the middle hepatic vein and tumor proximity to both the right and left hepatic veins. No extrahepatic disease was identified. The caudate and lateral left lobe comprised only 18 percent of total liver volume. The tumor was known to be K-ras wild type, and she received three months of preoperative FOLFIRI/cetuximab resulting in a 30 percent reduction in tumor volume. She then underwent right PVE, and a four-week follow-up CT scan suggested hypertrophy of the future remnant liver to 26 percent. She proceeded to extended right hepatectomy.
Case Discussion:
DR CURLEY: This was a 54-year-old woman who underwent a right hemicolectomy for a Stage III N1 right colon tumor and received six months of adjuvant FOLFOX. Approximately 20 months after her surgery, her CEA level was elevated and a follow-up PET/CT revealed four hepatic metastases involving segments IV, V, VII and VIII. The largest of these metastases was in segment VII, and it was approximately six centimeters in diameter. Based on both the CT findings and the PET scan, she had no evidence of extrahepatic disease.
The lesion in segment IV was close to segment III and clearly involved the middle hepatic vein. The segment VIII lesion was close to the right hepatic vein. We needed to reduce the size of the tumors because of the proximity to the left hepatic vein, specifically the tumor in segment IV. This patient needed to undergo an extended right hepatectomy, including segments IV, V, VI, VII and VIII — leaving segments I, II and III. The volumetric CT scan showed that segments I, II and III comprised only 18 percent of the total volume of the liver. After a long discussion, the patient went on to receive three months of FOLFIRI with cetuximab to reduce the lesion size. A biopsy of a liver metastasis was used to analyze her mutation status, and she was found to have wild-type K-ras.
Since the patient already received FOLFOX as adjuvant treatment following hemicolectomy, we felt that it would be better to use something new. Based on her K-ras wild type status, FOLFIRI with cetuximab was selected because good responses have been shown in properly selected patients. Since she had had a full course of FOLFOX previously, the use of FOLFOX was not preferable when she developed metastatic disease.
The primary reason that we administered the chemotherapy before portal vein embolization was that we were concerned about the potential for growth of metastatic disease after PVE. We know that growth factors are released, and we’ve all seen patients who have had actual progression of their disease fairly rapidly after PVE. This patient had a lesion that would have rendered her inoperable if the lesion progressed, so we opted to treat with the chemotherapy first , followed by the PVE. You have to decide the best sequence but generally, we administer two to three months of chemotherapy first, then perform the PVE, and proceed with the liver resection four weeks later.
The effects of chemotherapy on the liver have been well described in the recent literature. Regimens containing oxaliplatin can cause a sinusoidal injury to the liver sinusoids, the so-called blue liver, but that does not necessarily cause postoperative complications to the liver. We were cautious using the irinotecan in this patient, because it can cause a nonalcoholic steatohepatitis, and we know that patients with steatohepatitis who undergo a liver resection are at an increased risk for liver insufficiency or liver failure. Fortunately, this does not occur in all patients who receive irinotecan, and this patient tolerated it quite well and had no problems with her liver.
After three months of chemotherapy, a 30 percent reduction in the volume of her liver metastases was observed and no new lesions were found. Since the remnant had been estimated to be 18 percent, which is probably inadequate, we decided to perform PVE. Four weeks later, a repeat CT scan was performed and she had excellent hypertrophy of her future liver remnant, showing that segments I, II and III increased in size to 26 percent of the total liver volume.
She then underwent an extended right hepatectomy, and had an unremarkable postoperative course. At her three-month follow-up visit, she had excellent hypertrophy of the liver and a normal volume of liver. As a result, she resumed three additional cycles of FOLFIRI with cetuximab, which she will finish in another approximately six weeks.
