Case 25:

Discussant: RENE ADAM, MD

Case Description:

A 68 year-old man underwent a colectomy for a sigmoid adenocarcinoma and was intraoperatively found to have bilobar synchronous hepatic metastases. Of note, multiple liver lesions were present and they appeared to surround the hepatic vein and inferior vena cava, such that the disease was unresectable at presentation. Postoperatively, he received chronomodulated FOLFOX and experienced a decrease in tumor markers and more than 50 percent reduction in tumor burden, including retraction from the major vessels. He underwent a right extended hepatectomy (involving the caudate and part of the left lobe) with R1 (1-mm) margin. Pathology suggested mild “blue liver” secondary to cytotoxic damage. After surgery, he developed transient postoperative liver insufficiency, but recovered quickly and moved on to receive six additional cycles of chronomodulated FOLFOX.

Case Discussion:

This was a 68-year-old man with a colon tumor and bilobar synchronous metastases discovered intraoperatively during exploration of the abdominal cavity. His disease was initially considered unresectable because multiple tumors were found and tumor completely surrounded the vena cava and the entire hepatic vein, making it difficult to remove the tumor without sacrificing the hepatic vein.

After treatment with chronomodulated FOLFOX, the tumor markers decreased and the tumor size decreased by more than 50 percent. In fact, the tumor at the upper part of the liver was significantly reduced. When a tumor is in contact with a vessel, we don’t know whether the tumor will leave the vessel or remain in contact after downsizing. In this patient, the tumor remained in contact with one important hepatic vein, and this made the operation easier.

In the majority of patients with initially resectable disease, I prefer using perioperative chemotherapy. The first reason is that it provides additional time to determine who will benefit from surgery. I can learn more about the biology, the evolution of the disease and the efficacy of the chosen chemotherapy. The second reason for the perioperative approach is that it allows me to predict whether the chemotherapy will be efficient in the postoperative setting because all patients receive postoperative chemotherapy. One possible exception to using perioperative chemotherapy would be a patient with a metachronous single metastasis that developed late (ie, two years) after colectomy. I’m not convinced that this type of patient would benefit from perioperative chemotherapy. Although this is debatable, I’m not convinced that this patient would benefit the same way that a patient with a synchronous metastasis or with an early recurrence after colectomy would benefit. Conversely, all patients receive postoperative chemotherapy to prevent the recurrence.

The right hepatectomy extended to segment I and to part of the left lobe, representing approximately 60 to 70 percent of the total liver. Pathologically, five nodules were found — ranging from 16 to 25 millimeters — with a resection margin of only one millimeter. Vascular lesions were present in the nontumor parenchyma, probably related to the oxaliplatin administration. We saw that the liver was not normal — it appeared blue. Despite this, the extended hepatectomy was performed. At that time, no data were available describing the outcome associated with liver injury induced by chemotherapy, so we were not as careful then as we are now about this type of problem. We were fortunate because this patient did not develop liver insufficiency — he developed a transient postoperative liver insufficiency, but he recovered and had favorable postoperative course.

Another six courses of FOLFOX were administered for postoperative treatment. Twenty months after hepatectomy, he developed a pulmonary recurrence in June 2004. He was retreated with FOLFOX and then underwent pulmonary resection in October 2004. The patient developed portal hypertension and hyperplasia in the liver, most likely related to the prolonged administration of oxaliplatin, but is now asymptomatic. As of December 2008, the patient was alive without recurrence.

I feel the delivery of chemotherapy including biologics can be broadly classified according to three categories of disease: resectable, unresectable and potentially resectable. The first category includes the use of conventional neoadjuvant chemotherapy for patients with resectable disease. The other extreme category includes those patients whose disease is definitely nonresectable due to bone metastasis, multiple metastatic sites, et cetera. These patients will probably not benefit from the use of biologics, at least during first-stage chemotherapy. An intermediate category includes patients with marginally nonresectable metastasis that may be resectable if downsized. Within this category of patients, I feel that we should use potent chemotherapy along with biologics to induce resectability as soon as possible to potentially prolong survival.

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