Select Excerpts from the Interview

Track 3

DR LOVE: What is your usual treatment approach for patients who present with a simultaneous primary colon cancer and resectable liver metastases?

DR GELLER: If the patient is a reasonably healthy 40-or 50-year-old, I’ll work with the chief of colorectal surgery and we’ll perform a simultaneous colon resection — such as a lower anterior resection or right hemicolectomy — in addition to a liver resection.

This approach requires two perfect operations — a perfect colon resection and a technically perfect liver resection — because a complication in one can hinder the outcome of the other. We have probably performed 20 such operations in the last three years at Pittsburgh, and the outcomes have been excellent.

That’s not what generally happens in the community. It’s perfectly fine for the colorectal surgeon or the general surgeon to perform the colectomy. Most of those patients will have positive lymph nodes. If the surgeon can see the liver lesion at the time of the colon resection, I recommend a needle biopsy for confirmation. It just takes an extra moment, and then we don’t have to subject the patient to a biopsy later.

I’m never in a rush to operate on the liver. We let the patients recover from the colon surgery, complete their staging and administer two or three cycles of adjuvant chemotherapy. At three months, we restage with a CT/PET scan. If they have stable disease or a slight improvement, that’s the perfect time to perform the liver resection.

We don’t want the patients to receive six or nine months of chemotherapy because it damages the liver and causes steatosis or, worse, steatohepatitis. A syndrome called chemotherapy-associated steatohepatitis (CASH) is similar to nonalcoholic steatohepatitis (NASH) — fatty liver disease. Chemotherapy can cause the same condition, and fatty livers do not tolerate major hepatic resections.

Track 4

DR LOVE: Is there a current role for intrahepatic infusion of chemotherapy?

DR GELLER: Intrahepatic infusion of chemotherapy has fallen by the wayside. In December 1999, Kemeny’s article appeared in The New England Journal of Medicine and repopularized the placement of hepatic artery pumps for infusional therapy (Kemeny 1999). The only drug approved in the US was floxuridine — a cousin of 5-FU.

However, that was in an era in which we didn’t have these three-and four-drug combinations, whereas now, we are seeing the response rates around 50 percent. We can avoid the morbidities associated with the pumps, including a 20 percent incidence of biliary sclerosis from infusional floxuridine that is often irreversible.

I don’t believe much of a role exists for a pump in a patient who has received FOLFOX or FOLFIRI, and we see almost no referrals. In the last three years with the newer drug combinations, I’ve placed maybe two pumps and those were for patients who had failed systemic chemotherapy.

I believe the only role for hepatic artery pumps is in a randomized trial in which systemic chemotherapy is combined with intrahepatic infusional chemotherapy.

Track 5

DR LOVE: What are the surgical considerations in hepatic resection for a patient who receives bevacizumab?

DR GELLER: Bevacizumab can hinder wound healing, and it’s associated with an increased incidence of bleeding and cardiac events. Patients can even develop thrombotic events. Therefore, we need to use this agent cautiously in patients with a poor cardiac history.

In cases in which the patient is to receive FOLFOX combined with bevacizumab, I work with the oncologist to come up with a plan. Typically, patients will receive a couple of cycles of chemotherapy with bevacizumab, and then both the oncologist and I will see them. If the plan is to perform a liver resection, we’ll administer a third cycle of chemotherapy without bevacizumab.

I prefer for patients to be off of chemotherapy for three weeks before surgery — so the immune system recovers from the bone marrow nadir — and off of bevacizumab for six weeks. We’ve seen no complications when we have a four-to six-week window without bevacizumab.

Track 6

DR LOVE: Is there a specific number of liver metastases that you would not be willing to resect?

DR GELLER: If you look beyond a decade ago, the classic belief was that patients with up to four tumors in the liver were candidates for resection. Today, we resect way beyond that number — we push the envelope and resect as many as five to eight tumors. If I can remove all of the cancer safely and preserve enough liver mass, then that is the preferred approach.

In patients with only one metastatic lesion, resection alone will cure them approximately 40 percent of the time. However, that means 60 percent will experience recurrence. We have a few prognostic indicators, but we don’t yet have good biomarkers to predict which patients will experience a recurrence. In addition, if a patient has six or seven hepatic metastases, the chance for recurrence is much greater than for someone who has a solitary lesion. Therefore, I recommend that all patients receive some adjuvant chemotherapy after resection.

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