A 69-year-old Asian man is found to be mildly anemic upon routine checkup for chronic hepatitis B (HBV). Colonoscopy shows a tumor in the sigmoid colon and CT reveals a 1-cm indeterminate mass located in the dome of the liver, which is undetectable by ultrasound. His bilirubin is normal, but his AST is twice elevated from his baseline. He is otherwise healthy.
At the time of left hemicolectomy (T3N1), he underwent surgical exploration of his liver which confirmed a metastasis in the left lobe, and a wedge resection was performed. He completed 12 cycles of postoperative FOLFOX, experiencing moderate neuropathy and cytopenias. During the year after initial surgery, the patient experienced two liver only recurrences (right lobe) — the first successfully resected and the second deemed unresectable at the time of surgical attempt. He ultimately died of liver failure four years after diagnosis.
Case Discussion:
This was a 69-year-old man with Grade III/IV adenocarcinoma of the colon. He was originally from mainland China but had lived in the United States for about 15 years. During a routine checkup for his hepatitis B and liver disease, he was found to be mildly anemic, prompting a colonoscopy that showed a mass in the sigmoid colon. A CT scan showed a synchronous 1-cm indeterminate mass located in the dome of the liver, but the abnormality was undetectable by ultrasound. His AST was approximately two times the normal limit, related to his hepatitis B, but his bilirubin was normal, and he was otherwise healthy. In general practice, approximately 15 to 20 percent of patients present with synchronous metastatic disease at the time that their colon or rectal cancer is diagnosed.
As this man had a unilobar, single-liver metastasis in the presence of a primary intact tumor, I believed that the more desirable surgical approach was to evaluate the liver at the time of surgery and, if there was indeed only one metastasis, I would remove it. Given the size of the lesion, I thought it might disappear if we first removed the primary tumor and then administered chemotherapy — assuming the mass was truly cancerous — making it difficult for the surgeon to find and resect it. Even though this man did not have cirrhosis, he did have chronic active hepatitis. Therefore, if the spot disappeared and a more extended resection of the liver was needed to remove the entire area of concern, his liver function may have been somewhat jeopardized. So in this situation, we chose to identify the area of concern in the liver during colon surgery and then resect it. We did not biopsy the lesion because the area of abnormality was so high up in the liver. If the lesion was located in a more feasible location, a biopsy would have been used to differentiate between a metastasis from colon cancer or early hepatocellular carcinoma, given the history of chronic hepatitis B.
The patient underwent a left hemicolectomy and a wedge resection of the metastasis. No other signs of disease were evident at the time of surgery, and all of the margins were negative. Postoperatively, no complications occurred related to either his liver function or colon function.
Although some increased risk for liver toxicity was present because of the underlying hepatitis, I recommended postoperative chemotherapy because of the lymph node involvement, the solitary metastasis and the high risk for recurrent disease. He received 12 cycles of FOLFOX and tolerated it well. After the third treatment cycle, the dose was reduced by 20 percent because his white blood cell count and neutrophils decreased. Otherwise, treatment was tolerated fairly well, although he had a moderate neuropathy at the end of treatment, which did not limit any of his activities.
Without adjuvant chemotherapy, the risk of recurrent disease would have been from 70 to 80 percent, based on his initial staging. I told him that we could expect a five-year survival rate of 40 to 50 percent if he received postoperative chemotherapy. Early on, the biggest question in his situation was whether he could tolerate FOLFOX since he had underlying chronic active hepatitis. If there were problems, we planned to reduce treatment from FOLFOX to 5-fluorouracil and leucovorin alone (or capecitabine), but that might lessen the benefit to some degree.
Unfortunately, he developed a recurrence eight months after the initial surgery and, at that point, had three new metastases in the right lobe of the liver. We discussed several options including the use of chemotherapy or surgery alone to remove those areas. My recommendation was to administer three months of chemotherapy initially to make sure that we had control of disease and then to try to resect or ablate what was left of the disease, but he elected to proceed with surgery alone, because of family reasons.
Four months after surgery, he had evidence of recurrent disease along the resected area in the right lobe. At that point, the patient agreed to enter into a clinical trial of the drug CPT-11 and the EGFR inhibitor OSI-774rather than attempt any further resection or ablation. He fared well, although he had a fairly significant rash that required a reduction of the OSI dose, along with a moderate diarrhea that was adequately controlled. Based on the periodic CT scans that were performed, there was evidence of disease regression. His neuropathy did not resolve.
After four months, he asked for a break in treatment because of family issues. We decided to make one final attempt to resect the remaining disease since it seemed to be located on the edge of the prior resection. Unfortunately, we discovered that he had bilateral liver metastases, and so the resection could not be performed. He then received chemotherapy intermittently over the three years that followed, but passed away a few months ago. There never appeared to be any evidence of extrahepatic disease, at least up until the time of the third attempted resection. He lived four years after he was diagnosed. The patient died of liver failure.
During the treatment course, intermittent problems were caused by the chronic hepatitis B. For example, when liver function tests were elevated, we questioned whether the elevations were due to the chemotherapy or the hepatitis. When we adjusted the dose of medication for his hepatitis B, his liver function tests would normalize and we were able to resume the chemotherapy.
Considering the patient’s underlying liver problems and how his disease recurred so quickly after the second surgery, the third surgery was hard to justify. However, the patient hoped to return to China for a prolonged visit, so the hope was that the third surgery would prolong disease-free survival.
If disease recurs within one year, the likelihood that an additional surgery will help seems to be smaller. However, if the recurrence area appears to be isolated, it is reasonable to consider resecting. In this man’s case, he developed recurrent disease within four months of his second surgery, so the likelihood that surgery would have helped was quite small, even if disease was restricted to the right part of the liver.
