A 34-year-old woman in excellent health presented with primary sigmoid cancer and synchronous extensive right hemiliver metastases in addition to PET/CT evidence of an involved perihilar lymph node. No additional extrahepatic disease was identified. She received preoperative FOLFOX and experienced a partial response after six cycles, which was maximized through completion of nine cycles. She then went on to a two-stage resection of her primary and metastatic disease. Laparoscopic sigmoid colectomy closely preceded an extended right hepatectomy and radical regional lymphadenectomy, which uncovered multiple involved periportal nodes, extending to the celiac access. The postoperative course was complicated by steatohepatitis with some liver insufficiency and a five week hospital stay. Additional systemic therapy is under consideration.
Case Discussion:
DR PRIMROSE: A 34-year old woman who is a nurse presented with sigmoid cancer and extensive unresectable synchronous liver metastases mainly in the right liver with porta hepatis lymph node involvement, according to multiple scans. Because the patient had extrahepatic disease, we did not consider her a good candidate for excisional surgery.
The patient was treated using conventional FOLFOX chemotherapy. Although she was eligible for entry into the COIN trial, she refused that possibility because she was concerned about the development of skin rash with cetuximab. After undergoing treatment with FOLFOX chemotherapy, she had a partial response. The patient received nine of the 12 cycles of FOLFOX. The treatment was stopped because by nine cycles, her tumor marker levels had remained static and had not fallen further than at six cycles, so we felt it would be unlikely that there would be any additional benefit from another three cycles of chemotherapy. She then proceeded to surgery. If she had continued to respond, we would have completed the chemotherapy as originally scheduled.
Despite having extrahepatic disease, we felt that we should offer her surgical treatment because of her young age, her otherwise excellent health and the fact that only one site of extrahepatic disease was present. She underwent a laparoscopic sigmoid colectomy and recovered quickly. A couple of weeks later, she underwent an extended right hepatectomy, a radical lymphadenectomy and a biliary reconstruction because the lymph node deposit was closely adherent and probably involved the bile duct. We felt the best solution was to remove the entire extrahepatic biliary tree, perform a full lymphadenectomy toward the celiac access and in the aorta caval region, and then perform a biliary reconstruction.
Although the PET scan only showed activity in the one large node that was demonstrated on CT, most of the excised lymph nodes had small deposits of tumor. So this was regarded as an R1 resection — that is, a resection that did not satisfactorily remove the histologically all of the disease.
The patient had a difficult postoperative course. She received a total of approximately nine months of chemotherapy, and her liver showed some steatohepatitis. She suffered from liver insufficiency postoperatively and was hospitalized for five weeks. She remains jaundiced but is now improving. Because her prognosis is poor, she is likely going to receive postoperative chemotherapy.
It can be argued that a patient with obvious lymph node disease in the porta hepatis is a poor candidate for curative surgery. I think this is an area of uncertainty. Conventional thinking is that patients with extrahepatic disease — particularly disease in the lymph nodes around the porta hepatis — are not suitable for curative treatment. However, some data from Europe suggest that if the lymph nodes are in the region near to the liver, rather than centrally at the celiac axis, removing them confers a survival benefit in combination with liver resection. Hence, some patients with extrahepatic disease benefit from resection. We have no data for patients who present with obvious, bulky nodal disease on CT. I think most liver surgeons would regard this as a highly unfavorable situation that is probably not amenable to cure. Certainly, if this patient was elderly, we would not have offered surgery. However, bearing in mind her age and the single site of extrahepatic disease, we felt this was a judgment that was reasonable, and the patient was extremely keen to have surgery performed. In retrospect, the surgery was inappropriate, and the lymph node disease was quite extensive. It’s unlikely we could have cured this patient. We also subjected her to a large operation that kept her in the hospital for five weeks. She’ll be recovering for a significant length of time, which may be a significant proportion of her remaining survival. So, in retrospect, the decision was not appropriate, although prospectively it seemed a reasonable approach for someone at this age.
She probably will not tolerate any additional oxaliplatin and will likely be offered a regimen containing irinotecan. My own view is that it would be more appropriate for her to have irinotecan with an antibody, depending on her K-ras mutation status. However, because this patient is not privately insured, she will not receive reimbursement for bevacizumab or cetuximab on the national service, so she will not receive antibody treatment.
