In the United States, there are an estimated 5000 to 6000 new patients annually who might be candidates for major hepatic resection to treat their recurrent colon cancer. Since 1971, the program reported here has evaluated various factors that might influence the curative potential of such an approach. Sixty-five patients had a major hepatic resection from March 1971 through May 1982. Using a stepwise proportional hazard analysis, all data that had been stored in CLINFO (a data analysis system by Bolt, Beranek and Newman; Boston, MA) were evaluated for the effect of multiple variables on the survival of patients with resected hepatic metastases. Twenty-seven had a right hepatic lobectomy; 14 had extended right hepatectomy with one having the caudate lobe also removed; ten had left lobectomy, nine had left lateral segmentectomy; and five had a major hepatic resection with three-dimensional wedge excision of a metastatic deposit in the contralateral lobe. The 30-day operative mortality rate was 7% (4/58) for patients undergoing the standard major hepatic resection. It was 14% for seven patients in whom the isolation-hypothermic perfusion technique was used early in the series. In ten patients, wedge excision only was required to remove the tumor. Stage I disease is defined as tumor confined to the resected portion of the liver without invasion of major intrahepatic vessels or bile ducts. Stage II disease is regional spread and Stage III disease is metastasis to lymph nodes or extraregional sites. The 3-year survival estimate was 66% for the 37 patients with Stage I disease. The 3-year survival estimate for 13 patients with Stage II disease was 58%. Five of the nine patients with Stage III disease are presently alive from 3 to 23 months; one of the other four died at 35 months of disease. The stage of liver disease was the most significant variable in this survival analysis (p = 0.02); Dukes' classification of colorectal primary was significant at p less than 0.05. Those factors found not to be significant determinants of survival were: number of metastatic hepatic deposits, site of colon primary, age, sex, preoperative liver function tests, and CEA.
One hundred and seventeen patients with colorectal hepatic metastases had insertion of catheters for infusional chemotherapy. The two-year survival estimate of patients with less than 50% hepatic replacement and no other adverse factors was 37%. Nine of 39 patients in this group are alive at 24 months. The catheters were placed into the hepatic artery (HA), 23; into the portal venous system (PV), 18; into both HA and PV, 64; or into an accessory HA following ligation, 12. Fifty-nine patients had ligation of the common HA also. The 30-day postoperative mortality rate was 1.7% (2/117) and morbidity was 37.6%. The majority of complications were related to fever (61%, 27/44). Over the past 2 years, 87% of patients have been discharged within 10 days following surgery. Preoperative CEA ranged from 0.5-12,150 ng/ml (median 165 ng/ml); 93% (78/84) had plasma CEA levels exceeding 5 ng/ml. All patients had careful intraoperative staging: per cent hepatic replacement (PHR) ranged from 5-95% (median 60%); portal, celiac, or periaortic lymph node metastases were observed in 31% (36/117). Initial intrahepatic chemotherapy programs consisted of either CAMF (9 patients), MAFL (60 patients), BFS (22 patients), continuous infusion FUDR (14 patients), or miscellaneous drugs (4 patients). Median survival time of 109 evaluable patients was 11.5 months. The effect of 20 variables on the observed survival time was analyzed using a multivariate proportional hazard model. Three variables were found to have influenced survival: PHR emerged as the most significant, p = 0.000001. Increased PHR was associated with decreased survival time. Lymph node metastases and prior chemotherapy were prognostic factors also, p = 0.0006 and p = 0.03, respectively. No patient with PHR greater than 80% lived more than 8 months. Utilization of these variables would appear to be necessary for accurate stratification and evaluation of future chemotherapy trials in patients with colorectal hepatic metastases.
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