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From 1975 to 1985, 60 patients with isolated hepatic metastases from colorectal cancer were treated by 17 right trisegmentectomies, five left trisegmentectomies, 20 right lobectomies, seven left lobectomies, eight left lateral segmentectomies, and three nonanatomic wedge resections. The 1-month operative mortality rate was 0%. One- to 5-year actuarial survival rates of the 60 patients were 95%, 72%, 53%, 45%, and 45%, respectively. The survival rate after liver resection was the same when solitary lesions were compared with multiple lesions. However, none of the seven patients with four or more lesions survived 3 years. The interval after colorectal resection did not influence the survival rate after liver resection, and survival rates did not differ statistically when synchronous metastases were compared with metachronous tumors. A significant survival advantage of patients with Dukes’ B primary lesions was noted when compared with Dukes’ C and D lesions. The pattern of tumor recurrence after liver resection appeared to be systemic rather than hepatic. The patients who received systemic chemotherapy before clinical evidence of tumor recurrence after liver resection survived longer than those who did not.
The liver is a major site of metastatic spread of primary colorectal cancer, and it is the sole site of initial tumor recurrence in as many as 30% of patients. With further technical refinements in hepatic surgery and recent developments in sophisticated perioperative management, major liver resection can now be performed with an operative mortality rate of less than 5%.1–3 Thus surgical removal of hepatic metastases has been used with increasing frequency, particularly with colorectal carcinoma as the primary cancer.
In this article, our experience in 60 patients who had liver resections for metastatic colorectal cancer will be analyzed to identify factors that may influence the outcome of surgery and also to study the patterns of tumor recurrence after potentially curative hepatic resection of metastatic tumor.
During a 10-year period from 1975 to 1985, 60 patients with isolated hepatic metastasis from colorectal cancer were treated with various types of liver resection at the University Health Sciences Center of Colorado (16 patients before 1981) and the University Health Center of Pittsburgh (44 patients after 1981). There were 44 men and 16 women. The ages ranged from 25 to 76 years with a mean age of 55 years. The interval between colorectal resection and hepatic resection ranged from 0 (simultaneous resection) to 216 months, with the median interval of 19 months. There were 16 patients with Dukes’ B colorectal cancer, 31 patients with Dukes’ C, and 13 patients with Dukes’ D lesions. The colorectal cancer with synchronous hepatic metastases was classified as Dukes’ stage D, regardless of the stage of primary lesion. Thirty-eight patients had solitary hepatic lesion, and 22 patients had multiple lesions. Among the 22 patients with multiple hepatic lesion, seven patients had four or more lesions.
Liver resections for these 60 patients consisted of 17 right trisegmentectomies,4 five left trisegmentectomies,5 20 right lobectomies, seven left lobectomies, eight left lateral segmentectomies, and three nonanatomic wedge resections. The extent and location of the tumor determined the choice of resection. After liver resection, systemic chemotherapy was recommended to all patients and their referring physicians and surgeons. Twenty-two patients followed the recommendations and received systemic chemotherapy before clinical evidence of tumor recurrence and 28 patients did not. The most commonly used chemotherapeutic agent was 5-fluorouracil for 6 to 18 months.
Survival rates were calculated by the life table method of Kaplan-Meier, and statistical comparisons among the subgroups were performed with the log-rank test.
There were no deaths within a month after 22 trisegmentectomies, 27 lobectomies, eight segmentectomies, and three wedge resections. Thus the 30-day operative mortality rate was 0%. However, there were eight significant postoperative complications. Four patients developed subphrenic abscesses that required surgical drainage, two patients developed deep vein thrombosis, one of which caused a pulmonary embolus, and one patient developed small bowel obstruction. There were no postoperative hemorrhages that led to reexploration.
Overall actuarial survival rates calculated by the Kaplan-Meier method are shown in Fig. 1. One- to 5-year actuarial survival rates of the 60 patients were 95%, 72%, 53%, 45%, and 45%, respectively. When the survival rates of 38 patients with solitary hepatic lesions were compared with those of the 22 patients with multiple lesions, they were nearly identical as shown in Fig. 2. However, the survival rate of seven patients who had four or more hepatic lesions was significantly less than that of 38 patients with a solitary lesion (p = 0.05) (Fig. 2).
The influence of Dukes’ staging of primary colorectal cancer on survival after liver resection was examined (Fig. 3). The survival rate of 16 patients with Dukes’ B primary lesions was significantly higher than that of the 31 patients with Dukes’ C primary lesions or the 13 patients with Dukes’ D lesions (p < 0.05). However, there was no difference in survival rates, after liver resection between patients with Dukes’ C lesions and those with Dukes’ D stage (synchronous hepatic lesion) colorectal cancers.
The survival rates after liver resection were compared by the interval after colorectal resection (Fig. 4). There was no difference in survival rates between patients with intervals less than 1 year, 1 to 2 years, and longer than 2 years.
The survival rates were compared among 22 patients after trisegmentectomies, 27 patients after lobectomies, and 11 patients after left lateral segmentectomies or wedge resections (Fig. 5). The survival rate of patients whose hepatic metastases could be totally removed only by trisegmentectomies was significantly lower than that of patients whose hepatic lesions could be easily removed by lobectomies or smaller resections (p = 0.01). The survival rates after lobectomies and left lateral segmentectomies or wedge resections were essentially identical.
The survival rate of 22 patients who received systemic chemotherapy before clinical evidence of tumor recurrence after hepatic resection was better than that of 38 patients not so treated (Fig. 6) (p = 0.05).
Although the survival rate of patients who were 70 years old or older was the lowest, there were no statistically significant differences among the different age-groups (Fig. 7). There were no differences in survival rates between 44 men and 16 women.
Tumor recurrence was documented in 29 of the 60 patients from 3 months to 7 years after liver resection, most frequently during the second year. The liver was involved in 18 patients, the abdomen outside the liver in 17 patients, the lungs in 15 patients, the brain in five patients, the bones in four patients, and in one patient each, the abdominal wall, chest wall, and pericardium, respectively. It was difficult to determine the first site of recurrence in most of our patients by retrospective study. Most of the tumor recurrences involved multiple organs, and the liver was the isolated site of recurrence in only three patients. The lungs were the isolated site of recurrence in only two patients.
This study has confirmed earlier reports1–3 that major hepatic resections can be performed with a minimum of risk to the patient. Petrelli et al.6 reported that right trisegmentectomy had been abandoned at Rosewell Park Memorial Institute for metastatic colorectal cancer because of high surgical mortality rates. However, our experience of no operative deaths (death within 1 month) in 22 trisegmentectomies encourages the construed use of trisegmentectomy for extensive hepatic metastasis.
The 1-, 3- and 5-year survival rates of 95%, 53%, and 45%, respectively, in this study reemphasize that liver resection is the therapeutic modality that offers the best prospect of long-term survival to a small but significant proportion of patients with metastatic hepatic lesions from colorectal cancer. Although it is difficult to compare the survival rates of different series, slightly better results of current series than those of others2, 3, 6–8 may reflect the lack of operative deaths and the liberal use of lobectomies and trisegmentectomies in preference to the less radical nonanatomic resections often called “local excisions.”
Controversy has existed about the efficacy of major liver resection in controlling multiple hepatic metastasis. It has been reported that multiple hepatic lesions have a poorer prognosis than do solitary lesions after liver resection.9, 10 However, in more recent studies,2, 3, 6–8 statistically significant differences in survival rates could not be found after liver resections in patients with solitary versus multiple hepatic lesions, The present study supports the latter conclusion, but it is noteworthy that none of the seven patients with four or more hepatic lesions in this series survived 3 years after liver resection.
The stage of primary colorectal cancer appeared to be a determinant of survival after resection of hepatic metastases. A significant survival advantage was seen for patients with Dukes’ B primary lesions when compared with patients with Dukes’ C. Others have reported the same finding.2, 3, 7, 8 The survival rate of patients with synchronous hepatic metastasis (Dukes’ D) did not differ from that of patients with metachronous tumors of Dukes’ C primary lesions, but it was significantly less than that of patients with metachronous tumors Dukes’ B lesions. Because only two of the 13 patients with synchronous tumors had primary colorectal cancer of Dukes’ B stage, the real influence of synchronous hepatic metastasis on survival after liver resection could not be determined. However, the findings of this series and those of others2, 3, 7, 8 indicate that the interval between colorectal and hepatic resection is not a factor that affects survival after liver resection. Therefore, synchronous hepatic metastases appear to be treated by liver resection as effectively as metachronous metastases.
The extent of liver resection was determined by the degree of tumor involvement of the liver. Trisegmentectomies were applied to the tumors that involved both lobes. Inferior survival after trisegmentectomies merely reflected more advanced stage of metastatic colorectal cancer when compared with lobectomies or smaller resections.
The effect of systemic chemotherapy before clinical evidence of tumor recurrence after liver resection was not examined by a randomized study, but the survival rate of patients who received chemotherapy before tumor recurrence was significantly better than that of those who did not (p = 0.05). Well-designed multi-institutional studies involving a large number of patients will be required to confirm our finding.
The pattern of tumor recurrence or treatment failure after liver resection appeared to be systemic rather than hepatic in this experience and that of others,6, 11 realizing that any retrospective study to determine the first sites of recurrence by clinical tests has limitations. However, even the limited information now available suggests that systemic chemotherapy may be at least as effective in controlling tumor recurrences after liver resection as intrahepatic infusion chemotherapy.
The following multi-institutional study should be considered to determine the effect of systemic adjuvant chemotherapy on survival after potentially curative liver resection of metastases from colorectal cancer. Patients with an elevated carcinoembryogenetic antigen before liver resection, which falls to normal levels 1 month after liver resection, would be randomized into either one group receiving systemic chemotherapy or another without this adjuvant therapy. Carcinoembryogenetic antigen levels would be measured every 3 months as an indicator of treatment failure. If the treatment were to fail, the sites of recurrence would be investigated extensively every 3 months to determine the pattern of treatment failure. Tumor-free intervals and survival rates would be compared between the two groups. Our group would be compelled to refrain from participation in such a study, since the statistically significant better results in our patients given chemotherapy would not allow us to have a null hypothesis of no treatment difference.
Supported by the National Institutes of Health research project grant No. AM-29961.
Presented at the Forty-third Annual Meeting of the Central Surgical Association, Chicago, Ill., March 6–8, 1986.