From 1960 to 1992 a total of 1718 patients with liver metastases from colorectal carcinoma were recorded. Of these patients, 469 (27.3%) underwent hepatic resection, which was performed with curative intent in 434 patients (25.3%). Operative mortality in this group was 4.4%, being 1.8% (2 of 114) during the last 3 years. Significant morbidity was observed in 16% of patients with a decrease to 5% (6 of 112) for the last 3 years. A 99.8% follow-up until November 1, 1993 was achieved. Excluding operative mortality, there are 350 patients with "potentially curative" resection and 65 corresponding patients with minimal macroscopic (n = 19) or microscopic (n = 46) residual disease. The latter group demonstrated a poor prognosis, with median and maximum survival times of 14.4 and 56.0 months, respectively. Among the 350 patients having potentially curative resection, the actuarial 5-, 10-, and 20-year survivals were 39.3%, 23.6%, and 17.7%, respectively. Tumor-free survival was 33.6% at 5 years. In the univariate analysis, the following factors were associated with decreased crude survival: presence and extent of mesenteric lymph node involvement (p = 0.0001); grade III/IV primary tumor (p = 0.013); synchronous diagnosis of metastases (p = 0.014); satellite metastases (p = 0.00001); metastasis diameter of > 5 cm (p = 0.003); preoperative carcinoembryonic antigen (CEA) elevation (p = 0.03); limited resection margins (p = 0.009); extrahepatic disease (p = 0.009); and nonanatomic procedures (p = 0.008). With respect to disease-free survival, extrahepatic disease (p = 0.09) failed to achieve statistical significance, whereas patients with primary tumors in the colon did significantly better than those with rectal cancer (p = 0.04). The presence of five or more independent metastases adversely affected resectability (p or = 4) on either overall (p = 0.40) or disease-free (p = 0.64) survival was found. Using Cox's multivariate regression analysis, the presence of satellite metastases, primary tumor grade, the time of metastasis diagnosis, diameter of the largest metastasis, anatomic versus nonanatomic approach, year of resection, and mesenteric lymph node involvement each independently affected both crude and tumor-free survival.

Resection of colorectal liver metastases.

Background Two years after undergoing resection of liver metastases from colorectal cancer, about 65 percent of patients are alive and 25 percent are free of detectable disease. We tried to improve these outcomes by treating patients with hepatic arterial infusion of floxuridine plus systemic fluorouracil after liver resection. Methods We randomly assigned 156 patients at the time of resection of hepatic metastases from colorectal cancer to receive six cycles of hepatic arterial infusion with floxuridine and dexamethasone plus intravenous fluorouracil, with or without leucovorin, or six weeks of similar systemic therapy alone. Patients were stratified according to previous treatment and the number of liver metastases identified at operation. The study end points were overall survival, survival without recurrence of hepatic metastases, and survival without any metastases at two years. Results The actuarial rate of overall survival at two years was 86 percent in the group treated with combined therapy and 7...

Hepatic arterial infusion of chemotherapy after resection of hepatic metastases from colorectal cancer

From 1960 to 1987, 1209 patients with colorectal liver metastases were recorded, and followed until 1 January 1990. In 242 cases the diagnosis was based on external imaging, whereas 967 patients had operative confirmation and staging of their liver disease. Three groups of patients were analysed: group 1 involved 921 cases, of whom 902 were deemed non-resectable whereas 19 could not be unequivocally classified. Only 21 patients lived for longer than 3 years, seven survived for 4 years, but there were no 5-year survivors. Group 2 comprised 62 highly selected patients who at laparotomy demonstrated resectable metastatic spread confined to the liver, but this was not treated mainly because of a formerly different therapeutic approach. These patients had a significantly longer median survival time (14.2 versus 6.9 months), but also failed to achieve 5-year survival. The 226 patients forming group 3 underwent hepatic resection with intent to cure. Nine of them had minimal macroscopic disease left, and 34 with all gross tumour removed had positive margins. Survival of patients with these 43 eventually non-radical resections followed an identical course as in group 2 (median survival 13.3 months, maximum 42 months). Of the 183 patients with potentially curative resection ten died after surgery (5.5 per cent). Actuarial 5 and 10-year survival rates in the remaining 173 patients were 40 and 27 per cent with 25 and seven patients alive at respective periods of time. Until 1 January 1990, 64 patients remained free from recurrent disease for up to 24 years. In three patients the tumour status at death was unclear. The other 106 patients developed definite cancer relapse. Nevertheless they demonstrated a prolongation of survival time by a median of 1 year when compared with the 43 non-radically resected patients or the 62 untreated patients with resectable liver-only metastases, and accomplished a maximum survival time of 8 years. Radical excision of colorectal secondaries to the liver therefore offers effective palliation, and in a small number the chance of a cure.

Hepatic metastases from colorectal carcinoma: Impact of surgical resection on the natural history

No consensus on the indications for surgical resection of colorectal liver metastases exists. This systematic review has been undertaken to assess the published evidence for its efficacy and safety and to identify prognostic factors. Studies were identified by computerised and hand searches of the literature, scanning references and contacting investigators. The outcome measures were overall survival, disease-free survival, postoperative morbidity and mortality, quality of life and cost effectiveness, and a qualitative summary of the trends across all studies was produced. Only 30 of 529 independent studies met all the eligibility criteria for the review, and data on 30-day mortality and morbidity only were included from a further nine studies. The best available evidence came from prospective case series, but only two studies reported outcomes for all patients undergoing surgery. The remainder reported outcomes for selected groups of patients: those undergoing hepatic resection or those undergoing curative resection. Postoperative mortality rates were generally low (median 2.8%). The majority of studies described only serious postoperative morbidity, the most common being bile leak and associated perihepatic abscess. Approximately 30% of patients remained alive 5 years after resection and around two-thirds of these are disease free. The quality of the majority of published papers was poor and ascertaining the benefits of surgical resection of colorectal hepatic metastases is difficult in the absence of randomised trials. However, it is clear that there is group of patients with liver metastases who may become long-term disease- free survivors following hepatic resection. Such survival is rare in apparently comparable patients who do not have surgical treatment. Further work is needed to more accurately define this group of patients and to determine whether the addition of adjuvant treatments results in improved survival.

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Surgical resection of hepatic metastases from colorectal cancer: a systematic review of published studies.

OBJECTIVE: To update the analysis of technical and biologic factors related to hepatic resection for colorectal metastasis in a large single-institution series to identify important prognostic indicators and patterns of failure. SUMMARY BACKGROUND DATA: Surgical therapy for colorectal carcinoma metastatic to the liver is the only potentially curable treatment. Careful patient selection of those with resectable liver-only metastatic disease is crucial to the success of surgical therapy. METHODS: Two hundred forty-four consecutive patients undergoing curative hepatic resection for metastatic colorectal carcinoma were analyzed retrospectively. Variables examined included sex, stage of primary lesion, size of liver lesion(s), number of lesions, disease-free interval, ploidy, differentiation, preoperative carcinoembryonic antigen level, and operative factors such as resection margin, use of cryotherapy, intraoperative ultrasound, and blood loss. RESULTS: Surgical margin, number of lesions, and carcinoembryonic antigen (CEA) levels significantly control prognosis. Patients with only one or two liver lesions, a 1-cm surgical margin, and low CEA levels have a 5-year disease-free survival rate of more than 30%. Disease-free interval, original stage, bilobar involvement, size of metastasis, differentiation, and ploidy were not significant predictors of recurrence. The pattern of failure correlates with surgical margin. Routine use of intraoperative ultrasound resulted in an increased incidence of negative surgical margin during the period examined. CONCLUSIONS: Surgical resection or cryotherapy of hepatic metastasis from colorectal cancer is safe and curable in appropriately selected patients. Biologic factors, such as number of lesions and carcinoembryonic antigen levels, determine potential curability, and surgical margin governs the patterns of failure and outcome in potentially curable patients. Optimization of selection criteria and surgical resection margins will improve outcome.

Johannes Scheele

Papers

Surgery for colorectal cancer metastatic to the liver. Optimizing the results of treatment.