Analysis of Prognostic Factors Influencing Long-term Survival After Hepatic Resection for Metastatic Colorectal Cancer

Background The aim of this study was to analyze the prognostic factors associated with long-term outcome after liver resection for colorectal metastases. The retrospective analysis included 297 liver resections for colorectal metastases. Methods The variables considered included disease stage, differentiation grade, site and nodal metastasis of the primary tumor, number and diameter of the lesions, time from primary cancer to metastasis, preoperative carcinoembryonic antigen (CEA) level, adjuvant chemotherapy, type of resection, intraoperative ultrasonography and portal clamping use, blood loss, transfusions, complications, hospitalization, surgical margins status, and a clinical risk score (MSKCC-CRS). Results The univariate analysis revealed a significant difference (p < 0.05) in overall 5-year survival rates depending on the differentiation grade, preoperative CEA >5 and >200 ng/ml, diameter of the lesion >5 cm, time from primary tumor to metastases >12 months, MSKCC-CRS >2. The multivariate analysis showed three independent negative prognostic factors: G3 or G4 grade, CEA >5 ng/ml, and high MSKCC-CRS. Conclusions No single prognostic factor proved to be associated with a sufficiently disappointing outcome to exclude patients from liver resection. However, in the presence of some prognostic factors (G3–G4 differentiation, preoperative CEA >5 ng/ml, high MSKCC-CRS), enrollment of patients in trials exploring new adjuvant treatments is suggested to improve the outcome after surgery.     

Prognostic value of postoperative carcinoembryonic antigen concentration and extent of invasion of resection margins after hepatic resection for colorectal metastases.

OBJECTIVE: To evaluate the prognostic value of postoperative concentration of carcinoembryonic antigen (CEA) and extent of surgical margins after resection of liver metastases from colorectal cancer. DESIGN: Retrospective study. SETTING: Teaching hospital, Switzerland. SUBJECTS: 49 patients with hepatic metastases after primary colorectal cancer. INTERVENTIONS: Resection of hepatic metastases MAIN OUTCOME MEASURES: Assessment of prognostic value of variables by univariate and multivariate analysis. RESULTS: Median survival was 24 months (range 5-86 months). Resection margins were clear (> 1-cm) in 10, close (< 1-cm) in 25 and invaded in 9 patients. On univariate analysis, a postoperative concentration of CEA of <4ng/ml was correlated with prolonged survival (p < 0.001), but the width of the resection margin was not of prognostic importance. There was no correlation between width of resection margins and postoperative concentration of CEA (p = 0.5). On multivariate analysis, postoperative concentrations of CEA of 4 ng/ml or more were associated with increased risk of death (relative risk 7.3; 95% confidence interval (CI) 2.8-18.7, p < 0.001). CONCLUSION: Postoperative CEA offers better prognostic discrimination than the width of resection margins after resection of liver metastases from colorectal tumours. Some patients with invaded resection margins did survive for 3 years, but no patient did whose CEA concentration was 4 ng/ml or more. The definition of a potentially curative hepatic resection should include a postoperative CEA concentration of <4 ng/ml (within the reference range).     

Is carcino-embryonic antigen useful in the follow-up management of patients with colorectal liver metastases?

BACKGROUND: The role of carcino-embryonic antigen (CEA) in monitoring early detection of recurrent or metastatic colorectal cancer, and its impact on resectability rate and patient survival remains controversial. Our objective was to determine any association between the preoperative level of CEA and prognosis, and the resectability and survival by method of diagnosis of colorectal hepatic metastases. METHODS: We analyzed patients who underwent exploration for hepatic resection for metastatic colorectal cancer over a 15-year period. The patient population consisted of those patients who had undergone primary colon or rectal resection and were followed up with serial CEA levels and of patients who were followed up with physical examination, liver function tests (LFTs) or computed tomography (CT) of the abdomen and pelvis that led to the diagnosis of liver metastases. Also included in the study were patients who were diagnosed with liver metastases at the time of the primary colon or rectal resection and underwent planned hepatic resection at a later time. RESULTS: Three hundred and one (301) patients who underwent a total of 345 planned hepatic resections for metastatic colorectal cancer between January 1978 and December 1993 were included in this analysis. The median preoperative CEA level was 24.8 ng/mL in the resected group, 53.0 ng/mL in the incomplete resection group, and 49.1 ng/mL in the nonresected group (P = 0.02). More of the patients who had a preoperative CEA < or =30 ng/mL were in the resected group, while those who had a preoperative CEA >30 ng/mL were likely to be in the nonresected group (P = 0.002). The median survival was 25 months for patients with a preoperative CEA level < or =30 ng/mL and 17 months for patients with a preoperative CEA >30 ng/mL (P = 0.0005). The resectability rate and the survival of patients by method of diagnosing liver metastases-rising CEA versus history and physical, elevated LFTs, CT scan versus diagnosis at the time of primary resection-was not significant (P = 0.06 and P = 0.19, respectively). Given the nonstandardized retrospective nature of the study cohort and relative small groups of patients, the power to detect small differences in survival by method of diagnosis is limited. In the complete resection group of patients with unilobar liver disease (5-year survival of 28.8%) there was no difference in survival between those patients who had normal preoperative CEA and those who had elevated preoperative CEA, and approximately 90% of them had an abnormal preoperative serum CEA level. CONCLUSIONS: CEA is useful in the preoperative evaluation of patients with hepatic colorectal metastases for assessing prognosis and is complimentary to history and physical examination in the diagnosis of liver metastases. Patients with colorectal liver metastases and preoperative CEA < or =30 ng/mL are more likely to be resectable, and they have the longest survival.     

Resection of hepatic metastases from colorectal cancer

Summary Background: The aim of this paper is to analyze our experience with liver resection for metastatic colorectal cancer and to evaluate the prognostic significance of various parameters. Methods: 40 consecutive patients treated with potentially curative liver resection between 1984 and 1996 were included. The prognostic significance of various parameters was evaluated with respect to survival. Univariate and multivariate analyses were performed for following factors: age, gender, site and stage and grading of the primary tumor, size of metastases, number of metastases, lobar distribution of metastases, diagnostic interval, type of liver resection, resection margin, perioperative blood transfusion and preoperative carcinoembryonic antigen (CEA) level. Results: 3-year- and 5-year survival was 54% and 33%, median survival was 37 months. The 30 day mortality rate was 0%, postoperative complications occurred in 8 patients (20%). As single factors the following significantly affected the prognosis: number of metastases (p=0.0001), mesenteric lymphnode involvement of the primary tumor (p=0.002), lobar distribution (p=0.002) and intraoperative units of blood (p=0.05). Multivariate analysis revealed that age, gender, mesenteric lymphnode involvement, number of metastases and synchronous versus metachronous metastatic disease were independent predictors of survival. Conclusions: Liver resection is effective in selected patients with hepatic metastases from colorectal cancer. In resectable patients it is not possible to establish a clear prognosis based on the investigated factors. Therefore, patients with adverse prognostic factors should not be denied resection.      

Evaluation of long-term survival after hepatic resection for metastatic colorectal cancer: a multifactorial model of 929 patients

OBJECTIVE: To identify risk factors associated with cancer-specific survival and develop a predictive model for patients undergoing primary hepatic resection for metastatic colorectal cancer. BACKGROUND: No published studies investigated collectively the inter-relation of factors related to patient cancer-specific survival after hepatectomy for metastatic colorectal cancer. METHODS: Clinical, pathologic, and complete follow-up data were prospectively collected from 929 consecutive patients undergoing primary (n = 925) or repeat hepatic resection (n = 80) for colorectal liver metastases at a tertiary referral center from 1987 to 2005. Parametric survival analysis was used to identify predictors of cancer-specific survival and develop a predictive model. The model was validated using measures of discrimination and calibration. RESULTS: Postoperative mortality and morbidity were 1.5% and 25.9%, respectively. 5-year and 10-year cancer-specific survival were 36% and 23%. On multivariate analysis, 7 risk factors were found to be independent predictors of poor survival: number of hepatic metastases >3, node positive primary, poorly differentiated primary, extrahepatic disease, tumor diameter > or =5 cm, carcinoembryonic antigen level >60 ng/mL, and positive resection margin. The first 6 of these criteria were used in a preoperative scoring system and the last 6 in the postoperative setting. Patients with the worst postoperative prognostic criteria had an expected median cancer-specific survival of 0.7 years and a 5-year cancer-specific survival of 2%. Conversely, patients with the best prognostic postoperative criteria had an expected median cancer-specific survival of 7.4 years and a 5-year cancer-specific survival of 64%. When tested both predictive models fitted the data well with no significant differences between observed and predicted outcomes (P > 0.05). CONCLUSION: Resection of liver metastases provides good long-term cancer-specific survival benefit, which can be quantified pre- or postoperatively using the criteria described. The "Basingstoke Predictive Index" may be used for risk-stratifying patients who may benefit from intensive surveillance and selection for adjuvant therapy and trials.     

Pulmonary resection for metastases from colorectal cancer: factors influencing prognosis. Twenty-year experience.

OBJECTIVE: We reviewed our experience in the surgical management of 80 patients with colorectal pulmonary metastases and investigated factors affecting survival. MATERIAL AND METHODS: From January 1980 to December 2000, 80 patients, 43 women and 37 men with median age 63 years (range 38-79 years) underwent 98 open surgical procedure (96 muscle-sparing thoracotomy, one clamshell and one median sternotomy) for pulmonary metastases from colorectal cancer (three pneumonectomy, 17 lobectomy, seven lobectomy plus wedge resection, six segmentectomy, three segmentectomy plus wedge resection and 62 wedge resection). Pulmonary metastases were identified at a median interval of 37.5 months (range 0-167) from primary colorectal resection. Second and third resections for recurrent metastases were done in seven and in four patients, respectively. RESULTS: Operative mortality rate was 2%. Overall, 5-year survival was 41.1%. Five-year survival was 43.6% for patients submitted to single metastasectomy and 34% for those submitted to multiple ones. Five-year survival was 55% for patients with disease-free interval (DFI) of 36 months or more, 38% for those with DFI of 0-11 months and 22.6% for those with DFI of 12-35 months (P=0.04). Five-year survival was 58.2% for patients with normal preoperative carcino-embryonic antigen (CEA) levels and 0% for those with pathologic ones (P=0.0001). Patients submitted to second-stage operation for recurrent local disease had 5-year survival rate of 50 vs. 41.1% of those submitted to single resection (P=0.326). CONCLUSIONS: Pulmonary resection for metastases from colorectal cancer may help survival in selected patients. Single metastasis, DFI>36 months, normal preoperative CEA levels are important prognostic factors. When feasible, re-operation is a safe procedure with satisfactory long-term results.     

Preoperative prognostic score for predicting survival after hepatic resection for colorectal liver metastases

BACKGROUND: Despite indications for resection of colorectal liver metastases having expanded, debate continues about identifying patients that may benefit from surgery. METHODS: Clinicopathologic data from a total of 700 patients was gathered between January 1993 and January 2006 from a prospectively maintained dataset. Of these, 687 patients underwent resection for colorectal liver metastases. RESULTS: The median age of patient was 64 years and 36.8% of patients had synchronous disease. The overall 5-year survival was 45%. The presence of an inflammatory response to tumor (IRT), defined by an elevated C-reactive protein (>10 mg/L) or a neutrophil/lymphocyte ratio of >5:1, was noted in 24.5% of cases. Only the number of metastases and the presence or absence of an IRT influenced both overall and disease-free survival on multivariable analysis. A preoperative prognostic score was derived: 0 = less than 8 metastases and absence of IRT; 1 = 8 or more metastases or IRT, and 2 = 8 or more metastases and IRT-from the results of the multivariable analysis. The 5-year survival of those scoring 0 was 49% compared with 34% for those scoring 1. None of the patients that scored 2 were alive at 5 years. CONCLUSION: The preoperative prognostic score is a simple and effective system allowing preoperative stratification.     

Influence of postoperative morbidity on long-term survival following liver resection for colorectal metastases

BACKGROUND: Survival after resection of colorectal liver metastases may be influenced by the patient, the primary tumour and the liver metastases. Postoperative morbidity is associated with poor survival in several cancers. The aim of this retrospective study was to evaluate prognostic factors of survival after resection of colorectal liver metastases, including postoperative morbidity. METHODS: From 1985 to 2000, 311 consecutive patients with liver metastases from colorectal cancer underwent resection with curative intent. Univariate and multivariate analyses were performed to assess the influence of age, sex, site and stage of the colorectal tumour, disease-free interval, number, size and distribution of metastases, type of hepatectomy, pedicular clamping, resection margin, blood transfusion, postoperative morbidity and adjuvant chemotherapy on overall and disease-free survival. RESULTS: The postoperative mortality and morbidity rates were 3 and 30 per cent respectively. The 3- and 5-year overall survival rates were 53 and 36 per cent respectively. Both overall and disease-free survival rates were independently associated with nodal status of the colorectal tumour, number of metastases and postoperative morbidity. Patients with postoperative morbidity had an overall and disease-free 5-year survival rate half that of patients with no morbidity: 21 versus 42 per cent for overall survival (P < 0.001) and 12 versus 28 per cent for disease-free survival (P = 0.001) respectively. CONCLUSION: Long-term survival can be altered by postoperative morbidity after resection of colorectal liver metastases by increasing the risk of tumour recurrence. This justifies optimizing the surgical treatment of colorectal liver metastases to decrease postoperative morbidity and the use of efficient adjuvant treatments in patients with postoperative morbidity.     

The prognostic value of carcinoembryonic antigen in T1N1M0 and T2N1M0 non-small cell carcinoma of the lung.

OBJECTIVE: To evaluate the significance of preoperative clinicopathological factors, including serum carcinoembryonic antigen (CEA), as well as postoperative clinicopathological factors in T1-2N1M0 patients with non-small cell lung cancer who underwent curative pulmonary resection. METHODS: Twenty T1N1M0 disease patients and 25 T2N1M0 patients underwent standard surgical procedures between September 1996 and December 2005, and were found to have non-small lung cancer. As prognostic factors, we retrospectively investigated age, sex, Brinkman index, histologic type, primary site, tumor diameter, clinical T factor, clinical N factor, pathological T factor, preoperative serum CEA levels, surgical procedure, visceral pleural involvement, and the status of lymph node involvement (level and number). RESULTS: The overall 5-year survival rate of all patients was 59.6%. In univariate analysis, survival was related to age (<70/>or=70 years, p=0.0079), site (peripheral/central, p=0.043), and CEA level (<5.0/>or=5.0 ng/ml, p=0.0015). However, in multivariate analysis, CEA (<5.0/>or=5.0 ng/ml) was the only independent prognostic factor; the 5-year survival of the patients with an elevated serum CEA level (>or=5.0 ng/ml) was only 33.2% compared to 79.9% in patients with a lower serum CEA level (<5.0 ng/ml). CONCLUSIONS: An elevated serum CEA level (>or=5.0 ng/ml) was an independent predictor of survival in pN1 patients except for T3 and T4 cases. Therefore, even in completely resected pN1 non-small cell lung cancer, patients with a high CEA level might be candidates for multimodal therapy.     

Recurrence after complete cryoablation of colorectal liver metastases: analysis of prognostic features

This study critically evaluated the prognostic determinants for disease-free survival (DFS) after cryoablation for colorectal liver metastases. An observational cohort study of prospectively collected data on 135 patients who underwent cryoablation with or without resection for colorectal liver metastases was performed. Univariate and multivariate analyses were used to determine the prognostic factors for overall DFS, cryosite DFS, remaining liver DFS, and extrahepatic DFS. Overall, 115 patients (85%) developed recurrence at the cryosite (44%), and the remaining patients developed recurrence at the liver (62%) and extrahepatic site (71%). In univariate analysis, preoperative and postoperative carcinoembryonic antigen (CEA) were significant for overall DFS. Distribution of metastases, operation type, total number of metastases, number of cryotreated metastases, largest size of cryotreated metastasis, and postoperative CEA were significant for cryosite DFS. The number of cryotreated metastases and postoperative CEA were significant for remaining liver DFS. The largest size of cryotreated metastasis, and preoperative and postoperative CEA were significant for extrahepatic DFS. In multivariate analysis, resection plus cryoablation, < or =7 liver metastases and < or =3 cm cryotreated metastasis were independently associated with an improved cryosite DFS. Preoperative CEA of < or =5 ng/mL was independently associated with an improved overall and extrahepatic DFS. The role of CEA in colorectal metastasis is important. Resection plus cryoablation rather than cryoablation alone should be used for larger lesions.     

Surgery for pulmonary metastases from colorectal carcinoma

BACKGROUND: This study aims to clarify which patients would benefit by surgery for pulmonary metastases from colorectal carcinoma. METHODS: A retrospective study was undertaken in 25 patients who had undergone complete resection. In all cases, prethoracotomy carcinoembryonic antigen (CEA) level was measured and mediastinal or hilar lymph nodes were histologically examined. RESULTS: Overall 5-year survival was 39.2%. The 5-year survival rate for patients with a normal CEA level was 61.1%, as compared with 19.0% for patients with an elevated CEA level (p = 0.0423). The 5-year survival rate for patients without a lymph node metastasis was 49.5%, as compared with 14.3% for patients with a lymph node metastasis (p = 0.0032). No lymph node metastasis was a predictor of longer survival by univariate and multivariate analyses. The primary site, disease-free interval, and number and size of the metastasis were not significant prognostic factors. CONCLUSIONS: A resection for pulmonary metastasis from colorectal carcinoma is effective in patients with a normal CEA level and without a lymph node metastasis.     

Five-year survival after resection of hepatic metastases from colorectal cancer in patients screened by positron emission tomography with F-18 fluorodeoxyglucose (FDG-PET)

OBJECTIVE: To report the first 5-year overall survival results in patients with colorectal carcinoma metastatic to the liver who have undergone hepatic resection after staging with [18F] fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET). SUMMARY BACKGROUND DATA: The 5-year overall survival after hepatic resection for colorectal cancer metastases without preoperative FDG-PET has been established in 19 studies (6070 patients). The median 5-year overall survival rate in these studies is 30% and has not improved over time. FDG-PET detects unsuspected tumor in 25% of patients considered to have resectable hepatic metastasis by conventional staging. METHODS: From March 1995 to June 2002, all patients having hepatic resection for colorectal cancer metastases had preoperative FDG-PET. A prospective database was maintained. RESULTS: One hundred patients (56 men, 44 women) were studied. Metastases were synchronous in 52, single in 63, unilateral in 78, and <5 cm in diameter in 60. Resections were major (>3 segments) in 75 and resection margins were > or = 1 cm in 52. Median follow up was 31 months, with 12 actual greater than 5-year survivors. There was 1 postoperative death. The actuarial 5-year overall survival was 58% (95% confidence interval, 46-72%). Primary tumor grade was the only prognostic variable significantly correlated with overall survival. CONCLUSIONS: Screening by FDG-PET is associated with excellent postresection 5-year overall survival for patients undergoing resection of hepatic metastases from colorectal cancer. FDG-PET appears to define a new cohort of patients in whom tumor grade is a very important prognostic variable.     

Trends in long-term survival following liver resection for hepatic colorectal metastases

OBJECTIVE: To examine trends in outcomes of patients undergoing resection at a single tertiary care referral center over a 16-year period. SUMMARY BACKGROUND DATA: Hepatic resection is considered the treatment of choice in selected patients with colorectal metastasis confined to the liver. Although a variety of retrospective studies have demonstrated improvements in short-term outcomes in recent years, changes in long-term survival over time are less well-established. METHODS: Data from 226 consecutive patients undergoing potentially curative liver resection for colorectal metastases between 1984 and 1999 were analyzed. Actuarial survival rates related to prognostic determinants were analyzed using the log-rank test. RESULTS: The median survival for the entire cohort was 46 months, with 5- and 10-year survival rates of 40% and 26% respectively. Ninety-three patients operated on between 1984 and 1992 were found to have an overall survival of 31% at 5 years, compared to 58% for the 133 patients operated on during the more recent period (1993-1999). Both overall and disease-free survival were significantly better in the recent time period compared with the earlier period on both univariate and multivariate analyses. Other independent factors associated with improved survival included number of metastatic tumors < or = 3, negative resection margin, and CEA < 100. Comparisons were made between time periods for a variety of patient, tumor and treatment-related factors. Among all parameters studied, only resection type (anatomical versus nonanatomical), use of intraoperative ultrasonography, and perioperative chemotherapy administration differed between the early and recent time periods. CONCLUSIONS: Long-term survival following liver resection for colorectal metastases has improved significantly in recent years at our institution. Although the reasons for this survival trend are not clear, contributing factors may include the use of newer preoperative and intraoperative imaging, increased use of chemotherapy, and salvage surgical therapy.     

Pre- and postoperative carcinoembryonic antigen determinations in hepatic resection for colorectal metastases. Predictive value and implications for adjuvant treatment based on multivariate analysis.

OBJECTIVE: The object of this study was to evaluate the prognostic significance of pre- and postoperative serum carcinoembryonic antigen (CEA) levels in the resectional treatment of colorectal hepatic metastases. The main question was whether postoperative CEA levels correlated with survival and the time to recurrence. SUMMARY BACKGROUND DATA: Despite numerous investigations on prognostic factors in colorectal cancer, only sparse data are available to estimate the patient's individual risk for tumor recurrence postoperatively. It is controversial whether preoperative CEA values are of prognostic significance, and after observing the kinetics of CEA decline, elevated CEA levels postoperatively were found to be an ominous sign. CEA therefore could indicate the presence of a tumor burden after resection. METHODS: One hundred sixty-six patients undergoing hepatic resection for colorectal metastases with curative intent were prospectively documented and underwent multivariate analysis for indicators of prognosis. RESULTS: Abnormal preoperative CEA levels were not of prognostic significance compared with values within the normal range (survival, 36 vs. 30 months; p = 0.12; disease-free survival, 12 vs. 10 months; p = 0.82). The postoperative serum CEA level, however, was the most predictive factor with regard to survival and the disease-free interval. Patients in whom CEA levels were abnormal before surgery and returned into the normal range after resection had significantly better survival times (37 vs. 23 months, p = 0.0001) and disease-free survival times (12 vs. 6.2 months, p = 0.0001) compared with patients with persistently abnormal values. CONCLUSIONS: Pre- and postoperative determination of the serum CEA level is mandatory to judge whether a curative resection has been performed and whether tumor has been left behind after the operation. Postoperative CEA levels also should be used as a stratification criterion in adjuvant treatment studies after hepatic resection to indicate patients with a high risk of tumor recurrence.     

Technical and biological factors in disease-free survival after hepatic resection for colorectal cancer metastases.

Careful patient selection for hepatic resection of colorectal cancer metastases is essential to improve current poor results. Carcinoembryonic antigen level and number of metastases were significant preoperative prognostic indicators of 5-year disease-free survival in patients selected clinically for hepatic surgery. Surgical margin, weight of hepatic tissue resected, carcinoembryonic antigen level, and flow cytometry were significant postoperative prognostic indicators. Patients with a carcinoembryonic antigen level less than 200 ng/mL, 1-cm surgical margins, and less than 1,000 g of liver tissue removed had a greater than 50% estimated 5-year disease-free survival rate. If the metastases were diploid on flow cytometry, an additional survival advantage may have been gained. Inadequate surgical margins led to high rates of liver-only recurrence. Nonhepatic recurrence was unrelated to surgical margins. Intraoperative liver examination by ultrasound during primary colon cancer resection and adjuvant chemotherapy may offer earlier selection of biologically appropriate patients and improved outcome; both recommendations require clinical trials.     

Prognostic factors in survival of colorectal cancer patients with synchronous liver metastasis

Aim To determine the factors affecting the survival in colorectal cancer patients with synchronous liver metastases. Method A total of 168 patients who had been treated colorectal cancer with synchronous liver metastases at Guangxi Medical University from January 2000 to December 2005 were identified. Criteria studied consisted of gender, age, time of symptoms, primary tumour location, primary tumour circumference, histological type, grade (tumour differentiation), T‐status, N‐status, large bowel obstruction, type of operation, primary tumour resection, ascities, location, number and diameter of liver lesions, preoperative CEA and chemotherapy. Survival curves were plotted using the Kaplan–Meier method. Multivariate analysis was conducted by Cox regression analysis. Results The mean survival time for all patients was 18.71 (SEM = 1.59) months. The 1, 2, 3 and 5‐year survival rates were 55.95%, 23.21%, 12.30%, 8.0% respectively. Univariate analysis share of grade (tumour differentiation), N‐status, large bowel obstruction, operation, primary tumour resection, location, number and the most diameter of liver lesions, extrahepatic transfer, preoperative CEA level and chemotherapy to be predictors of survival. In the Cox regression analysis, the N‐status, large bowel obstruction, operation, diameter of liver lesion and extrahepatic transfer were independent factors related to survival. Conclusion Tumour differentiation, N‐status, bowel obstruction, operation, primary tumour resection, location of liver metastasis, number of liver metastasis, diameter of liver metastasis, extrahepatic transfer, preoperative CEA level and chemotherapy are related to the survival of patients with colorectal cancer and synchronous liver metastases.     

Effect of surgical margin status on survival and site of recurrence after hepatic resection for colorectal metastases

OBJECTIVE: To evaluate the influence of surgical margin status on survival and site of recurrence in patients treated with hepatic resection for colorectal metastases. METHODS: Using a multicenter database, 557 patients who underwent hepatic resection for colorectal metastases were identified. Demographics, operative data, pathologic margin status, site of recurrence (margin, other intrahepatic site, extrahepatic), and long-term survival data were collected and analyzed. RESULTS: On final pathologic analysis, margin status was positive in 45 patients, and negative by 1 to 4 mm in 129, 5 to 9 mm in 85, and > or =1 cm in 298. At a median follow-up of 29 months, the 1-, 3-, and 5-year actuarial survival rates were 97%, 74%, and 58%; median survival was 74 months. Tumor size > or =5 cm, >3 tumor nodules, and carcinoembryonic antigen level >200 ng/mL predicted poor survival (all P < 0.05). Median survival was 49 months in patients with positive margins and not yet reached in patients with negative margins (P = 0.01). After hepatic resection, 225 (40.4%) patients had recurrence: 21 at the surgical margin, 56 at another intrahepatic site, 82 at an extrahepatic site, and 66 at both intrahepatic and extrahepatic sites. Patients with negative margins of 1 to 4 mm, 5 to 9 mm, and > or =1 cm had similar overall recurrence rates (P > 0.05). Patients with positive margins were more likely to have surgical margin recurrence (P = 0.003). Adverse preoperative biologic factors including tumor number greater than 3 (P = 0.01) and a preoperative CEA level greater than 200 ng/mL (P = 0.04) were associated with an increased risk of positive surgical margin. CONCLUSIONS: A positive margin after resection of hepatic colorectal metastases is associated with adverse biologic factors and increased risk of surgical-margin recurrence. The width of a negative surgical margin does not affect survival, recurrence risk, or site of recurrence. A predicted margin of <1 cm after resection of hepatic colorectal metastases should not be used as an exclusion criterion for resection.     

Hepatic resection for colorectal metastases: can preoperative scoring predict patient outcome?

A retrospective study was performed to define patient selection, safety, and efficacy of hepatic resection for colorectal metastases. The recently proposed preoperative clinical risk score (CRS) for selection of patients for surgery was also assessed. In all, 146 consecutive hepatic resections in 137 patients operated in the period between 1977 and 1999 were studied. Of these patients, 113 were classified into five CRS groups. Perioperative mortality was 1.4% (2 patients; no death in 120 patients operated after 1985) and morbidity was 38%. Five-year actuarial survival (perioperative mortality included) was 29% (median 37 months), and actual 5-year survival was 25% (17/69 patients). Patients operated after 1995 lived longer than those operated before 1995. Multiple regression analyses identified preoperative carcinoembryonic antigen CEA <100 mg/L, nodal status at resection of primary tumor, and R0 vs. R1/R2 resection as prognostic parameters. CRS grouping had prognostic importance. The relative risk (hazard rate) of tumor recurrence in patients with CRS 3-4 was 2.1, compared to that of patients with CRS 0-2. Five-year actuarial survival in the two groups was 12% and 40%, respectively. Fourteen of 15 long-term survivors (>5 years) classified by the CRS system had CRS of 2 or less. Resection for colorectal liver metastases is safe, and long-term survival rates are acceptable. CRS predicts patient outcome, but the clinical role in patient selection will have to be defined in prospective studies.     

Cryotherapy for primary and secondary liver tumours

AIMS: We assessed the morbidity, mortality and efficacy of cryotherapy for primary and secondary malignant liver tumours in a prospective case control study. METHODS: Since 1996 we performed 77 cryosurgical procedures on 71 patients. 6 patients had hepatocellular carcinoma, the remainders metastases, mainly of colorectal origin (n = 49). Cryotherapy was used when a complete tumour resection was not feasible, but complete tumour destruction by cryotherapy seemed possible. Mean follow-up was 21 months. RESULTS: The mean number of lesions per patient was 2.6 (1-10) with a mean maximum diameter of 3.7 cm (1-11). In 36 of 71 patients cryotherapy was used in combination with liver resection. Morbidity and hospital mortality were 23 % and 2.8 %. In 25 of 34 patients with colorectal primary and preoperatively elevated CEA it returned to normal postoperatively (74 %). 40 of the 60 patients with "R0-treatment" developed tumour recurrence, 10 of these at the cryosite (17 %). Median survival for all patients (colorectal metastases) was 28 (29) months with a 3- and 5-year survival rate of 38 % (43 %) and 30 % (33 %), respectively. CONCLUSION: Cryotherapy is an effective parenchyma sparing method for the treatment of malignant liver tumours in a curative approach. It can be performed safely and a long-term local tumour control is achieved in a high percentage of patients. Survival rates following cryotherapy appear comparable to the results of liver resection. It seems justified to conduct a prospective randomised trial comparing liver resection and cryotherapy for resectable tumours.     

Resection rate and effect of postoperative chemotherapy on survival after surgery for colorectal liver metastases.

BACKGROUND: The purpose of this study was to investigate whether adjuvant therapy can improve survival after curative resection of colorectal liver metastases. METHODS: Some 235 patients had 256 liver resections for metastatic colorectal cancer. There were no predefined criteria for resectability with regard either to the number or size of the tumours or to locoregional invasion, except that resection had potentially to be complete and macroscopically curative. All patients who had curative hepatic resection were advised to start postoperative adjuvant chemotherapy. RESULTS: The resectability rate in screened patients was 91 per cent (235 of 259 patients); the postoperative mortality rate was 4 per cent. In 35 patients resection of the primary tumour was performed simultaneously with partial liver resection. Forty-four patients (19 per cent) developed intra-abdominal recurrence; 14 (6 per cent) underwent reoperation and the recurrent tumour was resected. Adjuvant chemotherapy was given to 99 patients (55 per cent), most treatments being based on 5-fluorouracil with folinic acid. The overall actuarial survival rates at 1, 3 and 5 years were 87, 60 and 36 per cent respectively. In a multivariate analysis, four or more metastases, preoperative carcinoembryonic antigen level higher than 5 ng/ml and a positive resection margin were independent predictors of poor outcome. Adjuvant chemotherapy improved the 5-year survival rate to 53 per cent. CONCLUSION: This study provides some evidence that postoperative chemotherapy is beneficial; however, prospective randomized studies are necessary to define its exact role.