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Original Article |

Perioperative Carcinoembryonic Antigen Measurements to Predict Curability After Liver Resection for Colorectal Metastases:  A Prospective Study FREE

Elie Oussoultzoglou, MD; Edoardo Rosso, MD; Pascal Fuchshuber, MD, PhD; Victor Stefanescu, MD; Bala Diop, MD; Giorgio Giraudo, MD; Patrick Pessaux, MD, PhD; Philippe Bachellier, MD; Daniel Jaeck, MD, PhD
[+] Author Affiliations

Author Affiliations: Centre de Chirurgie Visc[[eacute]]rale et de Transplantation, H[[ocirc]]pital de Hautepierre, H[[ocirc]]pitaux Universitaires de Strasbourg[[ndash]]Universit[[eacute]] Louis Pasteur, Strasbourg, France (Drs Oussoultzoglou, Rosso, Stefanescu, Diop, Giraudo, Pessaux, Bachellier, and Jaeck); and Department of Surgical Oncology, The Permanente Medical Group, Walnut Creek, California (Dr Fuchshuber).


Arch Surg. 2008;143(12):1150-1158. doi:10.1001/archsurg.143.12.1150.
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Hypothesis  Perioperative carcinoembryonic antigen (CEA) blood level is a predictor of outcome after resection of colorectal liver metastases (CLMs).

Design  Prospective clinical study.

Setting  Department of digestive surgery and transplantation.

Patients  Between January 1, 2000, and December 31, 2004, CEA levels were routinely measured 1 week before and 6 weeks after CLM resection in 213 patients. The patients were divided into the following 3 groups: group A (n = 69) with normal preoperative and postoperative CEA levels, group B (n = 111) with elevated preoperative and normal postoperative CEA levels, and group C (n = 33) with elevated preoperative and postoperative CEA levels.

Main Outcome Measures  The use of perioperative CEA levels to predict outcome after resection.

Results  The median survival was 45.4 months. The 5-year overall and disease-free survival rates were 50.2% and 21.9%, respectively, in group A, 38.5% and 18.3% in group B, and 0.0% and 0.0% in group C (P < .001). Univariate analysis showed that patients with elevated preoperative and postoperative CEA levels, multiple CLMs, large CLMs (≥5 cm), advanced Fong clinical risk score, bilobar distribution, and hepatic pedicle lymph node involvement had significantly poorer overall and disease-free survival. By multivariate analysis, only perioperative CEA level, hepatic pedicle lymph node involvement, and number and size of CLMs were independent prognostic factors. The 5-year survival rates showed good correlation with perioperative CEA levels in all 3 patient groups.

Conclusions  The predictive value of perioperative CEA levels is demonstrated. Carcinoembryonic antigen levels as early as 6 weeks after surgery may be helpful in assigning patients to adjuvant chemotherapy after resection of CLMs.

Figures in this Article

Liver resection has been recognized as the only potentially curative treatment for patients with colorectal liver metastases (CLMs).1,2 Despite curative intent, most patients who undergo surgical resection do not have long-term survival.14 Prognostic factors and clinical scoring systems for long-term survival and recurrence have been described for use after potentially curative CLM resection.1,324

However, the available prognostic factors and the current definition of curative resection consider only the resection margins and the absence of extrahepatic disease.4,23,25 They fall short of predicting overall curability after CLM resection because they evaluate only a static aspect of a progressive disease. Therefore, prognostic factors reflecting the biologic dynamics of the disease after surgical resection might be more helpful as predictors of outcome.

Carcinoembryonic antigen (CEA) blood level is the most widely used tumor marker to detect recurrences after resection of primary colorectal cancer and CLMs.2629 Considering the short half-life of CEA,30 this tumor marker may be of clinical value for a dynamic evaluation of this disease. Few series have studied the prognostic value of preoperative and postoperative changes in CEA levels among patients undergoing CLM resection.31,32 The aim of the present study was to prospectively evaluate the use of preoperative and postoperative CEA measurements to predict cure after CLM resection in a large single-institutional series.

STUDY DESIGN

During the study period, preoperative and postoperative CEA levels were measured according to an established protocol and were collected prospectively. The preoperative CEA measurement was performed within 1 week before liver resection. Blood samples for postoperative CEA measurement were obtained 6 weeks after liver resection during a short hospitalization scheduled for removal of a transcystic biliary drain routinely placed at the time of liver resection. Both CEA measurements were performed in our hospital laboratory using an electrochemiluminescence immunoassay (Elecsys 2010; Roche Diagnostics GmbH, Mannheim, Germany). A normal CEA level defined by this test is less than 5.0 ng/mL (to convert CEA level to micrograms per liter, multiply by 1.0). Patients who underwent noncurative liver resection (ie, grossly incomplete liver resection or complete resection with persistent extrahepatic disease) were excluded from this study. Patients in whom complete resection of all known extrahepatic disease was achieved at the time of liver resection were included. In patients who underwent planned 2-stage hepatectomy, only preoperative and postoperative CEA levels corresponding to the second liver resection were analyzed. The criteria for performance of preoperative portal vein embolization or staged hepatectomy (1-stage or 2-stage) were previously described.33,34 Briefly, they concern patients with initially nonresectable liver metastases (ie, multiple bilobar or small future remnant liver). Major liver resection was considered when at least 3 contiguous liver segments (as defined by Couinaud35) or 2 segments of the hepatic dome (IVb, VII, and VIII) were resected. The decision to perform hepatic lymph node dissection was based on prognostic factors described in a previous prospective study.14

STUDY POPULATION

Between January 1, 2000, and December 31, 2004, 233 patients were operated on for CLMs. Of these, 215 patients underwent curative R0 liver resection, defined as complete and microscopic margin free. Two patients were excluded because of incomplete CEA measurements. The remaining 213 patients constitute the study population. These patients were divided into 3 groups according to preoperative and postoperative CEA levels. Group A comprised 69 patients with normal preoperative and postoperative CEA levels. Group B comprised 111 patients with elevated preoperative and normal postoperative CEA levels. Group C comprised 33 patients with elevated preoperative and postoperative CEA levels.

ADJUVANT AND NEOADJUVANT CHEMOTHERAPY

Patients who had undergone neoadjuvant chemotherapy were referred to our department for further treatment planning. Among them, 23 patients (13.2%) had normal CEA levels and were assigned to group A. The decision to give additional adjuvant therapy was made after receiving final pathologic examination results in a multidisciplinary conference that included oncologists, gastroenterologists, radiologists, and surgeons. A change in CEA level from before to 6 weeks after liver resection was not considered in the decision to give adjuvant therapy in these patients. For patients treated with neoadjuvant chemotherapy, liver resection was delayed until at least 3 weeks after the last cycle. Postoperative adjuvant chemotherapy was postponed until measurement of the 6-week postoperative CEA level. This was facilitated by the fact that patients were admitted to the hospital 6 weeks after surgery for routine removal of the external transcystic biliary drain placed at the time of liver resection.

PREOPERATIVE WORKUP

Before hepatectomy, all patients underwent abdominal and thoracic computed tomography, as well as liver magnetic resonance imaging. To rule out primary tumor recurrence before resection of metachronous metastases, pelvic magnetic resonance imaging or rectal endoscopic ultrasonography was used in patients with rectal primary tumors, and colonoscopy was used in patients with colon primary tumors. Positron emission tomography was not routinely used for preoperative staging at the time of the study.

FOLLOW-UP

All patients were followed up every 3 to 6 months with a physical examination, CEA measurement, abdominal ultrasonography, or computed tomography. No patient was lost to follow-up. The diagnosis of recurrence was based on postoperative imaging or biopsy results. Patients with persistent elevated CEA levels 6 weeks after liver resection were not considered as having recurrences. In patients whose CEA levels remained elevated beyond 6 weeks on routine follow-up examinations, further imaging studies and biopsies as indicated were performed to detect measurable recurrent disease.

STATISTICAL ANALYSIS

Fisher exact, χ2, and Mann-Whitney tests were used. Survival was calculated from the date of surgery. Kaplan-Meier survival was calculated, and significant differences were examined using log-rank test. Multivariate analysis using Cox proportional hazards models was used to identify independent risk factors for overall and disease-free survival. A difference was considered statistically significant if P < .05. Only variables with P < .20 on univariate analysis were included in the multivariate analysis. All statistical calculations were performed using commercially available software (SPSS 10.0; SPSS Inc, Chicago, Illinois).

PATIENT CHARACTERISTICS

They were 136 male and 77 female patients. The mean (SD) age was 63.7 (9.6) years (age range, 39.7-84.2 years). Sixty-one patients were 70 years or older. The primary tumor was located in the colon in 164 patients and in the rectum in 49 patients. According to the pTNM classification, the primary tumor was staged pT1 or pT2 in 27 patients and pT3 or pT4 in 186 patients. The primary tumor lymph nodes were invaded in 135 patients, not invaded in 77 patients, and unknown in 1 patient. In group A patients, the carbohydrate antigen (CA) 19-9 level before hepatectomy was normal (<34 U/mL) in 56 patients, mildly elevated (34-44 U/mL) in 10 patients, and highly elevated (298-402 U/mL) in 3 patients (to convert CA 19-9 level to kilounits per liter, multiply by 1.0). The mean (SD) CA 19-9 level was 31.4 (69.5) U/mL (range, 1-402 U/mL).

CHARACTERISTICS OF LIVER METASTASES

Colorectal liver metastases were metachronous in 107 patients (50.2%) and bilobar in 90 patients (42.3%) (Table 1). The mean (SD) size of the largest liver metastases was 46.8 (27.4) mm (range, 15-160 mm). The mean (SD) interval between primary tumor resection and liver resection was 21.6 (17.8) months (range, 3-96 months). Eighty-two patients had solitary liver metastases, 36 had 2 metastases, 36 had 3 metastases, and 59 had more than 3 metastases.

Table Graphic Jump LocationTable 1. Univariate Analysis of Prognostic Factors for Overall and Disease-Free Survival
ASSOCIATED PROCEDURES

Twenty-seven patients underwent associated procedures at the time of hepatectomy. These included resection of colorectal primary tumors (n = 12), resection of solitary peritoneal implants (n = 12), partial diaphragmatic resection (n = 2), and right adrenal gland resection (n = 1). Hepatic pedicle and retroduodenopancreatic lymph node dissection was performed in 132 patients. Among them, 12 patients (9.1%) had microscopic hepatic pedicle lymph node metastases discovered at pathologic examination. No patient had macroscopic evidence of hepatic pedicle lymph node involvement.

COMPARABILITY OF THE STUDY GROUPS

The 3 study groups were similar in age, sex, primary tumor site, pTNM stage, type and topography of liver metastases, disease-free interval between primary tumor resection and diagnosis of liver metastases, number of liver metastases, size of largest liver metastases, presence of resectable solitary peritoneal implant, hepatic pedicle lymph node involvement, and neoadjuvant and adjuvant chemotherapy regimens. However, preoperative portal vein embolization was significantly more frequent in group C (39.4% [13 of 33 patients]) than in group A (15.9% [11 of 69 patients]) or group B (27.9% [31 of 111 patients]) (P =.03).

SURGICAL DATA

Major hepatectomy was performed in 98 patients. Preoperative right portal vein embolization was performed in 55 patients (28 before planned 1-stage hepatectomy and 27 before planned 2-stage hepatectomy). Liver resections included 47 bisegmentectomies (10 requiring additional subsegmental metastasectomies), 32 right hepatectomies (3 requiring additional metastasectomies in the left lobe), 23 extended right hepatectomies (7 requiring additional metastasectomies in the left lateral lobe), 5 left hepatectomies (1 requiring an additional metastasectomy), 2 extended left hepatectomies, 16 left lobectomies (13 requiring additional metastasectomies in the right lobe), 53 unisegmentectomies (18 requiring additional metastasectomies), 7 trisegmentectomies (1 requiring left lobectomy and 1 requiring an additional metastasectomy), and 28 subsegmental metastasectomies.

ADJUVANT CHEMOTHERAPY AFTER LIVER RESECTION

Adjuvant chemotherapy regimens included the following: fluorouracil plus folinic acid in 73 patients, fluorouracil plus folinic acid and oxaliplatin in 67 patients, and fluorouracil plus folinic acid and irinotecan in 38 patients.

PATIENTS UNDERGOING 1-STAGE OR 2-STAGE HEPATECTOMY WITH PORTAL VEIN EMBOLIZATION

The 1-year, 3-year, and 5-year overall survival rates in 55 patients who underwent staged hepatectomy (90.9%, 56.5%, and 29.4%, respectively) were similar to those in 158 patients who did not undergo staged hepatectomy (92.4%, 69.8%, and 38.4%, respectively) (P =.09). Moreover, the perioperative change in CEA level significantly predicted survival in patients undergoing staged hepatectomy combined with portal vein embolization (Figure 1 and Figure 2). Finally, the 5-year survival rate was significantly lower in patients undergoing 2-stage hepatectomy for initially nonresectable disease (18.9%) compared with that in patients with initially resectable liver metastases (38.4%) (P =.02).

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Figure 1.

Overall survival curves according to perioperative change in carcinoembryonic antigen levels among 55 patients undergoing staged hepatectomy combined with portal vein embolization. The 1-year, 3-year, and 5-year survival rates, respectively, were 81.8%, 47.7%, and not reached in group A; 96.8%, 66.1%, and 46.2% in group B; and 84.6%, 35.6%, and 0.0% in group C. A significant difference was observed between group B and group C (P = .007). No significant difference was observed between group A and group B (P = .19) or between group A and group C (P = .67).

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Figure 2.

Overall survival curves according to perioperative change in carcinoembryonic antigen levels among 158 patients seen with initially resectable liver metastases. The 1-year, 3-year, and 5-year survival rates, respectively, were 93.1%, 78.5%, and 54.8% in group A; 93.7%, 73.6%, and 36.6% in group B; and 85.0%, 21.2%, and 0.0% in group C. Significant differences were observed between group A and group C and between group B and group C (P < .001 for both). No significant difference was observed between group A and group B (P = .24).

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LONG-TERM OUTCOMES

The mean (SD) follow-up after hepatectomy was 34.7 (17.2) months (range, 3.1-78.5 months). Among 114 surviving patients (53.5%), 64 patients were recurrence free after a mean (SD) follow-up of 37.0 (16.5) months (range, 10.3-78.5 months). Fifty patients had recurrences after a mean (SD) follow-up of 44.6 (17.1) months (range, 20.0-77.4 months). The remaining 99 patients (46.5%) died after a mean (SD) follow-up of 28.1 (14.9) months (range, 3.1-66.3 months) after hepatectomy. Death was directly related to cancer relapse except in 2 patients, one with cardiac infarction 34.2 months after hepatectomy and the other with head and neck cancer 22.7 months after hepatectomy. Recurrences included the following: liver (n = 72), lung (n = 57), peritoneum (n = 14), bone (n = 10), primary tumor site (n = 9), disseminated disease (n = 9), retroperitoneal lymph nodes (n = 6), brain (n = 3), adrenal glands (n = 1), and ovary (n = 1). Perioperative change in CEA level did not correlate with site of recurrence. The overall median survival was 45.4 months. The 1-year, 3-year, and 5-year overall survival rates were 92.0%, 66.3%, and 35.8%, respectively. Disease-free survival rates were 74.1%, 32.3%, and 17.7% at 1 year, 3 years, and 5 years, respectively.

ANALYSIS OF PROGNOSTIC FACTORS FOR SURVIVAL

Univariate analysis showed that the status of hepatic pedicle lymph nodes, CEA level 6 weeks after hepatectomy (P < .001), perioperative change in CEA level, and number, size, and distribution of liver metastases were significant prognostic factors of overall survival and disease-free survival (Table 1). Analyzed as a continuous variable, the CEA level 6 weeks after hepatectomy also affects survival (P < .001). The primary tumor lymph node status, disease-free interval between primary tumor resection and diagnosis of liver metastases, CEA level before hepatectomy (<200 vs ≥200 ng/mL), and CEA level before neoadjuvant chemotherapy (normal vs abnormal) did not reach statistical significance (P = .06). Finally, the CEA level before hepatectomy (normal vs abnormal, P =.19) and the CEA level before neoadjuvant chemotherapy (<200 vs ≥200 ng/mL, P =.94) did not affect survival.

Analysis of the change in CEA level during neoadjuvant chemotherapy was performed by excluding patients with normal CEA levels before and after chemotherapy. The remaining 156 patients who received neoadjuvant chemotherapy were divided into the following 2 groups: group 1 comprising 49 patients with an increase in CEA level after completion of chemotherapy and group 2 comprising 107 patients with a stable CEA level or a decrease in CEA level after completion of chemotherapy. Univariate analysis showed that change in CEA level after neoadjuvant chemotherapy was also a predictor of overall survival (1-year, 3-year, and 5-year overall survival rates, respectively, were 91.8%, 54.7%, and 19.3% in group 1 vs 90.7%, 67.3%, and 34.9% in group 2; P =.048). However, disease-free survival was unaffected by change in CEA level after neoadjuvant chemotherapy (1-year, 3-year, and 5-year disease-free survival rates, respectively, were 69.3%, 12.7%, and 8.4% in group 1 vs 69.2%, 30.6%, and 16.4% in group 2; P =.12).

In group A patients, the preoperative CA 19-9 level did not affect survival (4-year survival, 56.6% for patients having normal levels vs 46.9% for patients having abnormal levels; P =.17). Patients having recurrence with an increased CEA level had similar survival vs those having recurrence with a normal CEA level (5-year survival, 28.8% vs 36.5%; P =.27).

In multivariate analysis, perioperative change in CEA level, hepatic pedicle lymph node metastases, and number and size of liver metastases were significant and independent prognostic factors for overall and disease-free survival (Table 2). In addition, sex was a significant prognostic indicator for disease-free survival.

Table Graphic Jump LocationTable 2. Multivariate Cox Proportional Hazards Regression Analysis of Prognostic Factors for Long-term Outcomes

The clinical risk score proposed by Fong et al4 for prediction of long-term outcomes after liver resection of CLMs was validated in the present series. Our study population was divided into the following 3 groups: 44 patients with a clinical risk score of 0 to 1, 135 patients with a clinical risk score of 2 to 3, and 34 patients with a clinical risk score of 4 to 5. As expected, patients with a clinical risk score representing more advanced disease (0-1 vs 2-3 vs 4-5) had significantly poorer overall and disease-free survival (P < .001 for both) (Figure 3 and Figure 4). For patients with a clinical risk score of 2 to 3, change in perioperative CEA level significantly correlated with survival. For these patients, 5-year survival rates were 45.0%, 40.2%, and 0.0% in groups A, B, and C, respectively, and the median survival times were 53.8, 45.5, and 28.3 months, respectively (Figure 5). For patients with clinical risk scores of 0 to 1 or 4 to 5, no such correlation was found, most likely because of small sample sizes.

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Figure 3.

Overall survival curves according to Fong et al4 clinical risk score. The 1-year, 3-year, and 5-year survival rates, respectively, were 97.7%, 88.6%, and 61.1% in patients with clinical risk scores of 0 to 1; 91.1%, 65.2%, and 35.1% in patients with clinical risk scores of 2 to 3; and 88.2%, 38.7%, and not reached in patients with clinical risk scores of 4 to 5. Significant differences were observed between patients with clinical risk scores of 0 to 1 vs 2 to 3 (P = .01), between patients with clinical risk scores of 0 to 1 vs 4 to 5 (P < .001), and between patients with clinical risk scores of 2 to 3 vs 4 to 5 (P = .001).

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Figure 4.

Disease-free survival curves according to Fong et al4 clinical risk score. The 1-year, 3-year, and 5-year disease-free survival rates, respectively, were 86.4%, 55.4%, and 24.5% in patients with clinical risk scores of 0 to 1; 74.0%, 29.3%, and 16.9% in patients with clinical risk scores of 2 to 3; and 58.8%, 7.1%, and not reached in patients with clinical risk scores of 4 to 5. Significant differences were observed between patients with clinical risk scores of 0 to 1 vs 2 to 3 (P = .02), between patients with clinical risk scores of 0 to 1 vs 4 to 5 (P < .001), and between patients with clinical risk scores of 2 to 3 vs 4 to 5 (P = .02).

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Figure 5.

Overall survival curves according to perioperative trend of carcinoembryonic antigen levels in 135 patients with Fong et al4 clinical risk scores of 2 to 3. Significant differences were observed between group A and group C and between group B and group C (P < .001 for both). No significant difference was observed between group A and group B (P = .98).

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The present prospective study demonstrates that postoperative CEA measurement, particularly preoperative and postoperative CEA levels after CLM resection, is a significant prognostic factor for overall and disease-free survival. Furthermore, normalization of CEA levels 6 weeks after CLM resection may indicate improved long-term outcomes in these patients.

Numerous tumor markers have been described to assess patients with colorectal cancer, including levels of p53, CEA, cytokeratin, vascular endothelial growth factor, and CAs such as CA 19-9, CA 242, and CA 72-4.3640 Among these markers, CEA level remains the most widely used. For colorectal cancer, the prognostic value of preoperative CEA measurement was highlighted by several studies.4145 Other studies32,4651 demonstrated the benefit of systematic postoperative CEA monitoring to diagnose early recurrence after resection or to assess response to chemotherapy in patients with CLMs. However, few studies32,51 have studied the usefulness of perioperative changes in CEA level for evaluating the success of surgical resection (ie, whether a presumed complete resection as defined by intraoperative and pathologic findings is effectively curative). The present study shows that patients with elevation of both preoperative and postoperative CEA levels have significantly lower median survival (28.3 months for group C) compared with patients with normal postoperative CEA levels (53.8 months for group A and 45.5 months for group B), indicating that postoperative CEA levels can be used as a marker for complete vs incomplete (cytoreductive) surgery. Therefore, patients with elevated postoperative CEA levels are particularly vulnerable to recurrence and should be considered for additional treatment. Finally, in the present series, the finding of the worst prognosis in patients requiring 2-stage hepatectomy was related to the predominance of these patients in group C. In fact, because of their higher disease burden, they are at higher risk of noncurative resection, as reflected by higher elevated postoperative CEA levels and worse outcomes. However, in selected patients, planned 2-stage hepatectomy remains the only surgical option that offers patients a chance of long-term survival.

The potential clinical value of preoperative and postoperative CEA levels was underscored several years ago by Hohenberger et al.32 They demonstrated that postoperative CEA level was the most important predictive factor for overall and disease-free survival among 141 patients who underwent R0 resection for CLMs. They suggested that CEA level was the best criterion to judge whether curative resection has been performed. However, their study included only patients with unilobar resectable disease and no more than 3 liver metastases. Moreover, data about chemotherapy were not reported. It is notable that preoperative vs postoperative change in CEA level remained the most powerful predictor of long-term outcomes in the present series, which included patients with more advanced metastatic disease such as multiple and bilobar metastases, patients with initially nonresectable disease, and patients requiring staged hepatectomy combined with portal vein embolization.

The clinical risk score developed by Fong et al4 and validated by Mann et al22 was also predictive of outcome and survival in the present series. In our study, persistent elevated postoperative CEA levels after CLM resection identified a subgroup of patients with the worst prognosis. This was particularly true for patients with a clinical risk score of 2 to 3. The clinical risk score is based on 5 static preoperative variables and evaluates disease status before CLM resection. The inclusion of postoperative CEA measurement allows assessment of tumor behavior in sequence, particularly in patients with elevated preoperative CEA levels. This measurement better identifies those patients with the best chance for cure after metastasectomy. For patients with normal preoperative CEA levels, the clinical risk score is the only good prognostic tool available because CA 19-9 is of no prognostic value in this situation, as shown by the present study and in a previous study by Weber et al.13

The reported rates of normal preoperative CEA levels in patients with CLM range from 16% to 35.1%.22,52 In a previous study13 of patients with CLMs operated on between 1988 and 1998, the percentage of patients with normal preoperative CEA levels was 19.5% (43 of 221 patients). At that time, patients received neither oxalipatin- nor irinotecan-based chemotherapy regimens. Therefore, in the present series, the wide range in the rates of patients with normal preoperative CEA levels could be explained by the effect of neoadjuvant chemotherapy on preoperative CEA levels. Indeed, 69 patients (32.4%) (group A) had normal preoperative CEA levels. This rate is an overestimation of patients not expressing CEA because 174 study patients (81.7%) received neoadjuvant chemotherapy, which led to a normalization of CEA levels in 23 patients (13.2%).

Several previous studies reported the usefulness of measuring changes in CEA level after complete tumor resection. The reported median half-life of CEA is 4 days (range, 1-88 days).30,53 This suggests that premature measurement of postoperative CEA levels may overestimate the number of patients with persistent CEA level elevation. Conversely, it has been demonstrated that prolonged CEA half-lives are often associated with the existence of overlooked synchronous metastases.53 We chose a 6-week interval for postoperative CEA measurements because we found that it accurately identified patients with persistent CEA level elevation without delaying the initiation of adjuvant chemotherapy. These arguments were sufficient for us to stop routine early postoperative CEA measurements after liver resection.

Carcinoembryonic antigen levels are an established prognostic indicator for monitoring disease progression and for early detection of recurrence.32,4651 The present series demonstrated better prognosis for patients having normal preoperative CEA levels compared with patients having elevated preoperative and postoperative CEA levels. However, the survival rates were similar in both groups of patients with normal postoperative CEA levels (groups A and B). There is no evidence that CEA-producing CLMs have more aggressive behavior than non–CEA-producing CLMs. Indeed, the primary tumor and CLM characteristics were similarly distributed in the 3 groups of patients. This study demonstrates that persistently elevated postoperative CEA levels indicate the presence of unidentified residual disease, with subsequent poor prognosis and increased risk of relapse. In this series, postoperative CEA measurements in patients with elevated preoperative CEA levels were useful in predicting ultimate surgical failure after intent-to-cure CLM resection. Elevated CEA levels in the immediate postoperative period can identify the subgroup of patients with clinically undetectable residual disease who will benefit from postoperative chemotherapy. In these patients, postoperative chemotherapy should be regarded as therapeutic rather than as adjuvant. Elevated CEA levels in the early postoperative period are not used as an indication for surgical intervention.

Most series about CLMs have reported various prognostic scoring systems based on different prognostic factors.1,3,4,10,17,22,24,54 All of them are useful in selecting patients for surgery and for predicting their outcomes. However, the major concern today is to better define the radicality of potentially curative resection rather than to identify patients at risk of recurrence. More efficient chemotherapy, multimodality treatment approaches, and innovation in surgical strategies (2-stage hepatectomy resection, portal vein embolization, and radiofrequency ablation) have increased the numbers of patients considered for liver resection and more frequently include patients initially considered as having nonresectable disease. The present study demonstrates the use of combined preoperative and postoperative CEA measurements to identify patients who had incomplete resection in the setting of intent-to cure metastasectomy for colorectal cancer. This study also shows that postoperative CEA measurements are of limited prognostic value in patients with normal preoperative CEA levels.

In conclusion, preoperative CEA measurement is a well-recognized prognostic factor. This study demonstrates that it is not a good predictor of postoperative outcome or of biologic aggressiveness of the disease. Preoperative CEA measurement did not predict performance of complete resection, nor did it accurately predict postoperative disease progression. However, our study showed that postoperative CEA level 6 weeks after CLM resection and its normalization represent the most reliable predictive criteria for complete and successful hepatic metastasectomy.

Correspondence: Daniel Jaeck, MD, PhD, Centre de Chirurgie Viscérale et de Transplantation, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg–Université Louis Pasteur, Avenue Molière, 67200 Strasbourg, France (Daniel.Jaeck@chru-strasbourg.fr).

Accepted for Publication: September 17, 2007.

Author Contributions:Study concept and design: Oussoultzoglou, Rosso, Fuchshuber, Giraudo, and Jaeck. Acquisition of data: Oussoultzoglou, Rosso, Stefanescu, Diop, and Giraudo. Analysis and interpretation of data: Oussoultzoglou, Rosso, Pessaux, and Bachellier. Drafting of the manuscript: Oussoultzoglou, Rosso, Fuchshuber, Stefanescu, Diop, Giraudo, and Bachellier. Critical revision of the manuscript for important intellectual content: Oussoultzoglou, Rosso, Fuchshuber, Pessaux, and Jaeck. Study supervision: Oussoultzoglou, Fuchshuber, Pessaux, Bachellier, and Jaeck.

Financial Disclosure: None reported.

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Iwatsuki  SDvorchik  IMadariaga  JR  et al.  Hepatic resection for metastatic colorectal adenocarcinoma: a proposal of a prognostic scoring system. J Am Coll Surg 1999;189 (3) 291- 299
PubMed Link to Article
Weber  SMJarnagin  WRDeMatteo  RPBlumgart  LHFong  Y Survival after resection of multiple hepatic colorectal metastases. Ann Surg Oncol 2000;7 (9) 643- 650
PubMed Link to Article
Weber  JCSchneider  ARohr  S  et al.  Analysis of allelic imbalance in patients with colorectal cancer according to stage and presence of synchronous liver metastases. Ann Surg 2001;234 (6) 795- 803
PubMed Link to Article
Weber  JCNakano  HBachellier  P  et al.  Is a proliferation index of cancer cells a reliable prognostic factor after hepatectomy in patients with colorectal liver metastases? Am J Surg 2001;182 (1) 81- 88
PubMed Link to Article
Jaeck  DNakano  HBachellier  P  et al.  Significance of hepatic pedicle lymph node involvement in patients with colorectal liver metastases: a prospective study. Ann Surg Oncol 2002;9 (5) 430- 438
PubMed Link to Article
Yamaguchi  JKomuta  KMatsuzaki  SOkudaira  SFujioka  HKanematsu  T Mode of infiltrative growth of colorectal liver metastases is a useful predictor of recurrence after hepatic resection. World J Surg 2002;26 (9) 1122- 1125
PubMed Link to Article
Choti  MASitzmann  JVTiburi  MF  et al.  Trends in long-term survival following liver resection for hepatic colorectal metastases. Ann Surg 2002;235 (6) 759- 766
PubMed Link to Article
Mala  TBøhler  GMathisen  ØBergan  ASøreide  O Hepatic resection for colorectal metastases: can preoperative scoring predict patient outcome? World J Surg 2002;26 (11) 1348- 1353
PubMed Link to Article
Sasaki  AAramaki  MKawano  KYasuda  KInomata  MKitano  S Prognostic significance of intrahepatic lymphatic invasion in patients with hepatic resection due to metastases from colorectal carcinoma. Cancer 2002;95 (1) 105- 111
PubMed Link to Article
Weber  JCBachellier  POussoultzoglou  EJaeck  D Simultaneous resection of colorectal primary tumour and synchronous liver metastases. Br J Surg 2003;90 (8) 956- 962
PubMed Link to Article
Nagakura  SShirai  YYokoyama  NWakai  TSuda  THatakeyama  K Major hepatic resection reduces the probability of intrahepatic recurrences following resection of colorectal carcinoma liver metastases. Hepatogastroenterology 2003;50 (51) 779- 783
PubMed
Tanaka  KShimada  HMiura  M  et al.  Metastatic tumor doubling time: most important prehepatectomy predictor of survival and nonrecurrence of hepatic colorectal cancer metastasis. World J Surg 2004;28 (3) 263- 270
PubMed Link to Article
Mann  CDMetcalfe  MSLeopardi  LNMaddern  GJ The clinical risk score: emerging as a reliable preoperative prognostic index in hepatectomy for colorectal metastases. Arch Surg 2004;139 (11) 1168- 1172
PubMed Link to Article
Pawlik  TMScoggins  CRZorzi  D  et al.  Effect of surgical margin status on survival and site of recurrence after hepatic resection for colorectal metastases. Ann Surg 2005;241 (5) 715- 724
PubMed Link to Article
Nagashima  ITakada  TNagawa  HMuto  TOkinaga  K Proposal of a new and simple staging system of colorectal liver metastasis. World J Gastroenterol 2006;12 (43) 6961- 6965
PubMed
Poston  GJAdam  RAlberts  S  et al.  OncoSurge: a strategy for improving resectability with curative intent in metastatic colorectal cancer. J Clin Oncol 2005;23 (28) 7125- 7134
PubMed Link to Article
Zeng  ZCohen  AMUrmacher  C Usefulness of carcinoembryonic antigen monitoring despite normal preoperative values in node-positive colon cancer patients. Dis Colon Rectum 1993;36 (11) 1063- 1068
PubMed Link to Article
Compton  CFenoglio-Preiser  CMPettigrew  NFielding  LP American Joint Committee on Cancer Prognostic Factors Consensus Conference: Colorectal Working Group. Cancer 2000;88 (7) 1739- 1757
PubMed Link to Article
Bast  RC  JrRavdin  PHayes  DF  et al. American Society of Clinical Oncology Tumor Markers Expert Panel, 2000 update of recommendations for the use of tumor markers in breast and colorectal cancer: clinical practice guidelines of the American Society of Clinical Oncology [published corrections appear in J Clin Oncol. 2001;19(21):4185-4188 and 2002;20(8):2213]. J Clin Oncol 2001;19 (6) 1865- 1878
PubMed
Duffy  MJvan Dalen  AHaglund  C  et al.  Clinical utility of biochemical markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines. Eur J Cancer 2003;39 (6) 718- 727
PubMed Link to Article
Choi  JSMin  JS Significance of postoperative serum level of carcinoembryonic antigen (CEA) and actual half life of CEA in colorectal cancer patients. Yonsei Med J 1997;38 (1) 1- 7
PubMed
Lokich  JEllenberg  SGerson  BKnox  WEZamcheck  N Plasma clearance of carcinoembryonic antigen following hepatic metastatectomy. J Clin Oncol 1984;2 (5) 462- 465
PubMed
Hohenberger  PSchlag  PMGerneth  THerfarth  C Pre- and postoperative carcinoembryonic antigen determinations in hepatic resection for colorectal metastases: predictive value and implications for adjuvant treatment based on multivariate analysis. Ann Surg 1994;219 (2) 135- 143
PubMed Link to Article
Jaeck  DBachellier  PNakano  H  et al.  One or two-stage hepatectomy combined with portal vein embolization for initially nonresectable colorectal liver metastases. Am J Surg 2003;185 (3) 221- 229
PubMed Link to Article
Jaeck  DOussoultzoglou  ERosso  EGreget  MWeber  JCBachellier  P A two-stage hepatectomy procedure combined with portal vein embolization to achieve curative resection for initially unresectable multiple and bilobar colorectal liver metastases. Ann Surg 2004;240 (6) 1037- 1051
PubMed Link to Article
Couinaud  C Le Foie: Etudes Anatomiques et Chirurgicales.  Paris, France Masson1957;
Kim  SBFernandes  LCSaad  SSMatos  D Assessment of the value of preoperative serum levels of CA 242 and CEA in the staging and postoperative survival of colorectal adenocarcinoma patients. Int J Biol Markers 2003;18 (3) 182- 187
PubMed
Carpelan-Holmström  MLouhimo  JStenman  UHAlfthan  HJärvinen  HHaglund  C CEA, CA 242, CA 19-9, CA 72-4 and hCGβ in the diagnosis of recurrent colorectal cancer. Tumour Biol 2004;25 (5-6) 228- 234
PubMed Link to Article
Fernandes  LCKim  SBSaad  SSMatos  D Value of carcinoembryonic antigen and cytokeratins for the detection of recurrent disease following curative resection of colorectal cancer. World J Gastroenterol 2006;12 (24) 3891- 3894
PubMed
Takeda  AShimada  HImaseki  H  et al.  Clinical significance of serum vascular endothelial growth factor in colorectal cancer patients: correlation with clinicopathological factors and tumor markers. Oncol Rep 2000;7 (2) 333- 338
PubMed
Hammel  PBoissier  BChaumette  MT  et al.  Detection and monitoring of serum p53 antibodies in patients with colorectal cancer. Gut 1997;40 (3) 356- 361
PubMed
Wolmark  NFisher  BWieand  HS  et al.  The prognostic significance of preoperative carcinoembryonic antigen levels in colorectal cancer: results from NSABP (National Surgical Adjuvant Breast and Bowel Project) clinical trials. Ann Surg 1984;199 (4) 375- 382
PubMed Link to Article
Wang  WSLin  JKChiou  TJ  et al.  Preoperative carcinoembryonic antigen level as an independent prognostic factor in colorectal cancer: Taiwan experience. Jpn J Clin Oncol 2000;30 (1) 12- 16
PubMed Link to Article
Reiter  WStieber  PReuter  CNagel  DLau-Werner  ULamerz  R Multivariate analysis of the prognostic value of CEA and CA 19-9 serum levels in colorectal cancer. Anticancer Res 2000;20 ((6D)) 5195- 5198
PubMed
Sasaki  AIwashita  YShibata  KMatsumoto  TOhta  MKitano  S Analysis of preoperative prognostic factors for long-term survival after hepatic resection of liver metastasis of colorectal carcinoma. J Gastrointest Surg 2005;9 (3) 374- 380
PubMed Link to Article
Aldrighetti  LCastoldi  RDi Palo  S  et al.  Prognostic factors for long-term outcome of hepatic resection for colorectal liver metastases. Chir Ital 2005;57 (5) 555- 570
PubMed
Chu  DZErickson  CARussell  MP  et al.  Prognostic significance of carcinoembryonic antigen in colorectal carcinoma: serum levels before and after resection and before recurrence. Arch Surg 1991;126 (3) 314- 316
PubMed Link to Article
Onik  GRubinsky  BZemel  R  et al.  Ultrasound-guided hepatic cryosurgery in the treatment of metastatic colon carcinoma: preliminary results. Cancer 1991;67 (4) 901- 907
PubMed Link to Article
Bakalakos  EABurak  WE  JrYoung  DCMartin  EW  Jr Is carcino-embryonic antigen useful in the follow-up management of patients with colorectal liver metastases? Am J Surg 1999;177 (1) 2- 6
PubMed Link to Article
Kahlenberg  MSSullivan  JMWitmer  DDPetrelli  NJ Molecular prognostics in colorectal cancer. Surg Oncol 2003;12 (3) 173- 186
PubMed Link to Article
Park  YASohn  SKSeong  J  et al.  Serum CEA as a predictor for the response to preoperative chemoradiation in rectal cancer. J Surg Oncol 2006;93 (2) 145- 150
PubMed Link to Article
Park  YALee  KYKim  NKBaik  SHSohn  SKCho  CW Prognostic effect of perioperative change of serum carcinoembryonic antigen level: a useful tool for detection of systemic recurrence in rectal cancer. Ann Surg Oncol 2006;13 (5) 645- 650
PubMed Link to Article
Fortner  JGSilva  JSGolbey  RBCox  EBMaclean  BJ Multivariate analysis of a personal series of 247 consecutive patients with liver metastases from colorectal cancer, I: treatment by hepatic resection. Ann Surg 1984;199 (3) 306- 316
PubMed Link to Article
Ito  KHibi  KAndo  H  et al.  Usefulness of analytical CEA doubling time and half-life time for overlooked synchronous metastases in colorectal carcinoma. Jpn J Clin Oncol 2002;32 (2) 54- 58
PubMed Link to Article
Nagashima  ITakada  TAdachi  MNagawa  HMuto  TOkinaga  K Proposal of criteria to select candidates with colorectal liver metastases for hepatic resection: comparison of our scoring system to the positive number of risk factors. World J Gastroenterol 2006;12 (39) 6305- 6309
PubMed

Figures

Place holder to copy figure label and caption
Figure 1.

Overall survival curves according to perioperative change in carcinoembryonic antigen levels among 55 patients undergoing staged hepatectomy combined with portal vein embolization. The 1-year, 3-year, and 5-year survival rates, respectively, were 81.8%, 47.7%, and not reached in group A; 96.8%, 66.1%, and 46.2% in group B; and 84.6%, 35.6%, and 0.0% in group C. A significant difference was observed between group B and group C (P = .007). No significant difference was observed between group A and group B (P = .19) or between group A and group C (P = .67).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Overall survival curves according to perioperative change in carcinoembryonic antigen levels among 158 patients seen with initially resectable liver metastases. The 1-year, 3-year, and 5-year survival rates, respectively, were 93.1%, 78.5%, and 54.8% in group A; 93.7%, 73.6%, and 36.6% in group B; and 85.0%, 21.2%, and 0.0% in group C. Significant differences were observed between group A and group C and between group B and group C (P < .001 for both). No significant difference was observed between group A and group B (P = .24).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Overall survival curves according to Fong et al4 clinical risk score. The 1-year, 3-year, and 5-year survival rates, respectively, were 97.7%, 88.6%, and 61.1% in patients with clinical risk scores of 0 to 1; 91.1%, 65.2%, and 35.1% in patients with clinical risk scores of 2 to 3; and 88.2%, 38.7%, and not reached in patients with clinical risk scores of 4 to 5. Significant differences were observed between patients with clinical risk scores of 0 to 1 vs 2 to 3 (P = .01), between patients with clinical risk scores of 0 to 1 vs 4 to 5 (P < .001), and between patients with clinical risk scores of 2 to 3 vs 4 to 5 (P = .001).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 4.

Disease-free survival curves according to Fong et al4 clinical risk score. The 1-year, 3-year, and 5-year disease-free survival rates, respectively, were 86.4%, 55.4%, and 24.5% in patients with clinical risk scores of 0 to 1; 74.0%, 29.3%, and 16.9% in patients with clinical risk scores of 2 to 3; and 58.8%, 7.1%, and not reached in patients with clinical risk scores of 4 to 5. Significant differences were observed between patients with clinical risk scores of 0 to 1 vs 2 to 3 (P = .02), between patients with clinical risk scores of 0 to 1 vs 4 to 5 (P < .001), and between patients with clinical risk scores of 2 to 3 vs 4 to 5 (P = .02).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 5.

Overall survival curves according to perioperative trend of carcinoembryonic antigen levels in 135 patients with Fong et al4 clinical risk scores of 2 to 3. Significant differences were observed between group A and group C and between group B and group C (P < .001 for both). No significant difference was observed between group A and group B (P = .98).

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Univariate Analysis of Prognostic Factors for Overall and Disease-Free Survival
Table Graphic Jump LocationTable 2. Multivariate Cox Proportional Hazards Regression Analysis of Prognostic Factors for Long-term Outcomes

References

Jaeck  DBachellier  PGuiguet  M  et al. Association Francaise de Chirurgie, Long-term survival following resection of colorectal hepatic metastases. Br J Surg 1997;84 (7) 977- 980
PubMed Link to Article
Abdalla  EKVauthey  JNEllis  LM  et al.  Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases. Ann Surg 2004;239 (6) 818- 827
PubMed Link to Article
Nordlinger  BGuiguet  MVaillant  JC  et al. Association Francaise de Chirurgie, Surgical resection of colorectal carcinoma metastases to the liver: a prognostic scoring system to improve case selection, based on 1568 patients. Cancer 1996;77 (7) 1254- 1262
PubMed Link to Article
Fong  YFortner  JSun  RLBrennan  MFBlumgart  LH Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg 1999;230 (3) 309- 321
PubMed Link to Article
Sugihara  KHojo  KMoriya  YYamasaki  SKosuge  TTakayama  T Pattern of recurrence after hepatic resection for colorectal metastases. Br J Surg 1993;80 (8) 1032- 1035
PubMed Link to Article
Scheele  JStang  RAltendorf-Hofmann  APaul  M Resection of colorectal liver metastases. World J Surg 1995;19 (1) 59- 71
PubMed Link to Article
Jenkins  LTMillikan  KWBines  SDStaren  EDDoolas  A Hepatic resection for metastatic colorectal cancer. Am Surg 1997;63 (7) 605- 610
PubMed
Taylor  MForster  JLanger  BTaylor  BRGreig  PDMahut  C A study of prognostic factors for hepatic resection for colorectal metastases. Am J Surg 1997;173 (6) 467- 471
PubMed Link to Article
Cady  BJenkins  RLSteele  GD  Jr  et al.  Surgical margin in hepatic resection for colorectal metastasis: a critical and improvable determinant of outcome. Ann Surg 1998;227 (4) 566- 571
PubMed Link to Article
Iwatsuki  SDvorchik  IMadariaga  JR  et al.  Hepatic resection for metastatic colorectal adenocarcinoma: a proposal of a prognostic scoring system. J Am Coll Surg 1999;189 (3) 291- 299
PubMed Link to Article
Weber  SMJarnagin  WRDeMatteo  RPBlumgart  LHFong  Y Survival after resection of multiple hepatic colorectal metastases. Ann Surg Oncol 2000;7 (9) 643- 650
PubMed Link to Article
Weber  JCSchneider  ARohr  S  et al.  Analysis of allelic imbalance in patients with colorectal cancer according to stage and presence of synchronous liver metastases. Ann Surg 2001;234 (6) 795- 803
PubMed Link to Article
Weber  JCNakano  HBachellier  P  et al.  Is a proliferation index of cancer cells a reliable prognostic factor after hepatectomy in patients with colorectal liver metastases? Am J Surg 2001;182 (1) 81- 88
PubMed Link to Article
Jaeck  DNakano  HBachellier  P  et al.  Significance of hepatic pedicle lymph node involvement in patients with colorectal liver metastases: a prospective study. Ann Surg Oncol 2002;9 (5) 430- 438
PubMed Link to Article
Yamaguchi  JKomuta  KMatsuzaki  SOkudaira  SFujioka  HKanematsu  T Mode of infiltrative growth of colorectal liver metastases is a useful predictor of recurrence after hepatic resection. World J Surg 2002;26 (9) 1122- 1125
PubMed Link to Article
Choti  MASitzmann  JVTiburi  MF  et al.  Trends in long-term survival following liver resection for hepatic colorectal metastases. Ann Surg 2002;235 (6) 759- 766
PubMed Link to Article
Mala  TBøhler  GMathisen  ØBergan  ASøreide  O Hepatic resection for colorectal metastases: can preoperative scoring predict patient outcome? World J Surg 2002;26 (11) 1348- 1353
PubMed Link to Article
Sasaki  AAramaki  MKawano  KYasuda  KInomata  MKitano  S Prognostic significance of intrahepatic lymphatic invasion in patients with hepatic resection due to metastases from colorectal carcinoma. Cancer 2002;95 (1) 105- 111
PubMed Link to Article
Weber  JCBachellier  POussoultzoglou  EJaeck  D Simultaneous resection of colorectal primary tumour and synchronous liver metastases. Br J Surg 2003;90 (8) 956- 962
PubMed Link to Article
Nagakura  SShirai  YYokoyama  NWakai  TSuda  THatakeyama  K Major hepatic resection reduces the probability of intrahepatic recurrences following resection of colorectal carcinoma liver metastases. Hepatogastroenterology 2003;50 (51) 779- 783
PubMed
Tanaka  KShimada  HMiura  M  et al.  Metastatic tumor doubling time: most important prehepatectomy predictor of survival and nonrecurrence of hepatic colorectal cancer metastasis. World J Surg 2004;28 (3) 263- 270
PubMed Link to Article
Mann  CDMetcalfe  MSLeopardi  LNMaddern  GJ The clinical risk score: emerging as a reliable preoperative prognostic index in hepatectomy for colorectal metastases. Arch Surg 2004;139 (11) 1168- 1172
PubMed Link to Article
Pawlik  TMScoggins  CRZorzi  D  et al.  Effect of surgical margin status on survival and site of recurrence after hepatic resection for colorectal metastases. Ann Surg 2005;241 (5) 715- 724
PubMed Link to Article
Nagashima  ITakada  TNagawa  HMuto  TOkinaga  K Proposal of a new and simple staging system of colorectal liver metastasis. World J Gastroenterol 2006;12 (43) 6961- 6965
PubMed
Poston  GJAdam  RAlberts  S  et al.  OncoSurge: a strategy for improving resectability with curative intent in metastatic colorectal cancer. J Clin Oncol 2005;23 (28) 7125- 7134
PubMed Link to Article
Zeng  ZCohen  AMUrmacher  C Usefulness of carcinoembryonic antigen monitoring despite normal preoperative values in node-positive colon cancer patients. Dis Colon Rectum 1993;36 (11) 1063- 1068
PubMed Link to Article
Compton  CFenoglio-Preiser  CMPettigrew  NFielding  LP American Joint Committee on Cancer Prognostic Factors Consensus Conference: Colorectal Working Group. Cancer 2000;88 (7) 1739- 1757
PubMed Link to Article
Bast  RC  JrRavdin  PHayes  DF  et al. American Society of Clinical Oncology Tumor Markers Expert Panel, 2000 update of recommendations for the use of tumor markers in breast and colorectal cancer: clinical practice guidelines of the American Society of Clinical Oncology [published corrections appear in J Clin Oncol. 2001;19(21):4185-4188 and 2002;20(8):2213]. J Clin Oncol 2001;19 (6) 1865- 1878
PubMed
Duffy  MJvan Dalen  AHaglund  C  et al.  Clinical utility of biochemical markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines. Eur J Cancer 2003;39 (6) 718- 727
PubMed Link to Article
Choi  JSMin  JS Significance of postoperative serum level of carcinoembryonic antigen (CEA) and actual half life of CEA in colorectal cancer patients. Yonsei Med J 1997;38 (1) 1- 7
PubMed
Lokich  JEllenberg  SGerson  BKnox  WEZamcheck  N Plasma clearance of carcinoembryonic antigen following hepatic metastatectomy. J Clin Oncol 1984;2 (5) 462- 465
PubMed
Hohenberger  PSchlag  PMGerneth  THerfarth  C Pre- and postoperative carcinoembryonic antigen determinations in hepatic resection for colorectal metastases: predictive value and implications for adjuvant treatment based on multivariate analysis. Ann Surg 1994;219 (2) 135- 143
PubMed Link to Article
Jaeck  DBachellier  PNakano  H  et al.  One or two-stage hepatectomy combined with portal vein embolization for initially nonresectable colorectal liver metastases. Am J Surg 2003;185 (3) 221- 229
PubMed Link to Article
Jaeck  DOussoultzoglou  ERosso  EGreget  MWeber  JCBachellier  P A two-stage hepatectomy procedure combined with portal vein embolization to achieve curative resection for initially unresectable multiple and bilobar colorectal liver metastases. Ann Surg 2004;240 (6) 1037- 1051
PubMed Link to Article
Couinaud  C Le Foie: Etudes Anatomiques et Chirurgicales.  Paris, France Masson1957;
Kim  SBFernandes  LCSaad  SSMatos  D Assessment of the value of preoperative serum levels of CA 242 and CEA in the staging and postoperative survival of colorectal adenocarcinoma patients. Int J Biol Markers 2003;18 (3) 182- 187
PubMed
Carpelan-Holmström  MLouhimo  JStenman  UHAlfthan  HJärvinen  HHaglund  C CEA, CA 242, CA 19-9, CA 72-4 and hCGβ in the diagnosis of recurrent colorectal cancer. Tumour Biol 2004;25 (5-6) 228- 234
PubMed Link to Article
Fernandes  LCKim  SBSaad  SSMatos  D Value of carcinoembryonic antigen and cytokeratins for the detection of recurrent disease following curative resection of colorectal cancer. World J Gastroenterol 2006;12 (24) 3891- 3894
PubMed
Takeda  AShimada  HImaseki  H  et al.  Clinical significance of serum vascular endothelial growth factor in colorectal cancer patients: correlation with clinicopathological factors and tumor markers. Oncol Rep 2000;7 (2) 333- 338
PubMed
Hammel  PBoissier  BChaumette  MT  et al.  Detection and monitoring of serum p53 antibodies in patients with colorectal cancer. Gut 1997;40 (3) 356- 361
PubMed
Wolmark  NFisher  BWieand  HS  et al.  The prognostic significance of preoperative carcinoembryonic antigen levels in colorectal cancer: results from NSABP (National Surgical Adjuvant Breast and Bowel Project) clinical trials. Ann Surg 1984;199 (4) 375- 382
PubMed Link to Article
Wang  WSLin  JKChiou  TJ  et al.  Preoperative carcinoembryonic antigen level as an independent prognostic factor in colorectal cancer: Taiwan experience. Jpn J Clin Oncol 2000;30 (1) 12- 16
PubMed Link to Article
Reiter  WStieber  PReuter  CNagel  DLau-Werner  ULamerz  R Multivariate analysis of the prognostic value of CEA and CA 19-9 serum levels in colorectal cancer. Anticancer Res 2000;20 ((6D)) 5195- 5198
PubMed
Sasaki  AIwashita  YShibata  KMatsumoto  TOhta  MKitano  S Analysis of preoperative prognostic factors for long-term survival after hepatic resection of liver metastasis of colorectal carcinoma. J Gastrointest Surg 2005;9 (3) 374- 380
PubMed Link to Article
Aldrighetti  LCastoldi  RDi Palo  S  et al.  Prognostic factors for long-term outcome of hepatic resection for colorectal liver metastases. Chir Ital 2005;57 (5) 555- 570
PubMed
Chu  DZErickson  CARussell  MP  et al.  Prognostic significance of carcinoembryonic antigen in colorectal carcinoma: serum levels before and after resection and before recurrence. Arch Surg 1991;126 (3) 314- 316
PubMed Link to Article
Onik  GRubinsky  BZemel  R  et al.  Ultrasound-guided hepatic cryosurgery in the treatment of metastatic colon carcinoma: preliminary results. Cancer 1991;67 (4) 901- 907
PubMed Link to Article
Bakalakos  EABurak  WE  JrYoung  DCMartin  EW  Jr Is carcino-embryonic antigen useful in the follow-up management of patients with colorectal liver metastases? Am J Surg 1999;177 (1) 2- 6
PubMed Link to Article
Kahlenberg  MSSullivan  JMWitmer  DDPetrelli  NJ Molecular prognostics in colorectal cancer. Surg Oncol 2003;12 (3) 173- 186
PubMed Link to Article
Park  YASohn  SKSeong  J  et al.  Serum CEA as a predictor for the response to preoperative chemoradiation in rectal cancer. J Surg Oncol 2006;93 (2) 145- 150
PubMed Link to Article
Park  YALee  KYKim  NKBaik  SHSohn  SKCho  CW Prognostic effect of perioperative change of serum carcinoembryonic antigen level: a useful tool for detection of systemic recurrence in rectal cancer. Ann Surg Oncol 2006;13 (5) 645- 650
PubMed Link to Article
Fortner  JGSilva  JSGolbey  RBCox  EBMaclean  BJ Multivariate analysis of a personal series of 247 consecutive patients with liver metastases from colorectal cancer, I: treatment by hepatic resection. Ann Surg 1984;199 (3) 306- 316
PubMed Link to Article
Ito  KHibi  KAndo  H  et al.  Usefulness of analytical CEA doubling time and half-life time for overlooked synchronous metastases in colorectal carcinoma. Jpn J Clin Oncol 2002;32 (2) 54- 58
PubMed Link to Article
Nagashima  ITakada  TAdachi  MNagawa  HMuto  TOkinaga  K Proposal of criteria to select candidates with colorectal liver metastases for hepatic resection: comparison of our scoring system to the positive number of risk factors. World J Gastroenterol 2006;12 (39) 6305- 6309
PubMed

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