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10.1245/s10434-006-9071-3
Annals of Surgical Oncology 14:1336-1346 (2007)
© 2007 Society of Surgical Oncology
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Original Article

Long-Term Characteristics of 5-Year Survivors After Liver Resection for Colorectal Metastases

Kuniya Tanaka, MD, PhD, Hiroshi Shimada, MD, PhD, Michio Ueda, MD, Kenichi Matsuo, MD, Itaru Endo, MD, PhD and Shinji Togo, MD, PhD

Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan

Correspondence: Address correspondence and reprint requests to: Kuniya Tanaka, MD, PhD; E-mail: ktrj112{at}urahp.yokohama-cu.ac.jp


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: We investigated factors affecting 5-year survival in patients undergoing hepatic resection for colorectal cancer metastases, including events long after initial hepatectomy. Although retrospective studies have demonstrated survival benefit of hepatectomy for metastatic colorectal cancer, few have included sufficient 5-year survivors to identify survival-related factors throughout the clinical course.

Methods: We divided 156 patients with hepatectomy for colorectal cancer metastases into 5-year survivors (n = 64) and patients dying before 5 years after hepatectomy (n = 92). Clinicopathologic data were compared retrospectively with respect to long-term outcome.

Results: By multivariate analysis, large liver tumors (adjusted relative risk, 2.029; P = .011), short tumor doubling time (1.809; P = .026), and origin from poorly differentiated primary adenocarcinoma (12.632; P = .001) compromised survival, whereas initial treatment-related variables did not. Although no difference was seen in initial treatment-related variables between 5-year survivors with recurrence after hepatectomy and patients dying before 5 years, repeat surgery was used more frequently in survivors (P < .001), typically with adjuvant chemotherapy.

Conclusions: Reoperations for each recurrence of metastases, followed by additional chemotherapy, frequently resulted in long survival.

Key Words: Colorectal cancer • Liver metastasis • Hepatectomy • Long survival


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Liver resection has proven to be safe and potentially curative for selected patients with isolated hepatic colorectal metastases, yielding 5-year survival rates from 30% to nearly 50% with an operative mortality of less than 5% in recent series.1–9 Although prognostic factors for 5-year survival of patients undergoing these liver resections have been studied extensively, few investigators have included sufficient follow-up duration or numbers of 5-year survivors to allow identification of survival-related factors beyond treatment of the initial hepatic metastases.

Despite the curative intent of liver surgery, approximately 60% of patients have a subsequent tumor recurrence;7,10,11 in 30% of instances, this takes the form of additional isolated liver metastases.10–13 Treatment in this setting involves mainly repeat hepatectomy, which carries risks and outcomes similar to those seen for initial liver resection.14–16 Even a third hepatectomy for liver recurrences after a second hepatectomy has been reported to be safe and to provide additional survival benefit similar to those of first and second liver resections.17

On the other hand, chemotherapy provided in either an adjuvant (postoperative) or a neoadjuvant (pre-operative) setting for hepatic and systemic metastases from a colorectal primary has been studied; some evidence indicates survival benefit from posthepatectomy adjuvant chemotherapy.18 Furthermore, curative surgery resulting in favorable long-term outcome was achieved in patients with initially unresectable lesions after downstaging by neoadjuvant chemotherapy.19–22 Modern chemotherapy for colorectal cancer metastases allows a median survival of approximately 20 months.23

In determining the implications of such recent advances in treatment for colorectal cancer metastases, determination of factors that might preclude 5-year survival or affect outcome beyond 5 years requires careful analysis of clinical events long after initial hepatectomy. We retrospectively analyzed patients treated at our institution to determine which factors most strongly influenced outcome in colorectal cancer metastatic to the liver, with special reference to events in the clinical course of long-term survivors after initial liver resection for colorectal cancer metastases.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Patients
From 1985 to 1999, our Department of Gastroenterological Surgery at the Yokohama City University Graduate School of Medicine, Yokohama, Japan, treated 177 patients diagnosed with liver metastasis from colorectal cancer by liver resection with curative intent. Among these patients, 12 (6.8%) were lost to follow-up, so no information was available concerning survival relative to the 5-year time point. Of the remaining 165 patients, curative hepatectomy could not be undertaken in one patient, and concomitant extrahepatic metastases precluded R0 resection status in another eight patients who had curative liver resection. All told, data from 156 patients undergoing R0 resection were included in the analysis. The median follow-up duration for these 156 patients was 41 months (range, 3–183 months).

Preoperative staging included a physical examination, measurement of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9, colonoscopy, barium enema, abdominal imaging with ultrasonography and computed tomography (CT), and chest imaging by routine chest radiographs or CT. After 1995, CT arterioportography was used for preoperative staging.

Hepatectomy Procedures
Hepatectomy was not necessarily performed according to the anatomic principles of resection; the guiding principle was assurance of tumor-free margins. To determine whether a hepatectomy procedure was acceptable for the patient, we used the prediction score system introduced by Yamanaka et al.24 When a one-stage combined resection was precluded by insufficient estimated postoperative liver volume, an excessive indocyanine green retention rate, or patient age considerations,24 portal vein embolization or two-stage hepatectomy22 was performed.

Intraoperative ultrasonography was used to identify any occult tumors not detected preoperatively and to confirm relationships between tumors and vasculobiliary structures. Parenchymal dissection was performed by ultrasonic dissectors. When necessary, the liver pedicle was clamped intermittently in cycles including 15 minutes of clamping and 5 minutes of reperfusion. Operative procedures were defined by the Brisbane Classification for liver resection,25 where segmentectomy represents resection of a Couinaud segment26 and sectionectomy denotes resection of one of Healey’s segments.27 Anatomic resections included segmentectomy, sectionectomy, hemihepatectomy, and trisectionectomy.

Any extrahepatic metastases were resected whenever possible, as decided on a case-by-case basis. In the presence of resectable metastases in both liver and lung, liver resection and primary tumor resection were performed before pulmonary resection, aiming to eliminate the liver as a source of potentially disseminating neoplastic cells. When liver metastases were associated with extrahepatic intra-abdominal metastases, both were resected at the same time.

Principles underlying selection criteria for resection of recurrent hepatic metastases were the same as those for initial hepatectomy. Technical considerations predominated in surgical decisions regarding feasibility of repeat hepatic resection. Because quality and quantity of remaining hepatic parenchyma were extremely important considerations, patients were excluded from repeat hepatic resection when the prognostic score was more than 50 on the basis of volumetric, indocyanine green, and age considerations.24

Whenever safe and complete (R0) resection of all sites of extrahepatic disease was deemed possible after identification of extrahepatic recurrences, resection was performed irrespective of sites of recurrence.

Neoadjuvant Chemotherapy
Some patients with five or more liver metastases in a bilobar distribution received neoadjuvant hepatic arterial chemotherapy with a combination of 5-fluorouracil (5-FU), L-folinic acid (FA), and cis-platin (CDDP). Treatment consisted of a 5-day course of infusions into the hepatic artery through an implanted arterial access port (Vital-Port; Cook Vascular, Leechburg, PA). On each of 5 days, 5-FU (500 to 600 mg/m2/day), FA (100 mg/m2/day), and CDDP (10 mg/m2/day) were delivered. This 5-day course was repeated four or more times at 9-day intervals.

Because oxaliplatin has been approved for use only since April 2005 by the Japanese health insurance system, CDDP in combination with 5-FU and FA was given in the present series.

These neoadjuvant chemotherapy regimens were carried out irrespective of initial resectability. In fact, nearly all cases involving neoadjuvant chemotherapy initially would have posed difficulties in safely removing all liver tumors by straightforward hepatectomy.

Adjuvant Therapy
After resection for initial liver metastases or liver recurrence, adjuvant chemotherapy was carried out through hepatic artery infusion (HAI) through an implanted port with 5-FU at a dose of 1500 mg provided over 24 hours and FA (50 mg over 24 hours), once a week for 8 weeks whenever possible. Adjuvant systemic chemotherapy also was provided after resection of extrahepatic recurrence, as a rule with 5-FU and FA, and sometimes combined with mitomycin C, CDDP, or irinotecan.

Calculation of Doubling Times of Tumors
Doubling time (DT) of liver tumors before hepatectomy were recorded as a markers of biologic behavior for each tumor. Tumor doubling time (T-DT) or carcinoembryonic antigen doubling time (CEA-DT) was computed for each tumor. T-DT was calculated as log2/3 x [(T2 – T1)/(logD2 – logD1)], with T1 and T2 representing any two time points in the clinical course before hepatectomy and D1 and D2 representing the tumor diameter at these respective time points. Similarly, CEA-DT was calculated by the following expression: log2 x [(T2 – T1)/(logC2 x logC1)], with T representing time and C representing CEA concentration, as previously reported.28–32 We have found T-DT of hepatic metastasis to correlate strongly with CEA-DT in patients without, but not with, extrahepatic metastases.31,32 Accordingly, patients with concomitant extrahepatic metastases were excluded from the CEA-DT analysis; in these cases only T-DT was informative. For the same reason, only T-DT was calculated when liver metastases were detected synchronously with the primary tumor.

In patients with multiple liver metastases, CEA-DT was measured, except that when their CEA-DT could not be calculated because the CEA concentration was not increased, T-DT was calculated on the basis of the size of measurable representative liver tumors among the multiple metastases. T-DT could be calculated only when patients underwent CT at two time points before hepatectomy. Almost all patients in whom we could calculate T-DT had previous CT performed at another hospital before referral to our institution. In all, 99 patients had data suitable for estimation of DT. None of these patients received any anticancer drug during the interval used for calculation of DT.

Patient Follow-up
Patients underwent follow-up evaluation monthly at our outpatient clinic. Data were obtained and recorded from each patient’s clinical record, and long-term outcome was obtained through clinical follow-up, tumor registry follow-up, and contact with the patient, family, or referring physician when necessary. No patients were lost to follow-up. Serum CEA was measured every month, CT was performed every 3 months, and a chest roentgenogram was obtained every 6 months for 5 years after the most recent operation.

Data Analysis
Statistical comparisons of baseline data were performed by the Mann-Whitney U-test, the {chi}2 test, or Fisher’s exact test. Survival rates were calculated by the Kaplan-Meier method. Differences between survival curves were analyzed by the log rank test. A difference was considered significant at P < .05.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Although 92 patients were documented to have died of disease less than 5 years after liver resection, 64 patients were documented to be alive 5 years after resection. Among these known 5-year survivors, 30 patients are alive and disease-free without recurrence as of this writing. Three patients have died of an other disease with no evidence of recurrence more than 5 years after liver resection. The 31 remaining 5-year survivors have had recurrence at one or more sites. Among them, 15 are disease-free, 5 are alive with recurrence, and 11 have died of disease (Fig. 1Go).


Figure 1
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  		FIG. 1. Selection and outcome of population of study. ANC, absolute noncurative; NED, no evidence of disease; DOD, died of other disease; AWD, alive with disease; DFD, died from disease.

 
Rates for 1-, 3-, and 5-year overall survival after hepatectomy were 85.9%, 54.4%, and 42.5%, respectively; rates for disease-free survival at these time points were 53.0%, 26.2%, and 23.5%, respectively (Fig. 2Go).


Figure 2
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  		FIG. 2. Overall and disease-free survival, by postoperative days.

 
Prognostic Factors
Influences of various clinicopathologic variables on survival after hepatectomy are listed in Table 1Go. Univariate analysis identified histologic degree of differentiation of the primary tumor (P < .01), number of metastatic lesions (P < .05), maximum size of metastases (P < .01), DT before hepatectomy (P < .01), and adjuvant HAI chemotherapy after hepatectomy (P < .01) as statistically significant prognostic determinants. Specifically, survival was significantly better in patients with well-differentiated to moderately differentiated primary adenocarcinoma, solitary metastasis, small liver tumor size, DT before hepatectomy exceeding 45 days, and administration of an effective total dose of 5-FU via the hepatic artery after hepatectomy (≥5000 mg). Multivariate regression analysis was carried out by a proportional hazard method by a Cox model, beginning with six factors. For entry, the limit was set at P < .1 (histologic differentiation of the primary tumor, P < .001; number of metastatic lesions, P = .033; maximum liver tumor size, P = .001; DT before hepatectomy, P = .009; tumor-free margin, P = .077; and adjuvant HAI, P < .001). Factors independently affecting survival in an adverse manner were large liver tumor size (adjusted relative risk [ARR], 2.029; P = .011), DT of 45 days or fewer (ARR, 1.809; P = .026), and primary tumors representing poorly differentiated adenocarcinoma or mucinous carcinoma (ARR, 12.632; P = .001; Table 2Go).


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  		TABLE 1. Univariate analysis of factors affecting survival after heptectomy
 

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  		TABLE 2. Multivariate analysis of prognostic factors by Cox proportional hazards methoda
 
Comparison of 5-Year Survivors with 5-Year Nonsurvivors
To identify factors with greatest influence on prognosis, we divided patients into three groups according to survival after hepatectomy: 5-year survivors with no recurrence throughout their clinical course; 5-year survivors with recurrence; and patients who died at times earlier than 5 years. Three patients who died of another disease after surviving 5 years or more without recurrence were included in the first group in this analysis (Table 3Go). When characteristics were compared between 5-year survivors without recurrence (n = 33) and patients known to have died of disease before 5 years (n = 92), 5-year survivors were more likely to have Dukes’ stage A or B (P = .032), fewer metastatic lesions (P = .029), lower serum CEA before hepatectomy (P = .009), histologically negative hepatic resection margins (P = .035), and adjuvant hepatic arterial chemotherapy after liver resection (P < .001). There were no significant differences in factors affecting survival by multiple logistic regression analysis beginning with five factors that showed statistically significant differences by univariate analysis.


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  		TABLE 3. Demographic and clinical characteristics in patient groups defined by long-term outcome
 
Characteristics of 5-year survivors who have had recurrence at one or more sites after hepatectomy (n = 31) also were compared with those of patients dying at intervals earlier than 5 years (n = 92). Maximum liver tumor size was smaller (P = .021), and prevalence of concomitant extrahepatic metastases was lower (P = .041) in the former than in the latter group. The disease-free interval between first hepatectomy and recurrence was almost twice as long in the former group than in the latter group (P = .002), whereas variables concerning treatment of the initial liver metastases did not differ between these survival-defined groups. On the other hand, the proportion of patients undergoing repeat resection for their recurrences was greater among 5-year survivors (P < .001). By multiple logistic regression analysis beginning with four factors that showed significant differences in univariate analysis, repeat resection for recurrence was found to be an independent factor (ARR, .019; 95% confidence interval, .004–.083; P < .01).

Details of 5-Year Survivors with Recurrence at Any Site
As of this writing, 5 years or more after the initial hepatectomy, 14 of the 31 patients who survived have no evidence of disease, and 1 died of another disease but was free from metastatic colorectal cancer. Another five patients have experienced recurrences but still are alive 5 years or more after initial resection. The other 11 patients died of disease.

After the initial hepatectomy, 14 patients developed recurrence in the liver alone, 2 in the liver plus a distant site, 12 in the lung alone, and 3 in a nonpulmonary distant site alone. A second liver resection was performed in all 14 patients with isolated liver recurrence and in 2 patients whose liver recurrence was associated with extrahepatic recurrence. Pulmonary resection was undertaken in 10 patients among 12 with isolated lung recurrence and in 1 patient with both liver and lung recurrence. Among three patients with recurrence at another site, two had their local recurrences removed completely, but the other had peritoneal carcinomatosis. Prolonged remission was obtained in 7 of 28 patients who underwent a second curative resection for recurrence. A second recurrence followed in the other 21 patients, 14 of whom were treated with a third resection. Of these 14 patients, 3 remained free of tumor. The other 11 developed a third recurrence; 6 of them underwent a fourth resection, with 5 patients ultimately being free of tumor. These five patients included one with a fourth recurrence who is alive and disease-free after a fifth curative resection. All told, the median number of surgical procedures was three (range, 1–5; mean ± SE, 2.8 ± 1.2), and the median number of hepatectomies was two (range, 1–5; mean ± SE, 1.8 ± .2).

With respect to perioperative chemotherapy, adjuvant hepatic arterial chemotherapy with 5-FU and FA after initial liver resection was carried out in 25 patients. Systemic chemotherapy with mainly 5-FU and FA was given postoperatively in one patient. Another five patients received oral anticancer drugs as a prophylactic treatment after liver resection. After the second resection (for a first recurrence), adjuvant chemotherapy was given through the hepatic artery and/or systemically conducted in 24 (85.7%) of 28 patients who underwent repeat resection. Of 14 patients who underwent a third resection (for a second recurrence), 12 (85.7%) received prophylactic systemic chemotherapy after surgery. Of six patients who underwent a fourth resection for a third recurrence, five (83.3%) also had systemic chemotherapy after this resection (Table 4Go).


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  		TABLE 4. Details of 31 five-year survivors with recurrence after liver resectiona
 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Many retrospective and prospective series of large numbers of patients have demonstrated long-term survival benefit of liver resection for patients with hepatic metastases from colorectal cancer and have examined various factors affecting survival. Some investigators have proposed prognostic scoring to improve patient selection for surgical therapy. Such studies have reported success in predicting survival outcomes in patients undergoing liver resection for colorectal metastases on the basis of tumor stage at time of diagnosis of the primary tumor; liver tumor bulk, either directly measured or estimated according to number, size, specimen weight, extent or distribution, and preoperative CEA;33 and presence or absence of extrahepatic disease.2,6,34,35 Tumor DT, initially reported as a way to estimate when pulmonary metastasis from a colorectal cancer might become apparent,28 can be used to assess aggressiveness; a short DT indicates rapid tumor growth. According to previous reports, DT correlated strongly both with survival of untreated patients with recurrent colorectal carcinoma29 and with survival after hepatic resection.36,37 The present study demonstrated similar clinicopathologic relationships, with degree of histologic differentiation of the primary tumor, maximum liver tumor size, and DT of the liver tumor being statistically significantly related to survival by multivariate analysis. Considering reported and present results, the factors whose prognostic significance was most frequently and strongly established were those related to the anatomic and structured characteristics of the colorectal primary tumor and the liver metastases.

When characteristics were compared between 5-year survivors with no recurrence and patients who died less than 5 years after initial hepatectomy, treatment-related variables such as tumor-free margin and posthepatectomy adjuvant chemotherapy differed markedly between groups, as did differences in primary tumor stage, maximum liver tumor size, and prehepatectomy CEA concentrations in serum. Several reports have included a tumor-free margin of less than 1 cm among significant unfavorable prognostic factors,4,5 but no significant difference in outcome between patients with a tumor-free margin less than 1 cm and those with a tumor-free margin greater than 1 cm was seen in other published series.1,2,6 However, in addition to the difference in tumor-free margin between 5-year survivors with no recurrence and patients who died in less than 5 years, when patients were divided according to tumor-free margin—a tumor-free margin of less than 5 mm (n = 58) and of 5 mm or more (n = 98)—survival was significantly better in patients with a tumor-free margin of 5 mm or more than in patients with that of less than 5 mm in the present study (P = .031, data not shown). According to some previous reports, marked improvement in hepatic recurrence was observed from HAI, but such treatment has not reliably translated into overall survival benefit.38,39 On the other hand, Kemeny et al.40 reported that postoperative treatment with a combination of HAI and intravenous chemotherapy improved outcomes for patients undergoing resection of liver metastases. Furthermore, for unresectable liver metastases, they recently reported that HAI provides longer survival with better overall function than the same chemo-therapeutic compound administered systemically.41 The importance of these treatment factors therefore has been debated; however, in obtaining long-term survival, we presently confirmed sufficient tumor-free margin and postoperative adjuvant chemotherapy given by HAI or the systemic route to be indispensable.

Tumor-related variables also were compared between 5-year survivors with recurrence and patients dying before 5 years. Disease-free interval from the first hepatectomy to recurrence was much longer in the former group, liver tumors were smaller, and concomitant extrahepatic metastases were less prevalent; disease-free interval has been well known as a powerful prognosticator.17,21 In contrast, treatment for initial liver metastases did not differ between these groups. Repeat surgery to treat the recurrence was the only treatment-related variable associated with difference. Repeat hepatectomy for liver recurrence is well known to be accompanied by both risks and outcomes similar to those seen for initial liver resection.13–16 In the present study, 26 patients (17 five-year survivors and 9 five-year nonsurvivors) underwent repeat hepatectomy, and their 1-, 3-, and 5-year survival after repeat resection were 96.2%, 76.1%, and 48.7%, respectively (data not shown). Of the patients who experienced recurrence of disease in the liver, those with resectable disease may have more favorable outcomes compared with those recurring with unresectable disease, irrespective of whether they undergo resection or not. However, among our 17 five-year survivors who underwent repeat resection for liver recurrence, 10 had solitary liver recurrence and the others had multiple liver recurrences (two recurrent tumors in two patients and three or more recurrent tumors in five; the maximum number of liver tumors in a repeat resection patient was five). Even a third hepatectomy for liver recurrences after a second hepatectomy has been reported to be safe and to provide additional survival benefit, in a manner similar to the first and second liver resections.17 Resection of colorectal cancer metastasis to the lung also has been reported to be safe and effective,42 even with a history of liver metastasis.43 When one considers details throughout the clinical course of the 31 long-term survivors with recurrence, multiple repeat resections for recurrent disease and postoperative adjuvant hepatic arterial or systemic chemotherapy stand out as important features. Thus, a very important observation in the present analysis was that making every effort to resect recurrent disease and repeat chemotherapy after these resections was crucial to improving patient survival, and survival after hepatectomy also was strongly restricted by characteristics of the tumor itself.

Chemotherapy, both through HAI and given systemically, is being used with increasing frequency, either before or after resection. Newer agents and drug combinations demonstrating increasing response rates in advanced disease and increasing survival in the adjuvant setting have fueled this enthusiasm. An aggressive surgical approach when confronted with recurrent disease after initial resection also is likely to have contributed to the improvement in overall survival. Of all patients who undergo liver resection for metastatic colorectal cancer, approximately 75% will experience recurrence.44 Many studies addressing management of patients with recurrent disease have demonstrated safety and long-term survival benefit after resecting isolated recurrent disease.14–16 Choti et al.45 demonstrated a favorable trend toward improved long-term outcome over time in a historical comparison of outcome after hepatectomy between time periods, concluding that greater use of perioperative chemotherapy and/or aggressive surgical therapy after recurrence have contributed more to this trend than changes in patient selection resulting from better preoperative and intraoperative imaging. For instance, although positron emission tomography (PET) was reported to increase survival after hepatectomy,46 PET imaging was introduced for preoperative staging after 2002 in our institution, and therefore, none of the patients enrolled onto this study underwent this imaging. Now that PET imaging has been introduced in our practice, we anticipate that survival will improve in our patients undergoing liver resection for colorectal liver metastases.

First-line 5-FU–based chemotherapy has been shown to prolong median survival from 8 to 12 months more than palliative care according to a meta-analysis.47 Some schedules combining 5-FU–FA and oxaliplatin or irinotecan have further increased median survival to 15 months or more in randomized multicenter phase 3 trials.48–50 Furthermore, the administration of second-line chemotherapy with these schedules has also markedly enhanced survival in patients with metastatic colorectal cancer.51,52 More recently, bevacizumab, a new monoclonal antibody that targets tumor angiogenesis by specifically binding to vascular endothelial growth factor, is approved for use in the first-line setting when combined with any intravenous 5-FU regimen.53,54 Cetuximab, a monoclonal antibody directed against the human epidermal growth factor receptor, was also approved for its activity in combination with irinotecan in the second- and third-line treatment of patients whose disease had recently progressed while receiving irinotecan or an irinotecan-containing regimen.55 However, in our institution, irinotecan has been in common use from 1998, and so 5-FU and FA were the regimens mainly used in this study, both through HAI and systemically. Furthermore, because oxaliplatin has been approved for use only since April 2005 by the Japanese health insurance system, CDDP in combination with 5-FU and FA sometimes was given as a neoadjuvant regimen in the present series. Better survival may be obtained by including administration of combinations such as 5-FU–FA and oxaliplatin or irinotecan and/or a monoclonal antibody such as bevacizumab or cetuximab.

Although the results of this retrospective study suggest that survival of patients with colorectal cancer liver metastases is determined predominantly by tumor biology, therapeutic benefits of multiple reoperations for multiple recurrences of metastases and additional chemotherapy were confirmed to increase likelihood of long survival despite recurrence after hepatectomy. Hepatic resection with an adequate surgical margin and prophylactic chemotherapy after surgery also were important for potential long-term survival. Given the implications of recent advances in chemotherapy for colorectal cancer metastases, indications for liver resection will soon need to be reassessed. However, at present, in the presence of recurrence after hepatectomy, good survival benefit requires aggressive treatment by repeat resection and effective chemotherapy such as new monoclonal antibodies with any 5-FU regimen.

Received for publication July 4, 2006. Accepted for publication July 4, 2006.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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