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10.1245/s10434-006-9067-z
Annals of Surgical Oncology 13:1579-1587 (2006)
© 2006 Society of Surgical Oncology
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Original Article

Second Hepatectomy for Recurrent Colorectal Liver Metastasis: Analysis of Preoperative Prognostic Factors

Seiji Ishiguro, MD1, Takayuki Akasu, MD1, Yoshiya Fujimoto, MD1, Junji Yamamoto, MD2, Yoshihiro Sakamoto, MD2, Tsuyoshi Sano, MD2, Kazuaki Shimada, MD2, Tomoo Kosuge, MD2, Seiichiro Yamamoto, MD1, Shin Fujita, MD1 and Yoshihiro Moriya, MD1

1 Colorectal Surgery Division, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
2 Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

Correspondence: Address correspondence and reprint requests to: Takayuki Akasu, MD; E-mail: takasu{at}ncc.go.jp


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: Second hepatectomy is a potentially curative treatment for patients with hepatic recurrence of colorectal cancer. However, there is still no consensus about the patient selection criteria for second hepatectomy under these circumstances, and the factors affecting prognosis after second hepatectomy remain uncertain.

Methods: Clinicopathologic data for 111 consecutive patients with colorectal liver metastasis who underwent second hepatectomy at a single institution between 1985 and 2004, and for whom complete clinicopathologic reports were available, were subjected to univariate and multivariate analyses.

Results: The morbidity and mortality rates were 14% and 0%, respectively, and the overall 5-year survival rate was 41%. Multivariate analysis revealed that synchronous resection for the first liver metastasis (hazard ratio, 1.8), more than three tumors at the second hepatectomy (1.9), and histopathological involvement of the hepatic vein and/or portal vein by the first liver metastasis (1.7) were independently associated with poor survival. We used these three risk factors to devise a preoperative model for predicting survival. The 5-year survival rates of patients without any risk factors, and with one, two, or three risk factors, were 62%, 38%, 19 %, and 0%, respectively.

Conclusions: Second hepatectomy is beneficial for patients without any risk factors. Before second hepatectomy, chemotherapy should be considered for patients with any of these risk factors, especially with two or three factors, in the adjuvant or neoadjuvant setting to prolong survival. These results need to be confirmed and validated in another data set or future prospective trial according to the scoring scheme we outline.

Key Words: Second hepatectomy • Colorectal cancer • Liver metastasis • Prognostic factor • Neoadjuvant chemotherapy


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Hepatectomy is the best and most potentially curative treatment for patients with colorectal liver metastases, yielding a 5-year survival rate of 38% to 51 %.1–5 After a first hepatectomy, 60% to 70% of patients will develop recurrent disease, and one-third of these recurrences are limited to the liver.6 The safety of hepatectomy has been increasing as a result of improvements in surgical techniques and perioperative management, and second liver resection has also been performed for patients with recurrent colorectal liver metastases. During the past decade, the reported outcomes of second hepatectomy have ranged from 21% to 49% in terms of 5-year survival after surgery. However, after second hepatectomy, some patients develop early recurrence in the liver, lung, and other organs, and in most of them, the disease is unresectable. Patients who experience recurrence within 6 months after second hepatectomy are already considered to have systemic disease before they undergo surgery. For such patients with systemic colorectal metastases, second hepatectomy is not beneficial and can even be harmful. However, the factors predicting early recurrence and poor outcome have not been established.

The purpose of this study was to find criteria that could be used to identify patients with recurrent liver metastases from colorectal cancer before surgery who would have a poor prognosis after second hepatectomy.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Between October 1985 and November 2004, data for 111 consecutive patients with recurrent liver metastases from colorectal cancer who underwent first and second hepatectomies at the National Cancer Center Hospital, Tokyo, were collected and reviewed. Patients who did not undergo initial liver resection at our hospital were excluded from the study because we were unable to obtain enough clinicopathologic data for them.

We investigated 27 clinicopathologic variables pertaining to patient characteristics, clinical data, and histopathologic findings, such as sex, age, primary cancer location, lymph node status, timing of first hepatectomy, number of hepatic metastases, tumor diameter, tumor distribution, preoperative serum carcinoembryonic antigen level, extent of liver resection, surgical margin, venous invasion by liver metastases, and bile duct invasion. The extent of liver resection was defined according to the nomenclature; wedge, segmental, and bisegmental resections were classified as minor resection, and hemihepatectomy or more extended resections were classified as major resection. Patient outcomes were determined on the basis of clinical data obtained from the files as of August 2005. The median follow-up period for the 111 patients after second liver resection was 43 months (range, 1–207 months).

The prognostic significance of clinicopathologic factors in relation to survival was investigated by univariate and multivariate analyses. Data were censored in the analysis of overall survival if a patient was alive, and in the analysis of disease-free survival if a patient was alive without recurrent colorectal cancer. Survival rates were calculated by the Kaplan-Meier method and compared statistically by the log-rank test. Univariate comparisons of survival were performed by the log-rank test and multivariate analysis by the Cox regression model with the forward stepwise method (likelihood ratio). All variables were dichotomized for analysis. All statistical analyses were performed by SPSS for Windows, version 6.0 (SPSS-Japan Inc., Tokyo, Japan). All P values were two-sided, and differences at P < .05 were considered to be statistically significant.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Patient Characteristics and Follow-up
The 111 patients who underwent second hepatic resection with curative intent included 74 men and 37 women with a mean age of 59 years. The median interval between the first and second hepatic resections was 16 months (range, 4–96 months). At the last follow-up, 37 patients (34%) were alive with no evidence of recurrence, 12 (11%) were alive with disease, 61 (55%) had died of disease, and 1 patient was lost to follow-up. There were 23 actual 5-year survivors. The median follow-up time from primary resection was 69 months (range, 11–249 months), and the median follow-up from the second liver resection was 43 months (range, 1–207 months).

Clinical Features and Pathology
Primary Tumor
The site of the primary cancer was the colon in 75 patients (68%) and the rectum in 36 (32%). Histologically, there were 50 well-differentiated, 58 moderately differentiated, and 1 poorly differentiated adenocarcinoma, and 2 mutinous carcinomas. Metastatic lesions in the liver were found synchronously with the primary tumor in 58 patients (stage IV). Of the 53 patients with metachronous liver metastases, 13 patients had no lymph node metastasis (stage I or II), and 40 patients had lymph node metastasis (stage III).

First Liver Resection
Of the 53 patients with metachronous liver metastases, the median interval between the primary resection and the first hepatectomy was 16 months (range, 4–60 months), and 25 patients (47%) underwent the second hepatectomy within 12 months. Unilobar involvement was observed in 68 patients and bilobar involvement in 43. At the first hepatectomy, 43 patients had a solitary hepatic lesion, 67 had 2 to 12 (median, 3) metastatic nodules, and one patient had more than 50 lesions. The median size of the largest hepatic lesion was 3.3 cm (range, 1.2–10 cm). Minor resection was performed in 93 patients and major resection in 18. The median blood loss was 698 mL (range, 50–3215 mL). Blood transfusion was performed in 17 patients. The surgical margin was negative in 89 patients and positive in 22. Invasions of the portal vein or hepatic vein by the liver metastases were found in 22 patients, and bile duct involvement was found in 39.

Second Liver Resection
The median interval between the first hepatectomy and detection of recurrence was 13 months (range, 2–92 months). Sixty-two patients had a solitary metastasis, and 49 had multiple metastases. The recurrent metastases ranged from 1.2 to 10 cm (median, 3.3 cm) in greatest dimension. Before second hepatectomy, pulmonary resection for lung metastasis was conducted in eight patients, and three patients underwent second hepatectomy and pulmonary resection simultaneously. After first hepatectomy, performed mostly in the 1980s, nine patients received adjuvant hepatic arterial infusion chemotherapy with 5-fluo-rouracil (5-FU), mitomycin C, and oral carmofur regimen,7 and six patients received oral anticancer drugs for adjuvant therapy (carmofur in five patients, uracil-tegafur in one). Two patients who underwent colectomy plus simultaneous hepatectomy received adjuvant intravenous 5-FU plus leucovorin or mitomycin C, and one who had initially unresectable liver metastases was provided irinotecan for downstaging.

The second hepatectomy procedures included minor resection in 99 patients, hemihepatectomy in 6 patients, extended hemihepatectomy in 5, extended hemihepatectomy with bile duct reconstruction in 1, and central bisectionectomy in 1. Ninety-three patients had negative margins and 18 had positive margins. The median blood loss during the second liver resection was 913 mL (range, 95–4803 mL), and 22 patients received blood transfusions. No patient died during the perioperative course. Complications occurred in 16 patients (14%), including bile leakage in 8, abscess formation in 4, pleural effusion in 3, cholangitis in 1, and wound infection in 1. Invasions of the portal vein or hepatic vein were found in 25 patients, and bile duct involvement was found in 40.

Survival and Recurrence After Second Hepatectomy
Of the 111 patients who underwent second hepatectomy with curative intent, 61 had died by August 31, 2005. Overall 1-, 3-, and 5-year survival rates were 91%, 74%, and 41%, respectively, from the time of second liver resection, with a median survival of 43 months (Fig. 1Go). There were 23 actual 5-year survivors. Recurrence after second hepatectomy occurred in 74 patients. Of these, 39 patients developed liver metastases (27 confined to the liver; 12 involving the liver plus other sites), and 37 developed lung metastases. Of them, 21 patients underwent surgery, including 13 third hepatectomies and 8 pulmonary resections. Twenty-seven patients experienced recurrence within 6 months after the second hepatectomy, and their median survival time was significantly worse than that of the others (15 vs. 60 months, P = .0001). Forty-four of the patients who experienced recurrence after second hepatectomy received chemotherapy for treatment. Hepatic arterial infusion chemotherapy was performed in seven patients who had isolated hepatic recurrence. 5-FU was given by infusion to 14 patients; seven received additional mitomycin C. Oral chemotherapy drugs were administered to 7 patients (uracil-tegafur plus leucovorin in 2, S-1 [tegafur/5-chloro-2,4-dihydroxy-pyridine/potassium oxonate] in 3, capecitabine in 1, and carmofur in 1), and intravenous 5-FU plus leucovorin was provided to 11. Twenty patients received irinotecan, eight received oxaliplatin, and one received bevacizumab. Irinotecan has been commonly used since 1999 in Japan, and most of the patients who experienced recurrence after 1999 benefited from irinotecan. The group that developed recurrence until 1998 (n = 19) had significantly worse survival than those after 1999 (n = 25) (median survival time, 23 months vs. 55 months, P = .004).


Figure 1
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  		FIG. 1. Overall survival after second hepatectomy in patients with colorectal liver metastases.

 
Univariate Analysis of Survival
Factors Related to Primary Lesion
The results of univariate analysis of survival are listed in Table 1Go. The presence of metastatic lymph nodes was a significant predictor of worse outcome after second liver resection (P = .03). The location of the primary colorectal cancer and the histology of the primary lesion did not influence survival.


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  		TABLE 1. Univariate analysis related to survival
 
Factors Related to First Hepatectomy
Patients with metachronous liver metastases had a significantly better median survival time after second hepatectomy (60 vs. 32 months, P = .009). The patients who received blood transfusions during the first hepatectomy had significantly worse survival (P = .049). The number of tumors, size of the largest tumor, bilobar involvement, extent of hepatectomy, and serum carcinoembryonic antigen level were not prognostic factors. In terms of microscopic findings, invasions of the portal vein or hepatic vein, and a positive surgical margin tended to be associated with poor survival, but the difference was marginal (P = .07 and .07, respectively). Bile duct invasion was not a prognostic factor.

Factors Related to Second Hepatectomy
The 5-year survival was significantly better for patients with a disease-free interval of more than 6 months between the first hepatectomy and recurrence, as compared with patients with a disease-free interval of less than 6 months (49% vs. 22%, P = .02). Patients who had less than four nodules had significantly better survival than those with four or more (45% vs. 18%, P = .001). The size of the largest lesion at the second operation influenced survival, but not to a significant degree (P = .09). Similar to the first hepatectomy, patients who received blood transfusions showed significantly worse survival (P = .03), and bilobar involvement, extent of hepatectomy, and serum carcinoembryonic antigen level were not prognostic factors. Patients who had undergone resection of extrahepatic disease before second hepatectomy did not show worse survival. With respect to the microscopic features of the recurrent metastatic disease, a surgical margin, invasions of the portal vein or hepatic vein, and bile duct invasion had no statistically significant influence on survival.

Multivariate Analysis of Survival
Multivariate analysis identified three independent risk factors: synchronous first hepatectomy, four or more lesions at second hepatectomy, and invasion of the portal vein or hepatic vein at first hepatectomy (Table 2Go). Any of the variables related to microscopic findings—information that could only be obtained after the second hepatectomy—were not statistically significant prognostic factors.


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  		TABLE 2. Multivariate analysis with Cox proportional hazard model
 
All three risk factors identified in the multivariate analysis were based on information obtained before the second hepatectomy. Therefore, we tried to group patients according to risk factors. Thirty-four patients had no risk factors, 53 had one factor, 22 had two factors, and 2 had three factors. Survival expectancies at 5 years for patients with no risk factors, one or two risk factors, and three risk factors were 62%, 31%, and 0%, respectively, and these differences were statistically significant (P = .001) (Fig. 2Go). Two patients with three risk factors developed recurrence within 6 months and died at 15 months and 19 months, respectively, after the second hepatectomy.


Figure 2
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  		FIG. 2. Overall survival according to groups divided by number of risk factors identified in current study.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
The only potentially curative treatment for patients with liver-isolated colorectal metastases is surgical resection. However, most cannot be considered candidates for surgery for reasons such as very large tumor, unfavorable tumor location, multinodularity, or inadequate hepatic reserve. Nevertheless, because of its impact on survival, surgical resection is the treatment of choice when it is feasible. Improvements in surgical techniques and perioperative management have made surgical resection more feasible, with a mortality rate of less than 3%.2–4,8 For patients with recurrent colorectal liver metastases, second hepatic resection has been performed more frequently during the past decade.6,9–22 The results of previous series involving more than 20 patients are listed in Table 3Go. Five-year survival rates of 38% to 51% have been reported for first hepatic resections,1–5,23 and similar 5-year survival rates, ranging from 21% to 49%, can be achieved after second hepatic resection for well-selected patients. In fact, morbidity and mortality after second hepatic resection are almost comparable to those after initial hepatic resection. The median survival and 5-year survival rate in the present series were 43 months and 41%, respectively. Because conventional chemotherapy alone cannot achieve such favorable results, a second hepatectomy has become the treatment of choice for recurrent liver metastases from colorectal cancer.


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  		TABLE 3. Reports of second hepatectomy
 
Recently, systemic chemotherapy has led to marked improvements in median overall survival and progression-free survival.24–26 These benefits are most pronounced with regimens containing irinotecan or oxaliplatin in combination with 5-FU plus leucovorin; median overall survival durations consistently approach 20 months, and some are as high as 24 months. Some patients experience early repeat recurrence within 6 months after second hepatectomy, and most of the disease is in an unresectable state when repeat recurrence is detected. In our series, 27 patients developed repeat recurrence within 6 months. Two patients underwent additional surgery, and the others received systemic chemotherapy, with a median survival time of 15 months. Considering these results, because their median survival was worse than that of patients who received systemic chemotherapy, the patients must have already had systemic disease at the time of surgery. Interestingly, we found that the patients who developed recurrence after 1999, when we started chemotherapy with irinotecan, had much better survival than those before 1998. This result seems mainly attributable to progress in chemotherapy, although diagnostic modality and perioperative management have been improved during these periods, and such improvements may have influenced survival. Now that we are in an era of effective chemotherapy, the indications for second liver resection need to be reconsidered. To improve the results of second hepatectomy, it is necessary to identify patients whose disease is likely to develop early repeat recurrence and who therefore should receive systemic chemotherapy.

Several studies have tried to identify factors predictive of a favorable outcome after repeat hepatectomy. To date, three reports have identified independent prognostic factors by multivariate analysis. Adam et al.6 showed that the disease-free interval between initial and second liver resections and a second liver resection with curative intent were independently associated with survival. In our study, univariate analysis showed that a disease-free interval of more than 6 months between the first hepatectomy and recurrence was a significant prognostic factor, although it did not reach statistical significance by multivariate analysis. Our multivariate analysis showed that synchronous first hepatectomy was an independently predictive factor. Petrowsky et al.18 showed that the presence of multiple lesions at repeat hepatectomy and a maximum tumor size exceeding 5 cm were independent prognostic factors after repeat hepatectomy. The third report, by Yamamoto et al.15 from our hospital in 1999, involved data from 90 repeat hepatectomies (second = 75; third = 12; fourth = 3). Multivariate analysis revealed two independent prognostic factors after the second hepatectomy: four or more tumors, and the presence of extrahepatic disease. The present study detected three independent prognostic factors: synchronous first hepatectomy, four or more lesions evident at the second hepatectomy, and invasions of the portal vein or hepatic vein at the first hepatectomy. Thus, only the number of lesions was a common predictor of outcome, whereas the other factors differed from those highlighted in the first study. We speculate that the reason for this difference was patient selection. In the prior report, 12 of the 75 patients who underwent second hepatectomy had received their first hepatectomy at other hospitals. In the present series, all the patients had undergone both first and second hepatectomies at our hospital. This means that we had full access to pathologic data from both procedures, ruling out any possibility that the first resection had been an incomplete one, and had not been performed at a specialized center such as ours. Okano et al.27 reported that portal vein invasion, hepatic vein invasion, neural invasion, and absence of macroscopic bile duct invasion were prognostic factors for poor outcome in patients undergoing initial hepatectomy. Similarly, we found that histopathologic evidence of invasions of the portal vein or hepatic vein at the first hepatectomy were associated with poor prognosis in patients undergoing a second hepatectomy. To date, to our knowledge, no previous report has indicated that pathological findings other than surgical margin can be predictive of survival after second hepatectomy. It is therefore suggested that not only adequate hepatic resection but also detailed examination by a specialized pathologist is important for more precise selection of patients for second hepatectomy.

All three independent risk factors we found to be important can be recognized before the second hepatectomy, thus permitting a prognosis to be estimated before patients undergo a second hepatectomy. We grouped the patients according to their risk factors. Survival expectancies at 5 years for patients with no risk factors, with one or two, and with three risk factors were 62%, 31%, and 0%, respectively. Considering these results, second hepatectomy will most benefit patients with no risk factors. In addition, no further treatments are needed for those patients. Patients with one or two of these risk factors may require adjuvant therapy after a second hepatectomy to improve survival. There is not much evidence of the efficacy of chemotherapy after hepatectomy, even now. So far, no evidence of improved overall survival has been shown, but the tested regimens included only fluorouracil, floxuridine, and leucovorin, and did not include irinotecan or oxaliplatin.28–30 A clinical trial comparing progression-free interval in patients undergoing surgical resection and/or ablation for hepatic metastases from colorectal cancer treated with adjuvant therapy comprising oxaliplatin and capecitabine versus without hepatic arterial infusion of floxuridine was conducted by National Surgical Adjuvant Breast and Bowel Project (NSABP-C09). This year, we are going to start a comparative trial to evaluate the efficacy of adjuvant chemotherapy with oxaliplatin added to the simplified bimonthly 5-FU and leucovorin regimen31 as compared with surgery alone in patients undergoing curative hepatectomy. These results will permit us to determine the strategy to take with patient treatment after hepatectomy.

Generally, neoadjuvant chemotherapy for the patients with hepatic metastases is the strategy for initially unresectable tumors. Adam et al.32 showed the results of neoadjuvant chemotherapy in 701 patients with initially unresectable colorectal liver metastases. Ninety-five cases (13.5%) were found to be resectable, and patients underwent a potentially curative resection with a 5-year survival rate of 35%. Tanaka et al.33 studied neoadjuvant chemotherapy for 48 patients with five or more bilobar hepatic metastases. They found that 25 patients with neoadjuvant chemotherapy had a better 5-year survival rate than 23 patients who did not receive neoadjuvant chemotherapy (39 vs. 21%, P = .039). Multivariate analysis showed that neoadjuvant chemotherapy was an independent predictor of survival. Adam et al.6 have adopted neoadjuvant chemotherapy for recurrent liver metastases before second hepatectomy, except in patients with small and solitary disease without concomitant extrahepatic disease.

Neoadjuvant chemotherapy before hepatectomy carries a risk of missing the opportunity for resection in patients whose tumors are initially resectable if tumor progression subsequently occurs during the course of chemotherapy. On the other hand, immediate resection carries a risk of missing occult metastases in the liver or at other sites. It was pointed out that the risk of missing the opportunity for resection could be avoided by frequent evaluation and the use of effective currently available chemotherapy regimens. Allen et al.,34 in a study of neo-adjuvant chemotherapy for patients with synchronous liver metastases, reported that none of those tumors became unresectable during the course of chemotherapy. Leonard et al.35 commented that the role of neoadjuvant chemotherapy in patients with resectable liver metastases was not confirmed, and well-designed prospective trials were needed. One clinical trial was conducted to evaluate the feasibility and risks of the preoperative chemotherapy with oxaliplatin, 5-FU, and leucovorin and surgery for resectable colorectal liver metastases by the European Organization for Research and Treatment of Cancer.36 The trial had been closed, and the interim results were that 93% of the patients receiving preoperative chemotherapy underwent surgery, and their surgery-related mortality and morbidity were low. The results on survival will be available in 2006. In our institution, the policy for liver metastases is immediate resection when the metastases are found to be resectable, even if they have recurred for the second or third time. For patients with no risk factors, or with one or two of these risk factors, immediate surgery without neoadjuvant chemotherapy is appropriate considering our results. Although we cannot deny that hepatectomy is the best and most potentially curative treatment for recurrent hepatic metastases, neoadjuvant chemotherapy followed by surgery is likely to be preferable for patients who have all three risk factors, to achieve better outcome.

Yamamoto et al.15 showed that the presence of extrahepatic disease was independently associated with poor survival, but because our series included only three patients with concomitant extrahepatic metastases, we were unable to confirm this. All three patients had solitary lung metastasis; one underwent pulmonary resection concomitant with second hepatectomy, and the other two underwent the two procedures synchronously. The first two patients died after 7 and 19 months, respectively, and the third is alive, without recurrence, at 37 months. Thus, we think that the presence of pulmonary metastases does not contraindicate repeat hepatic resection if it is anticipated that surgical resection of lung disease will result in cure.

In conclusion, we have been able to identify three risk factors that predict poor survival in patients with recurrent liver metastases from colorectal cancer: (1) synchronous first hepatectomy, (2) four or more lesions present at the time of second hepatectomy, and (3) invasions of the portal vein or hepatic vein evident at the first hepatectomy. Second hepatectomy is beneficial for patients without any risk factors. Before second hepatectomy, we should consider the use of chemotherapy for patients with any of these risk factors—especially in patients with two or three factors—in the adjuvant or neoadjuvant setting to prolong survival. These results need to be confirmed and validated with another data set or by future prospective trials according to the scoring scheme we showed.

Received for publication July 2, 2006. Accepted for publication July 3, 2006.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Scheele J, Stang R, Altendorf-Hofmann A, Paul M. Resection of colorectal liver metastases. World J Surg 1995; 19:59–71.[CrossRef][Medline]
  2. Yamamoto J, Shimada K, Kosuge T, Yamasaki S, Sakamoto M, Fukuda H. Factors influencing survival of patients undergoing hepatectomy for colorectal metastases. Br J Surg 1999; 86:332–7.[CrossRef][Medline]
  3. Minagawa M, Makuuchi M, Torzilli G, et al. Extension of the frontiers of surgical indications in the treatment of liver metastases from colorectal cancer: long-term results. Ann Surg 2000; 231:487–99.[CrossRef][Medline]
  4. Choti MA, Sitzmann JV, Tiburi MF, et al. Trends in long-term survival following liver resection for hepatic colorectal metastases. Ann Surg 2002; 235:759–66.[CrossRef][Medline]
  5. Adam R, Pascal G, Azoulay D, Tanaka K, Castaing D, Bismuth H. Liver resection for colorectal metastases: the third hepatectomy. Ann Surg 2003; 238:871–83; discussion 83–4.[CrossRef][Medline]
  6. Adam R, Bismuth H, Castaing D, et al. Repeat hepatectomy for colorectal liver metastases. Ann Surg 1997; 225:51–60.[CrossRef][Medline]
  7. Moriya Y, Sugihara K, Hojo K, Makuuchi M. Adjuvant hepatic intra-arterial chemotherapy after potentially curative hepatectomy for liver metastases from colorectal cancer: a pilot study. Eur J Surg Oncol 1991; 17:519–25.[Medline]
  8. Fong Y, Cohen AM, Fortner JG, et al. Liver resection for colorectal metastases. J Clin Oncol 1997; 15:938–46.[Abstract/Free Full Text]
  9. Fong Y, Blumgart LH, Cohen A, Fortner J, Brennan MF. Repeat hepatic resections for metastatic colorectal cancer. Ann Surg 1994; 220:657–62.[Medline]
  10. Nordlinger B, Vaillant JC, Guiguet M, et al. Survival benefit of repeat liver resections for recurrent colorectal metastases: 143 cases. Association Francaise de Chirurgie. J Clin Oncol 1994; 12:1491–6.[Abstract]
  11. Que FG, Nagorney DM. Resection of "recurrent" colorectal metastases to the liver. Br J Surg 1994; 81:255–8.[Medline]
  12. Fernandez-Trigo V, Shamsa F, Sugarbaker PH. Repeat liver resections from colorectal metastasis. Repeat Hepatic Metastases Registry. Surgery 1995; 117:296–304.[CrossRef][Medline]
  13. Riesener KP, Kasperk R, Winkeltau G, Schumpelick V. Repeat resection of recurrent hepatic metastases—improvement in prognosis?. Eur J Surg 1996; 162:709–15.[Medline]
  14. Tuttle TM, Curley SA, Roh MS. Repeat hepatic resection as effective treatment of recurrent colorectal liver metastases. Ann Surg Oncol 1997; 4:125–30.[Abstract]
  15. Yamamoto J, Kosuge T, Shimada K, Yamasaki S, Moriya Y, Sugihara K. Repeat liver resection for recurrent colorectal liver metastases. Am J Surg 1999; 178:275–81.[CrossRef][Medline]
  16. Muratore A, Polastri R, Bouzari H, Vergara V, Ferrero A, Capussotti L. Repeat hepatectomy for colorectal liver metastases: a worthwhile operation?. J Surg Oncol 2001; 76:127–32.[CrossRef][Medline]
  17. Suzuki S, Sakaguchi T, Yokoi Y, et al. Impact of repeat hepatectomy on recurrent colorectal liver metastases. Surgery 2001; 129:421–8.[Medline]
  18. Petrowsky H, Gonen M, Jarnagin W, et al. Second liver resections are safe and effective treatment for recurrent hepatic metastases from colorectal cancer: a bi-institutional analysis. Ann Surg 2002; 235:863–71.[CrossRef][Medline]
  19. Takahashi S, Inoue K, Konishi M, Nakagouri T, Kinoshita T. Prognostic factors for poor survival after repeat hepatectomy in patients with colorectal liver metastases. Surgery 2003; 133:627–34.[CrossRef][Medline]
  20. Tanaka K, Shimada H, Ohta M, et al. Procedures of choice for resection of primary and recurrent liver metastases from colorectal cancer. World J Surg 2004; 28:482–7.[CrossRef][Medline]
  21. Sugawara G, Isogai M, Kaneoka Y, Suzuki M, Yamaguchi A. Repeat hepatectomy for recurrent colorectal metastases. Surg Today 2005; 35:282–9.[CrossRef][Medline]
  22. Pessaux P, Lermite E, Brehant O, Tuech JJ, Lorimier G, Arnaud JP. Repeat hepatectomy for recurrent colorectal liver metastases. J Surg Oncol 2006; 93:1–7.[CrossRef][Medline]
  23. Kato T, Yasui K, Hirai T, et al. Therapeutic results for hepatic metastasis of colorectal cancer with special reference to effectiveness of hepatectomy: analysis of prognostic factors for 763 cases recorded at 18 institutions. Dis Colon Rectum 2003; 46(10 suppl):S22–31.[Medline]
  24. Simmonds PC. Palliative chemotherapy for advanced colorectal cancer: systematic review and meta-analysis. Colorectal Cancer Collaborative Group. BMJ 2000; 321:531–5.[Abstract/Free Full Text]
  25. Tournigand C, Andre T, Achille E, et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 2004; 22:229–37.[Abstract/Free Full Text]
  26. Goldberg RM, Sargent DJ, Morton RF, et al. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 2004; 22:23–30.[Abstract/Free Full Text]
  27. Okano K, Yamamoto J, Moriya Y, et al. Macroscopic intrabiliary growth of liver metastases from colorectal cancer. Surgery 1999; 126:829–34.[Medline]
  28. Kemeny N, Huang Y, Cohen AM, et al. Hepatic arterial infusion of chemotherapy after resection of hepatic metastases from colorectal cancer. N Engl J Med 1999; 341:2039–48.[Abstract/Free Full Text]
  29. Kemeny M. Hepatic artery infusion of chemotherapy as a treatment for hepatic metastases from colorectal cancer. Cancer J 2002; 8(suppl 1):S82–8.
  30. Kemeny N, Eid A, Stockman J, et al. Hepatic arterial infusion of floxuridine and dexamethasone plus high-dose Mitomycin C for patients with unresectable hepatic metastases from colorectal carcinoma. J Surg Oncol 2005; 91:97–101.[CrossRef][Medline]
  31. Maindrault-Goebel F, Louvet C, Andre T, et al. Oxaliplatin added to the simplified bimonthly leucovorin and 5-fluoro-uracil regimen as second-line therapy for metastatic colorectal cancer (FOLFOX6). GERCOR. Eur J Cancer 1999; 35:1338–42.[CrossRef][Medline]
  32. Adam R, Avisar E, Ariche A, et al. Five-year survival following hepatic resection after neoadjuvant therapy for nonresectable colorectal [liver] metastasis. Ann Surg Oncol 2001; 8:347–53.[Abstract/Free Full Text]
  33. Tanaka K, Adam R, Shimada H, Azoulay D, Levi F, Bismuth H. Role of neoadjuvant chemotherapy in the treatment of multiple colorectal metastases to the liver. Br J Surg 2003; 90:963–9.[CrossRef][Medline]
  34. Allen PJ, Kemeny N, Jarnagin W, DeMatteo R, Blumgart L, Fong Y. Importance of response to neoadjuvant chemotherapy in patients undergoing resection of synchronous colorectal liver metastases. J Gastrointest Surg 2003; 7:109–15; discussion 16–7.[CrossRef][Medline]
  35. Leonard GD, Brenner B, Kemeny NE. Neoadjuvant chemotherapy before liver resection for patients with unresectable liver metastases from colorectal carcinoma. J Clin Oncol 2005; 23:2038–48.[Abstract/Free Full Text]
  36. Nordlinger B, Sorbye H, Debois M, et al. Feasibility and risks of preoperative chemotherapy (CT) with FOLFOX 4 and surgery for resectable colorectal cancer liver metastases (LM). Interim results of the EORTC Intergroup randomized phase III study 40983 (abstract). J Clin Oncol 2005; 23(16 suppl):3528.



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