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ORIGINAL ARTICLE
Year : 2013  |  Volume : 9  |  Issue : 7  |  Page : 178-182

Retrospective analysis of clinical and pathologic risk factors in liver resection for hepatic colorectal metastases


1 Department of Gastrointestinal, China Japan Friendship Hospital, Beijing, China
2 Department of Emergency, China Japan Friendship Hospital, Beijing, China

Date of Web Publication30-Nov-2013

Correspondence Address:
Wenyue Wang
Gastrointestinal Department, China Japan Friendship Hospital, Beijing
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.122521

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 > Abstract 

Objective: To analyze the clinical and pathologic risk factors of surgical treatment for liver metastases from colorectal cancer.
Materials and Methods: The data on 98 patients who underwent liver resection for hepatic colorectal metastases were collected and analyzed retrospectively.
Results: Overall 1-, 3-, and 5-year survival rates after hepatectomy for metastases were 94.6%, 45.0%, and 22.3%, respectively. Gender, pathologic primary tumor stage, histologic differentiation, size of metastatic tumor, and type of metastases were not statistically significant prognostic factors (P > 0.05). The 5-year survival rate was significantly lower in patients with lymph node metastases from the primary site than that in patients without lymph node metastases (14.1% vs. 39.5%, P = 0.013); survival rate in patients with vascular invasion from the primary tumor was also significantly lower than in those without invasion (10.2% vs. 49.0%, P = 0.032). The survival rate in patients who had unilobar metastases was higher than that in patients who had bilobar metastases (25.3% vs. 0%, P = 0.012). The 5-year survival rates in solitary metastasis, two to three metastases, and with the transfer number ≥4 were 29.1%, 14.4%, and 0%, respectively (P = 0.019). Multivariate analysis revealed resection margin, distribution of metastases, and the number of metastases as the independent risk factors associated with the overall survival rates (P = 0.044, 0.037, and 0.005, respectively).
Conclusions: Surgical resection may be the only treatment modality for the cure of colorectal liver metastases. Negative resection margin, metastases confined to unilobar type, and number of metastases ≤3 are associated with better prognosis

Keywords: Colorectal cancer, hepatic metastases, liver resection, prognosis


How to cite this article:
Zhou L, Zhag G, Tang T, Lian R, Wang W. Retrospective analysis of clinical and pathologic risk factors in liver resection for hepatic colorectal metastases. J Can Res Ther 2013;9, Suppl S2:178-82

How to cite this URL:
Zhou L, Zhag G, Tang T, Lian R, Wang W. Retrospective analysis of clinical and pathologic risk factors in liver resection for hepatic colorectal metastases. J Can Res Ther [serial online] 2013 [cited 2019 Nov 18];9:178-82. Available from: http://www.cancerjournal.net/text.asp?2013/9/7/176/122521


 > Introduction Top


Liver metastasis from colorectal cancer is the most important prognostic factor for which surgical resection is the only curative modality. In most studies, the overall 5-year survival rate reported following hepatic resection with curative intent ranges from 25% to 37%, with a median survival between 24 and 40 months. [1],[2],[3],[4] But there is still controversy regarding patient selection. Many have addressed the influence of various clinical and pathologic parameters on the outcome or resective therapy, but the results vary considerably from study to study. We have reexamined our 127 consecutive patients who underwent hepatic resection for colorectal metastases during the last 13 years to identify the clinical and pathologic prognostic factors.


 > Materials and Methods Top


Patients

At the China-Japan Friendship Hospital, 127 patients underwent hepatic resection for metastatic colorectal carcinoma during a 13-year period from January 2000 to December 2012. These were all attempts at curative resection. Of these, 4 cases of perioperative death, 24 cases of clinical or incomplete follow-up data, and 1 case of occult colorectal liver metastases were excluded. Ninety-eight cases with complete data were included in the study. All patients were pathologically confirmed with hepatic colorectal metastases, in which there were 42 cases of synchronous liver metastases and 56 cases of metachronous liver metastases. The 60 men and 38 women ranged in age from 29 to 85 years, with a median age of 62 years. The primary tumor sites were: 25 cases of ascending colon, 5 cases of transverse colon, 9 cases of descending colon, 18 cases of sigmoid colon, 39 cases of rectum, and 2 cases of double primary colon. pT2 primary tumor was found in 3 cases, pT3 in 36 cases, and pT4 in 59 cases. The number of lymph node dissections ranged from 6 to 43, with a median of 14. There were 67 cases with lymph node metastases and 31 cases without lymph node metastases. Metastasis in the right lobe of the liver was found in 55 cases, in the left lobe of the liver in 34 cases, and it was bilobar in 9 cases. One single metastasis was found in 59 cases, two metastases in 15 cases, three metastases in 11 cases, four metastases in 8 cases, the remaining 5 patients had more than four metastases.

Surgical methods and postoperative pathologic conditions

Of the 98 patients, hepatic wedge resection was performed in 47 cases, 23 cases had hepatic segment resection, and 28 cases had hepatic lobe resection. Of the 59 cases with one single metastasis, hepatic wedge resection was done in 36 cases, hepatic segment resection in 9 cases, and hepatic lobe resection was performed in 14 cases. Of the 15 cases with two metastases, the above Figures were 6 cases, 5 cases, and 4 cases, respectively. In cases with three or more metastases, the proportion of hepatic lobe resection was increased. Six cases of 11 cases with three metastases, 5 cases of 8 cases with four metastases, and 4 cases of 5 cases with five or more than five metastases received hepatic lobe resection. Negative resection margin (R0 resection) was received by 83 cases and positive margin (R1 resection) by 15 cases. All cases were diagnosed as adenocarcinoma, which was poorly differentiated in 20 cases, moderately differentiated in 71 cases, and well differentiated in 7 cases.

Follow-up

Follow-up included outpatient, by letters and telephone. Patients' follow-up ranged from 3 to 105 months, with a median time of 29 months. If patients with simultaneous liver metastases received synchronous resection, the follow-up was from surgery to the time of death as the survival time and if they received staged resection, it was from the first operation to the time of death as the survival time. In patients with metachronous metastases to the liver, the follow-up was from the date of hepatic resection to the time of death as the survival time.

Statistical analysis

Survival analyses were done by the Kaplan-Meier method. Differences in survival were compared using the log-rank test. Multivariate analysis was performed with the Cox Proportional Hazard Model. Statistical analysis was performed using the SPSS Statistical Software Package (version 16.0). Differences were considered significant if P < 0.05.


 > Results Top


The Kaplan-Meier curve for overall survival is shown in [Figure 1]. The overall survival rate was 94.6% at 1 year, 45.0% at 3 years, and 22.3% at 5 years, with a median survival of 30 months. The survival rate in patients who received R0 resection was 94.9% at 1 year, 49.9% at 3 years, and 26.9% at 5 years, with a median survival of 36 months, higher than that of patients with R1 resection, which was 93.3% at 1 year, 20.1% at 3 years, and 0% at 5 years, with a median survival of 24 months [Figure 2].
Figure 1: Actuarial overall survival following hepatic resection for colorectal liver metastases

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Figure 2: Overall survival according to microscopic resection margin

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Primary tumor characteristics and prognosis

Gender, pathologic primary tumor stage (pT), and histologic differentiation degree showed no significant relationship with the 5-year survival rate (P = 0.84, 0.58, and 0.18, respectively), while the 5-year survival rate in pathologic lymph node stage (pN) positive (14.1%) was significantly lower than that in pN negative (39.5%). Vascular invasions (10.2%) were significantly lower than no vascular invasions (49.0%), and the difference was statistically significant (P = 0.013 and 0.032, respectively) [Table 1].
Table 1: Univariate and multivariate predictors of overall survival

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Relationship among characteristics of liver metastases, surgical type, and prognosis

While the 5-year survival rate of synchronous liver metastases (20.1%) was lower than that of metachronous liver metastases (24.2%), no significant difference was found (P = 0.53). Metastases with maximum diameter of ≤3 cm had higher 5-year survival rate than the metastases with maximum diameter >3 cm, but the difference was not statistically significant (22.4% vs. 19.6%, P = 0.18). With the increase in the number of metastases, the 5-year survival rate also decreased; the 5-year survival rates in solitary metastasis, two to three metastases, and with the transfer number ≥4 were 29.1%, 14.4%, and 0%, respectively, and the difference was statistically significant (P = 0.019). When the liver metastases were confined to half of the liver, the 5-year survival rate was significantly higher than that of bilateral diffusion, and the difference was statistically significant (25.3% vs. 0%, P = 0.012). The 5-year survival rates in wedge resection of the liver, hepatic segment resection, and hepatic lobe resection were 18.6%, 36.8%, and 17.7%, respectively, and there was no significant difference (P = 0.745) [Table 1]. In R0 resection of liver metastases, the 5-year survival rate (26.9%) was significantly higher than in R1 resection (0%), and the difference was statistically significant (P = 0.002) [Figure 2].

Multivariate analysis

Multivariate analysis of the prognostic factors for overall survival is shown in [Table 1]. Positive resection margin, number of metastases ≥4, and bilobar metastases were poor prognostic signs.


 > Discussion Top


Approximately 50-60% of patients diagnosed with colorectal cancer will develop colorectal metastases. [5],[6],[7] Metastatic disease most frequently develops metachronously after treatment for locoregional colorectal cancer, with the liver as the most common site of involvement. [8] However, 20-34% of patients with colorectal cancer present with synchronous liver metastases. [9],[10] In this study, we found 42 cases of synchronous liver metastases and 56 cases of metachronous liver metastases. This result is consistent with the previous reports.

Although metachronous metastases are often associated with local recurrence, lymph node metastases, or pulmonary metastases, and lost opportunities for radical surgery, the prognosis of metachronous liver metastases seems better than synchronous liver metastases. In a retrospective study of 155 patients who underwent hepatic resection for colorectal liver metastases, patients with synchronous liver metastases had more sites of liver involvement (P = 0.008) and more bilobar metastases (P = 0.016) than the patients diagnosed with metachronous liver metastases. [11] Multivariate analysis of the study showed that the distribution and the number of tumor metastases are independent prognostic factors. In addition, this analysis demonstrated the 5-year survival rate of synchronous liver metastases to be lower than that of metachronous liver metastases (20.1% vs. 24.2%). It can be explained by the fact that synchronous metastatic colorectal liver disease is associated with a more disseminated disease state than the metastatic colorectal liver disease that develops metachronously. But the difference was not statistically significant in this study, which may be due to the small number of cases.

Several studies have shown the rates of 5-year survival to be low in patients with metastatic liver disease not undergoing surgery. [6],[12] Factors influencing the prognosis of patients with hepatic colorectal metastases included the size, number, and distribution of metastases, condition of the primary tumor, the presence of extrahepatic tumor, preoperative carcino-embryonic antigen (CEA) level, synchronous or metachronous liver metastases, resection types, and microscopic resection margin. [13] However, some studies report different results. It may be due to the different inclusion criteria and difference in cases. Univariate analysis of the retrospective study showed that the primary tumor with lymph node metastases, vascular invasion, hepatic bilobar metastases, metastases number ≥4, and liver positive microscopic resection margin of liver metastases poor prognostic factors. Multivariate analysis of Cox showed that the microscopic resection margin, the distribution scope, and the number of liver metastases are independent prognostic factors. We found that positive resection margin, bilobar distribution of metastases, and liver metastases ≥4 had a significant deleterious effect on overall survival. In addition, this study showed that the 5-year survival rate in patients with poorly differentiated primary tumor and liver metastases with diameter >3 cm had decreased, but the difference was not statistically significant.

According to the National comprehensive cancer network (NCCN) guidelines, cytoreductive surgery is not beneficial to patients. So, we should try to do radical hepatectomy. Resection should include all possible metastases and at least 1 cm outside of metastases. The results of Are et al.[14] showed that cutting-edge distance of >1 cm is an independent prognostic factor. Our study showed that resection margin is an independent prognostic risk factor. The observations were not surprising because residual tumor constitutes surgical treatment failure from the outset and the outcome is expectedly poor. Generally, the most important factor affecting R0 resection of liver metastases and prognosis is the number of liver metastases. This study showed metastases number ≥4 and bilobar distribution of metastases are associated with poor prognosis, which may be due to missing tiny lesions or incomplete surgical margins. But with the advances in imaging and intraoperative ultrasound application, we believe that the number of liver metastases cannot serve as an absolute contraindication to surgery. As long as radical resection can be reached and can ensure adequate residual liver function, liver resection can be considered, especially for metastases confined to half of the liver and metastases <4. The type of liver resection is currently not conclusive, and mainly depends on the lesions' location, number, and scope. Our data showed that there were no significant differences in the 5-year survival rates among three resection types (hepatic wedge resection, segment resection, and lobe resection; P = 0.745).

In summary, for patients with liver metastases of colorectal cancer, microscopic resection margin, the distribution scope, and the number of liver metastases are independent prognostic factors. These parameters could be useful in identifying patients with poor prognosis who might be considered for enhanced follow-up. In the course of treatment, we should follow the principles of evidence-based medicine and select the appropriate cases for surgical treatment. For patients who cannot accept radical surgery or have a higher risk of recurrence, comprehensive and individualized treatment should be followed. Oncologists, radiotherapy physicians, and surgeons should keep close contact with this kind of patients. By doing this, they could formulate the best treatment strategy to get the best therapeutic effect.

 
 > References Top

1.Scheele J, Rudroff C, Altendorf-Hofman A. Resection of colorectal liver metastases revisited. J Gastrointest Surg 1997;1:408-22.  Back to cited text no. 1
    
2.Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: Analysis of 1001 consecutive cases. Ann Surg 1999;230:309-18.  Back to cited text no. 2
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5.Lee WS, Yun SH, Chun HK, Lee WY, Yun HR, Kim J, et al. Pulmonary resection for metastases from colorectal cancer: Prognostic factors and survival. Int J Colorectal Dis 2007;22:699-704.  Back to cited text no. 5
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7.Yoo PS, Lopez-Soler RI, Longo WE, Cha CH. Liver resection for metastatic colorectal cancer in the age of neoadjuvant chemotherapy and bevacizumab. Clin Colorectal Cancer 2006;6:202-7.  Back to cited text no. 7
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9.Muratore A, Zorzi D, Bouzari H, Amisano M, Massucco P, Sperti E, et al. Asymptomatic colorectal cancer with un-resectable liver metastases: Immediate colorectal resection or up-front systemic chemotherapy? Ann Surg Oncol 2007;14:766-70.  Back to cited text no. 9
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10.Hayashi M, Inoue Y, Komeda K, Shimizu T, Asakuma M, Hirokawa F, et al. Clinicopathological analysis of recurrence patients and prognostic factors for survival after hepatectomy for colorectal liver metastasis. BMC Surg 2010;10:27.  Back to cited text no. 10
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11.Tsai MS, Su YH, Ho MC, Liang JT, Chen TP, Lai HS, et al. Clinicopathological features and prognosis in resectable synchronous and metachronous colorectal liver metastasis. Ann Surg Oncol 2007;14:786-94.  Back to cited text no. 11
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12.Stangl R, Altendorf-Hofmann A, Charnley RM, Scheele J. Factors influencing the natural history of colorectal liver metastases. Lancet 1994;343:1405-10.  Back to cited text no. 12
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13.Wang X, Hershrnan DL, Abrams JA, Feingold D, Grann VR, Jacobson JS, et al. Predictors of survival after hepatie resection among patients with colorectal liver metastasis. Br J Cancer 2007;97:1606-12.  Back to cited text no. 13
    
14.Are C, Gonen M, Zazzali K, Dematteo RP, Jarnagin WR, Fong Y, et al. The impact of margins on outcome after hepatic resection for colorectal metastasis. Ann Surg 2007;246:295-300.  Back to cited text no. 14
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