Objective To study the impact of RAS status on prognosis of patients after liver resection for colorectal cancer liver metastases (CRLM).Methods The data of 545 consecutive CRLM patients who underwent liver resection at the Hepatopancreatobiliary Surgery Department I,Peking University Cancer Hospital between January 1st,2008 and December 31st,2016,were retrospectively reviewed.According to the inclusion and exclusion criteria,356 patients were eventually included into this study.There were 232 males and 124 females,with ages ranging from 21 to 83 years.The clinical and follow-up data of patients with wild-type and mutant RAS were compared.Survival was estimated by the Kaplan-Meier method,and the difference was compared by the log-rank test.Factors influencing survival of these patients were assessed by univariate and multivariate Cox regression analyses.Results There were 247 patients with wild-type RAS and 109 patients with mutant RAS,respectively.The median overall survival of patients with wild-type and mutant RAS were 74 and 30 months respectively.Compared with mutant RAS patients,wild-type RAS patients had significantly better cumulative survival and disease free survival rates (both P ＜ 0.05).Multivariate Cox regression analyses revealed disease free interval from primary to metastases ≤ 12 months (HR =1.673,95％ CI:1.016-2.637),largest hepatic tumor diameter ＞ 5 cm (HR =1.717,95 ％ CI:1.102-2.637),and mutant RAS (HR =1.836,95％ CI:1.322-2.550) were independent risk factors for patients with colorectal cancer liver metastases after hepatic resection.Conclusion Mutant RAS was a poor prognostic factor of survival after liver resection in CRLM patients

The incidence of colorectal cancer liver metastases (CRLM) has been gradually increased in recent years. Surgical resection is the most important treatment method for CRLM patients, but the recurrence rate was as high as 60%-70% after surgical resection. Therefore, it is very important to clarify the high-risk prognostic factors for tumor recurrence in patients with CRLM after surgery. Based on the prognostic factors we can accurately evaluate the biological behavior of each patient before surgery and select suitable preoperative chemotherapy regimen, timing and method of localized treatment for them. Thereby the survival benefit from surgical resection of those patients could be maximized. In this article we discussed several important factors affecting the tumor recurrence and survival of patients with CRLM undergoing surgical resection, including clinical risk factor score, preoperative chemotherapy response, the genetic status and the primary tumor location, and explain in detail.

Objective:To study the related factors of early recurrence and long-term survival after hepatectomy for patients with colorectal cancer liver metastases (CRLM) with a low-risk on clinical risk score (CRS).Methods:The clinicopathological data of 983 consecutive patients with CRLM who underwent liver resection at Department of Hepatopanereatobiliary Surgery Ⅰ, Peking University Cancer Hospital & Institute between January 2000 and November 2018 were studied retrospectively. A total of 420 patients with a CRS of 0-2 met the inclusion criteria of this study. There were 272 males and 148 females, aged from 21 to 83 years, with a median age 59 years. Univariate and multivariate logistic regression analyses were performed to identify the related factors associated with early recurrence. Survival curves were generated by the Kaplan-Meier method and compared by the log-rank test.Results:Of 420 patients, 272(64.8%) patients developed recurrence, with 163 patients developing early recurrence. Multivariate analysis revealed synchronous liver metastasis ( OR=1.587, 95% CI: 1.021-2.467), number of liver metastases ≥3( OR=1.904, 95% CI: 1.091-3.324) and RAS mutation ( OR=1.774, 95% CI: 1.157-2.270) were independent risk factors of early recurrence. The 5-year overall survival of patients with early recurrence was significantly lower than those with non-early recurrence (33.4% vs 71.1%, P<0.05). For the 163 patients with early recurrence, 41(25.2%) underwent repeat liver resection. When compared with the remaining 122(74.8%) patients who underwent non-resectional treatment, these 41 patients had a significantly higher 5-year overall survival rate (63.5% vs 21.1%, P<0.05). Conclusions:In patients with colorectal cancer liver metastases with a low risk on CRS, the independent risk factors for early recurrence were synchronous liver metastasis, number of liver metastases ≥3, and RAS mutation. Re-resection of early recurrent disease achieved better survival outcomes.

Objective:To compare the prognosis of patients with a single compared to multiple colorectal cancer liver metastases (CRLM) after hepatectomy.Methods:The clinical data of 490 patients with colorectal cancer liver metastases who underwent hepatectomy at Department of Hepatopancreatobiliary Surgery Ⅰ, Peking University Cancer Hospital & Institute from January 2006 to December 2016 were retrospectively studied. There were 314 males and 176 females. The median age was 58 years (range 21 to 83 years). There were 200 patients in the single liver metastasis group and 290 patients in the multiple liver metastases group. The tumor recurrence and survival outcomes on follow-up were analyzed. Survival curves were plotted using the Kaplan-Meier method. Both overall survival and disease-free survival between two groups were compared by the log-rank test. Univariate and multivariate Cox regression analyses were used to analyze independent risk factors of overall survival.Results:The 1-, 3-, 5-, 10-year overall survival rates for the single versus the multiple liver metastases groups were 92.5%, 58.6%, 51.0%, 38.8% versus 90.7%, 53.2%, 41.1%, 29.9%. The differences were significant ( P<0.05). The disease-free survival was also significantly better in the single than the multiple groups ( P<0.05). Cox multivariate analysis showed that right-sided primary colonic tumor, preoperative carbohydrate antigen 19-9 level ≥50 U/ml, and RAS mutant were independent factors influencing survival in patients with single liver metastasis; while primary colonic tumor N 1-2, liver metastases diameter ≥5 cm, and RAS mutant were independent factors influencing survival in patients with multiple tumors. If the three independent factors affecting overall survival of patients with multiple liver metastases were assigned 1 point for each factor, the number of patients with scores of 0, 1, 2, and 3 were 50, 145, 84, and 11, respectively. The long-term survival of patients with a low score (0, 1) was similar to those with a single liver metastasis (both P>0.05). However, patients with a high score (2, 3) showed significantly worse long-term survival when compared with patients with a single liver metastasis (both P<0.05). Conclusions:The prognosis of patients with single colorectal liver metastasis was better than those with multiple liver metastases after hepatectomy. For patients with multiple liver metastases with fewer associated risk factors, surgical resection could still result in long-term survival outcomes which were comparable to those patients with a single liver metastasis.

Objective:To study the impact of surgical treatment on long-term survival in patients with colorectal cancer liver metastases, and to identify the associated risk factors.Methods:The clinical, pathological, and follow-up data were prospectively collected from 781 consecutive patients who underwent hepatic resection for colorectal liver metastases at Hepatopancreatobiliary Surgery Department Ⅰ, Peking Cancer Hospital from Jan 2000 to Nov 2018. There were 497 males and 284 females. The average age was 56.7 years (range 19 to 83 years). The tumor recurrence and survival outcomes on follow-up were analyzed. Survival curves were plotted using the Kplan-Meier mothod. Parametric survival analysis was used to identify predictors of cancer-specific survival.Results:The 1-, 3-, 5- and 10-year overall survival rates were 91.6%, 57.3%, 45.2% and 27.6%, respectively. The median survival was 46 months. The 1-, 3-, 5- and 10-year disease-free survival rates were 45.3%, 26.0%, 22.9%, and 19.5%, respectively. The median disease-free survival was 11 months. On multivariate analysis, 5 risk factors were found to be independent predictors of poor survival: RAS/BRAF gene mutation ( HR=1.650, 95% CI: 1.302-2.089), right-sided colonic primary ( HR=1.361, 95% CI: 1.151-1.667), node-positive primary ( HR=1.660, 95% CI: 1.284-2.146), largest hepatic tumor ≥3 cm ( HR=1.473, 95% CI: 1.157-1.874), and extrahepatic disease ( HR=1.610, 95% CI: 1.294-2.003). Conclusion:Surgery is the key to long-term survival for patients with liver metastases from colorectal cancer. Right colonic primary, RAS/BRAF gene mutation, primary lymph node metastasis, hepatic metastasis with a maximum diameter ≥3 cm and extrahepatic metastasis were factors associated with poor prognosis.

Objective:To investigate the clinical efficacy of liver resection for colorectal liver metastases(CRLM)in elderly patients and to analyze factors influencing prognosis.Methods:Clinicopathological and follow-up data of 476 CRLM patients undergone liver resection at our department between January 2000 and August 2016 were retrospectively analyzed.Patients were divided into two groups according their ages: the elderly group(n=112, aged 65 years or older)and the young and middle-aged group(n=364, aged less than 65 years). The safety of the surgical treatment and long-term survival were compared between the two groups.Results:The overall postoperative complication rate was 30.3%.There was no significant difference in postoperative complication rates between the elderly group and the young and middle-aged group(32.1% vs. 29.7%, P=0.618). The mortality within 90 days after surgery was 0.9% in the elderly group and 0.5% in the young and middle-aged group( P=0.688). The 5-year survival rates after surgery were similar between the elderly group and the young and middle-aged group(42.4% vs.44.3%, P=0.672). Multivariate analysis revealed that clinical risk score(CRS)≥3 and RAS mutation were independent risk factors for prognosis. Conclusions:Liver resection is safe in carefully selected elderly CRLM patients and can achieve good long-term outcomes.The CRS and RAS genotype can help predict prognosis in elderly CRLM patients.

Objective:Liver is the most common site of distant metastasis in colorectal cancer patients. Currently, surgical resection of colorectal liver metastasis (CRLM) still remains the most curative therapeutic option which is associated with long-term survival. However, the outcome of CRLM patients with bilobar multiple lesions has been reported to be extremely poor due to the complex techniques of the surgery and the difficulties to achieve a negative resection margin. In this study, postoperative long-term outcome in patients with bilobar versus unilobar multiple CRLM undergoing surgical resection were compared and the prognostic factors of CRLM were analyzed.Methods:A retrospective cohort study was performed. The clinicopathological data were collected retrospectively from patients with multiple CRLM who received liver resection between January 2002 and November 2018 at our department. Inclusion criteria: (1) All CRLM lesions were confirmed by preoperative enhanced CT or MRI and enhanced ultrasonography. (2) All CRLM lesions were resectable either initially or converted by systemic treatments. The CRLM patients were considered as resectable, if their extrahepatic diseases were able to be completely removed. (3) Sufficient remnant liver volume was required to maintain normal liver function, which was defined by the ratio of remnant liver volume to total liver volume (RLV-TLV), of greater than 30% in general or 40% for the patients undergoing chemotherapy. (4) Medical records and follow-up information were intact. Those undergoing multiple operations after recurrence, with R2 resection, or with a single CRLM lesion were excluded. Patients were divided into bilobar and unilobar group according to tumor distribution. One-to-one propensity score matching (PSM) was performed to balance the covariates between the bilobar group and unilobar group. After PSM, the differences in long-term outcomes between the two groups were compared.Results:A total of 491 patients met the inclusion criteria, 344 (69.6%) with bilobar and 147 (30.4%) with unilobar CRLM. In the propensity-score-matched population (bilobar, 143; unilobar, 143), baseline characteristics were similar between the two groups. The 1-, 3-, and 5-year overall survival rates in the bilobar group were 91.6%, 52.1%, and 35.3% respectively, compared with 93.7%, 56.8%, and 43.8% in the unilobar group, and the difference was not statistically significant ( P=0.204). The 1-, 3-, and 5-year recurrence-free survival rates in the bilobar group were 45.7%, 33.7%, and 33.7% respectively, compared with 62.5%, 44.1%, and 42.1% in the unilobar group, and the difference was not statistically significant ( P=0.075). No significant difference was found in liver-only recurrence (45.6% in bilobar vs. 53.3% in unilobar, P=0.543). Univariate analysis showed that N stage of primary tumor, diameter of the largest liver metastases, carcinoembyonic antigen level, RAS gene status and clinical risk score (CRS) were significantly associated with the prognosis of CRLM (all P<0.05). Multivariate analysis indicated that diameter of largest liver metastases > 5 cm (HR=1.888, 95% CI: 1.251-2.848, P=0.002), CRS≥3 (HR=1.552,95% CI:1.050-2.294, P=0.027) and RAS gene mutation (HR=1.561, 95% CI: 1.102-2.212, P=0.012) were independent risk factors of poor overall survival after hepatectomy. Conclusions:Tumor distribution may not affect the prognosis of multiple CRLM after resection. Surgical removal in patients with bilobar multiple CRLM provides comparable long-term survival to unilobar multiple CRLM.

Objective:Liver is the most common site of distant metastasis in colorectal cancer patients. Currently, surgical resection of colorectal liver metastasis (CRLM) still remains the most curative therapeutic option which is associated with long-term survival. However, the outcome of CRLM patients with bilobar multiple lesions has been reported to be extremely poor due to the complex techniques of the surgery and the difficulties to achieve a negative resection margin. In this study, postoperative long-term outcome in patients with bilobar versus unilobar multiple CRLM undergoing surgical resection were compared and the prognostic factors of CRLM were analyzed.Methods:A retrospective cohort study was performed. The clinicopathological data were collected retrospectively from patients with multiple CRLM who received liver resection between January 2002 and November 2018 at our department. Inclusion criteria: (1) All CRLM lesions were confirmed by preoperative enhanced CT or MRI and enhanced ultrasonography. (2) All CRLM lesions were resectable either initially or converted by systemic treatments. The CRLM patients were considered as resectable, if their extrahepatic diseases were able to be completely removed. (3) Sufficient remnant liver volume was required to maintain normal liver function, which was defined by the ratio of remnant liver volume to total liver volume (RLV-TLV), of greater than 30% in general or 40% for the patients undergoing chemotherapy. (4) Medical records and follow-up information were intact. Those undergoing multiple operations after recurrence, with R2 resection, or with a single CRLM lesion were excluded. Patients were divided into bilobar and unilobar group according to tumor distribution. One-to-one propensity score matching (PSM) was performed to balance the covariates between the bilobar group and unilobar group. After PSM, the differences in long-term outcomes between the two groups were compared.Results:A total of 491 patients met the inclusion criteria, 344 (69.6%) with bilobar and 147 (30.4%) with unilobar CRLM. In the propensity-score-matched population (bilobar, 143; unilobar, 143), baseline characteristics were similar between the two groups. The 1-, 3-, and 5-year overall survival rates in the bilobar group were 91.6%, 52.1%, and 35.3% respectively, compared with 93.7%, 56.8%, and 43.8% in the unilobar group, and the difference was not statistically significant ( P=0.204). The 1-, 3-, and 5-year recurrence-free survival rates in the bilobar group were 45.7%, 33.7%, and 33.7% respectively, compared with 62.5%, 44.1%, and 42.1% in the unilobar group, and the difference was not statistically significant ( P=0.075). No significant difference was found in liver-only recurrence (45.6% in bilobar vs. 53.3% in unilobar, P=0.543). Univariate analysis showed that N stage of primary tumor, diameter of the largest liver metastases, carcinoembyonic antigen level, RAS gene status and clinical risk score (CRS) were significantly associated with the prognosis of CRLM (all P<0.05). Multivariate analysis indicated that diameter of largest liver metastases > 5 cm (HR=1.888, 95% CI: 1.251-2.848, P=0.002), CRS≥3 (HR=1.552,95% CI:1.050-2.294, P=0.027) and RAS gene mutation (HR=1.561, 95% CI: 1.102-2.212, P=0.012) were independent risk factors of poor overall survival after hepatectomy. Conclusions:Tumor distribution may not affect the prognosis of multiple CRLM after resection. Surgical removal in patients with bilobar multiple CRLM provides comparable long-term survival to unilobar multiple CRLM.

The incidence of colorectal cancer liver metastasis (CRLM) has gradually increased in recent years. Surgical resection is the main method to achieve long-term survival for patients with CRLM. However, only 20% of these patients have the chance to undergo surgical resection. If the unresectable metastases can be converted to resectable ones by effective conversion therapy, the 5-year survival rate of patients received liver resection can exceed to 30%, which is significantly better than palliative treatment. Therefore, for patients who are initially unresectable, rationally developing a conversion therapy strategy to convert the initial unresectable CRLM into resectable ones is the key to improve the long-term survival of CRLM patients. However, there are still many controversies in clinical practice. In this article, we discuss three critical issues related to the conversion therapy for CRLM based on previous related researches and our experience, including the applicable population of conversion therapy, how to choose a conversion regime and the recognition and treatment of disappeared lesions after chemotherapy.

The incidence of colorectal cancer liver metastasis (CRLM) increased gradually in recent years. Surgical resection is the most important treatment for CRLM patients to obtain long-term survival, with a 5-year survival rate of about 50%. However, only 20% of the CRLM patients are initially resectable. The recurrence rate after surgery is more than 70%. Perioperative chemotherapy has been widely used with the development of effective chemotherapy regimens and targeted therapies. For patients with initially resectable liver metastases, perioperative chemotherapy may help reduce recurrence and prolong survival. For patients with unresectable liver metastases, conversion chemotherapy with high efficiency provides opportunity for radical resection. However, CRLM is a disease with high heterogeneity and with many factors influencing prognosis, and there is a lack of large-scale prospective clinical trial evidence in many problems. Hence there are still many controversies in the clinical practice of perioperative chemotherapy, including whether chemotherapy alone is the best preoperative treatment for resectable CRLM, whether preoperative chemotherapy combined with targeted therapy is superior to chemotherapy alone, who can benefit most from preoperative chemotherapy combined with targeted therapy, who are the exact patients suitable for conversion therapy, how to choose the best first-line conversion therapy. Here we discuss the current status of research on perioperative chemotherapy in three aspects: neoadjuvant chemotherapy, conversion therapy and adjuvant chemotherapy. We also emphasized the importance of multidisciplinary team during the treatment process to give patients individualized therapy considering their specific conditions.