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 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.

Antioxidants are important substances in the body against oxidative stress,which can main-tain the balance of redox substances by reducing the content of reactive oxygen species in cells. Studies have shown that new antioxidants have significant inhibitory effects on the growth of urological neoplasms by inhibiting tumor cell proliferation,inducing apoptosis,disturbing angiogenesis and metastasis of tumor cells. Antioxidants are of great value in the prevention and treatment of urinary system tumors and are expected to become new anti-tumor drugs.

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.

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.

Uncovering the functionally essential variations related to tumorigenesis and tumor pro-gression from cancer genomics data is still challenging due to the genetic diversity among patients, and extensive inter-and intra-tumoral heterogeneity at different levels of gene expression regulation, including but not limited to the genomic, epigenomic, and transcriptional levels. To minimize the impact of germline genetic heterogeneities, in this study, we establish multiple primary cultures from the primary and recurrent tumors of a single patient with hepatocellular carcinoma (HCC). Multi-omics sequencing was performed for these cultures that encompass the diversity of tumor cells from the same patient. Variations in the genome sequence, epigenetic modification, and gene expression are used to infer the phylogenetic relationships of these cell cultures. We find the discrepancy among the relationships revealed by single nucleotide variations (SNVs) and transcriptional/epigenomic pro-files from the cell cultures. We fail to find overlap between sample-specific mutated genes and differ-entially expressed genes (DEGs), suggesting that most of the heterogeneous SNVs among tumor stages or lineages of the patient are functionally insignificant. Moreover, copy number alterations (CNAs) and DNA methylation variation within gene bodies, rather than promoters, are significantly correlated with gene expression variability among these cell cultures. Pathway analysis of CNA/DNA methylation-related genes indicates that a single cell clone from the recurrent tumor exhibits distinct cellular characteristics and tumorigenicity, and such an observation is further confirmed by cellular experiments both in vitro and in vivo. Our systematic analysis reveals that CNAs and epigenomic changes, rather than SNVs, are more likely to contribute to the phenotypic diversity among subpop-ulations in the tumor. These findings suggest that new therapeutic strategies targeting gene dosage and epigenetic modification should be considered in personalized cancer medicine. This culture model may be applied to the further identification of plausible determinants of cancer metastasis and relapse.

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.

Objective To analyze the clinical data of patients with post-hepatectomy haemorrhage (PHH) and to discuss the treatment strategies.Method The clinicopathologic data of patients with PHH between 2005-2014 in the HPB Surgery Ward I,Peking University Cancer Hospital,were studied retrospectively.Results In the study period of 10 years,25 of 1 548 patients who underwent hepatectomy suffered from PHH,and 76％ (19/25) of these patients had underlying liver diseases.The common surgical operations followed by PHH were right hemihepatectomy (11/25),and segment Ⅶ/Ⅷ resection (8/25).The median time for PHH to be diagnosed was 27 h,and the median time from diagnosis of postoperative bleeding to reoperation or intervention was 3.5 h.Using the classification of PHH by the International Study Group of Liver Surgery (ISGLS),there were 1 patient in grade A,16 patients in grade B,and 8 patients in grade C.The perioperative mortality of PHH was 8％ (2/25).The most common bleeding site was from the hepatic artery.Conclusions PHH is a serious complication after liver resection,with low occurrence but high mortality.Most patients with PHH can be managed by conservative treatment.Emergency reoperation is required when instability in vital signs appears.Careful evaluation before operation,strict hemostasis during operation,and close monitoring after operation can effectively reduce the incidence and mortality of PHH.