Tumour response following preoperative chemotherapy is affected by body mass index in patients with colorectal liver metastases

BACKGROUND Colorectal cancer is the third most prevalent malignancy globally and ranks second in cancer-related mortality,with the liver being the primary organ of metastasis.Preoperative chemotherapy is widely recommended for initially or potentially resectable colorectal liver metastases(CRLMs).Tumour pathological response serves as the most important and intuitive indicator for assessing the efficacy of chemotherapy.However,the postoperative pathological results reveal that a considerable number of patients exhibit a poor response to preoperative chemotherapy.Body mass index(BMI)is one of the factors affecting the tumori-genesis and progression of colorectal cancer as well as prognosis after various antitumour therapies.Several studies have indicated that overweight and obese patients with metastatic colorectal cancer experience worse prognoses than those with normal weight,particularly when receiving first-line chemotherapy regimens in combination with bevacizumab.AIM To explore the predictive value of BMI regarding the pathologic response following preoperative chemotherapy for CRLMs.METHODS A retrospective analysis was performed in 126 consecutive patients with CRLM who underwent hepatectomy following preoperative chemotherapy at four different hospitals from October 2019 to July 2023.Univariate and multivariate logistic regression models were applied to analyse potential predictors of tumour pathological response.The Kaplan-Meier method with log rank test was used to compare progression-free survival(PFS)between patients with high and low BMI.BMI<24.0 kg/m^(2) was defined as low BMI,and tumour regression grade 1-2 was defined as complete tumour response.RESULTS Low BMI was observed in 74(58.7%)patients and complete tumour response was found in 27(21.4%)patients.The rate of complete tumour response was significantly higher in patients with low BMI(29.7%vs 9.6%,P=0.007).Multivariate analysis revealed that low BMI[odds ratio(OR)=4.56,95%confidence interval(CI):1.42-14.63,P=0.011],targeted therapy with bevacizumab(OR=3.02,95%CI:1.10-8.33,P=0.033),preoperative carcinoembryonic antigen level<10 ng/mL(OR=3.84,95%CI:1.19-12.44,P=0.025)and severe sinusoidal dilatation(OR=0.17,95%CI:0.03-0.90,P=0.037)were independent predictive factors for complete tumour response.The low BMI group exhibited a significantly longer median PFS than the high BMI group(10.7 mo vs 4.7 mo,P=0.011).CONCLUSION In CRLM patients receiving preoperative chemotherapy,a low BMI may be associated with better tumour response and longer PFS.

Liver transplantation as an alternative for the treatment of non-resectable liver colorectal cancer: Advancing the therapeutic algorithm

Colorectal cancer is a leading cause of cancerrelated mortality,with nearly half of the affected patients developing liver metastases.For three decades,liver resection(LR)has been the primary curative strategy,yet its applicability is limited to about 20%of cases.Liver transplantation(LT)for unresectable metastases was attempted unsuccessfully in the 1990s,with high rates of perioperative death and recurrence.There is now more interest in this strategy due to improvements in systemic therapies and surgical techniques.A significant study conducted by the Oslo group showed that patients receiving liver transplants had a 60%chance of survival after five years.Significantly better results have been achieved by using advanced imaging for risk stratification and further refining selection criteria,especially in the Norvegian SECA trials.This review carefully charts the development and history of LT as a treatment option for colorectal cancer liver metastases.The revolutionary path from the early days of exploratory surgery to the current situation of cautious optimism is traced,highlighting the critical clinical developments and improved patient selection standards that have made LT a potentially curative treatment for such challenging very well selected cases.

The challenge of molecular selection in liver-limited metastatic colorectal cancer for surgical resection: a systematic review and meta-analysis in the context of current and future approaches

Objectives:Treatment of metastatic colorectal cancer(mCRC)includes resection of liver metastases(LM),however,no validated biomarker identifies patients most likely to benefit from this procedure.This meta-analysis aimed to assess the impact of the most relevant molecular alterations in cancer-related genes of CRC(i.e.,RAS,BRAF,SMAD4,PIK3CA)as prognostic markers of survival and disease recurrence in patients with mCRC surgically treated by LM resection.Methods:A systematic literature review was performed to identify studies reporting data regarding survival and/or recurrence in patients that underwent complete liver resection for CRC LM,stratified according to RAS,BRAF,PIK3CA,and SMAD4 mutational status.Hazard ratios(HRs)from multivariate analyses were pooled in the meta-analysis and various adjustment strategies for confounding factors were combined.The search was conducted in numerous databases,including MEDLINE(PubMed),Embase,Cumulative Index to Nursing and Allied Health Literature(CINAHL)(EBSCO host),and WHO Global Index Medicus,through March 18th,2022.Meta-analyses,editorials,letters to the editor,case reports,studies on other primary cancers,studies with primary metastatic sites other than the liver,studies lacking specific oncological outcome variables or genetic data,non-English language studies,and studies omitting residual disease data from liver metastasectomy were excluded.The remaining 47 studies were summarized in a descriptive table which outlines the key characteristics of each study and final results were graphically presented.Results:RAS mutation status was negatively associated with overall survival(OS)(HR,1.68;95%CI,1.54–1.84)and recurrence free survival(RFS)(HR,1.46;95%CI,1.33–1.61).A negative association was also found for BRAF regarding OS(HR,2.64;95%CI,2.15–3.24)and RFS(HR,1.89;95%CI,1.32–2.73)and SMAD4 regarding OS(HR,1.93;95%CI,1.56–2.38)and RFS(HR,1.95;95%CI,1.31–2.91).For PIK3CA only three studies were eligible and no significant association with either OS or RFS could be highlighted.Conclusion:RAS,BRAF,and SMAD4 are negatively associated with OS and RFS in patients undergoing curative liver metastasectomy from colorectal cancer.No conclusion can be drawn for PIK3CA due to the limited literature availability.These data support the integration of RAS,BRAF,and SMAD4 mutational status in the surgical decision-making for colorectal liver metastasis.Nevertheless,we have to consider several limitations,the major ones being the pooling of results from studies that evaluated patient outcomes as either disease-free survival(DFS)or RFS;the inclusion of patients with minimal residual disease and unconsidered potential confounding factors,such as variability in resectability definitions,chemotherapy use,and a potential interaction between biological markers and pre-and post-resection pharmacological treatments.

Multidisciplinary discussion and management of synchronous colorectal liver metastases: A single center study in China

BACKGROUND The multidisciplinary team(MDT)has been carried out in many large hospitals now.However,given the costs of time and money and with little strong evidence of MDT effectiveness being reported,critiques of MDTs persist.AIM To evaluate the effects of MDTs on patients with synchronous colorectal liver metastases and share our opinion on management of synchronous colorectal liver metastases.METHODS In this study we collected clinical data of patients with synchronous colorectal liver metastases from February 2014 to February 2017 in the Chinese People’s Liberation Army General Hospital and subsequently divided them into an MDT+group and an MDT-group.In total,93 patients in MDT+group and 169 patients in MDT-group were included totally.RESULTS Statistical increases in the rate of chest computed tomography examination(P=0.001),abdomen magnetic resonance imaging examination(P=0.000),and preoperative image staging(P=0.0000)were observed in patients in MDT+group.Additionally,the proportion of patients receiving chemotherapy(P=0.019)and curative resection(P=0.042)was also higher in MDT+group.Multivariable analysis showed that the population of patients assessed by MDT meetings had higher 1-year[hazard ratio(HR)=0.608,95%confidence interval(CI):0.398-0.931,P=0.022]and 5-year(HR=0.694,95%CI:0.515-0.937,P=0.017)overall survival.CONCLUSION These results proved that MDT management did bring patients with synchronous colorectal liver metastases more opportunities for comprehensive examination and treatment,resulting in better outcomes.

Multi-modality treatment of colorectal liver metastases

Liver metastases synchronously or metachronously occur in approximately 50% of colorectal cancer patients. Multimodality comprehensive treatment is the best therapeutic strategy for these patients. However, the optimal pattern of multimodality therapy is still controversial, and it raises several signif icant concerns. Liver resection is the most important treatment for colorectal liver metastases. The defi nition of resectability has shifted to focus on the completion of R0 resection and normal liver function maintenance. The role of neoadjuvant and adjuvant chemotherapy still needs to be clarified. The management of either progression or complete remission during neoadjuvant chemotherapy is challenging. The optimal sequencing of surgery and chemotherapy in synchronous colorectal liver metastases patients is still unclear. Conversional chemotherapy, portal vein embolization, two-stage resection, and tumor ablation are effective approaches to improve resectability for initially unresectable patients. Several technical issues and concerns related to these methods need to be further explored. For patients with def initely unresectable liver disease, the necessity of resecting the primary tumor is still debatable, and evaluatingand predicting the eff icacy of targeted therapy deserve further investigation. This review discusses different patterns and important concerns of multidisciplinary treatment of colorectal liver metastases.

An update on chemotherapy of colorectal liver metastases

Surgical resection of liver metastases of colorectal cancer greatly improves the clinical outcome of patients with advanced disease. Developments in chemotherapeutic agents and strategies bring hope of a cure to patients with initially unresectable colorectal liver metastases (CLM). Perioperative chemotherapy signif icantly improves the survival time of patients who receive curative-intent hepatectomy. Even for unresectable CLM, recent studies demonstrated that active preoperative chemotherapy could achieve shrinkage of liver metastasis and thus render some for resection. Furthermore, an increase in tumor resection rate and prolonged survival time among patients with CLM has been observed following the application of monoclonal antibodies in recent years. However, the value of chemotherapy via hepatic arterial infusion is still unclear. More trials should be conducted in patients with CLM in order to improve survival.

Colorectal liver metastases:An update on multidisciplinary approach

Liver metastasis is the commonest form of distant metastasis in colorectal cancer.Selection criteria for surgery and liver-directed therapies have recently been extended.However,resectability remains poorly defined.Tumour biology is increasingly recognized as an important prognostic factor;hence molecular profiling has a growing role in risk stratification and management planning.Surgical resection is the only treatment modality for curative intent.The most appropriate surgical approach is yet to be established.The primary cancer and the hepatic metastasis can be removed simultaneously or in a two-step approach;these two strategies have comparable long-term outcomes.For patients with a limited future liver remnant,portal vein embolization,combined ablation and resection,and associating liver partition and portal vein ligation for staged hepatectomy have been advocated,and each has their pros and cons.The role of neoadjuvant and adjuvant chemotherapy is still debated.Targeted biological agents and loco-regional therapies(thermal ablation,intra-arterial chemo-or radio-embolization,and stereotactic radiotherapy) further improve the already favourable results.The recent debate about offering liver transplantation to highly selected patients needs validation from large clinical trials.Evidencebased protocols are missing,and therefore optimal management of hepatic metastasis should be personalized and determined by a multi-disciplinary team.

Colorectal cancer with liver metastases:Neoadjuvant chemotherapy,surgical resection first or palliation alone?

Colorectal cancer (CRC) is one of the commonest cancers with 1.2 million new cases diagnosed each year in the world. It remains the fourth most common cause of cancer-related mortality in the world and accounts for &#x0003e; 600000 cancer-related deaths each year. There have been significant advances in treatment of metastatic CRC in last decade or so, due to availability of new active targeted agents and more aggressive approach towards the management of CRC, particularly with liver-only-metastases; however, these drugs work best when combined with conventional chemotherapy agents. Despite these advances, there is a lack of biomarkers to inform us about the accurate management of the patients with metastatic CRC. It is therefore imperative to carefully select the patients with comprehensive multi-disciplinary team input in order to optimise the management of these patients. In this review we will discuss various treatment options available in management of colorectal liver metastases with potential guidance on how and when to choose these options along with consideration on future directions in management of this disease.

Non-invasive diagnostic imaging of colorectal liver metastases

Colorectal cancer is one of the few malignant tumors in which synchronous or metachronous liver metastases [colorectal liver metastases(CRLMs)] may be treated with surgery. It has been demonstrated that resection of CRLMs improves the long-term prognosis. On the other hand, patients with un-resectable CRLMs may benefit from chemotherapy alone or in addition to liverdirected therapies. The choice of the most appropriate therapeutic management of CRLMs depends mostly on the diagnostic imaging. Nowadays, multiple non-invasive imaging modalities are available and those have a pivotal role in the workup of patients with CRLMs. Although extensive research has been performed with regards to the diagnostic performance of ultrasonography, computed tomography, positron emission tomography and magnetic resonance for the detection of CRLMs, the optimal imaging strategies for staging and follow up are still to be established. This largely due to the progressive technological and pharmacological advances which are constantly improving the accuracy of each imaging modality. This review describes the non-invasive imaging approaches of CRLMs reporting the technical features, the clinical indications, the advantages and the potential limitations of each modality, as well as including some information on the development of new imaging modalities, the role of new contrast media and the feasibility of using parametric image analysis as diagnostic marker of presence of CRLMs.

Anti-EGFR and anti-VEGF agents:Important targeted therapies of colorectal liver metastases

Colorectal liver metastasis (CLM) is common worldwide. Targeted therapies with monoclonal antibodies have been proven effective in numerous clinical trials, and are now becoming standards for patients with CLM. The development and application of anti-epidermal growth factor receptor (anti-EGFR) and anti-vascular endothelial growth factor (anti-VEGF) antibodies represents significant advances in the treatment of this disease. However, new findings continue to emerge casting doubt on the efficacy of this approach. The Kirsten rat sarcoma viral oncogene (KRAS) has been proven to be a crucial predictor of the success of anti-EGFR treatment in CLM. Whereas a recent study summarized several randomized controlled trials, and showed that patients with the KRAS G13D mutation significantly benefited from the addition of cetuximab in terms of progress-free survival (PFS, 4.0 mo vs 1.9 mo, HR = 0.51, P = 0.004) and overall survival (OS, 7.6 mo vs 5.7 mo, HR = 0.50, P = 0.005). Some other studies also reported that the KRAS G13D mutation might not be absolutely predictive of non-responsiveness to anti-EGFR therapy. At the same time, &#x0201c;new&#x0201d; RAS mutations, including mutations in neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) and exons 3 and 4 of KRAS, have been suggested to be predictors of a poor treatment response. This finding was first reported by the update of the PRIME trial. The update showed that for patients with non-mutated KRAS exon 2 but other RAS mutations, panitumumab-fluorouracil, leucovorin, and oxaliplatin (FOLFOX)4 treatment led to inferior PFS (HR = 1.28, 95%CI: 0.79-2.07) and OS (HR = 1.29, 95%CI: 0.79-2.10), which was consistent with the findings in patients with KRAS mutations in exon 2. Then, the update of the PEAK trial and the FIRE-III trial also supported this finding, which would reduce candidates for anti-EGFR therapy but enhance the efficacy. In first-line targeted combination therapy, the regimens of cetuximab plus FOLFOX was called into question because of the inferior prognosis in the COIN trial and the NORDIC-VII trial. Also, bevacizumab plus oxaliplatin-based chemotherapy was questioned because of the NO16966 trial. By the update and further analysis of the COIN trial and the NORDIC-VII trial, cetuximab plus FOLFOX was reported to be reliable again. But bevacizumab plus oxaliplatin-based chemotherapy was still controversial. In addition, some trials have reported that bevacizumab is not suitable for conversion therapy. The results of the FIRE-III trial showed that cetuximab led to a significant advantage over bevacizumab in response rate (72% vs 63%, P = 0.017) for evaluable population. With the balanced allocation of second-line treatment, the FIRE-III trial was expected to provide evidence for selecting following regimens after first-line progression. There is still no strong evidence for the efficacy of targeted therapy as a preoperative treatment for resectable CLM or postoperative treatment for resected CLM, although the combined regimen is often administered based on experience. Combination therapy with more than one targeted agent has been proven to provide no benefit, and even was reported to be harmful as first-line treatment by four large clinical trials. However, recent studies reported positive results of erlotinib plus bevacizumab for maintenance treatment. The mechanism of antagonism between different targeted agents deserves further study, and may also provide greater understanding of the development of resistance to targeted agents.

Treatment strategy for colorectal cancer with resectable synchronous liver metastases:Is any evidence-based strategy possible?

Fifteen percent to twenty-five percent of patients affected by colorectal cancer presents with liver metastases at diagnosis. In resectable cases, surgery is the only potentially curative treatment and achieves survival rates up to 50% at 5 years. Management is complex, as colorectal resection, liver resection, chemotherapy, and, in locally advanced mid/low rectal tumors, radiotherapy have to be integrated. Modern medical practice usually relies on evidence-based protocols. Levels of evidence for synchronous metastases are poor:published studies include few recent prospective series and several retrospective analyses collecting a limited number of patients across long periods of time. Data are difficult to be generalized and are mainly representative of single centre's experience, biased by local recruitment, indications and surgical technique. In this context, surgeons have to renounce to "evidence-based medicine" and to adopt a sort of "experience-based medicine". Anyway, some suggestions are possible. Simultaneous colorectal and liver resection can be safely performed whenever minor hepatectomies are planned, while a case-by-case evaluation is mandatory in case of more complex procedures. Neoadjuvant chemotherapy is preferentially scheduled for patients with advanced metastatic tumors to assess disease biology and to control lesions. It can be safely performed with primarytumor in situ , even planning simultaneous resection at its end. Locally advanced mid/low rectal tumor represents a further indication to neoadjuvant therapies, even if treatment's schedule is not yet standardized. In summary, several issues have to be solved, but every single HPB centre should define its proper strategy to optimize patient's selection, disease control and safety and completeness of surgery.

Chemokine expression in hepatocellular carcinoma versus colorectal liver metastases

AIM： To evaluate and compare the expression profiles of CXCL12 （SDF-1）, CCL19 （MIP-3β）, CCL20 （MIP-3a） and CCL21 （6Ckine, Exodus2） and their receptors on RNA and protein levels in hepatocellular carcinoma （HCC） versus colorectal liver metastases （CRLM） and to elucidate their impact on the carcinogenesis and progression of malignant liver diseases. METHODS： Chemokine expression was analyzed by RT-PCR and ELISA in 11 cases of HCC specimens and in 23 cases of CRLM and corresponding adjacent nontumorous liver tissues, respectively. Expressions of their receptors CXCR4, CCR6 and CCR7 were analyzed by RT- PCR and Western blot analysis in the same cases of HCC and CRLM. RESULTS： Significant up-regulation for CCL20/CCR6 was detected in both cancer types. Moreover, CCL20 demonstrated significant overexpression in CRLM in relation to the HCC tissues. Being significantly up-regulated only in CRLM, CXCR4 displayed an aberrant expression pattern with respect to the HCC tissues. CONCLUSION： Correlation of CXCR4 expression with CRLM suggests CXCR4 as a potential predictive factor for CRLM. High level expression of CCL20 and its receptor CCR6 in HCC and CRLM with marked up-regulation of CCL20 in CRLM in relation to HCC tissues indicates involvement of the CCL20/CCR6 ligand-receptor pair in the carcinogenesis and progression of hepatic malignancies.

Mini-invasive vs open resection of colorectal cancer and liver metastases: A meta-analysis

BACKGROUND The safety and feasibility of the simultaneous resection of primary colorectal cancer (CRC) and synchronous colorectal liver metastases (SCRLM) have been demonstrated in some studies. Combined resection is expected to be the optimal strategy for patients with CRC and SCRLM. However, traditional laparotomy is traumatic, and the treatment outcome of minimally invasive surgery (MIS) is still obscure. AIM To compare the treatment outcomes of MIS and open surgery (OS) for the simultaneous resection of CRC and SCRLM. METHODS A systematic search through December 22, 2018 was conducted in electronic databases (PubMed, EMBASE, Web of Science, and Cochrane Library). All studies comparing the clinical outcomes of MIS and OS for patients with CRC and SCRLM were included by eligibility criteria. The meta-analysis was performed using Review Manager Software. The quality of the pooled study was assessed using the Newcastle-Ottawa scale. The publication bias was evaluated by a funnel plot and the Begg’s and Egger’s tests. Fixed- and random-effects models were applied according to heterogeneity. RESULTS Ten retrospective cohort studies involving 502 patients (216 patients in the MIS group and 286 patients in the OS group) were included in this study. MIS was associated with less intraoperative blood loss [weighted mean difference (WMD)=-130.09, 95% confidence interval (CI):-210.95 to -49.23, P = 0.002] and blood transfusion [odds ratio (OR)= 0.53, 95%CI: 0.29 to 0.95, P = 0.03], faster recovery of intestinal function (WMD =-0.88 d, 95%CI:-1.58 to -0.19, P = 0.01) and diet (WMD =-1.54 d, 95%CI:-2.30 to -0.78, P < 0.0001), shorter length of postoperative hospital stay (WMD =-4.06 d, 95%CI:-5.95 to -2.18, P < 0.0001), and lower rates of surgical complications (OR = 0.60, 95%CI: 0.37 to 0.99, P = 0.04). However, the operation time, rates and severity of overall complications, and rates of general complications showed no significant differences between the MIS and OS groups. Moreover, the overall survival and disease-free survival after MIS were equivalent to those after OS. CONCLUSION Considering the studies included in this meta-analysis, MIS is a safe and effective alternative technique for the simultaneous resection of CRC and SCRLM. Compared with OS, MIS has less intraoperative blood loss and blood transfusion and quicker postoperative recovery. Furthermore, the two groups show equivalent long-term outcomes.

Parenchymal-sparing liver surgery in patients with colorectal carcinoma liver metastases

Liver resection is the treatment of choice for patients with colorectal liver metastases(CLM).However,major resections are often required to achieve R0 resection,which are associated with substantial rates of morbidity and mortality.Maximizing the amount of residual liver gained increasing significance in modern liver surgery due to the high incidence of chemotherapyassociated parenchymal injury.This fact,along with the progressive expansion of resectability criteria,has led to the development of a surgical philosophy known as "parenchymal-sparing liver surgery"(PSLS).This philosophy includes a variety of resection strategies,either performed alone or in combination with ablative therapies.A profound knowledge of liver anatomy and expert intraoperative ultrasound skills are required to perform PSLS appropriately and safely.There is a clear trend toward PSLS in hepatobiliary centers worldwide as current evidence indicates that tumor biology is the most important predictor of intrahepatic recurrence and survival,rather than the extent of a negative resection margin.Tumor removal avoiding the unnecessary sacrifice of functional parenchyma has been associated with less surgical stress,fewer postoperative complications,uncompromised cancer-related outcomes and higher feasibility of future resections.The increasing evidence supporting PSLS prompts its consideration as the gold-standard surgical approach for CLM.

Current state of surgical treatment of liver metastases from colorectal cancer

Hepatic resection is the procedure of choice for curative treatment of colorectal liver metastases(CLM).Objectives of surgical strategy are low intraoperative blood loss,short liver ischemic times and minor postoperative morbidity and mortality.Blood loss is an independent predictor of mortality and compromises,in common with postoperative complications,long-term outcome after hepatectomy for CLM.The type of liver resection has no impact on the outcome of patients with CLM;wedge resections are not inferior to anatomical resections in terms of tumor clearance,pattern of recurrence or survival.Despite the lack of proof of survival benef it,routine lymphadenectomy has been advocated,allowing the detection of microscopic lymph node metastases and with prognostic value.In experienced hands,minimally invasive liver surgery is safe with acceptable morbidity and mortality and oncological results comparable to open hepatic surgery,but with reduced blood loss and earlier recovery.The European Colorectal Metastases Treatment Group recommended treating up front with chemotherapy for patients with both resectable and unresectable CLM.However,neoadjuvant chemotherapy can induce damage to the remnant liver,dependent on the number of chemotherapy cycles.Therefore,in our opinion,preoperative chemotherapy should be reserved for patients whose CLM are marginally resectable or unresectable.A meta analysis of randomized trials dealing with perioperative chemotherapy for the treatment of resectable CLM demonstrated a benefit of systemic chemotherapy but did not answer the question of whether a neoadjuvant or adjuvant approach should be preferred.Analysis of the literature demonstrates that the results of specialized centers cannot be attained in the reality of comprehensive patient care.Reasons behind the commonly poorer results seen in cancer networks as compared with literature-based data are,on the one hand,geographical disparities in access to specialized surgical and medical care.On the other hand,a selection bias in the reports of the literature may be assumed.Studies of surgical resection for CLM derive almost exclusively from case series generally drawn from large academic centers where patient selection or surgical expertise is superior to what is found in many communities.Therefore,we may conclude that the comprehensive propagation of the standards outlined in this paper constitutes a major task in the near future to reduce the variations in survival of patients with CLM.

Pathologic response after preoperative therapy predicts prognosis of Chinese colorectal cancer patients with liver metastases

Background: Pathologic response is evaluated according to the extent of tumor regression and is used to estimate the efficacy of preoperative treatment. Several studies have reported the association between the pathologic response and clinical outcomes of colorecal cancer patients with liver metastases who underwent hepatectomy.However, to date, no data from Chinese patients have been reported. In this study, we aimed to evaluate the association between the pathologic response to pre-hepatectomy chemotherapy and prognosis in a cohort of Chinese patients.Patients and methods: In this retrospective study, we analyzed the data of 380 liver metastases in 159 patients.The pathologic response was evaluated according to the tumor regression grade(TRG).The prognostic role of pathologic response in recurrence-free survival(RFS) and overall survival(OS) was assessed using Kaplan-Meier curves with the log-rank test and multivariate Cox models. Factors that had potential influence on pathologic response were also analyzed using multivariate logistic regression and Kruskal-Wallis/Mann-Whitney U tests.Results: Patients whose tumors achieved pathologic response after preoperative chemotherapy had significant longer RFS and OS than patients whose tumor had no pathologic response to chemotherapy(median RFS: 9.9 vs.6.5 months, P = 0.009; median OS: 40.7 vs. 28.1 months, P = 0.040). Multivariate logistic regression and Kruskal-Wallis/Mann-Whitney U tests showed that metastases with small diameter, metastases from the left-side primary tumors,and metastases from patients receiving long-duration chemotherapy had higher pathologic response rates than their control metastases(all P < 0.05). A decrease in the serum carcinoembryonic antigen(CEA) level after preoperative chemotherapy predicted an increased pathologic response rate(P < 0.05). Although the application of targeted therapy did not significantly influence TRG scores of all cases of metastases, the addition of cetuximab to chemotherapy resulted in a higher pathologic response rate when combined with irinotecan-based regimens rather than with oxaliplatin-based regimens.Conclusions: We found that the evaluation of pathologic response may predict the prognosis of Chinese colorectal cancer patients with liver metastases after preoperative chemotherapy. Small tumor diameter, long-duration chemotherapy, left primary tumor, and decreased serum CEA level after chemotherapy are associated with increased pathologic response rates.

Simultaneous hepatic resection benefits patients with synchronous colorectal cancer liver metastases

Objective： The safety of the simultaneous resection of synchronous colorectal cancer liver metastases （SCRLM） is still being debated. However, this simultaneous operative approach is more commonly adopted at present than in the past. Therefore, we compared simultaneous hepatic resection with delayed hepatic resection in this study.Methods： All patients with SCRLM diagnosed before initial treatment between January 2009 and September 2013 were retrospectively included in our study. Short-term and long-term outcomes were compared in patients who underwent simultaneous colorectal and hepatic resection and those treated by delayed hepatectomy.Results： Among the 73 patients diagnosed with SCRLM, simultaneous coloreetal and hepatic resection was performed in 60 patients （82.2%）, while delayed hepatic resection was performed in 13 patients （17.8%）. The mortality rate was zero. The postoperative complication rate after delayed resection was higher than, but not significantly different from, that after simultaneous resection （46% vs. 23%, P=0.166）. The duration of operating time （240 vs. 420 min, P〈0.05） and postoperative hospital stay time （11 vs. 18 days, P〈0.05） were shorter in the simultaneous resection group. After the initial treatments were given, the 1-, 2-, and 3-year survival rates in the simultaneous resection group were 77%, 59%, and 53%, respectively, whereas those in the delayed resection group were 67%, 42%, and 10%, respectively. The 5-year survival rate in the simultaneous resection group was 23%; overall survival differed significantly between the two groups （P=0.037）. Median disease-free survival （DFS） times were 19.1 months in the simultaneous resection group and 8.8 months in the delayed resection group. DFS differed significantly between the two groups. Coenclusions： Simultaneous colorectal and hepatic resection is safe and exhibits advantages in the longtime survival of patients.

Management of potentially resectable colorectal cancer liver metastases

Colorectal cancer is a very common malignancy worldwide and development of liver metastases,both synchronous or metachronous,is a common event.Of all patients with metastatic colorectal cancer,up to 77% have a liver-only disease and approximately 10%-20% of patients with colorectal liver metastases are considered resectable at the time of diagnosis.Surgical resection of liver metastases remains the best treatment option and it is associated with a survival plateau and a 20%-25% of long-term survivors.Perioperative chemotherapy for resectable liver metastases may improve resecability of liver metastases and disease free survival,but its impact on overall survival is still unclear and more studies are needed.Moreover,preoperative chemotherapy can increase postoperative complications.Further studies are needed to define the role of adjuvant chemotherapy after a R0 resection of liver metastases and to define the criteria for a better selection of patients candidate to hepatectomy.New strategies such as targeted therapies are emerging with promising results.Optimal management requires a multidisciplinary approach,local and systemic,but it is a still pending question.Colorectal liver metastases represent a major challenge for oncologists and surgeons.In this review will be analyzed available data about assessment and management of the patients with potentially resectable colorectal liver metastases.

Role of surgery in colorectal liver metastases:Too early or too late?

As colorectal cancer and colorectal liver metastases become a serious public health problem,new treatment modalities are needed in order to achieve better results. In the last decade there has been very important progress in oncology,with new and more effective chemotherapeutic agents administered alone or in combination improving the resectability rate in up to 40%of patients with colorectal liver metastases.Advances in interventional radiology,in particular,with the use of portal vein embolization and radiofrequency thermal ablation are new strategies allowing major liver resections and treatment of small liver metastases or early recurrences.Surgery,however,remains the gold standard strategy with intention to treat.In this review article we will describe the advanced role of surgery in the multidisciplinary approach to colorectal liver metastases,and the clinical problems the liver surgeon has to deal with,such as theresectability of the metastases,the presence of bilobar liver lesions and extrahepatic disease,the impact of chemotherapy in already resectable liver metastases,the problem of vanishing metastases after chemotherapy and the dilemma of staged or combined liver and colon operations and which organ first in the clinical scenario of synchronous colorectal liver metastases.

Preoperative administration of bevacizumab is safe for patients with colorectal liver metastases

AIM:To assess the impact of preoperative neoadjuvant bevacizumab(Bev)on the outcome of patients undergoing resection for colorectal liver metastases(CLM). METHODS:Eligible trials were identified from Medline, Embase,Ovid,and the Cochrane database.The data were analyzed with fixed-effects or random-effects models using Review Manager version 5.0. RESULTS:Thirteen nonrandomized studies with a total of 1431 participants were suitable for meta-analysis. There was no difference in overall morbidity and severe complications between the Bev+group and Bev-group (43.3%vs 36.8%,P=0.06;17.1%vs 11.4%,P=0.07,respectively).Bev-related complications including wound and thromboembolic/bleeding events were also similar in the Bev+and Bev-groups(14.4%vs 8.1%, P=0.21;4.1%vs 3.8%,P=0.98,respectively).The incidence and severity of sinusoidal dilation were lower in patients treated with Bev than in patients treated without Bev(43.3%vs 63.7%,P<0.001;16.8%vs 46.5%,P<0.00,respectively). CONCLUSION:Bev can be safely administered before hepatic resection in patients with CLM,and has a protective effect against hepatic injury in patients treated with oxaliplatin chemotherapy.