BACKGROUND Liver metastases(LM)is the primary factor contributing to unfavorable outcomes in patients diagnosed with gastric cancer(GC).The objective of this study is to analyze significant prognostic risk factors for...BACKGROUND Liver metastases(LM)is the primary factor contributing to unfavorable outcomes in patients diagnosed with gastric cancer(GC).The objective of this study is to analyze significant prognostic risk factors for patients with GCLM and develop a reliable nomogram model that can accurately predict individualized prognosis,thereby enhancing the ability to evaluate patient outcomes.AIM To analyze prognostic risk factors for GCLM and develop a reliable nomogram model to accurately predict individualized prognosis,thereby enhancing patient outcome assessment.METHODS Retrospective analysis was conducted on clinical data pertaining to GCLM(type III),admitted to the Department of General Surgery across multiple centers of the Chinese PLA General Hospital from January 2010 to January 2018.The dataset was divided into a development cohort and validation cohort in a ratio of 2:1.In the development cohort,we utilized univariate and multivariate Cox regression analyses to identify independent risk factors associated with overall survival in GCLM patients.Subsequently,we established a prediction model based on these findings and evaluated its performance using receiver operator characteristic curve analysis,calibration curves,and clinical decision curves.A nomogram was created to visually represent the prediction model,which was then externally validated using the validation cohort.RESULTS A total of 372 patients were included in this study,comprising 248 individuals in the development cohort and 124 individuals in the validation cohort.Based on Cox analysis results,our final prediction model incorporated five independent risk factors including albumin levels,primary tumor size,presence of extrahepatic metastases,surgical treatment status,and chemotherapy administration.The 1-,3-,and 5-years Area Under the Curve values in the development cohort are 0.753,0.859,and 0.909,respectively;whereas in the validation cohort,they are observed to be 0.772,0.848,and 0.923.Furthermore,the calibration curves demonstrated excellent consistency between observed values and actual values.Finally,the decision curve analysis curve indicated substantial net clinical benefit.CONCLUSION Our study identified significant prognostic risk factors for GCLM and developed a reliable nomogram model,demonstrating promising predictive accuracy and potential clinical benefit in evaluating patient outcomes.展开更多
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 recomm...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.展开更多
This letter to the editor is a commentary on a study titled"Liver metastases:The role of magnetic resonance imaging."Exploring a noninvasive imaging evaluation system for the biological behavior of hepatocel...This letter to the editor is a commentary on a study titled"Liver metastases:The role of magnetic resonance imaging."Exploring a noninvasive imaging evaluation system for the biological behavior of hepatocellular carcinoma(HCC)is the key to achieving precise diagnosis and treatment and improving prognosis.This review summarizes the role of magnetic resonance imaging in the detection and evaluation of liver metastases,describes its main imaging features,and focuses on the added value of the latest imaging tools(such as T1 weighted in phase imaging,T1 weighted out of phase imaging;diffusion-weighted imaging,T2 weighted imaging).In this study,I investigated the necessity and benefits of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid for HCC diagnostic testing and prognostic evaluation.展开更多
Background:Liver transplantation(LT)for neuroendocrine liver metastases(NELM)is still in debate.Studies comparing LT with liver resection(LR)for NELM are scarce,as patient selection is heterogeneous and experience is ...Background:Liver transplantation(LT)for neuroendocrine liver metastases(NELM)is still in debate.Studies comparing LT with liver resection(LR)for NELM are scarce,as patient selection is heterogeneous and experience is limited.The goal of this review was to provide a critical analysis of the evidence on LT versus LR in the treatment of NELM.Data sources:A scoping literature search on LT and LR for NELM was performed with PubMed,including English articles up to March 2023.Results:International guidelines recommend LR for NELM in resectable,well-differentiated tumors in the absence of extrahepatic metastatic disease with superior results of LR compared to systemic or liver-directed therapies.Advanced liver surgery has extended resectability criteria whilst entailing increased perioperative risk and short disease-free survival.In highly selected patients(based on the Milan criteria)with unresectable NELM,oncologic results of LT are promising.Prognostic factors include tumor biology(G1/G2)and burden,waiting time for LT,patient age and extrahepatic spread.Based on low-level evi-dence,LT for low-grade NELM within the Milan criteria resulted in improved disease-free survival and overall survival compared to LR.The benefits of LT were lost in patients beyond the Milan NELM-criteria.Conclusions:With adherence to strict selection criteria especially tumor biology,LT for NELM is becoming a valuable option providing oncologic benefits compared to LR.Recent evidence suggests even stricter selection criteria with regard to tumor biology.展开更多
AIM: To investigate the effect of surgery and chemotherapy for gastric cancer with multiple synchronous liver metastases (GCLM). METHODS: A total of 114 patients were entered in this study, and 20 patients with multip...AIM: To investigate the effect of surgery and chemotherapy for gastric cancer with multiple synchronous liver metastases (GCLM). METHODS: A total of 114 patients were entered in this study, and 20 patients with multiple synchronous liver metastases were eligible. After screening with preoperative chemotherapy, 20 patients underwent curative gastrectomy and hepatectomy for GCLM; 14 underwent major hepatectomy, and the remaining six underwent minor hepatectomy. There were 94 patients without aggressive treatment, and they were in the non-operative group. Two regimens of perioperative chemotherapy were used: S-1 and cisplatin (SP) in 12 patients, and docetaxel, cisplatin and 5-fluorouracil (DCF) in eight patients. These GCLM patients were given preoperative chemotherapy consisting of two courses chemotherapy of SP or DCF regimens. After chemotherapy, gastrectomy and hepatectomy were preformed. Evaluation of patient survival was by follow-up contact using telephone and outpatient records. All patients were assessed every 3 mo during the first year and every 6 mo thereafter. RESULTS: Twenty patients underwent gastrectomy and hepatectomy and completed their perioperative chemotherapy and hepatic arterial infusion before and after surgery. Ninety-four patients had no aggressive treatment of liver metastases because of technical difficulties with resection and severe cardiopulmonary dysfunction. In the surgery group, there was no toxicity greater than grade 3 during the course of chemotherapy. The response rate was 100% according to the Response Evaluation Criteria in Solid Tumors Criteria. For all 114 patients, the overall survival rate was 8.0%, 4.0%, 4.0% and 4.0% at 1, 2, 3 and 4 years, respectively, with a median survival time (MST) of 8.5 mo (range: 0.5-48 mo). For the 20 patients in the surgery group, MST was 22.3 mo (range: 4-48 mo). In the 94 patients without aggressive treatment, MST was 5.5 mo (range: 0.5-21 mo). There was a significant difference between the surgery and unresectable patients (P = 0.000). Three patients in surgery group were still alive at the end of the cut-off date. CONCLUSION: Perioperative weekly DCF and SP achieved a good response, and combined with surgery, they could improve prognosis of GCLM.展开更多
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 optima...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.展开更多
Objective: To retrospectively investigate the role of contrast-enhanced ultrasonography (CEUS) in percutaneous radiofrequency ablation (RFA) in patients with liver metastases and evaluate the therapeutic efficacy...Objective: To retrospectively investigate the role of contrast-enhanced ultrasonography (CEUS) in percutaneous radiofrequency ablation (RFA) in patients with liver metastases and evaluate the therapeutic efficacy of RFA assisted by CEUS. Methods: From May 2004 to September 2010, 136 patients with 219 liver metastatic lesions received CEUS examination 1 h before RFA (CEUS group), and other 126 patients with 216 lesions without CEUS examination in the earlier period were served as a historical control group. The mean tumor size was 3.2 cm and the mean tumor number was 1.6 in the CEUS group, while 3.4 cm and 1.7 in the control group, respectively (P〉0.05). The clinical characteristics, recurrence results and survival outcomes were compared between two groups. Results: In the CEUS group, two isoechoic tumors were not demonstrated on unenhanced ultrasonography (US), and 63 (47%) of 134 tumors examined with CEUS were 0.3 cm larger than with unenhanced US. Furthermore, in 18.4% of 136 patients, additional 1-3 tumors were detected on CEUS. The CEUS group showed higher early tumor necrosis and lower intrahepatic recurrence than the control group. The 3-year overall survival (OS) rate and the 3-year local recurrence-free survival (LRFS) rate in the CEUS group were 50.1% and 38.3%, in contrast to 25.3% and 19.3% in the control group, respectively (P=0.002 and P〈0.001). Conclusions: CEUS provides important information for RFA treatment in patients with liver metastases and better therapeutic effect could be attained.展开更多
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 patie...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.展开更多
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 C...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.展开更多
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 de...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, “new” 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.展开更多
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 surviv...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.展开更多
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.Tu...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.展开更多
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 &a...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 > 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.展开更多
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 morbidit...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.展开更多
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 postoperat...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.展开更多
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 ...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.展开更多
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 pathol...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.展开更多
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 prog...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.展开更多
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 presen...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.展开更多
BACKGROUND In clinical practice,the diagnosis is sometimes difficult with contrast-enhanced ultrasound(CEUS)when the case has an atypical perfusion pattern.Color parametric imaging(CPI)is an analysis software for CEUS...BACKGROUND In clinical practice,the diagnosis is sometimes difficult with contrast-enhanced ultrasound(CEUS)when the case has an atypical perfusion pattern.Color parametric imaging(CPI)is an analysis software for CEUS with better detection of temporal differences in CEUS imaging using arbitrary colors.It measures the differences in arrival time of the contrast agent in lesions so that the perfusion features of atypical hemangioma and colorectal cancer(CRC)liver metastasis can be distinguished.AIM To evaluate the role of a novel type of CPI of CEUS in the differential diagnosis of atypical hemangioma from liver metastases in patients with a history of CRC.METHODS From January 2016 to July 2018,42 patients including 20 cases of atypical hemangioma and 22 cases of liver metastases from CRC were enrolled.These patients had a mean age of 60.5±9.3 years(range:39-75 years).All patients received ultrasound,CEUS and CPI examinations.Resident and staff radiologists independently and retrospectively reviewed CEUS and CPI images.Two sets of criteria were assigned:(1)Routine CEUS alone;and(2)CEUS and CPI.The diagnostic sensitivity,specificity,accuracy and receiver operating characteristic(ROC)curve of resident and staff radiologists were analyzed.RESULTS The following CPI features were significantly different between liver hemangioma and liver metastases analyzed by staff and resident radiologists:Peripheral nodular enhancement(65%-70.0%vs 4.5%-13.6%,P<0.001,P=0.001),mosaic/chaotic enhancement(5%-10%vs 68.2%-63.6%,P<0.001,P<0.001)and feeding artery(20%vs 59.1%-54.5%,P=0.010,P=0.021).CPI imaging offered significant improvements in detection rates compared with routine CEUS in both resident and staff groups.By resident radiologists,the specificity and accuracy of CEUS+CPI were significantly increased compared with that of CEUS(77.3%vs 45.5%,P=0.030;78.6%vs 50.0%,P=0.006).In addition,the area under the curve(AUC)of CEUS+CPI was significantly higher than that of CEUS(0.803 vs 0.757,P=0.036).By staff radiologists,accuracy was improved in CEUS+CPI(81.0%vs 54.8%,P=0.010),whereas no significant differences in specificity and sensitivity were found(P=0.144,P=0.112).The AUC of CEUS+CPI was significantly higher than that of CEUS(0.890 vs 0.825,P=0.013)by staff radiologists.CONCLUSION Compared with routine CEUS,CPI could provide specific information on the hemodynamic features of liver lesions and help to differentiate atypical hemangioma from liver metastases in patients with CRC,even for senior radiologists.展开更多
文摘BACKGROUND Liver metastases(LM)is the primary factor contributing to unfavorable outcomes in patients diagnosed with gastric cancer(GC).The objective of this study is to analyze significant prognostic risk factors for patients with GCLM and develop a reliable nomogram model that can accurately predict individualized prognosis,thereby enhancing the ability to evaluate patient outcomes.AIM To analyze prognostic risk factors for GCLM and develop a reliable nomogram model to accurately predict individualized prognosis,thereby enhancing patient outcome assessment.METHODS Retrospective analysis was conducted on clinical data pertaining to GCLM(type III),admitted to the Department of General Surgery across multiple centers of the Chinese PLA General Hospital from January 2010 to January 2018.The dataset was divided into a development cohort and validation cohort in a ratio of 2:1.In the development cohort,we utilized univariate and multivariate Cox regression analyses to identify independent risk factors associated with overall survival in GCLM patients.Subsequently,we established a prediction model based on these findings and evaluated its performance using receiver operator characteristic curve analysis,calibration curves,and clinical decision curves.A nomogram was created to visually represent the prediction model,which was then externally validated using the validation cohort.RESULTS A total of 372 patients were included in this study,comprising 248 individuals in the development cohort and 124 individuals in the validation cohort.Based on Cox analysis results,our final prediction model incorporated five independent risk factors including albumin levels,primary tumor size,presence of extrahepatic metastases,surgical treatment status,and chemotherapy administration.The 1-,3-,and 5-years Area Under the Curve values in the development cohort are 0.753,0.859,and 0.909,respectively;whereas in the validation cohort,they are observed to be 0.772,0.848,and 0.923.Furthermore,the calibration curves demonstrated excellent consistency between observed values and actual values.Finally,the decision curve analysis curve indicated substantial net clinical benefit.CONCLUSION Our study identified significant prognostic risk factors for GCLM and developed a reliable nomogram model,demonstrating promising predictive accuracy and potential clinical benefit in evaluating patient outcomes.
基金National Natural Science Foundation of China,No.82170618.
文摘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.
基金Chongqing Natural Science Foundation General Project,No.2023NSCQ-MSX1632 and No.2023NSCQ-MSX1633Key Scientific and Technological Research Project of Chongqing Municipal Education Commission,No.KJ202302884457913 and No.KJZDK202302801+1 种基金2022 Scientific Research Project of Chongqing Medical and Pharmaceutical College,No.ygz2022104Scientific Research and Seedling Breeding Project of Chongqing Medical Biotechnology Association,No.cmba2022kyym-zkxmQ0003.
文摘This letter to the editor is a commentary on a study titled"Liver metastases:The role of magnetic resonance imaging."Exploring a noninvasive imaging evaluation system for the biological behavior of hepatocellular carcinoma(HCC)is the key to achieving precise diagnosis and treatment and improving prognosis.This review summarizes the role of magnetic resonance imaging in the detection and evaluation of liver metastases,describes its main imaging features,and focuses on the added value of the latest imaging tools(such as T1 weighted in phase imaging,T1 weighted out of phase imaging;diffusion-weighted imaging,T2 weighted imaging).In this study,I investigated the necessity and benefits of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid for HCC diagnostic testing and prognostic evaluation.
文摘Background:Liver transplantation(LT)for neuroendocrine liver metastases(NELM)is still in debate.Studies comparing LT with liver resection(LR)for NELM are scarce,as patient selection is heterogeneous and experience is limited.The goal of this review was to provide a critical analysis of the evidence on LT versus LR in the treatment of NELM.Data sources:A scoping literature search on LT and LR for NELM was performed with PubMed,including English articles up to March 2023.Results:International guidelines recommend LR for NELM in resectable,well-differentiated tumors in the absence of extrahepatic metastatic disease with superior results of LR compared to systemic or liver-directed therapies.Advanced liver surgery has extended resectability criteria whilst entailing increased perioperative risk and short disease-free survival.In highly selected patients(based on the Milan criteria)with unresectable NELM,oncologic results of LT are promising.Prognostic factors include tumor biology(G1/G2)and burden,waiting time for LT,patient age and extrahepatic spread.Based on low-level evi-dence,LT for low-grade NELM within the Milan criteria resulted in improved disease-free survival and overall survival compared to LR.The benefits of LT were lost in patients beyond the Milan NELM-criteria.Conclusions:With adherence to strict selection criteria especially tumor biology,LT for NELM is becoming a valuable option providing oncologic benefits compared to LR.Recent evidence suggests even stricter selection criteria with regard to tumor biology.
文摘AIM: To investigate the effect of surgery and chemotherapy for gastric cancer with multiple synchronous liver metastases (GCLM). METHODS: A total of 114 patients were entered in this study, and 20 patients with multiple synchronous liver metastases were eligible. After screening with preoperative chemotherapy, 20 patients underwent curative gastrectomy and hepatectomy for GCLM; 14 underwent major hepatectomy, and the remaining six underwent minor hepatectomy. There were 94 patients without aggressive treatment, and they were in the non-operative group. Two regimens of perioperative chemotherapy were used: S-1 and cisplatin (SP) in 12 patients, and docetaxel, cisplatin and 5-fluorouracil (DCF) in eight patients. These GCLM patients were given preoperative chemotherapy consisting of two courses chemotherapy of SP or DCF regimens. After chemotherapy, gastrectomy and hepatectomy were preformed. Evaluation of patient survival was by follow-up contact using telephone and outpatient records. All patients were assessed every 3 mo during the first year and every 6 mo thereafter. RESULTS: Twenty patients underwent gastrectomy and hepatectomy and completed their perioperative chemotherapy and hepatic arterial infusion before and after surgery. Ninety-four patients had no aggressive treatment of liver metastases because of technical difficulties with resection and severe cardiopulmonary dysfunction. In the surgery group, there was no toxicity greater than grade 3 during the course of chemotherapy. The response rate was 100% according to the Response Evaluation Criteria in Solid Tumors Criteria. For all 114 patients, the overall survival rate was 8.0%, 4.0%, 4.0% and 4.0% at 1, 2, 3 and 4 years, respectively, with a median survival time (MST) of 8.5 mo (range: 0.5-48 mo). For the 20 patients in the surgery group, MST was 22.3 mo (range: 4-48 mo). In the 94 patients without aggressive treatment, MST was 5.5 mo (range: 0.5-21 mo). There was a significant difference between the surgery and unresectable patients (P = 0.000). Three patients in surgery group were still alive at the end of the cut-off date. CONCLUSION: Perioperative weekly DCF and SP achieved a good response, and combined with surgery, they could improve prognosis of GCLM.
文摘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.
基金supported by Chinese National High Technology Research and Development Program 863 (No.2009AA02Z4B8)Project of the Capital Public Health Cultivation (No. Z11110706730000)
文摘Objective: To retrospectively investigate the role of contrast-enhanced ultrasonography (CEUS) in percutaneous radiofrequency ablation (RFA) in patients with liver metastases and evaluate the therapeutic efficacy of RFA assisted by CEUS. Methods: From May 2004 to September 2010, 136 patients with 219 liver metastatic lesions received CEUS examination 1 h before RFA (CEUS group), and other 126 patients with 216 lesions without CEUS examination in the earlier period were served as a historical control group. The mean tumor size was 3.2 cm and the mean tumor number was 1.6 in the CEUS group, while 3.4 cm and 1.7 in the control group, respectively (P〉0.05). The clinical characteristics, recurrence results and survival outcomes were compared between two groups. Results: In the CEUS group, two isoechoic tumors were not demonstrated on unenhanced ultrasonography (US), and 63 (47%) of 134 tumors examined with CEUS were 0.3 cm larger than with unenhanced US. Furthermore, in 18.4% of 136 patients, additional 1-3 tumors were detected on CEUS. The CEUS group showed higher early tumor necrosis and lower intrahepatic recurrence than the control group. The 3-year overall survival (OS) rate and the 3-year local recurrence-free survival (LRFS) rate in the CEUS group were 50.1% and 38.3%, in contrast to 25.3% and 19.3% in the control group, respectively (P=0.002 and P〈0.001). Conclusions: CEUS provides important information for RFA treatment in patients with liver metastases and better therapeutic effect could be attained.
文摘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.
文摘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.
文摘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, “new” 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.
文摘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.
文摘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.
基金Supported by the National Institute for Health Research(NIHR)Biomedical Research Centre(BRC)at the Royal Marsden NHS Foundation Trust and Institute of Cancer Research and the Robert McAlpine Charity(partly,for Khurum Khan)
文摘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 > 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.
文摘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.
文摘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.
基金the National Natural Science Foundation of China,No.81660487
文摘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.
文摘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.
文摘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.
基金supported by the National High-Tech R&D Program (863 Program) of China (2015AA020408)the National Natural Science Foundation of China (81201967, 31470073)+2 种基金the Beijing Natural Science Foundation (7132193, 7144238)the Capital Health Research and Development of Special (2014-1-4022)Beijing Nova Program (No.2009A69)
文摘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.
基金Supported by Capital Medical Development Program,No.2018-2-2154National Natural Science Foundation of China,No.81773286
文摘BACKGROUND In clinical practice,the diagnosis is sometimes difficult with contrast-enhanced ultrasound(CEUS)when the case has an atypical perfusion pattern.Color parametric imaging(CPI)is an analysis software for CEUS with better detection of temporal differences in CEUS imaging using arbitrary colors.It measures the differences in arrival time of the contrast agent in lesions so that the perfusion features of atypical hemangioma and colorectal cancer(CRC)liver metastasis can be distinguished.AIM To evaluate the role of a novel type of CPI of CEUS in the differential diagnosis of atypical hemangioma from liver metastases in patients with a history of CRC.METHODS From January 2016 to July 2018,42 patients including 20 cases of atypical hemangioma and 22 cases of liver metastases from CRC were enrolled.These patients had a mean age of 60.5±9.3 years(range:39-75 years).All patients received ultrasound,CEUS and CPI examinations.Resident and staff radiologists independently and retrospectively reviewed CEUS and CPI images.Two sets of criteria were assigned:(1)Routine CEUS alone;and(2)CEUS and CPI.The diagnostic sensitivity,specificity,accuracy and receiver operating characteristic(ROC)curve of resident and staff radiologists were analyzed.RESULTS The following CPI features were significantly different between liver hemangioma and liver metastases analyzed by staff and resident radiologists:Peripheral nodular enhancement(65%-70.0%vs 4.5%-13.6%,P<0.001,P=0.001),mosaic/chaotic enhancement(5%-10%vs 68.2%-63.6%,P<0.001,P<0.001)and feeding artery(20%vs 59.1%-54.5%,P=0.010,P=0.021).CPI imaging offered significant improvements in detection rates compared with routine CEUS in both resident and staff groups.By resident radiologists,the specificity and accuracy of CEUS+CPI were significantly increased compared with that of CEUS(77.3%vs 45.5%,P=0.030;78.6%vs 50.0%,P=0.006).In addition,the area under the curve(AUC)of CEUS+CPI was significantly higher than that of CEUS(0.803 vs 0.757,P=0.036).By staff radiologists,accuracy was improved in CEUS+CPI(81.0%vs 54.8%,P=0.010),whereas no significant differences in specificity and sensitivity were found(P=0.144,P=0.112).The AUC of CEUS+CPI was significantly higher than that of CEUS(0.890 vs 0.825,P=0.013)by staff radiologists.CONCLUSION Compared with routine CEUS,CPI could provide specific information on the hemodynamic features of liver lesions and help to differentiate atypical hemangioma from liver metastases in patients with CRC,even for senior radiologists.