Colorectal cancer liver metastasis(CRLM)presents a clinical challenge,and optimizing treatment strategies is crucial for improving patient outcomes.Surgical resection,a key element in achieving prolonged survival,is o...Colorectal cancer liver metastasis(CRLM)presents a clinical challenge,and optimizing treatment strategies is crucial for improving patient outcomes.Surgical resection,a key element in achieving prolonged survival,is often linked to a heightened risk of recurrence.Acknowledging the potential benefits of preoperative neoadjuvant chemotherapy in managing resectable liver metastases,this approach has gained attention for its role in tumor downsizing,assessing biological behavior,and reducing the risk of postoperative recurrence.However,the use of neoadjuvant chemotherapy in initially resectable CRLM sparks ongoing debates.The balance between tumor reduction and the risk of hepatic injury,coupled with concerns about delaying surgery,necessitates a nuanced approach.This article explores recent research insights and draws upon the practical experiences at our center to address critical issues regarding considerations for initially resectable cases.Examining the criteria for patient selection and the judicious choice of neoadjuvant regimens are pivotal areas of discussion.Striking the right balance between maximizing treatment efficacy and minimizing adverse effects is imperative.The dynamic landscape of precision medicine is also reflected in the evolving role of gene testing,such as RAS/BRAF and PIK3CA,in tailoring neoadjuvant regimens.Furthermore,the review emphasizes the need for a multidisciplinary approach to navigate the comp-lexities of CRLM.Integrating technical expertise and biological insights is crucial in refining neoadjuvant strategies.The management of progression following neoadjuvant chemotherapy requires a tailored approach,acknowledging the diverse biological behaviors that may emerge.In conclusion,this review aims to provide a comprehensive perspective on the considerations,challenges,and advancements in the use of neoadjuvant chemotherapy for initially resectable CRLM.By combining evidencebased insights with practical experiences,we aspire to contribute to the ongoing discourse on refining treatment paradigms for improved outcomes in patients with CRLM.展开更多
BACKGROUND Colorectal cancer(CRC)is the third most prevalent form of cancer worldwide.Among patients with CRC,colorectal liver metastasis(CRLM)is the foremost direct contributor to mortality.In recent years,immunother...BACKGROUND Colorectal cancer(CRC)is the third most prevalent form of cancer worldwide.Among patients with CRC,colorectal liver metastasis(CRLM)is the foremost direct contributor to mortality.In recent years,immunotherapy has swiftly risen to prominence as a vital approach for treating a range of solid tumors,including CRC.We present a unique case of a patient suffering from CRLM,with the goal of offering an insightful example and relevant references for the treatment of CRLM.CASE SUMMARY We report a patient who experienced liver metastasis after undergoing successful surgical removal of CRC,with the postoperative pathological stage identified as pT4N2aM0.The patient has been receiving a combination treatment of Western and Traditional Chinese Medicine.Regular assessments of the patient’s condition have been conducted,encompassing evaluations of serum carcinoembryonic antigen levels,carbohydrate antigen 199,and observations of the tongue complexion and its coating.The patient achieved clinical remission after anti-programmed death-1 immunotherapy when various systemic therapies failed.Since the diagnosis of CRLM,the patient has survived for more than 6 years,surpassing the expected survival time for those with advanced CRC.CONCLUSION This case illustrates the considerable promise of anti-programmed death-1 immunotherapy in managing CRLM,especially in scenarios of drug resistance and disease progression.展开更多
AIM： To investigate the angiogenesis-related protein expression profile characterizing metastatic colorectal cancer （mCRC） with the aim of identifying prognostic markers.METHODS： The expression of 44 angiogenesis-...AIM： To investigate the angiogenesis-related protein expression profile characterizing metastatic colorectal cancer （mCRC） with the aim of identifying prognostic markers.METHODS： The expression of 44 angiogenesis- secreted factors was measured by a novel cytokine antibody array methodology. The study evaluated vas- cular endothelial growth factor （VEGF） and its soluble vascular endothelial growth factor receptor （sVEGFR）-I protein levels by enzyme immunoassay （EIA） in a panel of 16 CRC cell lines, mRNA VEGF and VEGF-A isoforms were quantified by quantitative reverse-transcription polymerase chain reaction （Q-RT-PCR） and vascular en- dothelial growth factor receptor （VEGFR）-2 expressionwas analyzed by flow cytometry.展开更多
AIM： To create a new, simple and useful staging system for colorectal liver metastasis analogous to the Tumor Node Metastasis classification system of International Union Against Cancer. METHODS： A retrospective rev...AIM： To create a new, simple and useful staging system for colorectal liver metastasis analogous to the Tumor Node Metastasis classification system of International Union Against Cancer. METHODS： A retrospective review was undertaken of 81 consecutive patients who underwent partial hepatectomy for colorectal liver metastases （group 1）. Clinical and pathological features of both primary and metastatic liver cancers were entered into a multivariate analysis to determine independent variables helpful in accurately predicting long-term prognosis after hepatectomy. Using selected variables, we created a new staging system like TNM classification. The usefulness of the new staging system was examined in a series of 92 patients from another hospital （group 2）. RESULTS： Multivariate analysis showed that 81 patients in group 1 had significant multiple hepatic tumors with the largest tumor being more than 5 cm in diameter, resectable extrahepatic distant metastases, and independent prognostic factors for poor survival after hepatectomy. Using these three variables, we created a new staging system to classify patients with colorectal liver metastases. Finally, our new staging system classified the patients both in group 1 and in group 2. CONCLUSION： Our new staging system of colorecta liver metastasis is simple and useful for staging patients.展开更多
Objective： Identification of colorectal cancer （CRC） metastasis genes is one of the most important issues in CRC research. For the purpose of mining CRC metastasis-associated genes, an integrated analysis of mJcroa...Objective： Identification of colorectal cancer （CRC） metastasis genes is one of the most important issues in CRC research. For the purpose of mining CRC metastasis-associated genes, an integrated analysis of mJcroarray data was presented, by combined with evidence acquired from comparative genornic hybridization （CGH） data. Methods： Gene expression profile data of CRC samples were obtained at Gene Expression Omnibus （GEO） website. The 15 important chromosomal aberration sites detected by using CGH technology were used for integrated genomic and transcriptomic analysis. Significant Analysis of Microarray （SAM） was used to detect significantly differentially expressed genes across the whole genome. The overlapping genes were selected in their corresponding chromosomal aberration regions, and analyzed by using the Database for Annotation, Visualization and Integrated Discovery （DAVID）. Finally, SVM-T-RFE gene selection algorithm was applied to identify ted genes in CRC. Results： A minimum gene set was obtained with the minimum number [14] of genes, and the highest classification accuracy （100%） in both PRI and META datasets. A fraction of selected genes are associated with CRC or its metastasis. Conclusions- Our results demonstrated that integration analysis is an effective strategy for mining cancer- associated genes.展开更多
AIM: To evaluate the effect of nigericin on colorectal cancer and to explore its possible mechanism. METHODS: The human colorectal cancer (CRC) cell lines HT29 and SW480 were treated with nigericin or oxaliplatin unde...AIM: To evaluate the effect of nigericin on colorectal cancer and to explore its possible mechanism. METHODS: The human colorectal cancer (CRC) cell lines HT29 and SW480 were treated with nigericin or oxaliplatin under the conditions specified. Cell viability assay and invasion and metastasis assay were performed to evaluate the effect of nigericin on CRC cells. Sphereforming assay and soft agar colony-forming assay were implemented to assess the action of nigericin on the cancer stem cell properties of CRC cells undergone epithelial-mesenchymal transition (EMT). RESULTS: Compared with oxaliplatin, nigericin showed more toxicity for the HT29 cell line (IC50, 12.92 ± 0.25 μmol vs 37.68 ± 0.34 μmol). A similar result was also obtained with the SW116 cell line (IC50, 15.86 ± 0.18 μmol vs 41.02 ± 0.23 μmol). A Boyden chamber assay indicated that a significant decrease in the number of HT29 cells migrating through polyvinylidene fluoride membrane was observed in the nigericin-treated group, relative to the vehicle-treated group [11 ± 2 cells per high-power field (HPF) vs 19.33 ± 1.52 cells per HPF, P < 0.05]. Compared to the control group, the numbers of HT29 cells invading through the Matrigel-coated membrane also decreased in the nigericin-treated group (6.66 ± 1.52 cells per HPF vs 14.66 ± 1.52 cells per HPF, P < 0.05). Nigericin also reduced the proportion of CD133+ cells from 83.57% to 63.93%, relative to the control group (P < 0.05). Nigericin decreased the number of spheres relative to the control group (0.14 ± 0.01 vs 0.35 ± 0.01, P < 0.05), while oxaliplatin increased the number of spheres relative to the control group (0.75 ± 0.02 vs 0.35 ± 0.01; P < 0.05). Nigericin also showed a decreased ability to form colonies under anchorage-independent conditions in a standard soft agar assay after 14 d in culture, relative to the control group (1.66 ± 0.57 vs 7 ± 1.15, P < 0.05), whereas the colony numbers were higher in the oxaliplatin group relative to the vehicle-treated controls (14.33 ± 0.57 vs 7 ± 1.15, P < 0.05). We further detected the expression of E-cadherin and vimentin in cells treated with nigericin and oxaliplatin. The results showed that HT29 cells treated with nigericin induced an increase in E-cadherin expression and a decrease in the vimentin expression relative to vehicle controls. In contrast, oxaliplatin downregulated the expression of E-cadherin and upregulated the expression of vimentin in HT29 cells relative to vehicle controls. CONCLUSION: This study demonstrated that nigericin could partly reverse the EMT process during cell invasion and metastasis.展开更多
BACKGROUND Carcinoembryonic antigen(CEA)is a broad-spectrum tumor marker for differential diagnosis,monitoring,and response assessment of a variety of malignancies.AIM To evaluate whether serum CEA could predict the p...BACKGROUND Carcinoembryonic antigen(CEA)is a broad-spectrum tumor marker for differential diagnosis,monitoring,and response assessment of a variety of malignancies.AIM To evaluate whether serum CEA could predict the prognosis in patients with colorectal cancer liver metastasis(CRCLM)before and after liver resection(LR).METHODS PubMed,Embase,Cochrane,and Web of Science were systematically searched to retrieve literature,with a search cut-off date of February 27,2023.Articles were strictly screened for inclusion according to pre-specified inclusion and exclusion criteria.Data were pooled and analyzed using Stata 16.0.RESULTS This meta-analysis included 36 studies involving a total of 11143 CRCLM patients.The results showed that a high pre-LR serum CEA level was correlated with poor overall survival(OS)[hazard ratio(HR)=1.61,95%confidence interval(CI):1.49-1.75,P<0.001]and recurrence-free survival(HR=1.27,95%CI:1.11-1.45,P<0.001)in CRCLM patients.A high post-LR serum CEA level predicted poor OS(HR=2.66,95%CI:2.10-3.38,P<0.001).A comparison by treatment modality,analysis modality,patient source,and cutoff-value showed that overall,high preoperative and postoperative serum CEA levels remained correlated with a poor prognosis.CONCLUSION This study concluded that high pre-LR and post-LR serum CEA levels were significantly correlated with a poor prognosis in CRCLM patients.展开更多
Despite the advent of improved surgical techniques and the development of cytotoxic chemotherapeutic agents useful for the treatment of colorectal cancer,the primary clinical challenge remains that of preventing and c...Despite the advent of improved surgical techniques and the development of cytotoxic chemotherapeutic agents useful for the treatment of colorectal cancer,the primary clinical challenge remains that of preventing and combating metastatic spread.Surgical resection is the best treatment for colorectal metastases isolated to the liver.However,in rodent models,the hepatic ischemia-reperfusion(I/R) applied during the surgery accelerates the outgrowth of implanted tumors.Among the adverse effects of I/R on cellular function,several studies have demonstrated an over expression of the matrix metalloproteinase-9(MMP-9) in the ischemic liver.Since several studies showed high local levels of expression and activity of this proteolytic enzyme in the primary colorectal adenocarcinoma,the role of MMP-9 might be considered as a potential common mediator,favoring both growth of local tumor and the dissemination of colorectal carcinoma metastases.展开更多
BACKGROUND Surgical resection is considered the standard treatment option for long-term survival in colorectal cancer liver metastasis(CRLM)patients,but only a small number of patients are suitable for resection follo...BACKGROUND Surgical resection is considered the standard treatment option for long-term survival in colorectal cancer liver metastasis(CRLM)patients,but only a small number of patients are suitable for resection following diagnosis.Radiofrequency ablation(RFA)is an accepted alternative therapy for CRLM patients who are not suitable for resection.However,the relatively high rate of local tumor progression(LTP)is an obstacle to the more widespread use of RFA.AIM To determine the oncological outcomes and predictors of RFA in CRLM patients.METHODS A retrospective analyze was performed on the clinical data of 85 consecutive CRLM patients with a combined total of 138 liver metastases,who had received percutaneous RFA treatment at our institution from January 2013 to December 2018.Contrast-enhanced computed tomography was performed the first month after RFA to assess the technique effectiveness of the RFA and to serve as a baseline for subsequent evaluations.The Kaplan-Meier method was used to calculate overall survival(OS)and LTP-free survival(LTPFS).The log-rank test and Cox regression model were used for univariate and multivariate analyses to determine the predictors of the oncological outcomes.RESULTS There were no RFA procedure-related deaths,and the technique effectiveness of the treatment was 89.1%(123/138).The median follow-up time was 30 mo.The LTP rate was 32.6%(45/138),and the median OS was 36 mo.The 1-,3-,and 5-year OS rates were 90.6%,45.6%,and 22.9%,respectively.Univariate analysis revealed that tumor size and ablative margin were the factors influencing LTPFS,while extrahepatic disease(EHD),tumor number,and tumor size were the factors influencing OS.Multivariate analysis showed that tumor size larger than 3 cm and ablative margin of 5 mm or smaller were the independent predictors of shorter LTPFS,while tumor number greater than 1,size larger than 3 cm,and presence of EHD were the independent predictors of shorter OS.CONCLUSION RFA is a safe and effective treatment method for CRLM.Tumor size and ablative margin are the important factors affecting LTPFS.Tumor number,tumor size,and EHD are also critical factors for OS.展开更多
Evaluation of response to chemotherapy in colorectal cancer patients with synchronous liver metastases is important in terms of treatment management.In this Letter to the Editor,several issues in the article are discu...Evaluation of response to chemotherapy in colorectal cancer patients with synchronous liver metastases is important in terms of treatment management.In this Letter to the Editor,several issues in the article are discussed.For the comparison of carbohydrate antigen 19-9(CA19-9)values referenced in the study,the patient group was not matched for cancer stage.Therefore,it may be more appropriate to select and compare CA19-9 values in patients with same-stage cancer.展开更多
The mechanism underlying CD4~＋CD25~＋Foxp3~＋ regulatory T cells（Tregs） promoting the development of colorectal cancer（CRC） was elucidated in the present study. Forty-eight cases of colorectal carcinomas, 22 case...The mechanism underlying CD4~＋CD25~＋Foxp3~＋ regulatory T cells（Tregs） promoting the development of colorectal cancer（CRC） was elucidated in the present study. Forty-eight cases of colorectal carcinomas, 22 cases of colon polyps and 21 cases of normal colorectal tissues were collected. The correlation among Foxp3, IL-10 and Stat3, and the clinical relevance of these three indexes were analyzed. The results showed that the levels of Foxp3 expressed in infiltrating CD4~＋CD25~＋Foxp3~＋Tregs, and IL-10 and Stat3 in CRC tissues were all significantly higher than those in polypus tissues and normal colon tissues（P〈0.01）. Pearson correlation analysis indicated that the expression level of Foxp3 was positively correlated with Stat3 at m RNA level（r=0.526, P=0.036）, and was positively correlated with IL-10 at protein level（r=0.314, P=0.030）. The Foxp3 expressed in CD4~＋CD25~＋Foxp3~＋Tregs was correlated with the histological grade, lymph node metastasis and TNM stage of CRC（P〈0.05 for all）. The IL-10 expression was correlated with the histological grade and TNM stage（both P〈0.05）. The Stat3 expression was correlated with the lymph node metastasis and TNM stage（both P〈0.05）. It was concluded that CD4~＋CD25~＋Foxp3~＋Tregs can inhibit tumor immunity in combination with some other related inhibitory cytokines and that Foxp3 expression in CD4~＋CD25~＋Foxp3~＋Tregs correlates with CRC progression.展开更多
BACKGROUND Liver metastasis is the most common form of distant metastasis in colorectal cancer,and the only possible curative treatment for patients with colorectal liver metastases(CRLM)is hepatectomy.However,approxi...BACKGROUND Liver metastasis is the most common form of distant metastasis in colorectal cancer,and the only possible curative treatment for patients with colorectal liver metastases(CRLM)is hepatectomy.However,approximately 25%of patients with CRLM have indications for liver resection at the initial diagnosis.Strategies aimed at downstaging large or multifocal tumors to enable curative resection are appealing.CASE SUMMARY A 42-year-old man was diagnosed with ascending colon cancer and liver metastases.Due to the huge lesion size and compression of the right portal vein,the liver metastases were initially diagnosed as unresectable lesions.The patient was treated with preoperative transcatheter arterial chemoembolization(TACE)consisting of 5-fluorouracil/Leucovorin/oxaliplatin/Endostar®.After four courses,radical right-sided colectomy and ileum transverse colon anastomosis were performed.Postoperatively,the pathological analysis revealed moderately differentiated adenocarcinoma with necrosis and negative margins.Thereafter,S7/S8 partial hepatectomy was performed after two courses of neoadjuvant chemotherapy.Pathological examination of the resected specimen revealed a pathologically complete response(pCR).Intrahepatic recurrence was detected more than two months after the operation,and the patient was then treated with TACE consisting of irinotecan/Leucovorin/fluorouracil therapy plus Endostar®.Subsequently,the patient was treated with aγ-knife to enhance local control.Notably,a pCR was reached,and the patient's overall survival time was>9 years.CONCLUSION Multidisciplinary treatment can promote the conversion of initially unresectable colorectal liver metastasis and facilitate complete pathological remission of liver lesions.展开更多
BACKGROUND The inflammatory response to tumor has been proven to be closely related to the prognosis of colorectal cancer.Neutrophil to lymphocyte ratio(NLR)is a widely available inflammatory biomarker that may have p...BACKGROUND The inflammatory response to tumor has been proven to be closely related to the prognosis of colorectal cancer.Neutrophil to lymphocyte ratio(NLR)is a widely available inflammatory biomarker that may have prognostic value for patients with colorectal liver metastasis(CRLM).AIM To assess the role of NLR as a prognostic factor of survival and tumor recurrence in patients with CRLM.METHODS A systematic literature search of PubMed,Cochrane Library and clinicaltrials.gov was conducted by two independent researchers in order to minimize potential errors and bias.Conflicts were discussed and settled between three researchers.Studies including patients undergoing different types of medical interventions for the treatment of CRLM and evaluating the correlation between pretreatment NLR and disease-free survival(DFS)and overall survival(OS)were included in the review.Nineteen studies,involving 3283 patients matched our inclusion criteria.RESULTS In the studies included,NLR was measured before the intervention and the NLR thresholds ranged between 1.9 and 7.26.Most studies used 5 as the cut-off value.Liver metastases were treated with hepatectomy with or without chemotherapy regimens in 13 studies and with radiofrequency ablation,radioembolization,chemoembolization or solely with chemotherapy in 6 studies.High NLR was associated with decreased OS and DFS after liver resection or other medical intervention.Moreover,high NLR was associated with poor chemosensitivity.On the contrary,CRLM patients with low pretreatment NLR demonstrated improved OS and DFS.NLR could potentially be used as a predictive factor of survival and tumor recurrence in patients with CRLM treated with interventions of any modality,including surgery,chemotherapy and ablative techniques.CONCLUSION NLR is an inflammatory biomarker that demonstrates considerable prognostic value.Elevated pretreatment NLR is associated with poor OS and DFS in patients with CRLM who are submitted to different treatments.展开更多
It is estimated that 50%of patients with colorectal cancer will develop liver metastasis.Surgical resection significantly improves survival and provides a chance of cure for patients with colorectal cancer liver metas...It is estimated that 50%of patients with colorectal cancer will develop liver metastasis.Surgical resection significantly improves survival and provides a chance of cure for patients with colorectal cancer liver metastasis(CRLM).Increasing the resectability of primary unresectable liver metastasis provides more survival benefit for those patients.Considerable surgical innovations have been made to increase the resection rate and decrease the potential risk of hepatic failure postoperation.Liver transplantation(LT)has been explored as a potential curative treatment for unresectable CRLM.However,candidate selection criteria,chemotherapy strategies,refined immunity regimens and resolution for the shortage of grafts are lacking.This manuscript discusses views on surgical indication,peritransplantation anti-tumor and anti-immunity therapy and updated advances in LT for unresectable CRLM.A literature review of published articles and registered clinical trials in PubMed,Google Scholar,and Clinicaltrials.gov was performed to identify studies related to LT for CRLM.Some research topics were identified,including indications for LT for CRLM,oncological risk,antitumor regimens,graft loss,administration of anti-immunity drugs and solutions for graft deficiency.The main candidate selection criteria are good patient performance,good tumor biological behavior and chemosensitivity.Chemotherapy should be administered before transplantation but is not commonly administered posttransplantation for preventive purposes.Mammalian target of rapamycin regimens are recommended for their potential oncological benefit,although there are limited cases.In addition to extended criterion grafts,living donor grafts and small grafts combined with two-stage hepatectomy are efficient means to resolve organ deficiency.LT has been proven to be an effective treatment for selected patients with liver-only CRLM.Due to limited donor grafts,high cost and poorly clarified oncological risks,LT for unresectable CRLM should be strictly performed under a well-organized study plan in selected patients.Some vital factors,like LT indication and anti-tumor and anti-immune treatment,remain to be confirmed.Ongoing clinical trials are expected to delineate these topics.展开更多
With great interest,we read the article by Lam et al.(1)entitled“A machine learning model for colorectal liver metastasis post-hepatectomy prognostications”.In this study,the authors included colorectal liver metast...With great interest,we read the article by Lam et al.(1)entitled“A machine learning model for colorectal liver metastasis post-hepatectomy prognostications”.In this study,the authors included colorectal liver metastasis(CRLM)patients from four hospitals in Hong Kong who underwent hepatic resection,and developed a survival prediction model based on the patients’demographic,oncologic,clinicopathologic,and therapeutic characteristics using machine learning.Through Cox proportional hazards and least absolute shrinkage and selection operator(LASSO)regression analyses,the authors successfully developed a predictive model consisting of eight predictors that could accurately predict overall survival(OS)and recurrence-free survival(RFS)after hepatectomy in patients with CRLM.This is an intriguing study with significant clinical value,and the authors deserve to be commended for their efforts.However,there are still several issues that need to be addressed in this study.展开更多
Background:Colorectal liver metastasis(CRLM)exhibits highly heterogeneity,with clinically and molecularly defined subgroups that differ in their prognosis.The aim of this study is to explore whether left-sided tumors ...Background:Colorectal liver metastasis(CRLM)exhibits highly heterogeneity,with clinically and molecularly defined subgroups that differ in their prognosis.The aim of this study is to explore whether left-sided tumors is clinically and gnomically distinct from right-sided tumors in CRLM.Methods:This retrospective study included 1,307 patients who underwent primary tumor and metastases resection at three academic centers in China from January 1,2012,to December 31,2020.Propensity score matching with 1:1 ratio matching was performed.The prognostic impact of tumor sidedness was determined after stratifying by the KRAS mutational status.Moreover,whole-exome sequencing(WES)of 200 liver tumor tissues were performed to describe the heterogeneity across the analysis of somatic and germline profiles.Results:The median follow-up was 68 months.Matching yielded 481 pairs of patients.Compared to right-sided CRLM,left-sided patients experienced with better 5-year overall survival(OS)in surgery responsiveness,with a 14.6 lower risk of death[hazard ratio(HR),1.36,95%confidence interval(CI),1.10-1.69,P=0.004].Interaction between tumor sidedness and KRAS status was statistically significant:left-sidedness was associated with better prognosis among KRAS wild-type patients(HR 1.71;95%CI:1.20-2.45;P=0.003),but not among KRAS mutated-type patients.Integrated molecular analyses showed that right-sided tumors more frequently harbored TP53,APC,KRAS,and BRAF alterations,and identified a critical role of KRAS mutation in correlation with their survival differences.Higher pathogenic germline variants were identified in the right-sided tumors compared with left-sided tumors(29.3%vs.15.5%,P=0.03).Conclusions:We demonstrated that the prognostic impacts of tumor sidedness in CRLM is restricted patients with KRAS wild-type tumors.Tumor sidedness displays considerable clinical and molecular heterogeneity that may associate with their therapy benefits and prognosis.展开更多
Approximately half of individuals diagnosed with colorectal cancer(CRC)will develop colorectal liver metastasis(CRLM)during the course of their disease(1,2).Liver resection is the only potentially curative treatment f...Approximately half of individuals diagnosed with colorectal cancer(CRC)will develop colorectal liver metastasis(CRLM)during the course of their disease(1,2).Liver resection is the only potentially curative treatment for patients with CRLM,yet less than 20%of individuals are candidates for resection due to the extent or location of liver disease,underlying liver function and/or presence of extrahepatic metastases(1,2).In addition,the oncologic benefit of liver resection for CRLM is limited by recurrence rates than can be as high as 70%(3).Liver transplantation(LT)for CRLM was initially proposed as an alternative treatment strategy in the early 1990s but was abandoned due to the initial poor outcomes(3,4).The concept of transplantation for CRLM was later revisited in the 2000s by a group in Oslo,Norway that reported promising results in the SECA-I pilot study(5).Since the completion of the SECA-I study,the Norwegian group has also published other promising data from the SECA-II study(6).In addition,other notable outcomes have been reported in the RAPID study(7),as well as another study from specialized centers in North America(8),both of which have revitalized the concept of LT for CRLM.展开更多
Recently,indocyanine green(ICG)fluorescence imaging has been widely used as a substitute for cholangiography in hepatobiliary surgery,to detect hepatic tumors,for accurate anatomical hepatectomy,and to increase the sa...Recently,indocyanine green(ICG)fluorescence imaging has been widely used as a substitute for cholangiography in hepatobiliary surgery,to detect hepatic tumors,for accurate anatomical hepatectomy,and to increase the safety and accuracy of minimally invasive(laparoscopic and robotic)hepatectomy.The clinical relevance of this method has been increasing gradually,as new procedures develop in this field.Various important roles and the latest added value of ICG fluorescence imaging in liver surgery are discussed in this report.展开更多
Background： Controversial results about the therapeutic value of radiofrequency ablation （RFA） and liver resection （LR） in the treatment of colorectal cancer liver metastasis （CRCLM） have been reported. Thus, w...Background： Controversial results about the therapeutic value of radiofrequency ablation （RFA） and liver resection （LR） in the treatment of colorectal cancer liver metastasis （CRCLM） have been reported. Thus, we performed the present meta-analysis to summarize the related clinical evidences. Methods： A systematic literature search was conducted using PubMed （Medline）, EMBASE, Cochrane Library, and Web of Science, for all years up to April 2016. Pooled analyses of the overall survival （OS）, progression-free survival （PFS）, and morbidity rates were performed. Results： A total of 14 studies were finally enrolled in the meta-analysis. Patients treated by LR gained a longer OS and PFS than those of patients treated by RFA. Patients in the RFA group had lower morbidity rates than those of patients in the LR group. Publication bias analysis revealed that there was no significant publication bias in the meta-analysis. Conclusions： Patients with CRCLM gained much more survival benefits from LR than that from RFA. RFA rendered lower rates of morbidities. More well-designed randomized controlled trails comparing the therapeutic value of LR and RFA are warranted.展开更多
Liver cancer is a leading cause of death worldwide,and hepatocellular carcinoma(HCC)is the most frequent primary liver tumour,followed by cholangiocarcinoma.Notably,secondary tumours represent up to 90% of liver tumou...Liver cancer is a leading cause of death worldwide,and hepatocellular carcinoma(HCC)is the most frequent primary liver tumour,followed by cholangiocarcinoma.Notably,secondary tumours represent up to 90% of liver tumours.Chronic liver disease is a recognised risk factor for liver cancer development.Up to 90% of the patients with HCC and about 20% of those with cholangiocarcinoma have an underlying liver alteration.The gut microbiota-liver axis represents the bidirectional relationship between gut microbiota,its metabolites and the liver through the portal flow.The interplay between the immune system and gut microbiota is also well-known.Although primarily resulting from experiments in animal models and on HCC,growing evidence suggests a causal role for the gut microbiota in the development and progression of chronic liver pathologies and liver tumours.Despite the curative intent of“traditional”treatments,tumour recurrence remains high.Therefore,microbiota modulation is an appealing therapeutic target for liver cancer prevention and treatment.Furthermore,microbiota could represent a non-invasive biomarker for early liver cancer diagnosis.This review summarises the potential role of the microbiota and immune system in primary and secondary liver cancer development,focusing on the potential therapeutic implications.展开更多
文摘Colorectal cancer liver metastasis(CRLM)presents a clinical challenge,and optimizing treatment strategies is crucial for improving patient outcomes.Surgical resection,a key element in achieving prolonged survival,is often linked to a heightened risk of recurrence.Acknowledging the potential benefits of preoperative neoadjuvant chemotherapy in managing resectable liver metastases,this approach has gained attention for its role in tumor downsizing,assessing biological behavior,and reducing the risk of postoperative recurrence.However,the use of neoadjuvant chemotherapy in initially resectable CRLM sparks ongoing debates.The balance between tumor reduction and the risk of hepatic injury,coupled with concerns about delaying surgery,necessitates a nuanced approach.This article explores recent research insights and draws upon the practical experiences at our center to address critical issues regarding considerations for initially resectable cases.Examining the criteria for patient selection and the judicious choice of neoadjuvant regimens are pivotal areas of discussion.Striking the right balance between maximizing treatment efficacy and minimizing adverse effects is imperative.The dynamic landscape of precision medicine is also reflected in the evolving role of gene testing,such as RAS/BRAF and PIK3CA,in tailoring neoadjuvant regimens.Furthermore,the review emphasizes the need for a multidisciplinary approach to navigate the comp-lexities of CRLM.Integrating technical expertise and biological insights is crucial in refining neoadjuvant strategies.The management of progression following neoadjuvant chemotherapy requires a tailored approach,acknowledging the diverse biological behaviors that may emerge.In conclusion,this review aims to provide a comprehensive perspective on the considerations,challenges,and advancements in the use of neoadjuvant chemotherapy for initially resectable CRLM.By combining evidencebased insights with practical experiences,we aspire to contribute to the ongoing discourse on refining treatment paradigms for improved outcomes in patients with CRLM.
基金Supported by the National Key R and D Program of China,No.2022YFC3500200 and No.2022YFC3500204Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine,No.ZYYCXTD-C-202208+3 种基金NATCM’s Project of Highlevel Construction of Key TCM Disciplines,No.[2023]85Qing Lan Project of Jiangsu Higher Education Institutions,No.[2023]27Jiangsu Postgraduate Practice Innovation Plan,No.SJCX22_0706General Project of Universities’Philosophy and Social Science in Jiangsu Province,No.2024SJYB0564.
文摘BACKGROUND Colorectal cancer(CRC)is the third most prevalent form of cancer worldwide.Among patients with CRC,colorectal liver metastasis(CRLM)is the foremost direct contributor to mortality.In recent years,immunotherapy has swiftly risen to prominence as a vital approach for treating a range of solid tumors,including CRC.We present a unique case of a patient suffering from CRLM,with the goal of offering an insightful example and relevant references for the treatment of CRLM.CASE SUMMARY We report a patient who experienced liver metastasis after undergoing successful surgical removal of CRC,with the postoperative pathological stage identified as pT4N2aM0.The patient has been receiving a combination treatment of Western and Traditional Chinese Medicine.Regular assessments of the patient’s condition have been conducted,encompassing evaluations of serum carcinoembryonic antigen levels,carbohydrate antigen 199,and observations of the tongue complexion and its coating.The patient achieved clinical remission after anti-programmed death-1 immunotherapy when various systemic therapies failed.Since the diagnosis of CRLM,the patient has survived for more than 6 years,surpassing the expected survival time for those with advanced CRC.CONCLUSION This case illustrates the considerable promise of anti-programmed death-1 immunotherapy in managing CRLM,especially in scenarios of drug resistance and disease progression.
基金Supported by A grant of "Department of Health,Government of Navarra,Spain (23/2009)"
文摘AIM： To investigate the angiogenesis-related protein expression profile characterizing metastatic colorectal cancer （mCRC） with the aim of identifying prognostic markers.METHODS： The expression of 44 angiogenesis- secreted factors was measured by a novel cytokine antibody array methodology. The study evaluated vas- cular endothelial growth factor （VEGF） and its soluble vascular endothelial growth factor receptor （sVEGFR）-I protein levels by enzyme immunoassay （EIA） in a panel of 16 CRC cell lines, mRNA VEGF and VEGF-A isoforms were quantified by quantitative reverse-transcription polymerase chain reaction （Q-RT-PCR） and vascular en- dothelial growth factor receptor （VEGFR）-2 expressionwas analyzed by flow cytometry.
文摘AIM： To create a new, simple and useful staging system for colorectal liver metastasis analogous to the Tumor Node Metastasis classification system of International Union Against Cancer. METHODS： A retrospective review was undertaken of 81 consecutive patients who underwent partial hepatectomy for colorectal liver metastases （group 1）. Clinical and pathological features of both primary and metastatic liver cancers were entered into a multivariate analysis to determine independent variables helpful in accurately predicting long-term prognosis after hepatectomy. Using selected variables, we created a new staging system like TNM classification. The usefulness of the new staging system was examined in a series of 92 patients from another hospital （group 2）. RESULTS： Multivariate analysis showed that 81 patients in group 1 had significant multiple hepatic tumors with the largest tumor being more than 5 cm in diameter, resectable extrahepatic distant metastases, and independent prognostic factors for poor survival after hepatectomy. Using these three variables, we created a new staging system to classify patients with colorectal liver metastases. Finally, our new staging system classified the patients both in group 1 and in group 2. CONCLUSION： Our new staging system of colorecta liver metastasis is simple and useful for staging patients.
基金supported by a grant from the National Natural Science Foundation of China(Grant No.61373057)a grant from the Zhejiang Provincial Natural Science Foundation of China(Grant No.Y1110763)
文摘Objective： Identification of colorectal cancer （CRC） metastasis genes is one of the most important issues in CRC research. For the purpose of mining CRC metastasis-associated genes, an integrated analysis of mJcroarray data was presented, by combined with evidence acquired from comparative genornic hybridization （CGH） data. Methods： Gene expression profile data of CRC samples were obtained at Gene Expression Omnibus （GEO） website. The 15 important chromosomal aberration sites detected by using CGH technology were used for integrated genomic and transcriptomic analysis. Significant Analysis of Microarray （SAM） was used to detect significantly differentially expressed genes across the whole genome. The overlapping genes were selected in their corresponding chromosomal aberration regions, and analyzed by using the Database for Annotation, Visualization and Integrated Discovery （DAVID）. Finally, SVM-T-RFE gene selection algorithm was applied to identify ted genes in CRC. Results： A minimum gene set was obtained with the minimum number [14] of genes, and the highest classification accuracy （100%） in both PRI and META datasets. A fraction of selected genes are associated with CRC or its metastasis. Conclusions- Our results demonstrated that integration analysis is an effective strategy for mining cancer- associated genes.
基金Supported by The National Natural Science Foundation, No.30901424the Leading Medical Talent Foundation of Shanghai Municipality, No. 10XD1402700
文摘AIM: To evaluate the effect of nigericin on colorectal cancer and to explore its possible mechanism. METHODS: The human colorectal cancer (CRC) cell lines HT29 and SW480 were treated with nigericin or oxaliplatin under the conditions specified. Cell viability assay and invasion and metastasis assay were performed to evaluate the effect of nigericin on CRC cells. Sphereforming assay and soft agar colony-forming assay were implemented to assess the action of nigericin on the cancer stem cell properties of CRC cells undergone epithelial-mesenchymal transition (EMT). RESULTS: Compared with oxaliplatin, nigericin showed more toxicity for the HT29 cell line (IC50, 12.92 ± 0.25 μmol vs 37.68 ± 0.34 μmol). A similar result was also obtained with the SW116 cell line (IC50, 15.86 ± 0.18 μmol vs 41.02 ± 0.23 μmol). A Boyden chamber assay indicated that a significant decrease in the number of HT29 cells migrating through polyvinylidene fluoride membrane was observed in the nigericin-treated group, relative to the vehicle-treated group [11 ± 2 cells per high-power field (HPF) vs 19.33 ± 1.52 cells per HPF, P < 0.05]. Compared to the control group, the numbers of HT29 cells invading through the Matrigel-coated membrane also decreased in the nigericin-treated group (6.66 ± 1.52 cells per HPF vs 14.66 ± 1.52 cells per HPF, P < 0.05). Nigericin also reduced the proportion of CD133+ cells from 83.57% to 63.93%, relative to the control group (P < 0.05). Nigericin decreased the number of spheres relative to the control group (0.14 ± 0.01 vs 0.35 ± 0.01, P < 0.05), while oxaliplatin increased the number of spheres relative to the control group (0.75 ± 0.02 vs 0.35 ± 0.01; P < 0.05). Nigericin also showed a decreased ability to form colonies under anchorage-independent conditions in a standard soft agar assay after 14 d in culture, relative to the control group (1.66 ± 0.57 vs 7 ± 1.15, P < 0.05), whereas the colony numbers were higher in the oxaliplatin group relative to the vehicle-treated controls (14.33 ± 0.57 vs 7 ± 1.15, P < 0.05). We further detected the expression of E-cadherin and vimentin in cells treated with nigericin and oxaliplatin. The results showed that HT29 cells treated with nigericin induced an increase in E-cadherin expression and a decrease in the vimentin expression relative to vehicle controls. In contrast, oxaliplatin downregulated the expression of E-cadherin and upregulated the expression of vimentin in HT29 cells relative to vehicle controls. CONCLUSION: This study demonstrated that nigericin could partly reverse the EMT process during cell invasion and metastasis.
文摘BACKGROUND Carcinoembryonic antigen(CEA)is a broad-spectrum tumor marker for differential diagnosis,monitoring,and response assessment of a variety of malignancies.AIM To evaluate whether serum CEA could predict the prognosis in patients with colorectal cancer liver metastasis(CRCLM)before and after liver resection(LR).METHODS PubMed,Embase,Cochrane,and Web of Science were systematically searched to retrieve literature,with a search cut-off date of February 27,2023.Articles were strictly screened for inclusion according to pre-specified inclusion and exclusion criteria.Data were pooled and analyzed using Stata 16.0.RESULTS This meta-analysis included 36 studies involving a total of 11143 CRCLM patients.The results showed that a high pre-LR serum CEA level was correlated with poor overall survival(OS)[hazard ratio(HR)=1.61,95%confidence interval(CI):1.49-1.75,P<0.001]and recurrence-free survival(HR=1.27,95%CI:1.11-1.45,P<0.001)in CRCLM patients.A high post-LR serum CEA level predicted poor OS(HR=2.66,95%CI:2.10-3.38,P<0.001).A comparison by treatment modality,analysis modality,patient source,and cutoff-value showed that overall,high preoperative and postoperative serum CEA levels remained correlated with a poor prognosis.CONCLUSION This study concluded that high pre-LR and post-LR serum CEA levels were significantly correlated with a poor prognosis in CRCLM patients.
基金Supported by The Swiss National Science Foundation,No. 32003B-134963/1,to Montecucco FEU FP7 Athero-Remo,No. 201668Swiss National Science Foundation,No. 310030B-133127,to Mach F
文摘Despite the advent of improved surgical techniques and the development of cytotoxic chemotherapeutic agents useful for the treatment of colorectal cancer,the primary clinical challenge remains that of preventing and combating metastatic spread.Surgical resection is the best treatment for colorectal metastases isolated to the liver.However,in rodent models,the hepatic ischemia-reperfusion(I/R) applied during the surgery accelerates the outgrowth of implanted tumors.Among the adverse effects of I/R on cellular function,several studies have demonstrated an over expression of the matrix metalloproteinase-9(MMP-9) in the ischemic liver.Since several studies showed high local levels of expression and activity of this proteolytic enzyme in the primary colorectal adenocarcinoma,the role of MMP-9 might be considered as a potential common mediator,favoring both growth of local tumor and the dissemination of colorectal carcinoma metastases.
基金Supported by National Natural Science Foundation of China,No.81470086 and No.81871465.
文摘BACKGROUND Surgical resection is considered the standard treatment option for long-term survival in colorectal cancer liver metastasis(CRLM)patients,but only a small number of patients are suitable for resection following diagnosis.Radiofrequency ablation(RFA)is an accepted alternative therapy for CRLM patients who are not suitable for resection.However,the relatively high rate of local tumor progression(LTP)is an obstacle to the more widespread use of RFA.AIM To determine the oncological outcomes and predictors of RFA in CRLM patients.METHODS A retrospective analyze was performed on the clinical data of 85 consecutive CRLM patients with a combined total of 138 liver metastases,who had received percutaneous RFA treatment at our institution from January 2013 to December 2018.Contrast-enhanced computed tomography was performed the first month after RFA to assess the technique effectiveness of the RFA and to serve as a baseline for subsequent evaluations.The Kaplan-Meier method was used to calculate overall survival(OS)and LTP-free survival(LTPFS).The log-rank test and Cox regression model were used for univariate and multivariate analyses to determine the predictors of the oncological outcomes.RESULTS There were no RFA procedure-related deaths,and the technique effectiveness of the treatment was 89.1%(123/138).The median follow-up time was 30 mo.The LTP rate was 32.6%(45/138),and the median OS was 36 mo.The 1-,3-,and 5-year OS rates were 90.6%,45.6%,and 22.9%,respectively.Univariate analysis revealed that tumor size and ablative margin were the factors influencing LTPFS,while extrahepatic disease(EHD),tumor number,and tumor size were the factors influencing OS.Multivariate analysis showed that tumor size larger than 3 cm and ablative margin of 5 mm or smaller were the independent predictors of shorter LTPFS,while tumor number greater than 1,size larger than 3 cm,and presence of EHD were the independent predictors of shorter OS.CONCLUSION RFA is a safe and effective treatment method for CRLM.Tumor size and ablative margin are the important factors affecting LTPFS.Tumor number,tumor size,and EHD are also critical factors for OS.
文摘Evaluation of response to chemotherapy in colorectal cancer patients with synchronous liver metastases is important in terms of treatment management.In this Letter to the Editor,several issues in the article are discussed.For the comparison of carbohydrate antigen 19-9(CA19-9)values referenced in the study,the patient group was not matched for cancer stage.Therefore,it may be more appropriate to select and compare CA19-9 values in patients with same-stage cancer.
基金supported by a grant from Natural Science Foundation of Hubei Province,China(No.2009CD201)
文摘The mechanism underlying CD4~＋CD25~＋Foxp3~＋ regulatory T cells（Tregs） promoting the development of colorectal cancer（CRC） was elucidated in the present study. Forty-eight cases of colorectal carcinomas, 22 cases of colon polyps and 21 cases of normal colorectal tissues were collected. The correlation among Foxp3, IL-10 and Stat3, and the clinical relevance of these three indexes were analyzed. The results showed that the levels of Foxp3 expressed in infiltrating CD4~＋CD25~＋Foxp3~＋Tregs, and IL-10 and Stat3 in CRC tissues were all significantly higher than those in polypus tissues and normal colon tissues（P〈0.01）. Pearson correlation analysis indicated that the expression level of Foxp3 was positively correlated with Stat3 at m RNA level（r=0.526, P=0.036）, and was positively correlated with IL-10 at protein level（r=0.314, P=0.030）. The Foxp3 expressed in CD4~＋CD25~＋Foxp3~＋Tregs was correlated with the histological grade, lymph node metastasis and TNM stage of CRC（P〈0.05 for all）. The IL-10 expression was correlated with the histological grade and TNM stage（both P〈0.05）. The Stat3 expression was correlated with the lymph node metastasis and TNM stage（both P〈0.05）. It was concluded that CD4~＋CD25~＋Foxp3~＋Tregs can inhibit tumor immunity in combination with some other related inhibitory cytokines and that Foxp3 expression in CD4~＋CD25~＋Foxp3~＋Tregs correlates with CRC progression.
文摘BACKGROUND Liver metastasis is the most common form of distant metastasis in colorectal cancer,and the only possible curative treatment for patients with colorectal liver metastases(CRLM)is hepatectomy.However,approximately 25%of patients with CRLM have indications for liver resection at the initial diagnosis.Strategies aimed at downstaging large or multifocal tumors to enable curative resection are appealing.CASE SUMMARY A 42-year-old man was diagnosed with ascending colon cancer and liver metastases.Due to the huge lesion size and compression of the right portal vein,the liver metastases were initially diagnosed as unresectable lesions.The patient was treated with preoperative transcatheter arterial chemoembolization(TACE)consisting of 5-fluorouracil/Leucovorin/oxaliplatin/Endostar®.After four courses,radical right-sided colectomy and ileum transverse colon anastomosis were performed.Postoperatively,the pathological analysis revealed moderately differentiated adenocarcinoma with necrosis and negative margins.Thereafter,S7/S8 partial hepatectomy was performed after two courses of neoadjuvant chemotherapy.Pathological examination of the resected specimen revealed a pathologically complete response(pCR).Intrahepatic recurrence was detected more than two months after the operation,and the patient was then treated with TACE consisting of irinotecan/Leucovorin/fluorouracil therapy plus Endostar®.Subsequently,the patient was treated with aγ-knife to enhance local control.Notably,a pCR was reached,and the patient's overall survival time was>9 years.CONCLUSION Multidisciplinary treatment can promote the conversion of initially unresectable colorectal liver metastasis and facilitate complete pathological remission of liver lesions.
文摘BACKGROUND The inflammatory response to tumor has been proven to be closely related to the prognosis of colorectal cancer.Neutrophil to lymphocyte ratio(NLR)is a widely available inflammatory biomarker that may have prognostic value for patients with colorectal liver metastasis(CRLM).AIM To assess the role of NLR as a prognostic factor of survival and tumor recurrence in patients with CRLM.METHODS A systematic literature search of PubMed,Cochrane Library and clinicaltrials.gov was conducted by two independent researchers in order to minimize potential errors and bias.Conflicts were discussed and settled between three researchers.Studies including patients undergoing different types of medical interventions for the treatment of CRLM and evaluating the correlation between pretreatment NLR and disease-free survival(DFS)and overall survival(OS)were included in the review.Nineteen studies,involving 3283 patients matched our inclusion criteria.RESULTS In the studies included,NLR was measured before the intervention and the NLR thresholds ranged between 1.9 and 7.26.Most studies used 5 as the cut-off value.Liver metastases were treated with hepatectomy with or without chemotherapy regimens in 13 studies and with radiofrequency ablation,radioembolization,chemoembolization or solely with chemotherapy in 6 studies.High NLR was associated with decreased OS and DFS after liver resection or other medical intervention.Moreover,high NLR was associated with poor chemosensitivity.On the contrary,CRLM patients with low pretreatment NLR demonstrated improved OS and DFS.NLR could potentially be used as a predictive factor of survival and tumor recurrence in patients with CRLM treated with interventions of any modality,including surgery,chemotherapy and ablative techniques.CONCLUSION NLR is an inflammatory biomarker that demonstrates considerable prognostic value.Elevated pretreatment NLR is associated with poor OS and DFS in patients with CRLM who are submitted to different treatments.
基金Natural Science Foundation of the Higher Education Institutions of Anhui Province,No.KJ2017A825Natural Science Foundation of Anhui Province,No.1808085MH270.
文摘It is estimated that 50%of patients with colorectal cancer will develop liver metastasis.Surgical resection significantly improves survival and provides a chance of cure for patients with colorectal cancer liver metastasis(CRLM).Increasing the resectability of primary unresectable liver metastasis provides more survival benefit for those patients.Considerable surgical innovations have been made to increase the resection rate and decrease the potential risk of hepatic failure postoperation.Liver transplantation(LT)has been explored as a potential curative treatment for unresectable CRLM.However,candidate selection criteria,chemotherapy strategies,refined immunity regimens and resolution for the shortage of grafts are lacking.This manuscript discusses views on surgical indication,peritransplantation anti-tumor and anti-immunity therapy and updated advances in LT for unresectable CRLM.A literature review of published articles and registered clinical trials in PubMed,Google Scholar,and Clinicaltrials.gov was performed to identify studies related to LT for CRLM.Some research topics were identified,including indications for LT for CRLM,oncological risk,antitumor regimens,graft loss,administration of anti-immunity drugs and solutions for graft deficiency.The main candidate selection criteria are good patient performance,good tumor biological behavior and chemosensitivity.Chemotherapy should be administered before transplantation but is not commonly administered posttransplantation for preventive purposes.Mammalian target of rapamycin regimens are recommended for their potential oncological benefit,although there are limited cases.In addition to extended criterion grafts,living donor grafts and small grafts combined with two-stage hepatectomy are efficient means to resolve organ deficiency.LT has been proven to be an effective treatment for selected patients with liver-only CRLM.Due to limited donor grafts,high cost and poorly clarified oncological risks,LT for unresectable CRLM should be strictly performed under a well-organized study plan in selected patients.Some vital factors,like LT indication and anti-tumor and anti-immune treatment,remain to be confirmed.Ongoing clinical trials are expected to delineate these topics.
基金Key University Natural Science Research Project of Anhui Province(No.2023AH053416)partly supported by the Open Funds of the Guangxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation(No.2023KF012)Anhui Provincial Postdoctoral Scientific Foundation(No.2023A660).
文摘With great interest,we read the article by Lam et al.(1)entitled“A machine learning model for colorectal liver metastasis post-hepatectomy prognostications”.In this study,the authors included colorectal liver metastasis(CRLM)patients from four hospitals in Hong Kong who underwent hepatic resection,and developed a survival prediction model based on the patients’demographic,oncologic,clinicopathologic,and therapeutic characteristics using machine learning.Through Cox proportional hazards and least absolute shrinkage and selection operator(LASSO)regression analyses,the authors successfully developed a predictive model consisting of eight predictors that could accurately predict overall survival(OS)and recurrence-free survival(RFS)after hepatectomy in patients with CRLM.This is an intriguing study with significant clinical value,and the authors deserve to be commended for their efforts.However,there are still several issues that need to be addressed in this study.
基金supported by National Natural Science Foundation of China(81874182,M-0334)Natural Science Foundation of Shanghai(22ZR1413300)+2 种基金National Science and Technology Major Project(2017ZX10203204-007-004)Shanghai Municipal Health Bureau(201940043)Shanghai Hospital Development Center(SHDC12019X19).
文摘Background:Colorectal liver metastasis(CRLM)exhibits highly heterogeneity,with clinically and molecularly defined subgroups that differ in their prognosis.The aim of this study is to explore whether left-sided tumors is clinically and gnomically distinct from right-sided tumors in CRLM.Methods:This retrospective study included 1,307 patients who underwent primary tumor and metastases resection at three academic centers in China from January 1,2012,to December 31,2020.Propensity score matching with 1:1 ratio matching was performed.The prognostic impact of tumor sidedness was determined after stratifying by the KRAS mutational status.Moreover,whole-exome sequencing(WES)of 200 liver tumor tissues were performed to describe the heterogeneity across the analysis of somatic and germline profiles.Results:The median follow-up was 68 months.Matching yielded 481 pairs of patients.Compared to right-sided CRLM,left-sided patients experienced with better 5-year overall survival(OS)in surgery responsiveness,with a 14.6 lower risk of death[hazard ratio(HR),1.36,95%confidence interval(CI),1.10-1.69,P=0.004].Interaction between tumor sidedness and KRAS status was statistically significant:left-sidedness was associated with better prognosis among KRAS wild-type patients(HR 1.71;95%CI:1.20-2.45;P=0.003),but not among KRAS mutated-type patients.Integrated molecular analyses showed that right-sided tumors more frequently harbored TP53,APC,KRAS,and BRAF alterations,and identified a critical role of KRAS mutation in correlation with their survival differences.Higher pathogenic germline variants were identified in the right-sided tumors compared with left-sided tumors(29.3%vs.15.5%,P=0.03).Conclusions:We demonstrated that the prognostic impacts of tumor sidedness in CRLM is restricted patients with KRAS wild-type tumors.Tumor sidedness displays considerable clinical and molecular heterogeneity that may associate with their therapy benefits and prognosis.
文摘Approximately half of individuals diagnosed with colorectal cancer(CRC)will develop colorectal liver metastasis(CRLM)during the course of their disease(1,2).Liver resection is the only potentially curative treatment for patients with CRLM,yet less than 20%of individuals are candidates for resection due to the extent or location of liver disease,underlying liver function and/or presence of extrahepatic metastases(1,2).In addition,the oncologic benefit of liver resection for CRLM is limited by recurrence rates than can be as high as 70%(3).Liver transplantation(LT)for CRLM was initially proposed as an alternative treatment strategy in the early 1990s but was abandoned due to the initial poor outcomes(3,4).The concept of transplantation for CRLM was later revisited in the 2000s by a group in Oslo,Norway that reported promising results in the SECA-I pilot study(5).Since the completion of the SECA-I study,the Norwegian group has also published other promising data from the SECA-II study(6).In addition,other notable outcomes have been reported in the RAPID study(7),as well as another study from specialized centers in North America(8),both of which have revitalized the concept of LT for CRLM.
基金supported by a grant from the Grants-in-Aid for Research from the National Center for Global Health and Medicine(21A1019 to N.T.)。
文摘Recently,indocyanine green(ICG)fluorescence imaging has been widely used as a substitute for cholangiography in hepatobiliary surgery,to detect hepatic tumors,for accurate anatomical hepatectomy,and to increase the safety and accuracy of minimally invasive(laparoscopic and robotic)hepatectomy.The clinical relevance of this method has been increasing gradually,as new procedures develop in this field.Various important roles and the latest added value of ICG fluorescence imaging in liver surgery are discussed in this report.
文摘Background： Controversial results about the therapeutic value of radiofrequency ablation （RFA） and liver resection （LR） in the treatment of colorectal cancer liver metastasis （CRCLM） have been reported. Thus, we performed the present meta-analysis to summarize the related clinical evidences. Methods： A systematic literature search was conducted using PubMed （Medline）, EMBASE, Cochrane Library, and Web of Science, for all years up to April 2016. Pooled analyses of the overall survival （OS）, progression-free survival （PFS）, and morbidity rates were performed. Results： A total of 14 studies were finally enrolled in the meta-analysis. Patients treated by LR gained a longer OS and PFS than those of patients treated by RFA. Patients in the RFA group had lower morbidity rates than those of patients in the LR group. Publication bias analysis revealed that there was no significant publication bias in the meta-analysis. Conclusions： Patients with CRCLM gained much more survival benefits from LR than that from RFA. RFA rendered lower rates of morbidities. More well-designed randomized controlled trails comparing the therapeutic value of LR and RFA are warranted.
文摘Liver cancer is a leading cause of death worldwide,and hepatocellular carcinoma(HCC)is the most frequent primary liver tumour,followed by cholangiocarcinoma.Notably,secondary tumours represent up to 90% of liver tumours.Chronic liver disease is a recognised risk factor for liver cancer development.Up to 90% of the patients with HCC and about 20% of those with cholangiocarcinoma have an underlying liver alteration.The gut microbiota-liver axis represents the bidirectional relationship between gut microbiota,its metabolites and the liver through the portal flow.The interplay between the immune system and gut microbiota is also well-known.Although primarily resulting from experiments in animal models and on HCC,growing evidence suggests a causal role for the gut microbiota in the development and progression of chronic liver pathologies and liver tumours.Despite the curative intent of“traditional”treatments,tumour recurrence remains high.Therefore,microbiota modulation is an appealing therapeutic target for liver cancer prevention and treatment.Furthermore,microbiota could represent a non-invasive biomarker for early liver cancer diagnosis.This review summarises the potential role of the microbiota and immune system in primary and secondary liver cancer development,focusing on the potential therapeutic implications.
