Current landscape of preoperative neoadjuvant therapies for initial resectable colorectal cancer liver metastasis

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.

Prognostic role of serum carcinoembryonic antigen in patients receiving liver resection for colorectal cancer liver metastasis:A meta-analysis

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.

A novel animal model for in vivo study of liver cancer metastasis

AIM:To establish an animal model with human hepatocyte-repopulated liver for the study of liver cancer metastasis.METHODS:Cell transplantation into mouse livers was conducted using alpha-fetoprotein(AFP)-producing hu-man gastric cancer cells(h-GCCs) and h-hepatocytes as donor cells in a transgenic mouse line expressing urokinase-type plasminogen activator(uPA) driven by the albumin enhancer/promoter crossed with a severe combined immunodeficient(SCID) mouse line(uPA/SCID mice).Host mice were divided into two groups(A and B).Group A mice were transplanted with h-GCCs alone,and group B mice were transplanted with h-GCCs and h-hepatocytes together.The replacement index(RI),which is the ratio of transplanted h-GCCs and h-hepatocytes that occupy the examined area of a histological section,was estimated by measuring h-AFP and h-albumin concentrations in sera,respectively,as well as by immunohistochemical analyses of h-AFP and human cytokeratin 18 in histological sections.RESULTS:The h-GCCs successfully engrafted,repopulated,and colonized the livers of mice in group A(RI = 22.0% ± 2.6%).These mice had moderately differentiated adenocarcinomatous lesions with disrupted glandular structures,which is a characteristics feature of gastric cancers.The serum h-AFP level reached 211.0 ± 142.2 g/mL(range,7.1-324.2 g/mL).In group B mice,the h-GCCs and h-hepatocytes independently engrafted,repopulated the host liver,and developed colonies(RI = 12.0% ± 6.8% and 66.0% ± 12.3%,respectively).h-GCC colonies also showed typical adenocarcinomatous glandular structures around the h-hepatocyte-colonies.These mice survived for the full 56 day-study and did not exhibit any metastasis of h-GCCs in the extrahepatic regions during the observational period.The mice with an h-hepatocyte-repopulated liver possessed metastasized h-GCCs and therefore could be a useful humanized liver animal model for studying liver cancer metastasis in vivo.CONCLUSION:A novel animal model of human liver cancer metastasis was established using the uPA/SCID mouse line.This model could be useful for in vivo testing of anti-cancer drugs and for studying the mechanisms of human liver cancer metastasis.

Irreversible electroporation for liver metastasis from pancreatic cancer: A case report

BACKGROUND Pancreatic cancer has a poor prognosis;40%–50% of patients have liver metastases at the time of initial diagnosis and only 15%–20% undergo surgical resection. Irreversible electroporation(IRE) is a new, non-thermal local ablation method for solid tumors, which can induce cell membrane permeabilization,resulting in unrecoverable nanoscale perforation and apoptotic cell death without damaging the structural components of tissues.CASE SUMMARY We report the case of a 66-year-old female patient with liver metastasis from pancreatic cancer with a pathological diagnosis of poorly differentiated adenocarcinoma. Carbohydrate antigen 19-9 was elevated to 420.3 U/m L.Computed tomography showed a pancreas mass of 2.7 cm × 2.5 cm and single liver metastasis of 1.4 cm × 1.1 cm in the S6 area. The patient underwent IRE and arterial infusion chemotherapy and received tegafur. The therapeutic effect of the combination treatment has been evaluated as complete response. To date, the patient has survived for > 12 mo and is receiving tegafur as maintenance therapy(at the time this case report was written).CONCLUSION IRE plus arterial infusion chemotherapy and tegafur may be synergistic,providing a reference for treating liver metastasis from pancreatic cancer.

Advances in liver transplantation for unresectable colon cancer liver metastasis

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.

A STUDY OF THE FORMATION OF LIVER METASTASIS AND ITS MECHANISM USING THE INTRASPLENIC INOCULATION OF CANCER CELLS

In order to establish an animal model with hepatic metastasis intrasplenic inoculation of carcinoma cells from murine uterine cervical carcinoma (U14) was employed. Results showed a high incidence of hepatic metastasis could be obtained through the intrasplenic inoculation of 1 × 106 carcinoma cells. Removal of the primary carcinoma through splenec-tomy at different intervals after intrasplenic inoculation proved that the hepatic metastatic mechanism was not due to mechanical pressure but occurred spontaneously. This experimental model provides a useful means for studying the mechanism and prevention of hepatic metastasis.

Oncological outcomes and predictors of radiofrequency ablation of colorectal cancer liver metastases

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.

Is CA19-9 effective in predicting chemotherapeutic response in patients with synchronous liver metastases with colorectal cancer?

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.

Enhanced recovery nursing and mental health education on postoperative recovery and mental health of laparoscopic liver resection

BACKGROUND Patients undergoing laparoscopic resection of liver metastases of colorectal cancer are prone to negative emotions and decrease of digestive function.Early nursing and psychological intervention are necessary.AIM To observe the effect of enhanced recovery nursing combined with mental health education on postoperative recovery and mental health of patients undergoing laparoscopic resection of liver metastases of colorectal cancer.METHODS One hundred and twenty patients who underwent laparoscopic resection of liver metastases of colorectal cancer at our hospital between March 2021 and March 2023,were selected as participants.The patients admitted from March 1,2021 to February 28,2022 were set as the control group,and they were given routine nursing combined with mental health education intervention.While the patients admitted from March 1,2022 to March 31,2023 were set as the observation group,they were given accelerated rehabilitation surgical nursing combined with mental health education intervention.The differences in postoperative recovery-related indices,complications and pain degrees,and mental health-related scores were compared between groups.The T lymphocyte subset levels of the two groups were also compared.RESULTS The postoperative exhaust,defecation,eating and drainage time of the observation group were shorter than those of the control group.The pain scores of the observation group were lower than those of the control group at 6,12,24,48,and 72 h after surgery.The cumulative complication rate of the observation group was lower than that of the control group(P<0.05).The CD4+/CD8+in the observation group was higher than that in the control group 3 d after surgery(P<0.05).After intervention,the self-rating depression scale,self-rating anxiety scale,avoidance dimension,and yielding dimension in Medical coping style(MCMQ)scores of the two groups were lower than those prior to intervention,and the scores in the observation group were lower than those in the control group(P<0.05).The face dimension score in the MCMQ score was higher than that before intervention,and that of the observation group was higher than that of the control group(P<0.05).After intervention,the total scores of the life function index scale(FLIC)and psychological well-being scores of cancer patients in the two groups,and the physical and social well-being scores in the observation group,were higher than those before intervention.The nursing satisfaction of the observation group was higher than that of the control group(P<0.05).The physical,psychological,and social well-being,and the total FLIC scores of the observation group were higher than those in the control group after surgery(P<0.05).CONCLUSION Enhanced recovery nursing combined with mental health education can promote the recovery of gastrointestinal function,improve the mental health and quality of life of patients after laparoscopic resection of colorectal cancer liver metastases,and reduce the incidence of complications.

Gastric cancer liver metastasis will reduce the efficacy of immunotherapy

Immune checkpoint inhibitors augment the antitumor activity of T cells by inhibiting the negative regulatory pathway of T cells,leading to notable efficacy in patients with non-small cell lung cancer,melanoma,and other malignancies through immunotherapy utilization.However,secondary malignant liver tumors not only lower the liver's sensitivity to immunotherapy but also trigger systemic immune suppression,resulting in reduced overall effectiveness of immune therapy.Patients receiving immunotherapy for non-small cell lung cancer and melanoma experience reduced response rates,progression-free survival,and overall survival when secondary malignant tumors develop in the liver.Through Liu's retrospective analysis,valuable insights are provided for the future clinical management of these patients.Therefore,in patients with gastric cancer(GC),the occurrence of liver metastasis might be indicative of reduced efficacy of immuno-therapy.Overcoming liver immune tolerance mechanisms and their negative impacts allows for the potential benefits of immunotherapy in patients with GC and liver metastasis.INTRODUCTION Gastric cancer(GC)ranks among the prevalent malignancies affecting the digestive system globally.Based on the latest epidemiological data[1,2],it holds the fifth position for incidence and the fourth position for mortality among all malignant tumors.GC cases and fatalities in China make up roughly half of the worldwide figures.Earlier investigations[3]have demonstrated that the median overall survival(mOS)among advanced GC patients left untreated typically ranges from 3 to 4 months.Systemic chemotherapy recipients often experience a mOS of around one year,accompanied by a marked improvement in the quality of life among patients with advanced GC.The mainstay of treatment for advanced GC patients involves chemotherapeutic medications such as fluoropyrimidines,platinum compounds,and taxanes.However,their efficacy in tumor control is constrained by acquired resistance and primary resistance.The rise of personalized precision therapy has propelled immunotherapy into the spotlight as a crucial component of comprehensive treatment[4].By blocking the negative regulatory pathways of T cells,immune checkpoint inhibitors(ICIs)boost the anti-tumor effect of T cells.Immunotherapy has brought about significant therapeutic benefits for patients diagnosed with non-small cell lung cancer,melanoma,and related illnesses[5,6],instilling newfound hope in those with advanced GC[7].However,phase III clinical trial data[8-12]reveals that the incorporation of immunotherapy into chemotherapy regimens improves overall survival(OS)outcomes for patients with advanced GC.The liver's immune-exempt nature renders it less responsive to immunotherapy when secondary malignant tumors are present,fostering systemic immune suppression and yielding unfavorable outcomes in immune therapy[13-15].In retrospective research[16-20]pertaining to non-small cell lung cancer and melanoma,it has been observed that the presence of secondary liver malignancies may lower the response rate,progression-free survival(PFS),and OS rates in patients treated with immunotherapy,independent of factors such as tumor mutation burden and PD-L1 expression.Despite this,there is a paucity of studies examining whether the existence of secondary malignant liver tumors affects the effectiveness of immunotherapy in patients diagnosed with advanced HER-2 negative GC.

Liver metastasis of pancreatic cancer: the new choice at the crossroads

In recent years,the incidence of pancreatic cancer has increased markedly both in China and internationally.For patients with pancreatic cancer,surgical resection remains the only effective method of obtaining a cure and long-term survival,although only few patients can expect this benefit.

Role of surgical resection for non-colorectal non-neuroendocrine liver metastases

It is widely accepted that the indications for hepatectomy in colorectal cancer liver metastases and liver metastases of neuro-endocrine tumors result in relatively better prognoses, whereas, the indications and prognoses of hepatectomy for non-colorectal non-neuroendocrine liver metastases(NCNNLM) remain controversial owing to the limited number of cases and the heterogeneity of the primary diseases. There have been many publications on NCNNLM; however, its background heterogeneity makes it difficult to reach a specific conclusion. This heterogeneous disease group should be discussed in the order from its general to specific aspect. The present review paper describes the general prognosis and risk factors associated with NCNNLM while specifically focusing on the liver metastases of each primary disease. A multidisciplinary approach that takes into consideration appropriate timing for hepatectomy combined with chemotherapy may prolong survival and/or contribute to the improvement of the quality of life while giving respite from systemic chemotherapy.

Radiofrequency ablation versus hepatic resection for breast cancer liver metastasis: a systematic review and meta-analysis

Objective： To evaluate the comparative therapeutic efficacy of radiofrequency ablation （RFA） and hepatic resection （HR） for breast cancer liver metastases （BCLMs）. Methods： Studies that had examined the outcomes for both RFA and HR for BCLM were identified by searching the electronic databases PubMed, EMBASE, and the Cochrane Library. Pooled analyzes of the overall survival （OS）, disease-free survival （DFS）, and short-term outcomes of BCLM were performed. Results： Patients with BCLM gained many more survival benefits from HR than from RFA with regard to the 3-year OS rate （combined odds ratio （OR） 0.41, 95% confidence interval （CI） 0.29-0.59, P〈0.001）, 5-year OS rate （combined OR 0.38, 95% CI 0.32-0.46, P〈0.001）, 3-year DFS （combined OR 0.36, 95% CI 0.27-0.49, P〈0.001）, and 5-year DFS （combined OR 0.51, 95% CI 0.40-0.66, P〈0.001）. RFA had fewer postoperative compli- cations （combined OR 0.30, 95% CI 0.20-0.44, P〈0.001） and shorter hospital stays （combined OR -9.01, 95% CI -13.49-4.54, P〈0.001） than HR. Conclusions： HR takes precedence over RFA in the treatment of patients with BCLM, considering the better survival rate. RFA gives rise to fewer complications and can be carried out with a shorter hos- pital stay, compared to HR. RFA should be reserved for patients who are not optimum candidates for resection.

Study on Preventive and Therapeutic Effect of Radix Salviae Miltiorrhizae on Recurrence and Metastasis of Liver Cancer

Objective: To study the inhibitory effect of Radix Salviae Miltiorrhizae (RSM) on adhesive and invasive ability of SMMC 7721 liver cancer cells, and on the metastasis and recurrence on post hepatectomy liver cancer in nude mice. Methods: Effect of RSM on SMMC 7721 cell membrane intercellular adhesive molecule 1 (ICAM 1) expression was observed by immunofluorescence flow cytometry; effect on invasive ability and of SMMC 7721 cell and the detachment of which attached to fibronectin (FN) by cell migration experiment; effect on adhesion of SMMC 7721 cell with FN by MTT method and effect on adhesion between 7721 7721, 7721 lymphocyte and 7721 endothelial cell by cell adhesion experiment. LCI D20 human liver cancer metastasis model, after hepatectomy, was used to observe the effect of RSM on recurrence and metastasis of liver carcinoma in nude mice. Results: ICAM 1 expression in SMMC 7721 cells incubated with RSM was significantly lower than that in cells did not treated with RSM. RSM could inhibit the invasive ability of SMMC 7721 cell and made the cells already attached to FN exfoliated. It could also inhibit the adhesion of 7721 7721, 7721 lymphocyte and 7721 endothelial cell. And RSM showed preventive and therapeutic effect on intrahepatic and remote metastasis/recurrence of early and late human post hepatectomy liver cancer in nude mice. Conclusion: RSM could inhibit the invasion and adhesion of SMMC 7721 cell and could also prevent and inhibit metastasis and recurrence of human liver cancer after hepatectomy in nude mice.

Liver transplantation for non-resectable colorectal metastases-an evolving paradigm in transplant oncology

A better understanding of colorectal liver metastasis(CRLM)onco-genomics and the improvement of systemic treatments,including targeted and immune therapies,have shifted the paradigm of CRLM prognosis over the past two decades.While 40%of the patients with colorectal cancers are likely to develop CRLM[and 50%of them to be non-resectable(nCRLM)],current oncologic management allows for the identification of a subset of CRLM patients with controlled diseases likely to highly benefit from curative resections and,perhaps,liver transplantation(LT).Indeed,the Norwegian SECA I trial in 2013(1)triggered a growing interest in LT as a curative treatment for non-resectable colorectal liver metastasis(nCRLM).This strategy is supported by several pilot studies reporting up to 80%of 5-year estimated overall survival(OS)after LT for CRLM,in contrast to the poor results obtained in the early 80’s series.

Radiofrequency ablation versus microwave ablation for colorectal liver metastases:long-term results of a retrospective cohort surgical experience

Background:Ablation is an alternative treatment modality for selected patients with colorectal liver metastases(CRLMs).Although initially widely performed via radiofrequency ablation(RFA),more recently,microwave ablation(MWA)is being preferred due to its perceived superiority in creating the ablation zones.The aim of this study is to compare the long-term efficacy of these two modalities performed surgically.Methods:Patients undergoing surgical liver ablation from 2005-2023 at a tertiary center by a single surgeon for CRLM were included in a retrospective institutional review board-approved study.Outcomes were compared using Wilcoxon,Chi-square,Kaplan-Meier,and Cox multivariate regression analyses.Continuous data are presented as median(interquartile range).Results:There were a total of 242 patients.Laparoscopic RFA was done in 121 patients with 303 lesions and laparoscopic MWA in 121 patients with 300 lesions.There was no difference between the groups regarding operative time(161 vs.147 minutes,respectively,P=0.4),perioperative morbidity(3%vs.8%,respectively,P=0.2)or hospital stay(1 vs.1 day,P=0.05).Local recurrence(LR)per lesion with at least 1 year of imaging follow-up was 29%in the RFA and 13%in the MWA group(P<0.001).Based on univariate survival analysis,tumor size,blood vessel proximity,ablation margin,and ablation modality were independent predictors of LR.To control these variables,direct matching was performed.Each cohort included 189 lesions.Kaplan-Meier analysis of these cohorts showed increased LR-free survival in the MWA group vs.the RFA group(P=0.005).Conclusions:This large study confirms our initial observation that local tumor control rate is better after MWA vs.RFA.