Composite Configuration Interventional Therapy Robot for the Microwave Ablation of Liver Tumors

The existing interventional therapy robots for the microwave ablation of liver tumors have a poor clinical applicability with a large volume, low positioning speed and complex automatic navigation control. To solve above problems, a composite configuration interventional therapy robot with passive and active joints is developed. The design of composite configuration reduces the size of the robot under the premise of a wide range of movement, and the robot with composite configuration can realizes rapid positioning with operation safety. The cumulative error of positioning is eliminated and the control complexity is reduced by decoupling active parts. The navigation algo- rithms for the robot are proposed based on solution of the inverse kinematics and geometric analysis. A simulation clinical test method is designed for the robot, and the functions of the robot and the navigation algorithms are verified by the test method. The mean error of navigation is 1.488 mm and the maximum error is 2.056 mm, and thepositioning time for the ablation needle is in 10 s. The experimental results show that the designed robot can meet the clinical requirements for the microwave ablation of liver tumors. The composite configuration is proposed in development of the interventional therapy robot for the microwave ablation of liver tumors, which provides a new idea for the structural design of medical robots.

Chinese clinical practice guidelines for ultrasound-guided irreversible electroporation of liver cancer(version 2022)

Introduction Liver cancer remains a global health challenge,and its incidence is increasing worldwide.It is estimated that by 2025,more than one million individuals will be affected by liver cancer annually[1,2].In recent years,ablation has become a widely accepted treatment option for patients with primary and secondary liver malignancies[3].The commonly used ablation method for liver cancer is thermal ablation,including radiofrequency ablation.

Camrelizumab,apatinib and hepatic artery infusion chemotherapy combined with microwave ablation for advanced hepatocellular carcinoma

BACKGROUND Hepatic arterial infusion chemotherapy and camrelizumab plus apatinib(TRIPLET protocol)is promising for advanced hepatocellular carcinoma(Ad-HCC).However,the usefulness of microwave ablation(MWA)after TRIPLET is still controversial.AIM To compare the efficacy and safety of TRIPLET alone(T-A)vs TRIPLET-MWA(TM)for Ad-HCC.METHODS From January 2018 to March 2022,217 Ad-HCC patients were retrospectively enrolled.Among them,122 were included in the T-A group,and 95 were included in the T-M group.A propensity score matching(PSM)was applied to balance bias.Overall survival(OS)was compared using the Kaplan-Meier curve with the log-rank test.The overall objective response rate(ORR)and major complications were also assessed.RESULTS After PSM,82 patients were included both the T-A group and the T-M group.The ORR(85.4%)in the T-M group was significantly higher than that(65.9%)in the T-A group(P<0.001).The cumulative 1-,2-,and 3-year OS rates were 98.7%,93.4%,and 82.0%in the T-M group and 85.1%,63.1%,and 55.0%in the T-A group(hazard ratio=0.22;95%confidence interval:0.10-0.49;P<0.001).The incidence of major complications was 4.9%(6/122)in the T-A group and 5.3%(5/95)in the T-M group,which were not significantly different(P=1.000).CONCLUSION T-M can provide better survival outcomes and comparable safety for Ad-HCC than T-A.

Practice guidelines for ultrasound-guided percutaneous microwave ablation for hepatic malignancy

Primary liver cancer and liver metastases are among the most frequent malignancies worldwide,with an increasing number of new cases and deaths every year.Traditional surgery is only suitable for a limited proportion of patients and imaging-guided percutaneous thermal ablation has achieved optimistic results for management of hepatic malignancy.This synopsis outlines the first clinical practice guidelines for ultrasoundguided percutaneous microwave ablation therapy for hepatic malignancy,which was created by a joint task force of the Society of Chinese Interventional Ultrasound.The guidelines aim at standardizing the microwave ablation procedure and therapeutic efficacy assessment,as well as proposing the criteria for the treatment candidates.

Nomogram based on albumin-bilirubin grade to predict outcome of the patients with hepatitis C virus-related hepatocellular carcinoma after microwave ablation

Objective:To construct a nomogram based on the albumin-bilirubin(ALBI)grade to provide prognostic value for hepatitis C virus(HCV)-related hepatocellular carcinoma(HCC)patients who underwent ultrasound-guided percutaneous microwave ablation(US-PMWA).Methods:From April 2005 to January 2018,183 treatment-naIve patients with 251 HCV-related HCCs according to the Milan criteria received US-PMWA subsequently.The overall survival(OS)and recurrence-free survival(RFS)were compared between groups classified by ALBI grade.Cox proportional hazard regression model based on risk factors for survival and recurrence was used to construct the nomogram.Results:The cumulative OS rates at 1-,3-,5-and 10-year were 97.7%,73.6%,54.5%and 34.5%,respectively.Stratified according to ALBI grade,the 1-,3-,and 5-year OS in the ALBI grade 1 group and grade 2 group were 99.2%,92.4%,77.9% and 97.7%,52.3%,38.6%,respectively,with significant statistical difference(P<0.001).No significant statistical difference was detected in the1-,3-,and 5-year RFS rates in the ALBI grade 1 group and grade 2 group(P=0.220).The major complication rate was 1.6%.Multivariate analysis results showed age,α-fetoprotein level,tumor number,platelet count,location,Child-Turcotte-Pugh(CTP)and ALBI grade were associated with OS,which generated the nomograms.Internal validation with 1000 bootstrapped sample sets had good concordance index of 0.769(95%CI 0.699-0.839)in OS.Conclusions:This nomogram based on ALBI grade was a visualization risk model,which could provide personalized prediction of long-term outcomes for HCV-related HCC patients after US-PMWA.

Characterization of primary hepatic carcinosarcoma by contrast-enhanced ultrasonography: A case report

Primary hepatic carcinosarcoma is a rare tumor and is comprised of a mixture of carcinomatous and sarcomatous elements. We present a case of primary carcinosarcoma of the liver in a 59-year-old woman, which was confirmed by pathology following surgical resection. Using contrast-enhanced ultrasonography, the tumor showed peripheral nodular hyperenhancement in the arterial phase with two feeding arterial vessels and a large internal non-enhancing portion in the center. The peripheral nodular portion of the tumor showed hypoenhancement in the later phase.

Cholecystectomy is associated with higher risk of recurrence after microwave ablation of hepatocellular carcinoma:a propensity score matching analysis

Objective:To explore the association between cholecystectomy and the prognostic outcomes of patients with hepatocellular carcinoma(H CC)who underwent microwave ablation(MWA).Methods:Patients with HCC(«=921)who underwent MWA were included and divided into cholecystectomy(n=114)and non-cholecystectomy groups(n=807).After propensity score matching(PSM)at a 1:2 ratio,overall survival(OS)and disease-free survival(DFS)rates were analyzed to compare prognostic outcomes between the cholecystectomy(«=114)and non-cholecystectomy groups(n=228).Univariate and multivariate Cox analyses were performed to assess potential risk factors for OS and DFS.Major complications were also compared between the groups.Results:After matching,no significant differences between groups were observed in baseline characteristics.The 1-,3-,and 5-year OS rates were 96.5%,82.1%,and 67.1%in the cholecystectomy group,and 97.4%,85.2%,and 74.4%in the non-cholecystectomy group(P=0.396);the 1-,3-,and 5-year DFS rates were 58.4%,34.5%,and 26.6%in the cholecystectomy group,and 73.6%,44.7%,and 32.2%in the non-cholecystectomy group(P=0.026),respectively.The intrahepatic distant recurrence rate in the cholecystectomy group was significantly higher than that in the non-cholecystectomy group(P=0.026),and the local tumor recurrence and extrahepatic recurrence rates did not significantly differ between the groups(P=0.609 and P=0.879).Multivariate analysis revealed that cholecystectomy(HR=1.364,95%Cl 1.023-1.819,P=0.035),number of tumors(2 vs.1:HR=2.744,95%Cl 1.925-3.912,P<0.001;3 vs.1:HR=3.411,95%Cl 2.021-5.759,P<0.001),and y-GT levels(HR=1.003,95%Cl 1.000-1.006,P<0.024)were independent risk factors for DFS.The best y-GT level cut-off value for predicting median DFS was 39.6 U/L(area under the curve=0.600,P<0.05).A positive correlation was observed between cholecystectomy and y-GT level(r=0.108,95%Cl-0.001-0.214,P=0.047).Subgroup analysis showed that the DFS rates were significantly higher in the non-cholecystectomy group than the cholecystectomy group when Y-GT>39.6 U/L(i3=0.044).The 5-,10-,15-,20-,and 25-year recurrence rates from the time of cholecystectomy were 2.63%,21.93%,42.11%,58.77%,and 65.79%,respectively.A significant positive correlation was observed between cholecystectomy and the time from cholecystectomy to recurrence(r=0.205,95%Cl 0.016-0.379,P=0.029).There were no significant differences in complications between groups(P=0.685).Conclusions:Patients with HCC who underwent cholecystectomy were more likely to develop intrahepatic distant recurrence after MWA,an outcome probably associated with increased y-GT levels.Moreover,the recurrence rates increased with time.

Immune responses of dendritic cells combined with tumor-derived autophagosome vaccine on hepatocellular carcinoma

Background： To induce and collect tumor-derived autophagosomes （DRibbles） from tumor cells as an antitumor vaccine by inhibiting the functions of proteasomes and lysosomes. Methods： Dendritic cells （DCs） generated from peripheral blood mononuclear cell （PBMC） of hepatocellular carcinoma （HCC） patients were cocultured with DRibbles, and then surface molecules of DCs, as well as surface molecules on DCs, were determined by flow cytometry. Meanwhile, immune responses of the DCs-DRibbles were examined by mixed lymphocyte reactions. Results： DRibbles significantly induced the expression of CD80, CD83, CD86 and HLA-DR on DCs. The enzyme-linked immunosorbnent assay （ELISA） showed that IFN-γ, levels after vaccination increased than before in most patients, but CDS＋ proportion of PBMC increased only in nine patients. Higher levels of IFN-γ, were detected in the CD8＋ cells than CD4＋ T cells. These results suggested that DCs-DRibbles vaccine could induce antigen-specific cellular immune response on HCC and could prime strong CD8＋ T cell responses, supporting it as a tumor vaccine candidate. Conclusions： Our results demonstrate that HCC/DRibbles-pulsed DCs immunotherapy might be deployed as an effective antitumor vaccine for HCC immunotherapy in clinical trials.

Microwave ablation vs. surgical resection for treatment naïve hepatocellular carcinoma within the Milan criteria: a follow-up of at least 5 years

Objective:Thermal ablation poses challenges in the surgical resection(SR)of small hepatocellular carcinoma(HCC),and its therapeutic outcomes for larger lesions remain debated.Methods:This retrospective study evaluated 729 patients with HCC meeting the Milan criteria,who were treated with curative SR or microwave ablation(MWA)between 2008 and 2014.Overall survival(OS),cancer-specific survival(CSS),disease-free survival(DFS),and local tumor progression(LTP)were compared after propensity score matching(PSM).Co-variates associated with OS,CSS,LTP,and DFS were identified.The risk of death and tumor progression were compared.Results:During the median follow-up of 78.6 months,253 patients were included in each group after PSM.For tumors≤3.0 cm and 3.1–4.0 cm,MWA achieved comparable results in terms of OS,CSS,DFS,and LTP.For tumors 4.1–5.0 cm,MWA had lower OS,CSS,and DFS rates(all P<0.05)than SR.Higher LTP rates were observed in the MWA group for tumors 4.1–5.0 cm,although the difference was not significant(P=0.18).Complication rates(P=0.41)were similar,but MWA led to less estimated blood loss(P<0.01)and shorter postoperative hospitalization times(P<0.01).Conclusions:MWA achieved comparable long-term oncologic outcomes with SR for≤4 cm HCC,with lower complication rates and faster recovery.

The multiple faces of cGAS-STING in antitumor immunity:prospects and challenges

As a key sensor of double-stranded DNA(dsDNA),cyclic GMP-AMP synthase(cGAS)detects cytosolic dsDNA and initiates the synthesis of 2′3′cyclic GMP-AMP(cGAMP)that activates the stimulator of interferon genes(STING).This finally promotes the production of type I interferons(IFN-I)that is crucial for bridging innate and adaptive immunity.Recent evidence show that several antitumor therapies,including radiotherapy(RT),chemotherapy,targeted therapies and immunotherapies,activate the cGAS-STING pathway to provoke the antitumor immunity.In the last decade,the development of STING agonists has been a major focus in both basic research and the pharmaceutical industry.However,up to now,none of STING agonists have been approved for clinical use.Considering the broad expression of STING in whole body and the direct lethal effect of STING agonists on immune cells in the draining lymph node(dLN),research on the optimal way to activate STING in tumor microenvironment(TME)appears to be a promising direction.Moreover,besides enhancing IFN-I signaling,the cGAS-STING pathway also plays roles in senescence,autophagy,apoptosis,mitotic arrest,and DNA repair,contributing to tumor development and metastasis.In this review,we summarize the recent advances on cGAS-STING pathway’s response to antitumor therapies and the strategies involving this pathway for tumor treatment.

Reengineering Surgical Patient Transfer and Handover Process in Operating Room

Objective:To reform the transfer process of surgical patients,standardize the transfer process,and improve the quality of safe transfer;unify the intrahospital transfer process to achieve standardized management;ensure patient safety,improve work efficiency,and reduce the occurrence of adverse events.Methods:A transfer team was formed,a handover record sheet for surgical patients was designed,and the workflow and specifications for handover and transfer of surgical patients were formulated.Results:After using the re-designed handover record sheet for surgical patients and improving the procedure for transferring surgical patients,the accuracy of surgical patient handover was ensured,the handover and transfer time was shortened,and the surgical turnover rate improved.Conclusion:By designing and reforming the service model,it is possible to change and standardize the transfer process of surgical patients and improve the quality of safe transfer,the operating room management system so that it is more rational and humanized,the management model,the working environment,as well as the overall quality and efficiency of operating room nursing.

Selective expansion and enhanced anti-tumor effect of antigen-specific CD4^(+)T cells by retrovirus-mediated IL-15 expression

Mounting evidence has demonstrated that CD4^(+)T cells play an important role in anti-tumor immune responses.Thus,adoptive transfer of these cells may have great potential for anti-cancer therapy.However,due to the difficulty to generate sufficient tumor-specific CD4^(+)T cells,the use of CD4^(+)T cells in tumor therapy is limited.It has been found that IL-15 transfection enhances the proliferation and anti-tumor activity of tumor-specific CD8+Tcells,but the effect of IL-15 transfection on CD4^(+)T cells remains unknown.Here,the effects of retrovirusmediated IL-15 expression in Ova-specific CD4^(+)T cells from Do11.10 mice were evaluated and it was discovered that IL-15 transfected CD4^(+)T cells expressed both soluble and membrane-bound IL-15.Retrovirusmediated IL-15 expression led to a selective expansion of antigen-specific CD4^(+)T cells by inhibiting their apoptosis.In vivo IL-15 transfected CD4^(+)T cells were more effective in suppressing tumor growth than control retroviral vector transfected ones.To ensure the safety of the method,the employment of thymidine kinase gene made it possible to eliminate these transgenic CD4^(+)T cells following ganciclovir treatment.Together,we show that IL-15 transfection induced a selective expansion of antigen-specific CD4^(+)T cells ex vivo and enhanced their tumor-suppression effects in vivo.This has an important significance for improving the efficacy of adoptive T cell therapy.

Combination therapy using microwave ablation and d-mannose-chelated iron oxide nanoparticles inhibits hepatocellular carcinoma progression

Despite being a common therapy for hepatocellular carcinoma(HCC),insufficient thermal ablation can leave behind tumor residues that can cause recurrence.This is believed to augment M2 inflammatory macrophages that usually play a pro-tumorigenic role.To address this problem,we designed D-mannose-chelated iron oxide nanoparticles(man-IONPs) to polarize M2-like macrophages into the antitumor Ml phenotype.In vitro and in vivo experiments demonstrated that man-IONPs specifically targeted M2-like macrophages and accumulated in peri-ablation zones after macrophage infiltration was augmented under insufficient microwave ablation(MWA).The nanoparticles simultaneously induced polarization of pro-tumorigenic M2 macrophages into antitumor M1 phenotypes,enabling the transformation of the immunosuppressive microenvironment into an immunoactivating one.Post-MWA macrophage polarization exerted robust inhibitory effects on HCC progression in a well-established orthotopic liver cancer mouse model.Thus,combining thermal ablation with man-IONPs can salvage residual tumors after insufficient MWA.These results have strong potential for clinical translation.

Pulsed low-dose rate radiotherapy has an improved therapeutic effect on abdominal and pelvic malignancies

Until now,there has been a lack of standard and effective treatments for patients with recurrent malignant tumors or abdominal and pelvic malignancies with extensive invasion(Morris,2000).Generally,these patients face problems such as inability to undergo surgery or chemotherapy resistance(Combs et al.,2016).Re-radiotherapy has achieved a prominent place in the treatment of patients who have received radiotherapy previously and developed in-field recurrences(Straube et al.,2018).However,re-radiotherapy is very complicated,requiring comprehensive consideration of appropriate radiation dose,interval from first radiotherapy,boundary of the radiotherapy target area,and damage to surrounding normal tissues(Straube et al.,2019).In other words,it is necessary to focus on the protection of surrounding normal tissues while maximizing the eflFicacy of re-radiotherapy in such patients.