Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.

Adjuvant therapy for hepatocellular carcinoma:Dilemmas at the start of a new era

Approximately 50%-70%of patients with hepatocellular carcinoma experience recurrence within five years after curative hepatic resection or ablation.As a result,many patients receive adjuvant therapy after curative resection or ablation in order to prolong recurrence-free survival.The therapy recommended by national guidelines can differ,and guidelines do not specify when to initiate adjuvant therapy or how long to continue it.These and other unanswered questions around adjuvant therapies make it difficult to optimize them and determine which may be more appropriate for a given type of patient.These questions need to be addressed by clinicians and researchers.

Immunotherapy for esophageal cancer:Where are we now and where can we go

Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.

应对可转移多黏菌素耐药性--饲料添加剂来源的白屈菜红碱具有双重效应

The emergence and spread of the mobile colistin-resistance gene,mcr-1,and its variants pose achallenge to the use of colistin,a last-resort antibiotic used to treat severe infections caused by extensively drug-resistant(XDR)Gram-negative pathogens.Antibiotic adjuvants are a promising strategy to enhance the efficacy of colistin against colistin-resistant pathogens;however,few studies have considered the effects of adjuvants on limiting resistance-gene transmission.We found that chelerythrine(4 mg·L^(-1))derived from Macleaya cordata extract,which is used as an animal feed additive,reduced the minimal inhibitory concentration(MIC)of colistin against an mcr-1 positive Escherichia coli(E.coli)strain by 16-fold(from 2.000 to 0.125 mg·L^(-1)).eliminated approximately 10^(4) colony-forming units(CFUs)of an mcr-1-carrying strain in a murine intestinal infection model,and inhibited the conjugation of an mcr-1-bearing plasmid in vitro(by>100-fold)and in a mouse model(by up to 5-fold).A detailed analysis revealed that chelery-thrine binds to phospholipids on bacterial membranes and increases cytoplasmic membrane fluidity,thereby impairing respiration,disrupting proton motive force(PMF),generating reactive oxygen species(ROS),and decreasing intracellular adenosine triphosphate(ATP)levels,which subsequently downregu-lates mcr-1 and conjugation-associated genes.These dual effects of chelerythrine can expand the use of antibiotic adjuvants and may provide a new strategy for circumventing mobile colistin resistance.

Coordination of distinctive pesticide adjuvants and atomization nozzles on droplet spectrum evolution for spatial drift reduction

Pesticide adjuvants,as crop protection products,have been widely used to reduce drift loss and improve utilization efficiency by regulating droplet spectrum.However,the coordinated regulation mechanisms of adjuvants and nozzles on droplet spectrum remain unclear.Here,we established the relationship between droplet spectrum evolution and liquid atomization by investigating the typical characteristics of droplet diameter distribution near the nozzle.Based on this,the regulation mechanisms of distinctive pesticide adjuvants on droplet spectrum were clarified,and the corresponding drift reduction performances were quantitively evaluated by wind tunnel experiments.It shows that the droplet diameter firstly shifts to the smaller due to the liquid sheet breakup and then prefers to increase caused by droplet interactions.Reducing the surface tension of sprayed liquid facilitates the uniform liquid breakup and increasing the viscosity inhibits the liquid deformation,which prolong the atomization process and effectively improve the droplet spectrum.As a result,the drift losses of flat-fan and hollow cone nozzles are reduced by about 50%after adding organosilicon and vegetable oil adjuvants.By contrast,the air induction nozzle shows a superior anti-drift ability,regardless of distinctive adjuvants.Our findings provide insights into rational adjuvant design and nozzle selection in the field application.

Immunomodulatory activity of polycaprolactone nanoparticles with calcium phosphate salts against Leishmania infantum infection

Objective:To prepare and characterize polycaprolactone(PCL)nanoparticles loaded with sonicator fragmented(SLA)and freeze-thaw Leishmania antigens(FTLA)and to investigate the in vitro immunogenicity of antigen-encapsulated nanoparticles with calcium phosphate adjuvant.Methods:The water/oil/water binary emulsion solvent evaporation method was used to synthesize antigen-loaded PCL nanoparticles.Particles were characterized by scanning electron microscopy and zeta potential measurements.Their cytotoxicity in J774 macrophages in vitro was determined by MTT analysis.In addition,the amount of nitric oxide and the level of cytokines produced by macrophages were determined by Griess reaction and ELISA method,respectively.The protective effect of the developed formulations was evaluated by determining the infection index percentage in macrophages infected with Leishmania infantum.Results:Compared to the control group,SLA PCL and FTLA PCL nanoparticles with calcium phosphate adjuvant induced a 6-and 7-fold increase in nitric oxide,respectively.Additionally,the vaccine formulations promoted the production of IFN-γand IL-12.SLA PCL and FTLA PCL nanoparticles combined with calcium phosphate adjuvant caused an approximately 13-and 11-fold reduction in infection index,respectively,compared to the control group.Conclusions:The encapsulation of antigens obtained by both sonication and freeze-thawing into PCL nanoparticles and the formulations with calcium phosphate adjuvant show strong in vitro immune stimulating properties.Therefore,PCL-based antigen delivery systems and calcium phosphate adjuvant are recommended as a potential vaccine candidate against leishmaniasis.

A pilot clinical study to evaluate feasibility of using single patient classifier as a prognostic test in stage Ⅱ-Ⅲ gastric cancer patients

Objective:Precision medicine approaches emphasize the importance of reliable prognostic tools for guiding individualized therapy decisions.In this study,we evaluated the clinical feasibility of the single patient classifier(SPC)test,a new clinical-grade prognostic assay,in stageⅡ-Ⅲgastric cancer patients.Methods:A prospective multicenter study was conducted,involving 237 patients who underwent gastrectomy between September 2019 and August 2020 across nine hospitals.The SPC test was employed to stratify patients into risk groups,and its feasibility and performance were evaluated.The primary endpoint was the proportion of the cases in which the test results were timely delivered before selecting postoperative treatment.Furthermore,3-year disease-free survivals of risk groups were analyzed.Results:The SPC test met the primary endpoint criteria.The 99.5%of SPC tests were timely delivered to hospitals before the postoperative treatment started.In a clinical setting,the median time from the specimen transfer to laboratory to the result delivery to hospital was 4 d.Furthermore,3-year disease-free survivals were significantly different between risk groups classified with SPC tests.Conclusions:This study highlights the SPC test's feasibility in offering crucial information timely delivered for making informed decisions regarding postoperative treatment strategies.It also provides evidence to support the implementation of a future prospective clinical trial aimed at evaluating the clinical utility of the SPC test in guiding personalized treatment decisions for gastric cancer patients.

Comparison of clinical characteristics and prognostic factors in two site-specific categories of ampullary cancer

BACKGROUND Ampullary cancer is a relatively rare malignant tumor in the digestive system.Its incidence has increased in recent years.As for now,its biological characteristics have not been fully clarified.Recent studies have primarily focused on the histological classification and genetic changes,but there are fewer investigations into the differences among site-specific subgroups.The clinicopathological charac-teristics of ampullary cancer occurring in different positions have not been elucidated.Furthermore,the role of adjuvant therapy in the treatment of patients with ampullary cancer remains controversial.ampullary cancer and explore the factors affecting prognosis.METHODS A total of 356 patients who met the inclusion and exclusion criteria were enrolled.Patients were divided into ampulla of Vater cancer(AVC)and duodenal papilla cancer(DPC)based on the gross and microscopic findings.Baseline data,admission examination results,and perioperative outcomes were collected and analyzed.The Kaplan-Meier curve was used for survival analysis.Univariate and multivariate analysis was performed to explore the independent risk factors affecting the overall survival(OS)of both groups.RESULTS The preoperative total bilirubin level in patients with AVC was significantly higher than those with DPC(P=0.04).The OS for patients with DPC was 58.90±38.74 months,significantly longer than 44.31±35.90 months for patients with AVC(P<0.01).The independent risk factors affecting the OS of AVC included:Preoperative albumin level(P=0.009),total bilirubin level(P=0.017),and number of positive lymph nodes(P=0.005).For DPC,risk factors included:Age(P=0.004),tumor size(P=0.023),number of positive lymph nodes(P=0.010)and adjuvant treatment(P=0.020).Adjuvant therapy significantly improved the OS rate of patients with DPC,but not for those with AVC.CONCLUSION Patients with AVC had a shorter OS compared to those with DPC.The prognosis factors and the role of adjuvant therapy of two groups were different.

Mapping the metabolic responses to oxaliplatin-based chemotherapy with in vivo spatiotemporal metabolomics

Adjuvant chemotherapy improves the survival outlook for patients undergoing operations for lung metastases caused by colorectal cancer (CRC). However, a multidisciplinary approach that evaluates several factors related to patient and tumor characteristics is necessary for managing chemotherapy treatment in metastatic CRC patients with lung disease, as such factors dictate the timing and drug regimen, which may affect treatment response and prognosis. In this study, we explore the potential of spatial metabolomics for evaluating metabolic phenotypes and therapy outcomes during the local delivery of the anticancer drug, oxaliplatin, to the lung. 12 male Yorkshire pigs underwent a 3 h left lung in vivo lung perfusion (IVLP) with various doses of oxaliplatin (7.5, 10, 20, 40, and 80 mg/L), which were administered to the perfusion circuit reservoir as a bolus. Biocompatible solid-phase microextraction (SPME) microprobes were combined with global metabolite profiling to obtain spatiotemporal information about the activity of the drug, determine toxic doses that exceed therapeutic efficacy, and conduct a mechanistic exploration of associated lung injury. Mild and subclinical lung injury was observed at 40 mg/L of oxaliplatin, and significant compromise of the hemodynamic lung function was found at 80 mg/L. This result was associated with massive alterations in metabolic patterns of lung tissue and perfusate, resulting in a total of 139 discriminant compounds. Uncontrolled inflammatory response, abnormalities in energy metabolism, and mitochondrial dysfunction next to accelerated kynurenine and aldosterone production were recognized as distinct features of dysregulated metabolipidome. Spatial pharmacometabolomics may be a promising tool for identifying pathological responses to chemotherapy.

Recent advances on vaccines against malaria: A review

This review aims to summarize the currently viable vaccine strategies including the approved vaccines and the those in trials for next-generation malaria vaccines.Data on malaria vaccine development was collected through a comprehensive review.The literature search was performed using databases including Google Scholar,PubMed,NIH,and Web of Science.Various novel approaches of vaccination are being developed,including those based on radiation-attenuated strategies,monoclonal antibodies,targeted immunogenic peptides,RNA and DNA vaccines,nanoparticle-based vaccines,protein-based vaccination protocols,and whole organism-based vaccination strategies.Trials on RTS,S have entered phase Ⅲtesting,and those based on blood-stage vaccines and vaccines to interrupt malarial transmission have advanced to higher stages of trials.Mathematical modeling,combined drug and vaccine strategies,mass drug administration,polyvalent vaccine formulations,and targeted vaccination campaigns is playing an important role in malarial prevention.Furthermore,assessing coverage,accessibility,acceptability,deployment,compilation,and adherence to specific vaccination strategies in endemic regions is essential for vaccination drives against malaria.

TRIANGLE operation,combined with adequate adjuvant chemotherapy,can improve the prognosis of pancreatic head cancer:A retrospective study

BACKGROUND The TRIANGLE operation involves the removal of all tissues within the triangle bounded by the portal vein-superior mesenteric vein,celiac axis-common hepatic artery,and superior mesenteric artery to improve patient prognosis.Although previously promising in patients with locally advanced pancreatic ductal adenocarcinoma(PDAC),data are limited regarding the long-term oncological outcomes of the TRIANGLE operation among resectable PDAC patients undergoing pancreaticoduodenectomy(PD).AIM To evaluate the safety of the TRIANGLE operation during PD and the prognosis in patients with resectable PDAC.METHODS This retrospective cohort study included patients who underwent PD for pancreatic head cancer between January 2017 and April 2023,with or without the TRIANGLE operation.Patients were divided into the PD_(TRIANGLE)and PD_(non-TRIANGLE)groups.Surgical and survival outcomes were compared between the two groups.Adequate adjuvant chemotherapy was defined as adjuvant chemotherapy≥6 months.RESULTS The PD_(TRIANGLE)and PD_(non-TRIANGLE) groups included 52 and 55 patients,respectively.There were no significant differences in the baseline characteristics or perioperative indexes between the two groups.Furthermore,the recurrence rate was lower in the PD_(TRIANGLE) group than in the PD_(non-TRIANGLE) group(48.1%vs 81.8%,P<0.001),and the local recurrence rate of PDAC decreased from 37.8%to 16.0%.Multivariate Cox regression analysis revealed that PD_(TRIANGLE)(HR=0.424;95%CI:0.256-0.702;P=0.001),adequate adjuvant chemotherapy≥6 months(HR=0.370;95%CI:0.222-0.618;P<0.001)and margin status(HR=2.255;95%CI:1.252-4.064;P=0.007)were found to be independent factors for the recurrence rate.CONCLUSION The TRIANGLE operation is safe for PDAC patients undergoing PD.Moreover,it reduces the local recurrence rate of PDAC and may improve survival in patients who receive adequate adjuvant chemotherapy.

Epidemiology and prognostic nomogram for locally advanced gastric signet ring cell carcinoma:A population-based study

BACKGROUND Gastric signet ring cell carcinoma(GSRC)represents a specific subtype of gastric cancer renowned for its contentious epidemiological features,treatment principles,and prognostic factors.AIM To investigate the epidemiology of GSRC and establish an improved model for predicting the prognosis of patients with locally advanced GSRC(LAGSRC)after surgery.METHODS The annual rates of GSRC incidence and mortality,covering the years 1975 to 2019,were extracted from the Surveillance,Epidemiology,and End Results(SEER)database to explore the temporal trends in both disease incidence and mortality rates using Joinpoint software.The clinical data of 3793 postoperative LAGSRC patients were collected from the SEER database for the analysis of survival rates.The Cox regression model was used to explore the independent prognostic factors for overall survival(OS).The risk factors extracted were used to establish a prognostic nomogram.RESULTS The overall incidence of GSRC increased dramatically between 1975 and 1998,followed by a significant downward trend in incidence after 1998.In recent years,there has been a similarly optimistic trend in GSRC mortality rates.The trend in GSRC showed discrepancies based on age and sex.Receiver operating characteristic curves,calibration curves,and decision curve analysis for 1-year,3-year,and 5-year OS demonstrated the high discriminative ability and clinical utility of this nomogram.The area under the curve indicated that the performance of the new model outperformed that of the pathological staging system.CONCLUSION The model we established can aid clinicians in the early prognostication of LAGSRC patients,resulting in improved clinical outcomes by modifying management strategies and patient health care.

Survival benefit of concurrent chemoradiotherapy for advanced ampulla of Vater cancer

BACKGROUND Currently,there is no standard adjuvant therapy for patients with resected ampulla of Vater(AoV)cancer.AIM To evaluate the effectiveness of adjuvant concurrent chemoradiotherapy(CCRT)in patients with advanced AoV cancer who underwent curative resection.METHODS This single-centered,retrospective study included 29 patients with advanced AoV cancer who underwent pancreaticoduodenectomy between 2006 and 2018.The impact of CCRT on advanced AoV cancer was analyzed.RESULTS The 1-,3-,and 5-yr recurrence-free survival(RFS)rates for patients with advanced AoV cancer were 82.8%,48.3%,and 40.8%,respectively,and the overall survival(OS)rates were 89.7%,62.1%,and 51.7%,respectively.Lymphovas-cular invasion was found to be a significant risk factor for RFS and OS in patients with advanced AoV cancer in the univariate analysis,whereas T stage and lymph node metastasis were significantly associated with OS in the multivariate analysis.Compared to the patients who did not receive adjuvant CCRT,those who received adjuvant CCRT did not show statistically significant improvements in the RFS and OS,although they had a significantly lower average age and significantly higher platelet-to-lymphocyte ratio.CONCLUSION Adjuvant CCRT did not improve survival outcomes in patients with advanced AoV cancer.These findings contribute to existing knowledge on the effectiveness of CCRT in this patient population and provide important insights for clinical decision-making.

Rare esophageal carcinoma-primary adenoid cystic carcinoma of the esophagus: A case report

BACKGROUND Esophageal adenoid cystic carcinoma(EACC)is an exceedingly rare malignant tumor of the esophagus,posing significant challenges in the clinic.CASE SUMMARY This report detailed the case of a 72-year-old male whose diagnosis of EACC was confirmed through postoperative histopathological examination.The patient underwent thoracoscopy-assisted radical resection of the esophageal tumor,coupled with lymph node dissection.Pathological findings revealed an adenoid cystic carcinoma infiltrating the entire layer of the muscularis propria,locally extending into the outer membrane of the esophageal fiber,involving the cardia and exhibiting no lymph node metastasis.The patient’s condition was classified as primary EACC,T3N0M0,per the American Joint Committee on Cancer(2017;8th edition).One month after surgery,the patient received postoperative adjuvant radiation therapy.CONCLUSION In addressing the rarity and high potential for biopsy misdiagnosis of EACC,this study delved into its diagnostic methods and treatment.

Optimal extent of lymphadenectomy improves prognosis and guides adjuvant chemotherapy in esophageal cancer: A propensity scorematched analysis

BACKGROUND The optimal extent of lymphadenectomy in esophageal squamous cell carcinoma(ESCC)patients remained debatable.AIM To explore the ideal number of cleared lymph nodes in ESCC patients undergoing upfront surgery.METHODS In this retrospective,propensity score-matched study,we included 1042 ESCC patients who underwent esophagectomy from November 2008 and October 2019.Patients who underwent neoadjuvant therapy were excluded.We collected pa-tients’clinicopathological features and information regarding lymph nodes,in-cluding the total number of resected lymph nodes(NRLN),and pathologically diagnosed positive lymph nodes(RPLN).SPSS and R software were used for statistical analysis.RESULTS Among the included 1042 patients,two cohorts:≤21(n=664)and>21 NRLN(n=378)were identified.The final prognostic model included four variables:T stage,N,venous thrombus,and the number of removed lymph nodes.Among them,NRLN>21 was determined as an independent prognosticator after surgery for esophageal cancer(hazards regression=0.66,95%confidence interval:0.50-0.87,P=0.004).A nomogram was created based on the regression coefficients of the variables in the final model.In the training cohort,the predictive model dis-played an uncorrected five-year overall survival C-index of 0.659,with a bootstrap-corrected C-index of 0.654.In the subgroup analysis,adjuvant chemotherapy was beneficial in the subgroup with NRLN>21 and RPLN≤0.16 and NRLN≤21 and RPLN>0.16.CONCLUSION NRLN>21 was an independent prognostic factor after ESCC surgery.The combination of NRLN and RPLN may provide a reference for adjuvant chemotherapy use in potential beneficiaries.

New method of local adjuvant therapy with bicarbonate Ringer’s solution for tumoral calcinosis: A case report

BACKGROUND Tumoral calcinosis is a condition characterized by deposits of calcium phosphate crystals in extra-articular soft tissues,occurring in hemodialysis patients.Calcium phosphate crystals are mainly composed of hydroxyapatite,which is highly infilt-rative to tissues,thus making complete resection difficult.An adjuvant method to remove or resolve the residual crystals during the operation is necessary.CASE SUMMARY A bicarbonate Ringer’s solution with bicarbonate ions(28 mEq/L)was used as the adjuvant.After resecting calcium phosphate deposits of tumoral calcinosis as much as possible,while filling with the solution,residual calcium phosphate deposits at the pseudocyst wall can be gently scraped by fingers or gauze in the operative field.A 49-year-old female undergoing hemodialysis for 15 years had swelling with calcium deposition for 2 years in the shoulders,bilateral hip joints,and the right foot.A shoulder lesion was resected,but the calcification remained and early re-deposition was observed.Considering the difficulty of a complete rection,we devised a bicarbonate dissolution method and excised the foot lesion.After resection of the calcified material,the residual calcified material was washed away with bicarbonate Ringer’s solution.CONCLUSION The bicarbonate dissolution method is a new,simple,and effective treatment for tumoral calcinosis in hemodialysis patients.

Comparative effectiveness of several adjuvant therapies after hepatectomy for hepatocellular carcinoma patients with microvascular invasion

BACKGROUND For resectable hepatocellular carcinoma(HCC),radical hepatectomy is commonly used as a curative treatment.However,postoperative recurrence significantly diminishes the overall survival(OS)of HCC patients,especially with microva-scular invasion(MVI)as an independent high-risk factor for recurrence.While some studies suggest that postoperative adjuvant therapy may decrease the risk of recurrence following liver resection in HCC patients,the specific role of adju-vant therapies in those with MVI remains unclear.AIM To conduct a network meta-analysis(NMA)to evaluate the efficacy of various adjuvant therapies and determine the optimal adjuvant regimen.METHODS A systematic literature search was conducted on PubMed,EMBASE,and Web of Science until April 6,2023.Studies comparing different adjuvant therapies or comparing adjuvant therapy with hepatectomy alone were included.Hazard ratios(HRs)with 95%confidence intervals were used to combine data on recurrence free survival and OS in both pairwise meta-analyses and NMA.RESULTS Fourteen eligible trials(2268 patients)reporting five different therapies were included.In terms of reducing the risk of recurrence,radiotherapy(RT)[HR=0.34(0.23,0.5);surface under the cumulative ranking curve(SUCRA)=97.7%]was found to be the most effective adjuvant therapy,followed by hepatic artery infusion chemotherapy[HR=0.52(0.35,0.76);SUCRA=65.1%].Regarding OS improvement,RT[HR:0.35(0.2,0.61);SUCRA=93.1%]demonstrated the highest effectiveness,followed by sorafenib[HR=0.48(0.32,0.69);SUCRA=70.9%].INTRODUCTION Hepatocellular carcinoma(HCC)is the sixth most common malignant tumor in the world and ranks third in terms of worldwide malignant tumor mortality rates in 2020[1].Curative treatments for HCC include ablation,radical hepatectomy,and liver transplantation.However,ablation is suitable only for early-stage HCC patients,who represent a small percentage of the overall HCC population.Although liver transplantation serves as the optimal treatment for HCC patients,the scarcity of donor organs restricts the availability of this procedure.Therefore,hepatectomy is the most commonly employed curative treatment for resectable HCC.Unfortunately,the 5-year recurrence rate for patients who undergoing hepatectomy ranges from 50%to 70%[2,3].Recurrence of HCC is associated with several risk factors[4],including single nodule>5 cm,vascular invasion,and multiple nodules.Among these factors,microvascular invasion(MVI)is an independent risk factor for recurrence.MVI is defined as the presence of cancer cells in the lumen of endothelium-lined vessels,typically in the small branches of the portal and hepatic veins of the paracancerous liver tissue,visible only under the microscope[5].Previous studies have shown that among HCC patients who underwent hepatectomy,those with MVI had a higher risk of recurrence and shorter overall survival(OS)than those without MVI[6].Several studies have indicated that adjuvant therapy following curative hepatectomy can prevent recurrence and improve OS in HCC patients with MVI.These postoperative adjuvant therapies include transarterial chemoembolization(TACE)[7],sorafenib[8],hepatic artery infusion chemotherapy(HAIC)[9],and radiotherapy(RT)[10].However,the existing studies mostly compare individual adjuvant therapy with hepatectomy alone.Direct or indirect comparisons between the various adjuvant therapies are lacking.Therefore,we performed the network meta-analysis(NMA)to compare the relative efficacy of each adjuvant therapy to determine the optimal treatment.

Adjuvant chemotherapy for isolated resectable colorectal lung metastasis: A retrospective study using inverse probability treatment weighting propensity analysis

BACKGROUND The benefit of adjuvant chemotherapy(ACT)for patients with no evidence of disease after pulmonary metastasis resection(PM)from colorectal cancer(CRC)remains controversial.AIM To assess the efficacy of ACT in patients after PM resection for CRC.METHODS This study included 96 patients who underwent pulmonary metastasectomy for CRC at a single institution between April 2008 and July 2023.The primary end-point was overall survival(OS);secondary endpoints included cancer-specific survival(CSS)and disease-free survival(DFS).An inverse probability of treat-ment-weighting(IPTW)analysis was conducted to address indication bias.Sur-vival outcomes compared using Kaplan-Meier curves,log-rank test,Cox regre-ssion and confirmed by propensity score-matching(PSM).RESULTS With a median follow-up of 27.5 months(range,18.3-50.4 months),the 5-year OS,CSS and DFS were 72.0%,74.4%and 51.3%,respectively.ACT had no significant effect on OS after PM resection from CRC[original cohort:P=0.08;IPTW:P=0.15].No differences were observed for CSS(P=0.12)and DFS(P=0.68)between the ACT and non-ACT groups.Multivariate analysis showed no association of ACT with better survival,while sublobar resection(HR=0.45;95%CI:0.20-1.00,P=0.049)and longer disease-free interval(HR=0.45;95%CI:0.20-0.98,P=0.044)were associated with improved survival.CONCLUSION ACT does not improve survival after PM resection for CRC.Further well-designed randomized controlled trials are needed to determine the optimal ACT regimen and duration.

Enhancing ulcerative colitis treatment with traditional Chinese medicine

Inflammatory bowel disease,particularly ulcerative colitis(UC),poses significant treatment challenges due to its chronic nature and potential for severe complications.This editorial reviews a recent network meta-analysis that evaluated the efficacy of and highlighted the superior outcomes achieved by combining each of five traditional Chinese medicine(TCM)formulations with mesalazine for the adjuvant treatment of UC.Clinical outcomes included enhanced mucosal healing,improved quality of life,and reduced recurrence rates.Additionally,the combination therapy resulted in a lower incidence of adverse reactions compared with mesalazine monotherapy.Despite these promising results,limitations such as variability in study quality and TCM dosage highlight the need for further highquality,large-sample,multicenter randomized controlled trials.This editorial underscores the potential of TCM in enhancing UC management and calls for more rigorous research to substantiate these findings and refine clinical guidelines.

Postoperative serum tumor markers-based nomogram predicting early recurrence for patients undergoing radical resections of pancreatic ductal adenocarcinoma

BACKGROUND Early recurrence(ER)is associated with dismal outcomes in patients undergoing radical resection for pancreatic ductal adenocarcinoma(PDAC).Approaches for predicting ER will help clinicians in implementing individualized adjuvant therapies.Postoperative serum tumor markers(STMs)are indicators of tumor progression and may improve current systems for predicting ER.AIM To establish an improved nomogram based on postoperative STMs to predict ER in PDAC.METHODS We retrospectively enrolled 282 patients who underwent radical resection for PDAC at our institute between 2019 and 2021.Univariate and multivariate Cox regression analyses of variables with or without postoperative STMs,were performed to identify independent risk factors for ER.A nomogram was constructed based on the independent postoperative STMs.Receiver operating characteristic curve analysis was used to evaluate the area under the curve(AUC)of the nomogram.Survival analysis was performed using Kaplan-Meier survival plot and log-rank test.RESULTS Postoperative carbohydrate antigen 19-9 and carcinoembryonic antigen levels,preoperative carbohydrate antigen 125 levels,perineural invasion,and pTNM stage III were independent risk factors for ER in PDAC.The postoperative STMs-based nomogram(AUC:0.774,95%CI:0.713-0.835)had superior accuracy in predicting ER compared with the nomogram without postoperative STMs(AUC:0.688,95%CI:0.625-0.750)(P=0.016).Patients with a recurrence nomogram score(RNS)>1.56 were at high risk for ER,and had significantly poorer recurrence-free survival[median:3.08 months,interquartile range(IQR):1.80-8.15]than those with RNS≤1.56(14.00 months,IQR:6.67-24.80),P<0.001).CONCLUSION The postoperative STMs-based nomogram improves the predictive accuracy of ER in PDAC,stratifies the risk of ER,and identifies patients at high risk of ER for tailored adjuvant therapies.