Efficacy and safety of targeted therapy plus immunotherapy combined with hepatic artery infusion chemotherapy (FOLFOX) for unresectable hepatocarcinoma

BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than mono-therapy.However,the mechanisms underlying this innovative treatment modality have not been elucidated.AIM To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy(HAIC)of FOLFOX in patients with unresectable HCC.METHODS We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy,immunotherapy,and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen.RESULTS The objective response rate was 60.4%(32/53),complete response was 24.5%(13/53),partial response was 35.9%(19/53),and stable disease was 39.6%(21/53).The median duration of response and median progression-free survival were 9.1 and 13.9 months,respectively.The surgical conversion rate was 34.0%(18/53),and 1-year overall survival was 83.0%without critical complicating diseases or adverse events(AEs).CONCLUSION The regimen of HAIC of FOLFOX,targeted therapy,and immunotherapy was curative for patients with unresectable HCC,with no serious AEs and a high rate of surgical conversion.

Predicting the prognosis of hepatic arterial infusion chemotherapy in hepatocellular carcinoma

Hepatic artery infusion chemotherapy(HAIC)has good clinical efficacy in the treatment of advanced hepatocellular carcinoma(HCC);however,its efficacy varies.This review summarized the ability of various markers to predict the efficacy of HAIC and provided a reference for clinical applications.As of October 25,2023,51 articles have been retrieved based on keyword predictions and HAIC.Sixteen eligible articles were selected for inclusion in this study.Comprehensive literature analysis found that methods used to predict the efficacy of HAIC include serological testing,gene testing,and imaging testing.The above indicators and their combined forms showed excellent predictive effects in retrospective studies.This review summarized the strategies currently used to predict the efficacy of HAIC in middle and advanced HCC,analyzed each marker's ability to predict HAIC efficacy,and provided a reference for the clinical application of the prediction system.

Efficacy of hepatic arterial infusion chemotherapy and its combination strategies for advanced hepatocellular carcinoma:A network meta-analysis

BACKGROUND With the rapid progress of systematic therapy for hepatocellular carcinoma(HCC),therapeutic strategies combining hepatic arterial infusion chemotherapy(HAIC)with systematic therapy arised increasing concentrations.However,there have been no systematic review comparing HAIC and its combination strategies in the first-line treatment for advanced HCC.AIM To investigate the efficacy and safety of HAIC and its combination therapies for advanced HCC.METHODS A network meta-analysis was performed by including 9 randomized controlled trails and 35 cohort studies to carry out our study.The outcomes of interest comprised overall survival(OS),progression-free survival(PFS),tumor response and adverse events.Hazard ratios(HR)and odds ratios(OR)with a 95% confidence interval(CI)were calculated and agents were ranked based on their ranking probability.RESULTS HAIC outperformed Sorafenib(HR=0.55,95%CI:0.42-0.72;HR=0.51,95%CI:0.33-0.78;OR=2.86,95%CI:1.37-5.98;OR=5.45,95%CI:3.57-8.30;OR=7.15,95%CI:4.06-12.58;OR=2.89,95%CI:1.99-4.19;OR=0.48,95%CI:0.25-0.92,respectively)and transarterial chemoembolization(TACE)(HR=0.50,95%CI:0.33-0.75;HR=0.62,95%CI:0.39-0.98;OR=3.08,95%CI:1.36-6.98;OR=2.07,95%CI:1.54-2.80;OR=3.16,95%CI:1.71-5.85;OR=2.67,95%CI:1.59-4.50;OR=0.16,95%CI:0.05-0.54,respectively)in terms of efficacy and safety.HAIC+lenvatinib+ablation,HAIC+ablation,HAIC+anti-programmed cell death 1(PD-1),and HAIC+radiotherapy had the higher likelihood of providing better OS and PFS outcomes compared to HAIC alone.HAIC+TACE+S-1,HAIC+lenvatinib,HAIC+PD-1,HAIC+TACE,and HAIC+sorafenib had the higher likelihood of providing better partial response and objective response rate outcomes compared to HAIC.HAIC+PD-1,HAIC+TACE+S-1 and HAIC+TACE had the higher likelihood of providing better complete response and disease control rate outcomes compared to HAIC alone.CONCLUSION HAIC proved more effective and safer than sorafenib and TACE.Furthermore,combined with other interventions,HAIC showed improved efficacy over HAIC monotherapy according to the treatment ranking analysis.

Current efficacy of hepatic arterial infusion chemotherapy in hepatocellular carcinoma

Newer systemic therapies for hepatocellular carcinoma(HCC)have led to growing interest in combining hepatic arterial infusion chemotherapy(HAIC)with systemic treatments.To evaluate the effectiveness and safety of HAIC and combination therapies in treating advanced HCC,a network meta-analysis was conducted by Zhou et al.The study included data from 44 articles.HAIC was superior in overall survival(OS),progression-free survival(PFS),and response rates compared to transarterial chemoembolization and sorafenib.Moreover,combinations of HAIC with other treatments and single agents(e.g.,lenvatinib,ablation,anti-programmed cell death 1 therapy,radiotherapy)provided better OS and PFS outcomes than HAIC alone.In this editorial,we will discuss the study findings,the strengths and weaknesses of the metanalysis,and future advances in the field of HAIC for advanced HCC.

PD-1 antibody in combination with chemotherapy for the treatment of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum:Two case reports

BACKGROUND SMARCA4 is a component of chromatin remodeling of SWItch/sucrose-nonfermenting(SWI/SNF)complexes and plays an essential role in oncogenesis.SMARCA4-deficient malignancies arising from the gastrointestinal tract are rare and have a poor prognosis.There is no standard treatment for advanced and undifferentiated SMARCA4-deficient duodenal malignancies.Programmed death 1(PD-1)antibodies,known as immune checkpoint inhibitor antibodies,potentially play a role in treating gastrointestinal tract malignancies.CASE SUMMARY We present two patients with SMARCA4 deficiency and TP53 gene mutation in advanced undifferentiated carcinomas of the duodenum.For both patients,SMARCA4 deficiency was confirmed by immunohistochemical staining for the BRG1 protein,while TP53 gene mutations were observed via next-generation sequencing.Both patients were administered chemotherapy in combination with an anti-PD-1 antibody.The two patients exhibited completely different responses to treatment and had different prognoses.Case 1 experienced rapid progression after PD-1 infusion and chemotherapy,case 2 experienced a remarkable response after treatment,and the progression-free survival was more than 6 months.CONCLUSION This study described our clinical and pathological observations of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum.PD-1 combined with chemotherapy showed a certain efficacy in select patients,providing options for treating these highly malignant tumors.Patients with liver metastases had a worse prognosis than did those with only lymph node metastasis.

Hepatic arterial infusion chemotherapy with anti-angiogenesis agents and immune checkpoint inhibitors for unresectable hepatocellular carcinoma and meta-analysis

BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.However,large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking.AIM To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors,programmed cell death of protein 1(PD-1)and its ligand(PD-L1)blockers(triple therapy)under real-world conditions.METHODS Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis.Study-level pooled analyses of hazard ratios(HRs)and odds ratios(ORs)were performed.This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades(AIPB)at Sun Yat-sen University Cancer Center from January 2018 to April 2023.Propensity score matching(PSM)was performed to balance the bias between the groups.The Kaplan-Meier method and cox regression were used to analyse the survival data,and the log-rank test was used to compare the suvival time between the groups.RESULTS A total of 13 randomized controlled trials were included.HAIC alone and in combination with sorafenib were found to be effective treatments(P values for ORs:HAIC,0.95;for HRs:HAIC+sorafenib,0.04).After PSM,176 HCC patients were included in the analysis.The triple therapy group(n=88)had a longer median overall survival than the AIPB group(n=88)(31.6 months vs 14.6 months,P<0.001)and a greater incidence of adverse events(94.3%vs 75.4%,P<0.001).CONCLUSION This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC.Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.

Efficacy of continuous arterial perfusion chemotherapy combined with transarterial chemoembolization regional arterial thermal perfusion in the treatment of pancreatic cancer with liver metastases

Background:The aim of the study was to investigate the efficacy of continuous transcatheter arterial infusion chemotherapy combined with transarterial chemoembolization(TACE)for the treatment of advanced pancreatic cancer with liver metastasis.Methods:Sixty patients with advanced pancreatic cancer and liver metastases were enrolled in this study.In the treatment group,31patients underwent continuous transcatheter arterial infusion chemotherapy combined with TACE regional arterial thermal perfusion,whereas 29 patients included in the control group received intravenous chemotherapy with gemcitabine and S-1.All patients received maintenance chemotherapy with S-1 after 4 cycles of the study regimen.Treatment efficacy,quality of life,survival,and toxicity were evaluated.Results:Efficacy was better in the treatment group than in the control group,as reflected by the objective remission,partial remission,and disease progression rates(all P<0.05).The Eastern Cooperative Oncology Group and Numerical Rating Scale pain scores were also higher in the treatment group(both P<0.05).In survival analysis,the 1-year overall survival rates in the treatment and control groups were64.516%and 10.345%,respectively,whereas the median overall survival times were 16 and 6 months,respectively(both P<0.05).The6-month progression-free survival rates in the treatment and control groups were 77.419%and 13.790%,respectively,and the median progression-free survival times were 12 and 3 months,respectively(both P<0.05).The rates of hematological and nonhematological toxicological adverse effects were also lower in the treatment group(both P<0.05).Although the rate of liver dysfunction was higher in the treatment group,this finding had no adverse effects on prognosis.Conclusions:Continuous transcatheter arterial infusion chemotherapy combined with TACE regional arterial perfusion chemotherapy resulted in better efficacy and safety outcomes in patients with pancreatic cancer and liver metastasis,suggesting its utility as a reference method for the clinical treatment of advanced pancreatic cancer.

Advancing hepatocellular carcinoma treatment with hepatic arterial infusion chemotherapy

Hepatocellular carcinoma(HCC)remains a major challenge in oncology,being a leading cause of cancer-related mortality worldwide.Early-stage HCC is typically treated with surgical resection,transplantation,or ablation,while advanced-stage HCC relies on systemic therapies like sorafenib and newer combinations such as atezolizumab-bevacizumab.Despite these advancements,there is still a need for effective treatments for unresectable HCC,especially in cases with macroscopic vascular invasion.Hepatic arterial infusion chemotherapy(HAIC)has demonstrated promising outcomes in Asia for the treatment of unresectable HCC,yet its application in Western countries has been relatively limited.This letter reviews the recent meta-analysis by Zhou et al published in the World Journal of Gastrointestinal Oncology,which demonstrates the efficacy and safety of HAIC vs sorafenib.The analysis includes 9 randomized controlled trials and 35 cohort studies,highlighting significant improvements in overall survival,progressionfree survival,and objective response rates with HAIC and its combinations.The editorial explores the reasons behind the limited use of HAIC in Western countries.It underscores the potential of HAIC to enhance treatment outcomes for advanced HCC and calls for more research and broader adoption of HAIC in clinical practice globally.

Tumour response following preoperative chemotherapy is affected by body mass index in patients with colorectal liver metastases

BACKGROUND Colorectal cancer is the third most prevalent malignancy globally and ranks second in cancer-related mortality,with the liver being the primary organ of metastasis.Preoperative chemotherapy is widely recommended for initially or potentially resectable colorectal liver metastases(CRLMs).Tumour pathological response serves as the most important and intuitive indicator for assessing the efficacy of chemotherapy.However,the postoperative pathological results reveal that a considerable number of patients exhibit a poor response to preoperative chemotherapy.Body mass index(BMI)is one of the factors affecting the tumori-genesis and progression of colorectal cancer as well as prognosis after various antitumour therapies.Several studies have indicated that overweight and obese patients with metastatic colorectal cancer experience worse prognoses than those with normal weight,particularly when receiving first-line chemotherapy regimens in combination with bevacizumab.AIM To explore the predictive value of BMI regarding the pathologic response following preoperative chemotherapy for CRLMs.METHODS A retrospective analysis was performed in 126 consecutive patients with CRLM who underwent hepatectomy following preoperative chemotherapy at four different hospitals from October 2019 to July 2023.Univariate and multivariate logistic regression models were applied to analyse potential predictors of tumour pathological response.The Kaplan-Meier method with log rank test was used to compare progression-free survival(PFS)between patients with high and low BMI.BMI<24.0 kg/m^(2) was defined as low BMI,and tumour regression grade 1-2 was defined as complete tumour response.RESULTS Low BMI was observed in 74(58.7%)patients and complete tumour response was found in 27(21.4%)patients.The rate of complete tumour response was significantly higher in patients with low BMI(29.7%vs 9.6%,P=0.007).Multivariate analysis revealed that low BMI[odds ratio(OR)=4.56,95%confidence interval(CI):1.42-14.63,P=0.011],targeted therapy with bevacizumab(OR=3.02,95%CI:1.10-8.33,P=0.033),preoperative carcinoembryonic antigen level<10 ng/mL(OR=3.84,95%CI:1.19-12.44,P=0.025)and severe sinusoidal dilatation(OR=0.17,95%CI:0.03-0.90,P=0.037)were independent predictive factors for complete tumour response.The low BMI group exhibited a significantly longer median PFS than the high BMI group(10.7 mo vs 4.7 mo,P=0.011).CONCLUSION In CRLM patients receiving preoperative chemotherapy,a low BMI may be associated with better tumour response and longer PFS.

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.

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.

Predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa squamous cell lung cancer:A retrospective analysis

BACKGROUND Lung cancer(LC)is a global medical,social and economic problem and is one of the most common cancers and the leading cause of mortality from malignant neoplasms.LC is characterized by an aggressive course,and in the presence of disease recurrence risk factors,patients,even at an early stage,may be indicated for adjuvant therapy to improve survival.However,combined treatment does not always guarantee a favorable prognosis.In this regard,establishing predictors of LC recurrence is highly important both for determining the optimal treatment plan for the patients and for evaluating its effectiveness.AIM To establish predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa lung squamous cell carcinoma(LSCC).METHODS A retrospective case-control cohort study included 69 patients with LSCC who underwent radical surgery at the Orenburg Regional Clinical Oncology Center from 2009 to 2018.Postoperatively,all patients received adjuvant chemotherapy.Histological samples of the resected lung were stained with Mayer's hematoxylin and eosin and examined under a light microscope.Univariate and multivariate analyses were used to identify predictors associated with the risk of disease recurrence.Receiver operating characteristic curves were constructed to discriminate between patients with a high risk of disease recurrence and those with a low risk of disease recurrence.Survival was analyzed using the Kaplan-Meier method.The log-rank test was used to compare survival curves between patient subgroups.Differences were considered to be significant at P<0.05.RESULTS The following predictors of a high risk of disease recurrence in patients with stage IIb-IIa LSCC were established:a low degree of tumor differentiation[odds ratio(OR)=7.94,95%CI=1.08-135.81,P=0.049];metastases in regional lymph nodes(OR=5.67,95%CI=1.09-36.54,P=0.048);the presence of loose,fine-fiber connective tissue in the tumor stroma(OR=21.70,95%CI=4.27-110.38,P=0.0002);and fragmentation of the tumor solid component(OR=2.53,95%CI=1.01-12.23,P=0.049).The area under the curve of the predictive model was 0.846(95%CI=0.73-0.96,P<0.0001).The sensitivity,accuracy and specificity of the method were 91.8%,86.9%and 75.0%,respectively.In the group of patients with a low risk of LSCC recurrence,the 1-,2-and 5-year disease-free survival(DFS)rates were 84.2%,84.2%and 75.8%,respectively,while in the group with a high risk of LSCC recurrence the DFS rates were 71.7%,40.1%and 8.2%,respectively(P<0.00001).Accordingly,in the first group of patients,the 1-,2-and 5-year overall survival(OS)rates were 94.7%,82.5%and 82.5%,respectively,while in the second group of patients,the OS rates were 89.8%,80.1%and 10.3%,respectively(P<0.00001).CONCLUSION The developed method allows us to identify a group of patients at high risk of disease recurrence and to adjust to ongoing treatment.

Role of adjuvant chemotherapy on recurrence and survival in patients with resected ampulla of Vater carcinoma

BACKGROUND Owing to rarity of disease and lack of prospective studies, data supporting the role of adjuvant chemotherapy in ampulla of Vater(AoV) carcinoma is limited.AIM To evaluate whether adjuvant chemotherapy cases for AoV carcinoma had better disease-free survival(DFS) rates than cases of observation following curative surgery.METHODS We retrospectively analyzed the association between adjuvant chemotherapy and DFS and overall survival(OS) in patients with stage IB-Ⅲ AoV carcinoma who underwent curative surgical resection. Fluorouracil-based adjuvant chemotherapy was administered after surgery at the discretion of the physician. Adjusted multivariate regression models were used to evaluate the association between adjuvant chemotherapy and survival outcomes.RESULTS Of the total 104 patients who underwent curative surgery, 52 received adjuvant chemotherapy. Multivariate analysis revealed that higher histologic grade [hazard ratio(HR) = 2.24, P = 0.046], advanced tumor stage(HR = 1.85, P = 0.030), and vascular invasion(HR = 2.14, P = 0.010) were associated with shorter DFS. Adjuvant chemotherapy improved DFS compared to the observation group(HR =0.50, P = 0.015) and tended to be associated with a longer OS, although the difference was not statistically significant(HR = 0.58, P = 0.098).CONCLUSION Among patients with resected AoV carcinoma, the adjuvant chemotherapy group was not associated with a significant survival benefit compared to the observation group. However, on multivariate analysis adjusting for prognostic factors, adjuvant chemotherapy following surgery was an independent prognostic factor for DFS in patients with resected AoV carcinoma. Further studies are needed to investigate the effectiveness of adjuvant chemotherapy according to histologic phenotype.

Cetuximab combined with chemotherapy for simultaneous esophageal squamous cell carcinoma and colon adenocarcinoma:A case report

BACKGROUND Multiple primary carcinomas(MPCs)are defined as two or more independent primary cancers that occur simultaneously or sequentially in the same individual.Synchronous MPCs are rarer than solitary cancers or metachronous MPCs.Accurate diagnoses of synchronous MPCs and the choice of treatment are critical for successful outcomes in these cases.CASE SUMMARY A 64-year-old patient presented with dysphagia,without obvious cause.A diagnosis of synchronous esophageal squamous cell carcinoma and colon adenocarcinoma with liver metastasis was confirmed based on examination and laboratory results.After multi-disciplinary consultations,combination chemotherapy(a 3-wk cycle with oxaliplatin 212 mg administered on day 1 and capecitabine 1.5 g twice daily on days 1-14)and esophageal cancer radiotherapy were initiated.Based on the results of genetic testing,we switched to a regimen of leucovorin+fluorouracil+oxaliplatin and cetuximab regimen for 8 cycles.Subsequently,capecitabine and bevacizumab were administered until the most recent follow-up,at which the tumor remained stable.CONCLUSION Successful cetuximab chemotherapy treatment provides a reference for the nonoperative and homogeneous treatment of different pathological types of synchronous MCPs.

Toripalimab in combination with chemotherapy effectively suppresses local recurrence and metastatic sarcomatoid renal cell carcinoma:A case report

BACKGROUND Sarcomatoid renal cell carcinoma(SRCC)is a rare variant of renal cell carcinoma associated with an unfavorable prognosis.The efficacy of conventional chemo-therapy and targeted therapies are limited,whereas the emergence of immune checkpoint inhibitor has introduced new avenues for managing advanced SRCC.CASE SUMMARY A 77-year-old female patient was referred to our hospital following the incidental detection of a right kidney tumor without specific symptoms.The tumor was successfully resected,and subsequent pathological examination confirmed SRCC.She experienced both local recurrence and distant metastasis eight months after the initial laparoscopic resection.Following six cycles of toripalimab combined with pirarubicin chemotherapy,the patient achieved a partial response.Subse-quently,the patient attained an almost-complete continuous response to toripa-limab monotherapy maintenance for an additional six cycles.She has not experienced disease progression for 15 months,and her overall survival has reached 24 months thus far.CONCLUSION Combination therapy with programmed death 1 antibodies and cytotoxic agents may be a recommended first-line treatment approach for SRCC.

Jianpi-Huatan-Huoxue-Anshen formula ameliorates gastrointestinal inflammation and microecological imbalance in chemotherapytreated mice transplanted with H22 hepatocellular carcinoma

BACKGROUND Jianpi-Huatan-Huoxue-Anshen formula[Tzu-Chi cancer-antagonizing&lifeprotecting II decoction(TCCL)]is a Chinese medical formula that has been clinically shown to reduce the gastrointestinal side effects of chemotherapy in cancer patients and improve their quality of life.However,its effect and mechanism on the intestinal microecology after chemotherapy are not yet clear.AIM To discover the potential mechanisms of TCCL on gastrointestinal inflammation and microecological imbalance in chemotherapy-treated mice transplanted with hepatocellular carcinoma(HCC).METHODS Ninety-six mice were inoculated subcutaneously with HCC cells.One week later,the mice received a large dose of 5-fluorouracil by intraperitoneal injection to establish a HCC chemotherapy model.Thirty-six mice were randomly selected before administration,and feces,ileal tissue,and ileal contents were collected from each mouse.The remaining mice were randomized into normal saline,continuous chemotherapy,Yangzheng Xiaoji capsulestreated,and three TCCL-treated groups.After treatment,feces,tumors,liver,spleen,thymus,stomach,jejunum,ileum,and colon tissues,and ileal contents were collected.Morphological changes,serum levels of IL-1β,IL-6,IL-8,IL-10,IL-22,TNF-α,and TGF-β,intestinal SIgA,and protein and mRNA expression of ZO-1,NF-κB,Occludin,MUC-2,Claudin-1,and IκB-αin colon tissues were documented.The effect of TCCL on the abundance and diversity of intestinal flora was analyzed using 16S rDNA sequencing.RESULTS TCCL treatment improved thymus and spleen weight,thymus and spleen indexes,and body weight,decreased tumor volumes and tumor tissue cell density,and alleviated injury to gastric,ileal,and colonic mucosal tissues.Among proteins and genes associated with inflammation,IL-10,TGF-β,SIgA,ZO-1,MUC-2,and Occludin were upregulated,whereas NF-κB,IL-1β,IL-6,TNF-α,IL-22,IL-8,and IκB-αwere downregulated.Additionally,TCCL increased the proportions of fecal Actinobacteria,AF12,Adlercreutzia,Clostridium,Coriobacteriaceae,and Paraprevotella in the intermediate stage of treatment,decreased the proportions of Mucipirillum,Odoribacter,RF32,YS2,and Rikenellaceae but increased the proportions of p_Deferribacteres and Lactobacillus at the end of treatment.Studies on ileal mucosal microbiota showed similar findings.Moreover,TCCL improved community richness,evenness,and the diversity of fecal and ileal mucosal flora.CONCLUSION TCCL relieves pathological changes in tumor tissue and chemotherapy-induced gastrointestinal injury,potentially by reducing the release of pro-inflammatory factors to repair the gastrointestinal mucosa,enhancing intestinal barrier function,and maintaining gastrointestinal microecological balance.Hence,TCCL is a very effective adjuvant to chemotherapy.

Effectiveness and tolerability of programmed cell death protein-1 inhibitor+chemotherapy compared to chemotherapy for upper gastrointestinal tract cancers

BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,it is unclear whether this combination is superior to chemotherapy alone.AIM To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer,gastroesophageal junction(GEJ)cancer,or oesophageal carcinoma.METHODS We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric cancer.We employed either random or fixed models to analyze the outcomes of each clinical trial,en-compassing data on overall survival(OS),progression-free survival(PFS),objective response rate,and adverse events(AEs).RESULTS Nine phase 3 clinical trials(7016 advanced oesophageal and gastric cancer patients)met the inclusion criteria.Our meta-analysis demonstrated that the pooled PD-1 inhibitor+chemotherapy group had a significantly longer OS than the chemotherapy-alone group[hazard ratio(HR)=0.76,95%confidence interval(CI):0.71-0.81];the pooled PFS result was consistent with that of OS(HR=0.67,95%CI:0.61-0.74).The count of patients achieving an objective response in the PD-1 inhibitor+chemotherapy group surpassed that of the chemotherapy-alone group[odds ratio(OR)=1.86,95%CI:1.59-2.18].AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group,regardless of whether≥grade 3 only(OR=1.30,95%CI:1.07-1.57)or all AE grades(OR=1.88,95%CI:1.39-2.54)were examined.We performed a subgroup analysis based on the programmed death-ligand 1(PD-L1)combined positive score(CPS)and noted extended OS and PFS durations within the CPS≥1,CPS≥5,and CPS≥10 subgroups of the PD-1 inhibitor+chemotherapy group.CONCLUSION In contrast to chemotherapy alone,the combination of PD-1 inhibitor and chemotherapy appears to present a more favorable option for initial or subsequent treatment in patients with gastric cancer,GEJ tumor,or oesophageal cancer.This holds true particularly for individuals with PD-L1 CPS scores of≥5 and≥10.

The DMRTA1-SOX2 positive feedback loop promotes progression and chemotherapy resistance of esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma(ESCC)is among the most prevalent causes of cancer-related death in patients worldwide.Resistance to immunotherapy and chemotherapy results in worse survival outcomes in ESCC.It is urgent to explore the underlying molecular mechanism of immune evasion and chemoresistance in ESCC.Here,we conducted RNA-sequencing analysis in ten ESCC tissues from cisplatin-based neoadjuvant chemotherapy patients.We found that DMRTA1 was extremely upregulated in the non-pathologic complete response(non-pCR)group.The proliferation rate of esophageal squamous carcinoma cells was markedly decreased after knockdown of DMRTA1 expression,which could increase cisplatin sensitivity in ESCC.Additionally,suppression of DMRTA1 could decrease the immune escape of esophageal squamous carcinoma cells.Further mechanistic studies suggest that DMRTA1 can promote its expression by binding to the promoter of SOX2,which plays important roles in the progression and chemoresistance of ESCC in the form of positive feedback.Therefore,DMRTA1 could be a potential target to suppress immune escape and overcome chemoresistance in ESCC.

Clinical Effect of Biafine in Preventing and Treating Radioactive Skin Destruction of Nasopharyngeal Carcinoma Patients Caused by Concurrent Intensity- Modulated Radiotherapy and Chemotherapy

OBJECTIVE To observe the clinical effect of Biafine cream in preventing and treating radioactive skin destruction of nasopharyngeal carcinoma （NPC） patients induced by synchronized intensity-modulated radiotherapy and chemotherapy. METHODS The patients were treated with Varian-600CD 6 MV X-ray three-dimensional （3D） conformal intensity-modulation radiotherapy （IMRT）, with a 120-blade multiple leaf-blade grating and in combination with synchronal Capecitabine chemotherapy. Fifty-one patients undergoing radiotherapy and chemotherapy were randomized into 2 groups： 25 in the treatment group received a Biafine cream application following the first radiotherapy and / or chemotherapy, while the other 26, served as controls. They received no application of the cream, but only followed normal procedures for conventional radiotherapy and health education. RESULTS The rate of the skin-reaction was 100% in the patients of both groups. A mild radiation reaction （grade-Ⅰ and Ⅱ） occurred as follows： 88.0% （22/25 cases） in the treatment group and 57.7% （15/26 cases） in the control group. A grade-Ⅲ radiation reaction developed in 12.0% （3/25 cases） in the treatment group, and 42.3% （11/26 cases） in the controls. There was a significant difference, P〈0.01 between the two groups. Concerning the degree of the skin response before the patients received a dose of 40 Gy, the radiation reaction emerged in 32.0% （8/25） of the cases in the treatment group, and in 96.2% （25/26） of the cases of the control group. CONCLUSION Biafine cream can effectively reduce the acute irradiation or chemotherapy-induced dermal injury. It can alleviate the patients＇ suffering, improve their quality of life, and can ensure less injurious radiotherapy.

Conversion of Unresectable to Resectable Liver Metastases from Colorectal Carcinoma Using Hepatic Arterial Chronomodulated Chemotherapy: A Case Report and Short Literature Review

Background: The regional chronomodulated hepatic arterial infusion chemotherapy (HAIC) is an effective regimen for the treatment of patients with unresectable liver metastases from colorectal cancer, especially for the conversion into resectability. Aim: To demonstrate that chronomodulated HAI triplet chemotherapy according to OPTILIV protocol is well tolerated and displayed high antitumor activity in this heavily-pretreated patient. Case Presentation: A 54 years old patient from Russia was treated for a tumor in the ascending colon presented with 13 hepatic metastases ranging from 0.3 to 2.7 cm in diameter. He underwent a laparoscopic right hemicolectomy, 12 cycles of FOLFIRINOX combined to bevacizumab for the last 5 cycles, resulting in a partial response according to CT scan. It was decided to perform a two-stage hepatectomy at Paul Brousse hospital: left partial hepatectomy allowed the excision of 9 lesions. Radio frequency ablation was performed in 2 nodular lesions. Afterwards, the patient received 5 cycles of chronomodulated triplet chemotherapy into the hepatic artery, according to the OPTILIV protocol design, yet without cetuximab, because of the KRAS mutation in the liver metastases, with a partial re-sponse. The patient could then undergo the second stage of the planned right hepatectomy, which turned out to be an R0 resection followed by receiving three courses of chronomodulated HAIC. Disease progression was documented after 3 months. Chronomodulated FOLFIRI chemotherapy was re-started intravenously, in combination with Aflibercept and it was associated with further disease progression. The genetic analysis of our patient’s cancer revealed a high level of MSI. The patient was included in the Phase 2 CheckMate-142 trial and received nivolumab 3 mg/kg every 2 weeks within 3 months. Treatment was discontinued due to ineffectiveness. Then the patient underwent radiotherapy geared towards reduction of pain. Afterwards, the patient died from the disease progression 2 years after the beginning of treatment. Conclusion: In this article, the authors report a clinical case with chronomodulated HAIC as rescue therapy in a heavily pretreated patient with metastatic colorectal cancer, allowing to achieve an objective response despite prior progression on FOLFIRINOX (the same triplet chemo by IV route). This strategy permitted to overcome drug resistance and to perform further complete resection of the liver me-tastases with prolonged patient survival. Thus, chronomodulated HAI is useful in patients with liver metastases from colorectal cancer and de-serves to be further assessed prospectively in clinical trials chemotherapy.