Objective:This study aimed to evaluate the associations of baseline income,cumulative income exposure,and income volatility with the incidence of pancreatic and biliary tract cancers in a nationwide Korean cohort.Meth...Objective:This study aimed to evaluate the associations of baseline income,cumulative income exposure,and income volatility with the incidence of pancreatic and biliary tract cancers in a nationwide Korean cohort.Methods:We analyzed 3,361,091 adults aged 30-65 years who underwent the 2012 National Health Insurance Service(NHIS)health screening.Income level was derived from insurance premium data assessed over the five years preceding baseline(2008-2012)and categorized into baseline income quartiles,cumulative exposure to low or high income,and income volatility based on annual percentage changes.Incident pancreatic and biliary tract cancers were identified using diagnostic codes and the copayment reduction registry.Associations were evaluated using Cox proportional hazards models with adjustment for demographic,lifestyle,and clinical covariates,and cumulative incidence was compared using Kaplan-Meier curves.Results:During a median follow-up of 9.6 years,14,469 pancreatic cancers and 6,647 biliary tract cancers were newly diagnosed.Lower baseline income was associated with a higher risk of pancreatic and biliary tract cancers,whereas sustained high-income exposure was associated with reduced risk.Cumulative low-income exposure showed a positive linear trend with pancreatic cancer incidence.Income volatility was modestly associated with pancreatic cancer and was positively associated with biliary tract cancer in the fully adjusted model.These associations were generally consistent across subgroups,with a stronger inverse association between prolonged high-income exposure and pancreatic cancer among individuals without diabetes.Conclusions:Income level and income stability were significantly associated with the incidence of pancreatic and biliary tract cancers.Lower baseline income was associated with higher risk,whereas sustained high-income exposure was protective.Income volatility was associated with increased cancer risk,particularly for biliary tract cancer.These findings highlight the importance of incorporating income dynamics into cancer prevention strategies and addressing socioeconomic instability among vulnerable populations.展开更多
Biliary tract cancer(BTC)is a group of heterogeneous sporadic diseases,including intrahepatic,hilar,and distal cholangiocarcinoma,as well as gallbladder cancer.BTC is characterized by high invasiveness and extremely p...Biliary tract cancer(BTC)is a group of heterogeneous sporadic diseases,including intrahepatic,hilar,and distal cholangiocarcinoma,as well as gallbladder cancer.BTC is characterized by high invasiveness and extremely poor prognosis,with a global increased incidence due to intrahepatic cholangiocarcinoma(ICC).The 18Ffludeoxyglucose positron emission tomography(PET)computed tomography(18F-FDG PET/CT)combines glucose metabolic information(reflecting the glycolytic activity of tumor cells)with anatomical structure to assess tumor metabolic heterogeneity,systemic metastasis,and molecular characteristics noninvasively,overcoming the limitations of traditional imaging in the detection of micrometastases and recurrent lesions.18F-FDG PET/CT offers critical insights in clinical staging,therapeutic evaluation,and prognostic prediction of BTC.This article reviews research progress in this field over the past decade,with a particular focus on the advances made in the last 3 years,which have not been adequately summarized and recognized.The research paradigm in this field is shifting from qualitative to quantitative studies,and there have been significant breakthroughs in using 18F-FDG PET/CT metabolic information to predict gene expression in ICC.Radiomics and deep learning techniques have been applied to ICC for prognostic prediction and differential diagnosis.Additionally,PET/magnetic resonance imaging is increasingly demonstrating its value in this field.展开更多
Background:Immune checkpoint inhibitors(ICIs)are effective in a subset of patients with metastatic solid tumors.However,the patients who would benefit most from ICIs in biliary tract cancer(BTC)are still controversial...Background:Immune checkpoint inhibitors(ICIs)are effective in a subset of patients with metastatic solid tumors.However,the patients who would benefit most from ICIs in biliary tract cancer(BTC)are still controversial.Materials and methods:We molecularly characterized tissues and blood from 32 patients with metastatic BTC treated with the ICI pembrolizumab as second-line therapy.Results:All patients had microsatellite stable(MSS)type tumors.Three of the 32 patients achieved partial response(PR),with an objective response rate(ORR)of 9.4%(95%confidence interval[CI],2.0–25.2)and nine showed stable disease(SD),exhibiting a disease control rate(DCR)of 37.5%(95%CI,21.1–56.3).For the 31 patients who had access to PD-1 ligand 1(PD-L1)combined positive score(CPS)testing(cut-off value≥1%),the ORR was not different between those who had PD-L1-positive(PD-L1+;1/11,9.1%)and PDL1-(2/20,10.0%)tumors(p=1.000).The tumor mutational burden(TMB)of PD-L1+BTC was comparable to that of PD-L1-BTC(p=0.630).TMB and any exonic somatic mutations were also not predictive of pembrolizumab response.Molecular analysis of blood and tumor samples demonstrated a relatively high natural killer(NK)cell proportion in the peripheral blood before pembrolizumab treatment in patients who achieved tumor response.Moreover,the tumors of these patients presented high enrichment scores for NK cells,antitumor cytokines,and Th1 signatures,and a low enrichment score for cancer-associated fibroblasts.Conclusions:This study shows the molecular characteristics associated with the efficacy of pembrolizumab in BTC of the MSS type.展开更多
A clinical trial of nab-paclitaxel plus capecitabine as a first-line treatment for advanced biliary tract cancers was conducted.We analyzed the development of systemic therapy recommended by the National Comprehensive...A clinical trial of nab-paclitaxel plus capecitabine as a first-line treatment for advanced biliary tract cancers was conducted.We analyzed the development of systemic therapy recommended by the National Comprehensive Cancer Network guidelines and the development of nab-paclitaxel combination chemotherapy for advanced biliary tract cancers(BTCs)and concluded that nab-paclitaxel plus capecitabine is a promising first-line regimen for advanced BTCs.展开更多
Molecular profiling of biliary tract cancers(BTCs)has paved the way for a broader range of therapeutic options,leading to improved survival outcomes.Given the challenges of tissue evaluation in BTCs,circulating tumor ...Molecular profiling of biliary tract cancers(BTCs)has paved the way for a broader range of therapeutic options,leading to improved survival outcomes.Given the challenges of tissue evaluation in BTCs,circulating tumor DNA(ct-DNA)has emerged as a promising non-invasive biomarker for genomic profiling.Bile has been proven to be a reliable ctDNA source,demonstrating higher concordance with tumor tissue than plasma.More importantly,ctDNA provides valuable insights into both clonal evolution and treatment response,including the detection of resistance mechanisms and mutation clearance,which are often associated with disease control.Although its role in recurrence monitoring remains investigational,early studies suggest that ctDNA detection may precede radiological recurrences.This review examines recent advancements in ctDNA analysis for patients with BTC,highlighting key developments,current clinical implications,and ongoing challenges.Large-scale prospective studies are needed to validate the clinical utility of ctDNA and to support its integration into BTC management.展开更多
BACKGROUND Biliary tract cancer(BTC)is a rare,aggressive malignancy with increasing inci-dence and poor prognosis.Identifying preoperative prognostic factors is crucial for effective risk-benefit assessments and patie...BACKGROUND Biliary tract cancer(BTC)is a rare,aggressive malignancy with increasing inci-dence and poor prognosis.Identifying preoperative prognostic factors is crucial for effective risk-benefit assessments and patient stratification.The prognostic nutritional index(PNI),which reflects immune-inflammatory and nutritional status,has shown prognostic value in various cancers,but its significance in BTC remains unclear.AIM To assess the prognostic value of the preoperative PNI in BTC patients,with a focus on overall survival(OS)and disease-free survival(DFS).METHODS Comprehensive searches were conducted in the PubMed,EMBASE,and Web of Science databases from inception to April 2024.The primary outcomes of interest focused on the associations between the preoperative PNI and the prognosis of BTC patients,specifically OS and disease-free survival(DFS).Statistical analyses were conducted via STATA 17.0 software.RESULTS Seventeen studies encompassing 4645 patients met the inclusion criteria.Meta-analysis revealed that a low PNI was significantly associated with poorer OS[hazard ratio(HR)1.91,95%CI:1.59-2.29;P<0.001]and DFS(HR 1.93,95%CI:1.39-2.67;P<0.001).Subgroup analyses revealed consistent results across BTC subtypes(cholangiocarcinoma and gallbladder cancer)and stages(resectable and advanced).Sensitivity analyses confirmed the robustness of these findings,and no significant publication bias was detected.CONCLUSION This study demonstrated that a low preoperative PNI predicts poor OS and DFS in BTC patients,highlighting its potential as a valuable prognostic tool.Further prospective studies are needed to validate these findings and enhance BTC patient management.展开更多
Biliary tract cancer(BTC)is a rare disease with few available treatment options.Tumor malignancy and surgical invasiveness vary depending on the site of the lesion.Perioperative mortality remains high,particularly in ...Biliary tract cancer(BTC)is a rare disease with few available treatment options.Tumor malignancy and surgical invasiveness vary depending on the site of the lesion.Perioperative mortality remains high,particularly in patients with hilar cholangiocarcinoma and gallbladder cancer.Benchmark cases from high-volume centers have reported high surgical complications(87%)and 3-month mortality rates(13%).Japanese studies of hepatopancreatoduodenectomy have reported that although the complication rate is higher in high-volume centers than in other institutions,the mortality rate is low;operative safety depends on adequate liver volume after resection by portal vein embolization,cholangitis reduction,and comprehensive management of postoperative complications.Robot-assisted surgery is increasingly common in patients treated with pancreaticoduodenectomy even after distal pancreatectomy.However,many challenges exist due to device and visibility issues.Recently,adjuvant chemotherapies have been developed for the treatment of BTC.The introduction of immune checkpoint inhibitors and discovery of oncogenic driver genes have increased the number of promising treatment options.Innovations in targeted drug therapy,including fibroblast growth factor receptor inhibitors and immune checkpoint inhibitors,have shown efficacy and broadened the treatment options for unresectable BTC.Therefore,a multidisciplinary treatment strategy based on surgical intervention is desirable.展开更多
BACKGROUND Gallbladder and biliary tract cancer(GBTC)is a highly aggressive malignant tumor with a high fatality rate.The global incidence and mortality of GBTC continue to increase,presenting a significant challenge ...BACKGROUND Gallbladder and biliary tract cancer(GBTC)is a highly aggressive malignant tumor with a high fatality rate.The global incidence and mortality of GBTC continue to increase,presenting a significant challenge to public health.Strategies for preventing and controlling GBTC in Brazil,Russian Federation,India,China and South Africa(BRICS)countries offer valuable lessons for other developing nations.AIM To investigate GBTC burden trends in BRICS countries and perform an ageperiod-cohort(APC)analysis of Global Burden of Disease(GBD)from 1990-2021.METHODS Data on the incidences and crude incidence rates,the number of deaths and crude mortality rates,and the age-standardized incidence rate(ASIR)and agestandardized mortality rate(ASMR)of GBTC were obtained for BRICS countries from the GBD study 2021.Joinpoint regression analysis was employed to examine the trends in disease burden from 1990 to 2021.The APC model was utilized to assess the age,period,and birth cohort effects on the changes in GBTC disease burden worldwide and in the BRICS countries during the same time frame.Bayesian APC analysis was used to estimate the future burden.RESULTS The increases in incidence and deaths were 101.09%and 74.26%,respectively,compared with 1990.The ASMRs in Brazil,Russia,and China decreased,while those in India and South Africa increased.Among the BRICS countries,in most age groups in Brazil,Russia,India,and South Africa,the crude incidence and mortality rates in women were higher than those in men,whereas in China,the situation was the opposite.Joinpoint regression analysis revealed that from 1990 to 2021,the overall ASIR of gallbladder and bile duct cancer exhibited a declining trend.Although the incidence rate in China showed an increasing trend,the mortality rate exhibited a declining trend,which became more pronounced over time.CONCLUSION In BRICS countries,the number of incident cases and deaths from GBTC increased between 1990 and 2021,primarily due to rapid population growth.Nevertheless,the ASIR and ASMR declined during the same period.展开更多
Background:With increasing life expectancy and aging populations,Belt and Road Initiative(BRI)countries face various levels of gallbladder and biliary tract cancer(GBTC)impact.This study analyzed differences in the bu...Background:With increasing life expectancy and aging populations,Belt and Road Initiative(BRI)countries face various levels of gallbladder and biliary tract cancer(GBTC)impact.This study analyzed differences in the burden and trends of GBTC in BRI countries from 1990to 2021,providing a comprehensive understanding of geographic,temporal,and demographic variations to inform targeted public health strategies.Methods:Using the Global Burden of Disease(GBD)2021 database,we examined age-standardized incidence rate,age-standardized prevalence rate,age-standardized mortality rate,and age-standardized disability-adjusted life year rate of GBTC across 153 BRI countries.A Bayesian Age-Period-Cohort(BAPC)model analyzed temporal trends(1990-2021)and projected future burden(2035).We assessed the relationship between sociodemographic index(SDI)and GBTC burden,conducted sex-and age-stratified analyses,and evaluated geographic disparities.Results:In 2021,global age-standardized incidence rate was 2.56/100000(216768 cases),with agestandardized prevalence rate 3.69/100000(314465 cases),age-standardized mortality rate 2.04/100000(171961 deaths),and age-standardized disability-adjusted life year rate 43.2/100000(3.73 million disability-adjusted life years).Geographic analysis identified Thailand,Korea,and Chile as regions with the highest age-standardized incidence rate and age-standardized mortality rate.Age-standardized disability-adjusted life year rate correlated positively with SDI(R=0.38)across BRI countries.Between 1990and 2021,temporal trends showed age-standardized mortality rate and age-standardized disabilityadjusted life year rate declined globally(-24.09/100000and-26.25/100000),but South Asia showed increased mortality rate(+33.24/100000and+28.15/100000).Globally,age-standardized mortality rate and age-standardized disability-adjusted life year rate are projected to continue declining through 2035.Sex-and age-stratified analyses revealed that age-specific incidence,prevalence,mortality,and disabilityadjusted life year rates increased with age,peaking at 85-90years.Males had higher rates at 84-94 years,but absolute cases,deaths and disability-adjusted life years were higher in females after 70years.Conclusions:GBTC burden in BRI countries varies by regions,SDI,temporal trends,and demographic factors.While overall burden declines,addressing healthcare disparities,environmental risks,and early detection gaps is crucial in high-burden countries and populations.Strengthening collaboration among BRI countries is key to mitigating GBTC burden and advancing public health initiatives.展开更多
AIM： To investigate in vitro and in vivo therapeutic effects of histone deacetylase inhibitors NVP-LAQ824 and NVP-LBH589 on biliary tract cancer. METHODS： Cell growth inhibition by NVP-LAQ824 and NVP-LBH589 was stud...AIM： To investigate in vitro and in vivo therapeutic effects of histone deacetylase inhibitors NVP-LAQ824 and NVP-LBH589 on biliary tract cancer. METHODS： Cell growth inhibition by NVP-LAQ824 and NVP-LBH589 was studied in vitro in 7 human biliary tract cancer cell lines by MTT assay. In addition, the antitumoral effect of NVP-LBH589 was studied in a chimeric mouse model. Anti-tumoral drug mechanism was assessed by immunoblotting for acH4 and p21^WAFl/CIP-1, PARP assay, cell cycle analysis, TUNEL assay, and immunhistochemistry for MIB-1. RESULTS： In vitro treatment with both compounds significantly suppressed the growth of all cancer cell lines [mean IC50 （3 d） 0.11 and 0.05 μmol/L, respectively], and was associated with hyperacetylation of nucleosomal histone H4, increased expression of p21^WAF-1/CIP-1, induction of apoptosis （PARP cleavage）, and cell cycle arrest at G2/M checkpoint. After 28 d, NVP- LBH589 significantly reduced tumor mass by 66% （bile duct cancer） and 87% （gallbladder cancer） in vivo in comparison to placebo, and potentiated the efficacy of gemcitabine. Further analysis of the tumor specimens revealed increased apoptosis by TUNEL assay and reduced cell proliferation （MIB-1）. CONCLUSION： Our findings suggest that NVP-LBH589 and NVP-LAQ824 are active against human biliary tract cancer in vitro. In addition, NVP-LBH589 demonstrated significant in vivo activity and potentiated the efficacy of gemcitabine. Therefore, further clinical evaluation of this new drug for the treatment of biliary tract cancer is recommended.展开更多
AIM: To explore the effect of histone deacetylase inhibitor, trichostatin A (TSA) on the growth of biliary tract cancer cell lines (gallbladder carcinoma cell line and cholangiocarcinoma cell line) in vivo and in vitr...AIM: To explore the effect of histone deacetylase inhibitor, trichostatin A (TSA) on the growth of biliary tract cancer cell lines (gallbladder carcinoma cell line and cholangiocarcinoma cell line) in vivo and in vitro, and to investigate the perspective of histone deacetylase inhibitor in its clinical application. METHODS: The survival rates of gallbladder carcinoma cell line (Mz-ChA-l cell line) and cholangiocarcinoma cell lines (QBC939, KMBC and OZ cell lines) treated with various doses of TSA were detected by methylthiazoy tetrazolium (MTT) assay. A nude mouse model of transplanted gallbladder carcinoma (Mz-ChA-l cell line) was successfully established, and changes in the growth of transplanted tumor after treated with TSA were measured. RESULTS: TSA could inhibit the proliferation of gallbladder carcinoma cell line (Mz-ChA-l cell line) and cholangiocarcinoma cell lines (QBC939, KMBC and OZ cell lines) in a dose-dependent manner. After the nude mouse model of transplanted gallbladder carcinoma (Mz- ChA-l cell line) was successfully established, the growth of cancer was inhibited in the model after treated with TSA. CONCLUSION: TSA can inhibit the growth of cholangiocarcinoma and gallbladder carcinoma cell lines in vitro and in vivo.展开更多
Background:Biliary tract cancers(BTCs)comprise a heterogeneous group of aggressive malignancies with unfavorable prognoses.The benefit of chemotherapy seems to have reached a bottleneck and,therefore,new effective the...Background:Biliary tract cancers(BTCs)comprise a heterogeneous group of aggressive malignancies with unfavorable prognoses.The benefit of chemotherapy seems to have reached a bottleneck and,therefore,new effective therapeutic strategies for advanced BTCs are needed.Molecularly targeted therapies in selected patients are rapidly changing the situation.However,the low frequency of specific driver alterations in BTCs limits their wide application.Recently,immunotherapeutic approaches are also under active investigation in BTCs,but the role of immunotherapy in BTCs remains controversial.Data sources:Pub Med,Web of Science,and meeting resources were searched for relevant articles published from January 2017 to May 2022.The search aimed to identify current and emerging immunotherapeutic approaches for BTCs.Information on clinical trials was obtained from https://clinicaltrials.gov/and http://www.chictr.org.cn/.Results:Immunotherapy in BTC patients is currently under investigation,and most of the investigations focused on the application of immune checkpoint inhibitors(ICIs).However,only a subgroup of BTCs with microsatellite-instability high(MSI-H)/DNA mismatch repair-deficient(d MMR)or tumor mutational burden-high(TMB-H)benefit from monotherapy of ICIs,and limited activity was observed in the second or subsequent settings.Nevertheless,promising results come from studies of ICIs in combination with other therapeutic approaches,including chemotherapy,in advanced BTCs,with a moderate toxicity profile.Recent studies demonstrated that compared to GEMCIS alone,durvalumab plus GEMCIS significantly improved patient survival(TOPAZ-1 trial)and that ICIs-combined chemoimmunotherapy is poised to become a new frontline therapy option,regardless of TMB and MMR/MSI status.Adoptive cell therapy and peptide-or dendritic-based cancer vaccines are other immunotherapeutic options that are being studied in BTCs.Numerous biomarkers have been investigated to define their predictive role in response to ICIs,but no predictive biomarker has been validated,except MSI-H/dMMR.Conclusions:The role of immunotherapy in BTCs is currently under investigation and the results of ongoing studies are eagerly anticipated.Several studies have demonstrated the safety and efflcacy of ICIs in combination with chemotherapy in treatment-naive patients,such as the phaseⅢTOPAZ-1 trial,which will change the standard care of first-line chemotherapy for advanced BTCs.However,further research is needed to understand the best combination with immunotherapy and to discover more predictive biomarkers to guide clinical practice.展开更多
The limited efficacy of cytotoxic therapy for advanced biliary tract and gallbladder cancers emphasizes the need for novel and more effective medical treatment options. A better understanding of the specific biologica...The limited efficacy of cytotoxic therapy for advanced biliary tract and gallbladder cancers emphasizes the need for novel and more effective medical treatment options. A better understanding of the specific biological features of these neoplasms led to the development of new targeted therapies, which take the abundant expression of several growth factors and cognate tyrosine kinase receptors into account. This review will briefly summarize the status and future perspectives of antiangiogenic and growth factor receptor-based pharmacological approaches for the treatment of biliary tract and gallbladder cancers. In view of multiple novel targeted approaches, the rationale for innovative therapies, such as combinations of growth factor (receptor)-targeting agents with cytotoxic drugs or with other novel anticancer drugs will be highlighted.展开更多
Biliary tract cancer(BTC)is a group of rare malignancies that affect the gallbladder and bile ducts.Although rare,BTC is becoming a significant public health burden in China,particularly among males and older individu...Biliary tract cancer(BTC)is a group of rare malignancies that affect the gallbladder and bile ducts.Although rare,BTC is becoming a significant public health burden in China,particularly among males and older individuals.The increasing trends in BTC incidence and mortality in China are influenced by various demographic,environmental,and lifestyle factors.In this review,we examine available epidemiological data on the incidence,mortality,prognosis,and trends of different BTC subtypes in China.We also discuss the challenges and opportunities for improving the prevention,diagnosis,and management of BTC in China,and identify areas for further research and intervention.The article aims to provide a better understanding of the epidemiological features of BTC in China and to inform public health strategies and clinical practice.展开更多
Biliary tract cancer is a rare malignant tumor. There is limited knowledge about biology and natural history of this disease and considerable uncertainty remains regarding its optimal diagnostic and therapeutic man- a...Biliary tract cancer is a rare malignant tumor. There is limited knowledge about biology and natural history of this disease and considerable uncertainty remains regarding its optimal diagnostic and therapeutic man- agement. The role of adjuvant therapy is object of debate and controversy. Although resection is identified as the most effective and the only potentially curative treatment, there is no consensus on the impact of ad- juvant chemotherapy and/or radiotherapy on the high incidence of disease recurrence and on survival. This is mainly due to the rarity of this disease and the consequent difficulty in performing randomized trials. The only two prospectively controlled trials concluded that adjuvant chemotherapy did not improve survival. Most of the retrospective trials, which had limited sample size and included heterogeneous patients population and non-standardized therapies, suggested a marginal benefit of chemoradiotherapy in reducing locoregional recurrence and an uncertain impact on survival. Welldesigned multi-institutional randomized trials are necessary to clarify the role of adjuvant therapy. Two ongoing phase Ⅲ trials may provide relevant information.展开更多
AIM:To investigate the expression and clinical relevance of inhibitor of differentiation(ID)proteins in biliary tract cancer.METHODS:ID protein expression was analyzed in129 samples from patients with advanced biliary...AIM:To investigate the expression and clinical relevance of inhibitor of differentiation(ID)proteins in biliary tract cancer.METHODS:ID protein expression was analyzed in129 samples from patients with advanced biliary tract cancer(BTC)(45 extrahepatic,50 intrahepatic,and 34 gallbladder cancers),compared to normal controls and correlated with clinical an pathological parameters.RESULTS:ID1-3 proteins are frequently overexpressed in all BTC subtypes analyzed.No correlation between increased ID protein expression and tumor grading,tumor subtype or treatment response was detected.Survival was influenced primary tumor localization(extrahepatic vs intrahepatic and gall bladder cancer,OS 1.5 years vs 0.9 years vs 0.7 years,P=0.002),by stage at diagnosis(OS 2.7 years in stageⅠv s 0.6 years in stageⅣ,P<0.001),resection status and response to systemic chemotherapy.In a multivariate model,ID protein expression did not correlate with clinical prognosis.Nevertheless,there was a trend of shorter OS in patients with loss of cytoplasmic ID4 protein expression(P=0.076).CONCLUSION:ID protein expression is frequently deregulated in BTC but does not influence clinical prognosis.Their usefulness as prognostic biomarkers in BTC is very limited.展开更多
BACKGROUND Biliary tract cancers(BTCs)are a heterogeneous group of tumors with high malignancy,poor prognosis,and limited treatment options.AIM To explore the efficacy and safety of nab-paclitaxel plus capecitabine as...BACKGROUND Biliary tract cancers(BTCs)are a heterogeneous group of tumors with high malignancy,poor prognosis,and limited treatment options.AIM To explore the efficacy and safety of nab-paclitaxel plus capecitabine as first-line treatment for advanced and metastatic BTCs.METHODS This open-label,non-randomized,double-center,phase II clinical trial recruited systemic therapy-naive patients with unresectable or metastatic BTCs between April 2019 and June 2022 at Beijing Cancer Hospital and the First Hospital of China Medical University.Eligible patients were administered nab-paclitaxel(150 mg/m^(2),day 1)and capecitabine(2000 mg/m^(2),twice daily,days 1-7)in 14-day cycles until experiencing intolerable toxicity or disease progression.The primary outcome was the objective response rate(ORR).The secondary outcomes included the disease control rate(DCR),overall survival(OS),progression-free survival(PFS),and safety.RESULTS A total of 44 patients successfully completed the trial,with a median age of 64.00 years(interquartile range,35.00-76.00),and 26(59.09%)were females.Tumor response assessment was impeded for one patient due to premature demise from tumor hemorrhage.Among the remaining 43 patients undergoing at least one imaging assessment,the ORR was 23.26%[95%confidence interval(CI):11.80%-38.60%],and the DCR was 69.77%(95%CI:53.90%-82.80%).The median OS was 14.1 months(95%CI:8.3-19.9),and the median PFS was 4.4 months(95%CI:2.5-6.3).A total of 41 patients(93.18%)experienced at least one adverse event(AE),with 10 patients(22.73%)encountering grade≥3 AEs,and the most frequent AEs of any grade were alopecia(79.50%),leukopenia(54.55%),neutropenia(52.27%),and liver dysfunction(40.91%),and no treatment-related deaths were documented.CONCLUSION Nab-paclitaxel plus capecitabine may be an effective and safe first-line treatment strategy for patients with advanced or metastatic BTCs.展开更多
ABSTRACT： CD98 has been described to play a crucial role in tumor progression and survival. However, the role of CD98 in biliary tract cancer remains unclear. We found that 36.7% of all patients with biliary tract ca...ABSTRACT： CD98 has been described to play a crucial role in tumor progression and survival. However, the role of CD98 in biliary tract cancer remains unclear. We found that 36.7% of all patients with biliary tract cancer had a high CD98 expression. Statistical analysis using Spearman＇s rank correlation showed that CD98 was significantly correlated with L-type amino acid transporter 1 （LAT1, r=0.562, P〈0.001）, Ki-67 （r=0.230, P=0.006） and CD34 （r=0.290, P=0.005）. Multivariate analysis confirmed that a high CD98 expression was an independent prognostic factor for predicting poor outcome. CD98 is closely associated with tumor growth, biological aggressiveness, and survival of patients. With these data we proposed that CD98 expression is necessary for the development and pathogenesis of biliary tract cancer.展开更多
Biliary tract cancer,comprising gallbladder cancer,cholangiocarcinoma and ampullary cancer,represents a more uncommon entity outside high-endemic areas,though global incidence is rising.The majority of patients presen...Biliary tract cancer,comprising gallbladder cancer,cholangiocarcinoma and ampullary cancer,represents a more uncommon entity outside high-endemic areas,though global incidence is rising.The majority of patients present at a late stage,and 5-year survival remains poor.Advanced stage disease is incurable,and though palliative chemotherapy has been shown to improve survival,further diagnostic and therapeutic options are required in order to improve patient outcomes.Although certain subtypes of biliary tract cancer are relatively rich in targetable mutations,attaining tumour tissue for histological diagnosis and treatment monitoring is challenging due to locoregional anatomical constraints and patient fitness.Liquid biopsies offer a safe and convenient alternative to invasive procedures and have great potential as diagnostic,predictive and prognostic biomarkers.In this review,the current standard of care for patients with biliary tract cancer,future treatment horizons and the possible utility of liquid biopsies within a variety of contexts will be discussed.Circulating tumour DNA,circulating microRNA and circulating tumour cells are discussed with an overview of their potential applications in management of biliary tract cancer.A summary is also provided of currently recruiting clinical trials incorporating liquid biopsies within biliary tract cancer research.展开更多
基金supported and funded by Korea University Guro Hospital(KOREA RESEARCH-DRIVEN HOSPITAL)(No.O2208261)supported by the Korea University Guro Hospital(KOREA RESEARCH-DRIVEN HOSPITAL)+1 种基金grant funded by Korea University Medicine(No.K2313971)by Korea University。
文摘Objective:This study aimed to evaluate the associations of baseline income,cumulative income exposure,and income volatility with the incidence of pancreatic and biliary tract cancers in a nationwide Korean cohort.Methods:We analyzed 3,361,091 adults aged 30-65 years who underwent the 2012 National Health Insurance Service(NHIS)health screening.Income level was derived from insurance premium data assessed over the five years preceding baseline(2008-2012)and categorized into baseline income quartiles,cumulative exposure to low or high income,and income volatility based on annual percentage changes.Incident pancreatic and biliary tract cancers were identified using diagnostic codes and the copayment reduction registry.Associations were evaluated using Cox proportional hazards models with adjustment for demographic,lifestyle,and clinical covariates,and cumulative incidence was compared using Kaplan-Meier curves.Results:During a median follow-up of 9.6 years,14,469 pancreatic cancers and 6,647 biliary tract cancers were newly diagnosed.Lower baseline income was associated with a higher risk of pancreatic and biliary tract cancers,whereas sustained high-income exposure was associated with reduced risk.Cumulative low-income exposure showed a positive linear trend with pancreatic cancer incidence.Income volatility was modestly associated with pancreatic cancer and was positively associated with biliary tract cancer in the fully adjusted model.These associations were generally consistent across subgroups,with a stronger inverse association between prolonged high-income exposure and pancreatic cancer among individuals without diabetes.Conclusions:Income level and income stability were significantly associated with the incidence of pancreatic and biliary tract cancers.Lower baseline income was associated with higher risk,whereas sustained high-income exposure was protective.Income volatility was associated with increased cancer risk,particularly for biliary tract cancer.These findings highlight the importance of incorporating income dynamics into cancer prevention strategies and addressing socioeconomic instability among vulnerable populations.
文摘Biliary tract cancer(BTC)is a group of heterogeneous sporadic diseases,including intrahepatic,hilar,and distal cholangiocarcinoma,as well as gallbladder cancer.BTC is characterized by high invasiveness and extremely poor prognosis,with a global increased incidence due to intrahepatic cholangiocarcinoma(ICC).The 18Ffludeoxyglucose positron emission tomography(PET)computed tomography(18F-FDG PET/CT)combines glucose metabolic information(reflecting the glycolytic activity of tumor cells)with anatomical structure to assess tumor metabolic heterogeneity,systemic metastasis,and molecular characteristics noninvasively,overcoming the limitations of traditional imaging in the detection of micrometastases and recurrent lesions.18F-FDG PET/CT offers critical insights in clinical staging,therapeutic evaluation,and prognostic prediction of BTC.This article reviews research progress in this field over the past decade,with a particular focus on the advances made in the last 3 years,which have not been adequately summarized and recognized.The research paradigm in this field is shifting from qualitative to quantitative studies,and there have been significant breakthroughs in using 18F-FDG PET/CT metabolic information to predict gene expression in ICC.Radiomics and deep learning techniques have been applied to ICC for prognostic prediction and differential diagnosis.Additionally,PET/magnetic resonance imaging is increasingly demonstrating its value in this field.
基金supported by the MISP program at Merck Sharp&Dohme Corp.,USAa grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare,Republic of Korea(Grant Number:HR20C0025).
文摘Background:Immune checkpoint inhibitors(ICIs)are effective in a subset of patients with metastatic solid tumors.However,the patients who would benefit most from ICIs in biliary tract cancer(BTC)are still controversial.Materials and methods:We molecularly characterized tissues and blood from 32 patients with metastatic BTC treated with the ICI pembrolizumab as second-line therapy.Results:All patients had microsatellite stable(MSS)type tumors.Three of the 32 patients achieved partial response(PR),with an objective response rate(ORR)of 9.4%(95%confidence interval[CI],2.0–25.2)and nine showed stable disease(SD),exhibiting a disease control rate(DCR)of 37.5%(95%CI,21.1–56.3).For the 31 patients who had access to PD-1 ligand 1(PD-L1)combined positive score(CPS)testing(cut-off value≥1%),the ORR was not different between those who had PD-L1-positive(PD-L1+;1/11,9.1%)and PDL1-(2/20,10.0%)tumors(p=1.000).The tumor mutational burden(TMB)of PD-L1+BTC was comparable to that of PD-L1-BTC(p=0.630).TMB and any exonic somatic mutations were also not predictive of pembrolizumab response.Molecular analysis of blood and tumor samples demonstrated a relatively high natural killer(NK)cell proportion in the peripheral blood before pembrolizumab treatment in patients who achieved tumor response.Moreover,the tumors of these patients presented high enrichment scores for NK cells,antitumor cytokines,and Th1 signatures,and a low enrichment score for cancer-associated fibroblasts.Conclusions:This study shows the molecular characteristics associated with the efficacy of pembrolizumab in BTC of the MSS type.
文摘A clinical trial of nab-paclitaxel plus capecitabine as a first-line treatment for advanced biliary tract cancers was conducted.We analyzed the development of systemic therapy recommended by the National Comprehensive Cancer Network guidelines and the development of nab-paclitaxel combination chemotherapy for advanced biliary tract cancers(BTCs)and concluded that nab-paclitaxel plus capecitabine is a promising first-line regimen for advanced BTCs.
文摘Molecular profiling of biliary tract cancers(BTCs)has paved the way for a broader range of therapeutic options,leading to improved survival outcomes.Given the challenges of tissue evaluation in BTCs,circulating tumor DNA(ct-DNA)has emerged as a promising non-invasive biomarker for genomic profiling.Bile has been proven to be a reliable ctDNA source,demonstrating higher concordance with tumor tissue than plasma.More importantly,ctDNA provides valuable insights into both clonal evolution and treatment response,including the detection of resistance mechanisms and mutation clearance,which are often associated with disease control.Although its role in recurrence monitoring remains investigational,early studies suggest that ctDNA detection may precede radiological recurrences.This review examines recent advancements in ctDNA analysis for patients with BTC,highlighting key developments,current clinical implications,and ongoing challenges.Large-scale prospective studies are needed to validate the clinical utility of ctDNA and to support its integration into BTC management.
文摘BACKGROUND Biliary tract cancer(BTC)is a rare,aggressive malignancy with increasing inci-dence and poor prognosis.Identifying preoperative prognostic factors is crucial for effective risk-benefit assessments and patient stratification.The prognostic nutritional index(PNI),which reflects immune-inflammatory and nutritional status,has shown prognostic value in various cancers,but its significance in BTC remains unclear.AIM To assess the prognostic value of the preoperative PNI in BTC patients,with a focus on overall survival(OS)and disease-free survival(DFS).METHODS Comprehensive searches were conducted in the PubMed,EMBASE,and Web of Science databases from inception to April 2024.The primary outcomes of interest focused on the associations between the preoperative PNI and the prognosis of BTC patients,specifically OS and disease-free survival(DFS).Statistical analyses were conducted via STATA 17.0 software.RESULTS Seventeen studies encompassing 4645 patients met the inclusion criteria.Meta-analysis revealed that a low PNI was significantly associated with poorer OS[hazard ratio(HR)1.91,95%CI:1.59-2.29;P<0.001]and DFS(HR 1.93,95%CI:1.39-2.67;P<0.001).Subgroup analyses revealed consistent results across BTC subtypes(cholangiocarcinoma and gallbladder cancer)and stages(resectable and advanced).Sensitivity analyses confirmed the robustness of these findings,and no significant publication bias was detected.CONCLUSION This study demonstrated that a low preoperative PNI predicts poor OS and DFS in BTC patients,highlighting its potential as a valuable prognostic tool.Further prospective studies are needed to validate these findings and enhance BTC patient management.
文摘Biliary tract cancer(BTC)is a rare disease with few available treatment options.Tumor malignancy and surgical invasiveness vary depending on the site of the lesion.Perioperative mortality remains high,particularly in patients with hilar cholangiocarcinoma and gallbladder cancer.Benchmark cases from high-volume centers have reported high surgical complications(87%)and 3-month mortality rates(13%).Japanese studies of hepatopancreatoduodenectomy have reported that although the complication rate is higher in high-volume centers than in other institutions,the mortality rate is low;operative safety depends on adequate liver volume after resection by portal vein embolization,cholangitis reduction,and comprehensive management of postoperative complications.Robot-assisted surgery is increasingly common in patients treated with pancreaticoduodenectomy even after distal pancreatectomy.However,many challenges exist due to device and visibility issues.Recently,adjuvant chemotherapies have been developed for the treatment of BTC.The introduction of immune checkpoint inhibitors and discovery of oncogenic driver genes have increased the number of promising treatment options.Innovations in targeted drug therapy,including fibroblast growth factor receptor inhibitors and immune checkpoint inhibitors,have shown efficacy and broadened the treatment options for unresectable BTC.Therefore,a multidisciplinary treatment strategy based on surgical intervention is desirable.
基金Supported by the Key Project of Science&Technology Development Fund of Tianjin Education Commission for Higher Education,No.2024ZD023.
文摘BACKGROUND Gallbladder and biliary tract cancer(GBTC)is a highly aggressive malignant tumor with a high fatality rate.The global incidence and mortality of GBTC continue to increase,presenting a significant challenge to public health.Strategies for preventing and controlling GBTC in Brazil,Russian Federation,India,China and South Africa(BRICS)countries offer valuable lessons for other developing nations.AIM To investigate GBTC burden trends in BRICS countries and perform an ageperiod-cohort(APC)analysis of Global Burden of Disease(GBD)from 1990-2021.METHODS Data on the incidences and crude incidence rates,the number of deaths and crude mortality rates,and the age-standardized incidence rate(ASIR)and agestandardized mortality rate(ASMR)of GBTC were obtained for BRICS countries from the GBD study 2021.Joinpoint regression analysis was employed to examine the trends in disease burden from 1990 to 2021.The APC model was utilized to assess the age,period,and birth cohort effects on the changes in GBTC disease burden worldwide and in the BRICS countries during the same time frame.Bayesian APC analysis was used to estimate the future burden.RESULTS The increases in incidence and deaths were 101.09%and 74.26%,respectively,compared with 1990.The ASMRs in Brazil,Russia,and China decreased,while those in India and South Africa increased.Among the BRICS countries,in most age groups in Brazil,Russia,India,and South Africa,the crude incidence and mortality rates in women were higher than those in men,whereas in China,the situation was the opposite.Joinpoint regression analysis revealed that from 1990 to 2021,the overall ASIR of gallbladder and bile duct cancer exhibited a declining trend.Although the incidence rate in China showed an increasing trend,the mortality rate exhibited a declining trend,which became more pronounced over time.CONCLUSION In BRICS countries,the number of incident cases and deaths from GBTC increased between 1990 and 2021,primarily due to rapid population growth.Nevertheless,the ASIR and ASMR declined during the same period.
基金supported by a grant from the National Natural Science Foundation of China(82000618)。
文摘Background:With increasing life expectancy and aging populations,Belt and Road Initiative(BRI)countries face various levels of gallbladder and biliary tract cancer(GBTC)impact.This study analyzed differences in the burden and trends of GBTC in BRI countries from 1990to 2021,providing a comprehensive understanding of geographic,temporal,and demographic variations to inform targeted public health strategies.Methods:Using the Global Burden of Disease(GBD)2021 database,we examined age-standardized incidence rate,age-standardized prevalence rate,age-standardized mortality rate,and age-standardized disability-adjusted life year rate of GBTC across 153 BRI countries.A Bayesian Age-Period-Cohort(BAPC)model analyzed temporal trends(1990-2021)and projected future burden(2035).We assessed the relationship between sociodemographic index(SDI)and GBTC burden,conducted sex-and age-stratified analyses,and evaluated geographic disparities.Results:In 2021,global age-standardized incidence rate was 2.56/100000(216768 cases),with agestandardized prevalence rate 3.69/100000(314465 cases),age-standardized mortality rate 2.04/100000(171961 deaths),and age-standardized disability-adjusted life year rate 43.2/100000(3.73 million disability-adjusted life years).Geographic analysis identified Thailand,Korea,and Chile as regions with the highest age-standardized incidence rate and age-standardized mortality rate.Age-standardized disability-adjusted life year rate correlated positively with SDI(R=0.38)across BRI countries.Between 1990and 2021,temporal trends showed age-standardized mortality rate and age-standardized disabilityadjusted life year rate declined globally(-24.09/100000and-26.25/100000),but South Asia showed increased mortality rate(+33.24/100000and+28.15/100000).Globally,age-standardized mortality rate and age-standardized disability-adjusted life year rate are projected to continue declining through 2035.Sex-and age-stratified analyses revealed that age-specific incidence,prevalence,mortality,and disabilityadjusted life year rates increased with age,peaking at 85-90years.Males had higher rates at 84-94 years,but absolute cases,deaths and disability-adjusted life years were higher in females after 70years.Conclusions:GBTC burden in BRI countries varies by regions,SDI,temporal trends,and demographic factors.While overall burden declines,addressing healthcare disparities,environmental risks,and early detection gaps is crucial in high-burden countries and populations.Strengthening collaboration among BRI countries is key to mitigating GBTC burden and advancing public health initiatives.
文摘AIM： To investigate in vitro and in vivo therapeutic effects of histone deacetylase inhibitors NVP-LAQ824 and NVP-LBH589 on biliary tract cancer. METHODS： Cell growth inhibition by NVP-LAQ824 and NVP-LBH589 was studied in vitro in 7 human biliary tract cancer cell lines by MTT assay. In addition, the antitumoral effect of NVP-LBH589 was studied in a chimeric mouse model. Anti-tumoral drug mechanism was assessed by immunoblotting for acH4 and p21^WAFl/CIP-1, PARP assay, cell cycle analysis, TUNEL assay, and immunhistochemistry for MIB-1. RESULTS： In vitro treatment with both compounds significantly suppressed the growth of all cancer cell lines [mean IC50 （3 d） 0.11 and 0.05 μmol/L, respectively], and was associated with hyperacetylation of nucleosomal histone H4, increased expression of p21^WAF-1/CIP-1, induction of apoptosis （PARP cleavage）, and cell cycle arrest at G2/M checkpoint. After 28 d, NVP- LBH589 significantly reduced tumor mass by 66% （bile duct cancer） and 87% （gallbladder cancer） in vivo in comparison to placebo, and potentiated the efficacy of gemcitabine. Further analysis of the tumor specimens revealed increased apoptosis by TUNEL assay and reduced cell proliferation （MIB-1）. CONCLUSION： Our findings suggest that NVP-LBH589 and NVP-LAQ824 are active against human biliary tract cancer in vitro. In addition, NVP-LBH589 demonstrated significant in vivo activity and potentiated the efficacy of gemcitabine. Therefore, further clinical evaluation of this new drug for the treatment of biliary tract cancer is recommended.
文摘AIM: To explore the effect of histone deacetylase inhibitor, trichostatin A (TSA) on the growth of biliary tract cancer cell lines (gallbladder carcinoma cell line and cholangiocarcinoma cell line) in vivo and in vitro, and to investigate the perspective of histone deacetylase inhibitor in its clinical application. METHODS: The survival rates of gallbladder carcinoma cell line (Mz-ChA-l cell line) and cholangiocarcinoma cell lines (QBC939, KMBC and OZ cell lines) treated with various doses of TSA were detected by methylthiazoy tetrazolium (MTT) assay. A nude mouse model of transplanted gallbladder carcinoma (Mz-ChA-l cell line) was successfully established, and changes in the growth of transplanted tumor after treated with TSA were measured. RESULTS: TSA could inhibit the proliferation of gallbladder carcinoma cell line (Mz-ChA-l cell line) and cholangiocarcinoma cell lines (QBC939, KMBC and OZ cell lines) in a dose-dependent manner. After the nude mouse model of transplanted gallbladder carcinoma (Mz- ChA-l cell line) was successfully established, the growth of cancer was inhibited in the model after treated with TSA. CONCLUSION: TSA can inhibit the growth of cholangiocarcinoma and gallbladder carcinoma cell lines in vitro and in vivo.
文摘AIM: To investigate the efficacy and safety of gemcitabine (Gem)-based combination chemotherapies for the treatment of advanced biliary tract cancer.
文摘Background:Biliary tract cancers(BTCs)comprise a heterogeneous group of aggressive malignancies with unfavorable prognoses.The benefit of chemotherapy seems to have reached a bottleneck and,therefore,new effective therapeutic strategies for advanced BTCs are needed.Molecularly targeted therapies in selected patients are rapidly changing the situation.However,the low frequency of specific driver alterations in BTCs limits their wide application.Recently,immunotherapeutic approaches are also under active investigation in BTCs,but the role of immunotherapy in BTCs remains controversial.Data sources:Pub Med,Web of Science,and meeting resources were searched for relevant articles published from January 2017 to May 2022.The search aimed to identify current and emerging immunotherapeutic approaches for BTCs.Information on clinical trials was obtained from https://clinicaltrials.gov/and http://www.chictr.org.cn/.Results:Immunotherapy in BTC patients is currently under investigation,and most of the investigations focused on the application of immune checkpoint inhibitors(ICIs).However,only a subgroup of BTCs with microsatellite-instability high(MSI-H)/DNA mismatch repair-deficient(d MMR)or tumor mutational burden-high(TMB-H)benefit from monotherapy of ICIs,and limited activity was observed in the second or subsequent settings.Nevertheless,promising results come from studies of ICIs in combination with other therapeutic approaches,including chemotherapy,in advanced BTCs,with a moderate toxicity profile.Recent studies demonstrated that compared to GEMCIS alone,durvalumab plus GEMCIS significantly improved patient survival(TOPAZ-1 trial)and that ICIs-combined chemoimmunotherapy is poised to become a new frontline therapy option,regardless of TMB and MMR/MSI status.Adoptive cell therapy and peptide-or dendritic-based cancer vaccines are other immunotherapeutic options that are being studied in BTCs.Numerous biomarkers have been investigated to define their predictive role in response to ICIs,but no predictive biomarker has been validated,except MSI-H/dMMR.Conclusions:The role of immunotherapy in BTCs is currently under investigation and the results of ongoing studies are eagerly anticipated.Several studies have demonstrated the safety and efflcacy of ICIs in combination with chemotherapy in treatment-naive patients,such as the phaseⅢTOPAZ-1 trial,which will change the standard care of first-line chemotherapy for advanced BTCs.However,further research is needed to understand the best combination with immunotherapy and to discover more predictive biomarkers to guide clinical practice.
文摘The limited efficacy of cytotoxic therapy for advanced biliary tract and gallbladder cancers emphasizes the need for novel and more effective medical treatment options. A better understanding of the specific biological features of these neoplasms led to the development of new targeted therapies, which take the abundant expression of several growth factors and cognate tyrosine kinase receptors into account. This review will briefly summarize the status and future perspectives of antiangiogenic and growth factor receptor-based pharmacological approaches for the treatment of biliary tract and gallbladder cancers. In view of multiple novel targeted approaches, the rationale for innovative therapies, such as combinations of growth factor (receptor)-targeting agents with cytotoxic drugs or with other novel anticancer drugs will be highlighted.
文摘Biliary tract cancer(BTC)is a group of rare malignancies that affect the gallbladder and bile ducts.Although rare,BTC is becoming a significant public health burden in China,particularly among males and older individuals.The increasing trends in BTC incidence and mortality in China are influenced by various demographic,environmental,and lifestyle factors.In this review,we examine available epidemiological data on the incidence,mortality,prognosis,and trends of different BTC subtypes in China.We also discuss the challenges and opportunities for improving the prevention,diagnosis,and management of BTC in China,and identify areas for further research and intervention.The article aims to provide a better understanding of the epidemiological features of BTC in China and to inform public health strategies and clinical practice.
文摘Biliary tract cancer is a rare malignant tumor. There is limited knowledge about biology and natural history of this disease and considerable uncertainty remains regarding its optimal diagnostic and therapeutic man- agement. The role of adjuvant therapy is object of debate and controversy. Although resection is identified as the most effective and the only potentially curative treatment, there is no consensus on the impact of ad- juvant chemotherapy and/or radiotherapy on the high incidence of disease recurrence and on survival. This is mainly due to the rarity of this disease and the consequent difficulty in performing randomized trials. The only two prospectively controlled trials concluded that adjuvant chemotherapy did not improve survival. Most of the retrospective trials, which had limited sample size and included heterogeneous patients population and non-standardized therapies, suggested a marginal benefit of chemoradiotherapy in reducing locoregional recurrence and an uncertain impact on survival. Welldesigned multi-institutional randomized trials are necessary to clarify the role of adjuvant therapy. Two ongoing phase Ⅲ trials may provide relevant information.
文摘AIM:To investigate the expression and clinical relevance of inhibitor of differentiation(ID)proteins in biliary tract cancer.METHODS:ID protein expression was analyzed in129 samples from patients with advanced biliary tract cancer(BTC)(45 extrahepatic,50 intrahepatic,and 34 gallbladder cancers),compared to normal controls and correlated with clinical an pathological parameters.RESULTS:ID1-3 proteins are frequently overexpressed in all BTC subtypes analyzed.No correlation between increased ID protein expression and tumor grading,tumor subtype or treatment response was detected.Survival was influenced primary tumor localization(extrahepatic vs intrahepatic and gall bladder cancer,OS 1.5 years vs 0.9 years vs 0.7 years,P=0.002),by stage at diagnosis(OS 2.7 years in stageⅠv s 0.6 years in stageⅣ,P<0.001),resection status and response to systemic chemotherapy.In a multivariate model,ID protein expression did not correlate with clinical prognosis.Nevertheless,there was a trend of shorter OS in patients with loss of cytoplasmic ID4 protein expression(P=0.076).CONCLUSION:ID protein expression is frequently deregulated in BTC but does not influence clinical prognosis.Their usefulness as prognostic biomarkers in BTC is very limited.
文摘BACKGROUND Biliary tract cancers(BTCs)are a heterogeneous group of tumors with high malignancy,poor prognosis,and limited treatment options.AIM To explore the efficacy and safety of nab-paclitaxel plus capecitabine as first-line treatment for advanced and metastatic BTCs.METHODS This open-label,non-randomized,double-center,phase II clinical trial recruited systemic therapy-naive patients with unresectable or metastatic BTCs between April 2019 and June 2022 at Beijing Cancer Hospital and the First Hospital of China Medical University.Eligible patients were administered nab-paclitaxel(150 mg/m^(2),day 1)and capecitabine(2000 mg/m^(2),twice daily,days 1-7)in 14-day cycles until experiencing intolerable toxicity or disease progression.The primary outcome was the objective response rate(ORR).The secondary outcomes included the disease control rate(DCR),overall survival(OS),progression-free survival(PFS),and safety.RESULTS A total of 44 patients successfully completed the trial,with a median age of 64.00 years(interquartile range,35.00-76.00),and 26(59.09%)were females.Tumor response assessment was impeded for one patient due to premature demise from tumor hemorrhage.Among the remaining 43 patients undergoing at least one imaging assessment,the ORR was 23.26%[95%confidence interval(CI):11.80%-38.60%],and the DCR was 69.77%(95%CI:53.90%-82.80%).The median OS was 14.1 months(95%CI:8.3-19.9),and the median PFS was 4.4 months(95%CI:2.5-6.3).A total of 41 patients(93.18%)experienced at least one adverse event(AE),with 10 patients(22.73%)encountering grade≥3 AEs,and the most frequent AEs of any grade were alopecia(79.50%),leukopenia(54.55%),neutropenia(52.27%),and liver dysfunction(40.91%),and no treatment-related deaths were documented.CONCLUSION Nab-paclitaxel plus capecitabine may be an effective and safe first-line treatment strategy for patients with advanced or metastatic BTCs.
基金supported by a grant from the Advanced Research for Medical Products Mining Programme of the National Institute of Biomedical Innovation (NIBIO)
文摘ABSTRACT： CD98 has been described to play a crucial role in tumor progression and survival. However, the role of CD98 in biliary tract cancer remains unclear. We found that 36.7% of all patients with biliary tract cancer had a high CD98 expression. Statistical analysis using Spearman＇s rank correlation showed that CD98 was significantly correlated with L-type amino acid transporter 1 （LAT1, r=0.562, P〈0.001）, Ki-67 （r=0.230, P=0.006） and CD34 （r=0.290, P=0.005）. Multivariate analysis confirmed that a high CD98 expression was an independent prognostic factor for predicting poor outcome. CD98 is closely associated with tumor growth, biological aggressiveness, and survival of patients. With these data we proposed that CD98 expression is necessary for the development and pathogenesis of biliary tract cancer.
文摘Biliary tract cancer,comprising gallbladder cancer,cholangiocarcinoma and ampullary cancer,represents a more uncommon entity outside high-endemic areas,though global incidence is rising.The majority of patients present at a late stage,and 5-year survival remains poor.Advanced stage disease is incurable,and though palliative chemotherapy has been shown to improve survival,further diagnostic and therapeutic options are required in order to improve patient outcomes.Although certain subtypes of biliary tract cancer are relatively rich in targetable mutations,attaining tumour tissue for histological diagnosis and treatment monitoring is challenging due to locoregional anatomical constraints and patient fitness.Liquid biopsies offer a safe and convenient alternative to invasive procedures and have great potential as diagnostic,predictive and prognostic biomarkers.In this review,the current standard of care for patients with biliary tract cancer,future treatment horizons and the possible utility of liquid biopsies within a variety of contexts will be discussed.Circulating tumour DNA,circulating microRNA and circulating tumour cells are discussed with an overview of their potential applications in management of biliary tract cancer.A summary is also provided of currently recruiting clinical trials incorporating liquid biopsies within biliary tract cancer research.
