AIM: To evaluate the dose-limiting toxicities(DLTs)and determine the maximum-tolerated dose(MTD) and recommended dose(RD) of combination chemotherapy with gemcitabine, cisplatin and S-1 which is an oral fluoropyrimidi...AIM: To evaluate the dose-limiting toxicities(DLTs)and determine the maximum-tolerated dose(MTD) and recommended dose(RD) of combination chemotherapy with gemcitabine, cisplatin and S-1 which is an oral fluoropyrimidine pro-drug in patients with advanced biliary tract cancer.METHODS: Patients with histologically or cytologically confirmed unresectable or recurrent biliary tract cancer were enrolled. The planned dose levels of gemcitabine(mg/m2), cisplatin(mg/m2), and S-1(mg/m2 per day) were as follows: level-1, 800/20/60;level 0, 800/25/60; level 1, 1000/25/60; and level 2,1000/25/80. In each cycle, gemcitabine and cisplatin were administered intravenously on days 1 and 15,and S-1 was administered orally twice daily on days 1to 7 and days 15 to 21, every 4 wk.RESULTS: Twelve patients were enrolled, and level0 was chosen as the starting dose. None of the first three patients had DLTs at level 0, and the dose was escalated to level 1. One of six patients had DLTs(grade 4 febrile neutropenia, leucopenia, and neutropenia; grade 3 thrombocytopenia) at level 1.We then proceeded to level 2. None of three patients had DLTs during the first cycle. Although the MTD was not determined, level 2 was designated at the RD for a subsequent phase Ⅱ study.CONCLUSION: The RD was defined as gemcitabine1000 mg/m2(days 1, 15), cisplatin 25 mg/m2(days1, 15), and S-1 80 mg/m2 per day(days 1-7, 15-21),every 4 weeks. A phase Ⅱ study is planned to evaluate the effectiveness of combination chemotherapy withgemcitabine, cisplatin, and S-1 in advanced biliary tract cancer.展开更多
BACKGROUND Targeted therapy(TT)has resulted in controversial efficacy as first-line treatment for biliary tract cancer(BTC).More efficacy comparisons are required to clarify the overall effects of chemotherapy(CT)comb...BACKGROUND Targeted therapy(TT)has resulted in controversial efficacy as first-line treatment for biliary tract cancer(BTC).More efficacy comparisons are required to clarify the overall effects of chemotherapy(CT)combined with TT and CT alone on advanced BTC.AIM To conduct a meta-analysis of the available evidence on the efficacy of CT combined with TT for advanced BTC.METHODS The PubMed,EMBASE,ClinicalTrials,Scopus and Cochrane Library databases were systematically searched for relevant studies published from inception to August 2022.Only randomized clinical trials(RCTs)including comparisons between the combination of gemcitabine-based CT with TT and CT alone as firstline treatment for advanced BTC were eligible(PROSPERO-CRD42022313001).The odds ratios(ORs)for the objective response rate(ORR)and hazard ratios(HRs)for both progression-free survival(PFS)and overall survival(OS)were calculated and analyzed.Subgroup analyses based on different targeted agents,CT regimens and tumor locations were prespecified.RESULTS Nine RCTs with a total of 1361 individuals were included and analyzed.The overall analysis showed a significant improvement in ORR in patients treated with CT+TT compared to those treated with CT alone(OR=1.43,95%CI:1.11-1.86,P=0.007)but no difference in PFS or OS.Similar trends were observed in the subgroup treated with agents targeting epidermal growth factor receptor(OR=1.67,95%CI:1.17-2.37,P=0.004)but not in the subgroups treated with agents targeting vascular endothelial growth factor receptor or mesenchymal-epithelial transition factor.Notably,patients who received a CT regimen of gemcitabine+oxaliplatin in the CT+TT arm had both a higher ORR(OR=1.75,95%CI:1.20-2.56,P=0.004)and longer PFS(HR=0.83,95%CI:0.70-0.99,P=0.03)than those in the CT-only arm.Moreover,patients with cholangiocarcinoma treated with CT+TT had significantly increased ORR and PFS(ORR,OR=2.06,95%CI:1.27-3.35,PFS,HR=0.79,95%CI:0.66-0.94).CONCLUSION CT+TT is a potential first-line treatment for advanced BTC that leads to improved tumor control and survival outcomes,and highlighting the importance of CT regimens and tumor types in the application of TT.展开更多
Objective:To investigate the effect of oxaliplatin combined with tiggio in the treatment of advanced biliary tract tumors.Methods:The research period was from November 2019 to November 2020.80 patients with advanced b...Objective:To investigate the effect of oxaliplatin combined with tiggio in the treatment of advanced biliary tract tumors.Methods:The research period was from November 2019 to November 2020.80 patients with advanced biliary tumor disease were enrolled.They were divided into groups according to the order of admission,with 40 cases in each group.The control group received oxaliplatin combined with gemcitabine,and the experimental group received oxaliplatin combined with tiggio.Incidence of adverse reactions,time to disease progression,survival time and clinical efficacy were checked and assessed.Results:Compared with the incidence of adverse reaction of the experimental group,which was 5.00%(2/40),the incidence of adverse reaction of the control group was 25.00%(10/40).The chi-square value=6.2745,p-value=0.0122.The time to progression and survival time of patients in the experimental group were shorter than those of the control group,with significant differences between the groups(p<0.05);the clinical efficacy of the experimental group and the control group were 97.50%(39/40)and 77.50%(31/40)respectively,the comparative chi-square value=7.3143,p-value=0.0068.Conclusion:The combined treatment of oxaliplatin and Tiggio in the treatment of advanced biliary tract tumors has higher safety and reduces the incidence of adverse reactions.展开更多
BACKGROUND For cases of middle and low biliary obstruction with left and right hepatic duct dilatation,the type of approach and whether different approaches affect the difficulty of puncture operation and intraoperati...BACKGROUND For cases of middle and low biliary obstruction with left and right hepatic duct dilatation,the type of approach and whether different approaches affect the difficulty of puncture operation and intraoperative and postoperative complications have not been discussed in detail.AIM To compare the efficacy of different percutaneous transhepatic biliary stent placements and catheter drainage in treating middle and low biliary obstruction.METHODS A retrospective analysis was performed on the medical records of 424 patients with middle and low biliary obstruction who underwent percutaneous liver puncture biliary stent placement and catheter drainage at the Department of Interventional Radiology,Shaanxi Provincial People’s Hospital between March 2016 and March 2022.Based on the puncture path,patients were categorized into two groups:Subxiphoid left hepatic lobe approach group(Group A,224 cases)and right intercostal,right hepatic lobe approach group(Group B,200 cases).Liver function improvement,postoperative biliary bleeding incidence,postoperative pain duration,and abdominal effusion leakage around the drainage tube were compared between the two groups at 3 d and 1 wk after the surgery.Patient survival time was recorded during follow-up.RESULTS All 424 surgeries were successful without adverse events.Group A comprised 224 cases,and Group B had 200 cases.There was no statistically significant difference in basic data between Group A and Group B(P>0.05).No significant difference in postoperative biliary bleeding incidence was observed between the groups(P>0.05).The decreased rates for total bilirubin(Group A:69.23±4.50,Group B:63.79±5.65),direct bilirubin(Group A:79.30±11.19,Group B:63.62±5.64),and alkaline phosphatase(Group A:60.51±12.23,Group B:42.68±23.56)in the 1st wk after surgery were significantly faster in Group A than in Group B.The decreased rate of gamma-glutamyl transpeptidase was also significantly faster in Group A at both 3 d(Group A:40.56±10.32,Group B:32.22±5.12)and 1 wk(Group A:73.19±7.05,Group B:58.81±18.98)after surgery(P<0.05).Group A experienced significantly less peritoneal effusion leakage around the drainage tube than Group B(P<0.05).The patient survival rate was higher in Group A compared to Group B(P<0.05).CONCLUSION In treating jaundice patients with middle and low biliary obstruction,a percutaneous left liver puncture demonstrated better clinical efficacy than a percutaneous right liver puncture.展开更多
AIM: To determine the impact(morbidity/mortality) of biliary stent-related events(SRE)(cholangitis or stent obstruction) in chemotherapy-treated pancreaticobiliary patients.METHODS: All consecutive patients with advan...AIM: To determine the impact(morbidity/mortality) of biliary stent-related events(SRE)(cholangitis or stent obstruction) in chemotherapy-treated pancreaticobiliary patients.METHODS: All consecutive patients with advanced pancreatobiliary cancer and a biliary stent in-situ prior to starting palliative chemotherapy were identified retrospectively from local electronic case-note records(Jan 13 to Jan 15). The primary end-point was SRE rate and the time-to-SRE(defined as time from first stenting before chemotherapy to date of SRE). Progressionfree survival and overall survival were measured from the time of starting chemotherapy. Kaplan-Meier, Cox and Fine-Gray regression(univariate and multivariable) analyses were employed, as appropriate. For the analysis of time-to-SRE, death was considered as a competing event.RESULTS: Ninety-six out of 693 screened patients were eligible; 89% had a metal stent(the remainder were plastic). The median time of follow-up was 9.6 mo(range 2.2 to 26.4). Forty-one patients(43%)developed a SRE during follow-up [cholangitis(39%), stent obstruction(29%), both(32%)]. There were no significant differences in baseline characteristics between the SRE group and no-SRE groups. Recorded SRE-consequences were: none(37%), chemotherapy delay(24%), discontinuation(17%) and death(22%). The median time-to-SRE was 4.4 mo(95%CI: 3.6-5.5). Patients with severe comorbidities(P < 0.001) and patients with ≥ 2 baseline stents/biliary procedures [HR = 2.3(95%CI: 1.2-4.44), P = 0.010] had a shorter time-to-SRE on multivariable analysis. Stage was an independent prognostic factor for overall survival(P = 0.029) in the multivariable analysis adjusted for primary tumour site, performance status and development of SRE(SRE group vs no-SRE group).CONCLUSION: SREs are common and impact on patient's morbidity. Our results highlight the need for prospective studies exploring the role of prophylactic strategies to prevent/delay SREs.展开更多
AIM: To determine the role of circulating tumor cells (CTCs) in prediction of the overall survival of patients with advanced malignant biliary tract obstruction. METHODS: We investigated the prognostic value of CTCs b...AIM: To determine the role of circulating tumor cells (CTCs) in prediction of the overall survival of patients with advanced malignant biliary tract obstruction. METHODS: We investigated the prognostic value of CTCs by examining two markers, cytokeratin (CK) 19 and human telomerase reverse transcriptase (hTERT) mRNA, in 40 patients diagnosed with advanced malig- nant biliary tract diseases. Quantitative real-time re- verse transcription polymerase chain reaction was used to detect CK19 and hTERT mRNA in the peripheral blood of these patients. Overall survival was analyzed using the Kaplan-Meier method and Cox regression modeling.RESULTS: Positive CK19 and hTERT mRNA expression was detected in 45% and 60%, respectively, of the 40 patients. Univariable analysis indicated that positive CK19 mRNA expression was significantly associated with worse overall survival (P = 0.009). Multivariable analysis determined that positive CK19 mRNA expres- sion, patient's age and serum bilirubin were each inde- pendently associated with overall survival. CONCLUSION: CK19 mRNA expression levels in pe- ripheral blood appear to provide a valuable marker to predict the overall survival of patients with advanced malignant biliary tract obstruction.展开更多
AIM: To gain a better understanding of biliary tract intraductal papillary mucinous neoplasm(BT-IPMN).METHODS: From January 2000 to December 2013, 19cases of BT-IPMN were retrospectively identified from a total of 343...AIM: To gain a better understanding of biliary tract intraductal papillary mucinous neoplasm(BT-IPMN).METHODS: From January 2000 to December 2013, 19cases of BT-IPMN were retrospectively identified from a total of 343 biliary tract tumors resected in our single institution.Demographic characteristics, clinical data, pathology, surgical strategies, and long-term follow-up were analyzed.RESULTS: The mean age of the 19 BT-IPMN cases was 53.8 years(range: 25-74 years).The most common symptom was abdominal pain(15/19; 78.9%), followed by jaundice(7/19; 36.8%).Cholangitis was associated with most(16/19; 84.2%) of the BT-IPMN cases.Macroscopically visible mucin was detected in all 19 patients, based on original surgical reports.The most common abnormal preoperative imaging findings for BT-IPMN were bile duct dilation(19/19; 100%) and intraluminal masses(10/19; 52.6%).Thirteen(68.4%) cases involved the intrahepatic bile duct and hilum.We performed left hepatectomy in 11/19(57.9%), right hepatectomy in 2/19(10.5%), bile duct resection in 4/19(21.1%), and pancreatoduodenectomy in 1/19(5.3%) patients.One(5.3%) patient was biopsied and received a choledochojejunostomy because of multiple tumors involving the right extrahepatic and left intrahepatic bile ducts.Histology showed malignancy in 10/19(52.6%) patients.The overall median survival was 68 mo.The benign cases showed a non-significant trend towards improved survival compared to malignant cases(68 mo vs 48 mo, P = 0.347).The patient without tumor resection died of liver failure 22 mo after palliative surgery.CONCLUSION: BT-IPMN is a rare biliary entity.Complete resection of the tumor is associated with good survival, even in patients with malignant disease.展开更多
Bile duct tumors are comprised of tumors that originate from both intrahepatic and extrahepatic bile ducts and gallbladder tumors.These are aggressive tumors and chemotherapy is still the main treatment for advanced-s...Bile duct tumors are comprised of tumors that originate from both intrahepatic and extrahepatic bile ducts and gallbladder tumors.These are aggressive tumors and chemotherapy is still the main treatment for advanced-stage disease and most of these cases have a poor overall survival.Strategies are aimed at treatments with better outcomes and less toxicity which makes immunotherapy an area of significant importance.Recent Food and Drug Administration approvals of immune checkpoint inhibitors(ICI)for agnostic tumors based on biomarkers such as microsatellite instability-high and tumor mutation burden-high are important steps in the treatment of patients with advanced bile duct tumors.Despite limited responses with isolated checkpoint inhibitors in later lines of systemic treatment in advanced disease,drug combination strategies have been demonstrating encouraging results to enhance ICI efficacy.展开更多
Advanced cholangiocarcinoma is associated with poor prognostic survival and has limited therapeutic options available at present. The importance of angiogenesis and expression of pro-angiogenic factors in intrahepatic...Advanced cholangiocarcinoma is associated with poor prognostic survival and has limited therapeutic options available at present. The importance of angiogenesis and expression of pro-angiogenic factors in intrahepatic forms of cholangiocarcinoma suggest that therapies targeting angiogenesis might be useful for the treatment of this disease. Here we report three cases of patients with advanced intrahepatic cholangiocarcinoma progressive after standard chemotherapy and treated with sunitinib 50 mg/d in 6-wk cycles of 4 wk on treatment followed by 2 wk off treatment(Schedule 4/2). In all three patients, sunitinib treatment was associated with a sustained disease control superior to 4 mo, patients achieving either a partial response or stable disease. A reduction in tumor size and density was observed in all cases, suggesting tumor necrosis as a result of sunitinib treatment in these patients. In addition, sunitinib was generally well tolerated and the occurrence of side effects was managed with standard medical interventions, as required. Our results suggest that sunitinib therapy maybe associated with favorable outcomes and tolerability in patients with advanced cholangiocarcinoma. Those observations contributed to launch a prospective phase Ⅱ multicenter trial investigating sunitinib in advanced intrahepatic cholangiocarcinoma(SUN-CK study; NCT01718327).展开更多
Management of biliary tract cancer remains challenging. Tumors show high recurrence rates and therapeutic resistance, leading to dismal prognosis and short survival. The cancer stem cell model states that a tumor is a...Management of biliary tract cancer remains challenging. Tumors show high recurrence rates and therapeutic resistance, leading to dismal prognosis and short survival. The cancer stem cell model states that a tumor is a heterogeneous conglomerate of cells, in which a certain subpopulation of cells-the cancer stem cells-possesses stem cell properties. Cancer stem cells have high clinical relevance due to their potential contributions to development, progression and aggressiveness as well as recurrence and metastasis of malignant tumors. Consequently, reliable identification of as well as pharmacological intervention with cancer stem cells is an intensively investigated and promising research field. The involvement of cancer stem cells in biliary tract cancer is likely as a number of studies demonstrated their existence and the obvious clinical relevance of several established cancer stem cell markers in biliary tract cancer models and tissues. In the present article, we review and discuss the currently available literature addressing the role of putative cancer stem cells in biliary tract cancer as well as the connection between known contributors of biliary tract tumorigenesis such as oncogenic signaling pathways, micro-RNAs and the tumor microenvironment with cancer stem cells.展开更多
Epidemiological data show that the incidence rate of cholangiocarcinoma(CCA)has been increasing over the past 20 years.Due to its concealment of clinical manifestations,most patients are diagnosed with CCA at a late s...Epidemiological data show that the incidence rate of cholangiocarcinoma(CCA)has been increasing over the past 20 years.Due to its concealment of clinical manifestations,most patients are diagnosed with CCA at a late stage.On this premise,this review not only discusses the research progress related to CCA diagnosis,but also focuses on the concept of circulating tumor cell(CTC),its evaluation value,application,and prospects for the early diagnosis of extrahepatic cholangiocarcinoma.展开更多
Mucin-producing bile duct tumors (MPBTs) are characterized by intraductal papillary tumorsproducing large amounts of mucin. The tumor comprises macroscopically prominent intraductal papillary neoplastic epithelia an...Mucin-producing bile duct tumors (MPBTs) are characterized by intraductal papillary tumorsproducing large amounts of mucin. The tumor comprises macroscopically prominent intraductal papillary neoplastic epithelia and produces a large amount of viscid mucin, resulting in dilatation of the bile ducts.1 These tumors of the peripheral bile duct, which include benign and malignant lesions, have also been referred to as intraductal growth- type peripheral cholangiocarcinomas,2 mucin-producing cholangiocellular carcinomas,3 intraductal papillary neoplasms (IPNs) of the biliary tract,4 IPNs of the liver,5 or IPNs of the bile duct.6 MPBTs have been the subject of recent attention due to its peculiar histopathology, biological and clinical behavior, varied radiological manifestations, and good prognosis of the patients] Due to the rarity of this disease entity and the non-specific clinical presentation, MPBTs are not well characterized. The purpose of this study was to define the precise diagnosis and correct management of MPBTs with the help of nine clinical cases observed in the last 10 years. The preoperative differential diagnosis, surgical procedure, and postoperative course of these nine cases were retrospectively reviewed.展开更多
文摘AIM: To evaluate the dose-limiting toxicities(DLTs)and determine the maximum-tolerated dose(MTD) and recommended dose(RD) of combination chemotherapy with gemcitabine, cisplatin and S-1 which is an oral fluoropyrimidine pro-drug in patients with advanced biliary tract cancer.METHODS: Patients with histologically or cytologically confirmed unresectable or recurrent biliary tract cancer were enrolled. The planned dose levels of gemcitabine(mg/m2), cisplatin(mg/m2), and S-1(mg/m2 per day) were as follows: level-1, 800/20/60;level 0, 800/25/60; level 1, 1000/25/60; and level 2,1000/25/80. In each cycle, gemcitabine and cisplatin were administered intravenously on days 1 and 15,and S-1 was administered orally twice daily on days 1to 7 and days 15 to 21, every 4 wk.RESULTS: Twelve patients were enrolled, and level0 was chosen as the starting dose. None of the first three patients had DLTs at level 0, and the dose was escalated to level 1. One of six patients had DLTs(grade 4 febrile neutropenia, leucopenia, and neutropenia; grade 3 thrombocytopenia) at level 1.We then proceeded to level 2. None of three patients had DLTs during the first cycle. Although the MTD was not determined, level 2 was designated at the RD for a subsequent phase Ⅱ study.CONCLUSION: The RD was defined as gemcitabine1000 mg/m2(days 1, 15), cisplatin 25 mg/m2(days1, 15), and S-1 80 mg/m2 per day(days 1-7, 15-21),every 4 weeks. A phase Ⅱ study is planned to evaluate the effectiveness of combination chemotherapy withgemcitabine, cisplatin, and S-1 in advanced biliary tract cancer.
基金Supported by China Academy of Medical Science Innovation Fund for Medical Sciences,CIFMS,No.2021-I2M-1-022-2021-S4.
文摘BACKGROUND Targeted therapy(TT)has resulted in controversial efficacy as first-line treatment for biliary tract cancer(BTC).More efficacy comparisons are required to clarify the overall effects of chemotherapy(CT)combined with TT and CT alone on advanced BTC.AIM To conduct a meta-analysis of the available evidence on the efficacy of CT combined with TT for advanced BTC.METHODS The PubMed,EMBASE,ClinicalTrials,Scopus and Cochrane Library databases were systematically searched for relevant studies published from inception to August 2022.Only randomized clinical trials(RCTs)including comparisons between the combination of gemcitabine-based CT with TT and CT alone as firstline treatment for advanced BTC were eligible(PROSPERO-CRD42022313001).The odds ratios(ORs)for the objective response rate(ORR)and hazard ratios(HRs)for both progression-free survival(PFS)and overall survival(OS)were calculated and analyzed.Subgroup analyses based on different targeted agents,CT regimens and tumor locations were prespecified.RESULTS Nine RCTs with a total of 1361 individuals were included and analyzed.The overall analysis showed a significant improvement in ORR in patients treated with CT+TT compared to those treated with CT alone(OR=1.43,95%CI:1.11-1.86,P=0.007)but no difference in PFS or OS.Similar trends were observed in the subgroup treated with agents targeting epidermal growth factor receptor(OR=1.67,95%CI:1.17-2.37,P=0.004)but not in the subgroups treated with agents targeting vascular endothelial growth factor receptor or mesenchymal-epithelial transition factor.Notably,patients who received a CT regimen of gemcitabine+oxaliplatin in the CT+TT arm had both a higher ORR(OR=1.75,95%CI:1.20-2.56,P=0.004)and longer PFS(HR=0.83,95%CI:0.70-0.99,P=0.03)than those in the CT-only arm.Moreover,patients with cholangiocarcinoma treated with CT+TT had significantly increased ORR and PFS(ORR,OR=2.06,95%CI:1.27-3.35,PFS,HR=0.79,95%CI:0.66-0.94).CONCLUSION CT+TT is a potential first-line treatment for advanced BTC that leads to improved tumor control and survival outcomes,and highlighting the importance of CT regimens and tumor types in the application of TT.
文摘Objective:To investigate the effect of oxaliplatin combined with tiggio in the treatment of advanced biliary tract tumors.Methods:The research period was from November 2019 to November 2020.80 patients with advanced biliary tumor disease were enrolled.They were divided into groups according to the order of admission,with 40 cases in each group.The control group received oxaliplatin combined with gemcitabine,and the experimental group received oxaliplatin combined with tiggio.Incidence of adverse reactions,time to disease progression,survival time and clinical efficacy were checked and assessed.Results:Compared with the incidence of adverse reaction of the experimental group,which was 5.00%(2/40),the incidence of adverse reaction of the control group was 25.00%(10/40).The chi-square value=6.2745,p-value=0.0122.The time to progression and survival time of patients in the experimental group were shorter than those of the control group,with significant differences between the groups(p<0.05);the clinical efficacy of the experimental group and the control group were 97.50%(39/40)and 77.50%(31/40)respectively,the comparative chi-square value=7.3143,p-value=0.0068.Conclusion:The combined treatment of oxaliplatin and Tiggio in the treatment of advanced biliary tract tumors has higher safety and reduces the incidence of adverse reactions.
文摘BACKGROUND For cases of middle and low biliary obstruction with left and right hepatic duct dilatation,the type of approach and whether different approaches affect the difficulty of puncture operation and intraoperative and postoperative complications have not been discussed in detail.AIM To compare the efficacy of different percutaneous transhepatic biliary stent placements and catheter drainage in treating middle and low biliary obstruction.METHODS A retrospective analysis was performed on the medical records of 424 patients with middle and low biliary obstruction who underwent percutaneous liver puncture biliary stent placement and catheter drainage at the Department of Interventional Radiology,Shaanxi Provincial People’s Hospital between March 2016 and March 2022.Based on the puncture path,patients were categorized into two groups:Subxiphoid left hepatic lobe approach group(Group A,224 cases)and right intercostal,right hepatic lobe approach group(Group B,200 cases).Liver function improvement,postoperative biliary bleeding incidence,postoperative pain duration,and abdominal effusion leakage around the drainage tube were compared between the two groups at 3 d and 1 wk after the surgery.Patient survival time was recorded during follow-up.RESULTS All 424 surgeries were successful without adverse events.Group A comprised 224 cases,and Group B had 200 cases.There was no statistically significant difference in basic data between Group A and Group B(P>0.05).No significant difference in postoperative biliary bleeding incidence was observed between the groups(P>0.05).The decreased rates for total bilirubin(Group A:69.23±4.50,Group B:63.79±5.65),direct bilirubin(Group A:79.30±11.19,Group B:63.62±5.64),and alkaline phosphatase(Group A:60.51±12.23,Group B:42.68±23.56)in the 1st wk after surgery were significantly faster in Group A than in Group B.The decreased rate of gamma-glutamyl transpeptidase was also significantly faster in Group A at both 3 d(Group A:40.56±10.32,Group B:32.22±5.12)and 1 wk(Group A:73.19±7.05,Group B:58.81±18.98)after surgery(P<0.05).Group A experienced significantly less peritoneal effusion leakage around the drainage tube than Group B(P<0.05).The patient survival rate was higher in Group A compared to Group B(P<0.05).CONCLUSION In treating jaundice patients with middle and low biliary obstruction,a percutaneous left liver puncture demonstrated better clinical efficacy than a percutaneous right liver puncture.
基金Supported by Pancreatic Cancer Research Fund and Spanish society of Medical Oncology(Lamarca A)
文摘AIM: To determine the impact(morbidity/mortality) of biliary stent-related events(SRE)(cholangitis or stent obstruction) in chemotherapy-treated pancreaticobiliary patients.METHODS: All consecutive patients with advanced pancreatobiliary cancer and a biliary stent in-situ prior to starting palliative chemotherapy were identified retrospectively from local electronic case-note records(Jan 13 to Jan 15). The primary end-point was SRE rate and the time-to-SRE(defined as time from first stenting before chemotherapy to date of SRE). Progressionfree survival and overall survival were measured from the time of starting chemotherapy. Kaplan-Meier, Cox and Fine-Gray regression(univariate and multivariable) analyses were employed, as appropriate. For the analysis of time-to-SRE, death was considered as a competing event.RESULTS: Ninety-six out of 693 screened patients were eligible; 89% had a metal stent(the remainder were plastic). The median time of follow-up was 9.6 mo(range 2.2 to 26.4). Forty-one patients(43%)developed a SRE during follow-up [cholangitis(39%), stent obstruction(29%), both(32%)]. There were no significant differences in baseline characteristics between the SRE group and no-SRE groups. Recorded SRE-consequences were: none(37%), chemotherapy delay(24%), discontinuation(17%) and death(22%). The median time-to-SRE was 4.4 mo(95%CI: 3.6-5.5). Patients with severe comorbidities(P < 0.001) and patients with ≥ 2 baseline stents/biliary procedures [HR = 2.3(95%CI: 1.2-4.44), P = 0.010] had a shorter time-to-SRE on multivariable analysis. Stage was an independent prognostic factor for overall survival(P = 0.029) in the multivariable analysis adjusted for primary tumour site, performance status and development of SRE(SRE group vs no-SRE group).CONCLUSION: SREs are common and impact on patient's morbidity. Our results highlight the need for prospective studies exploring the role of prophylactic strategies to prevent/delay SREs.
基金Supported by Rajavithi Hospital Project Grant and Thailand Research Fund,No.RSA52
文摘AIM: To determine the role of circulating tumor cells (CTCs) in prediction of the overall survival of patients with advanced malignant biliary tract obstruction. METHODS: We investigated the prognostic value of CTCs by examining two markers, cytokeratin (CK) 19 and human telomerase reverse transcriptase (hTERT) mRNA, in 40 patients diagnosed with advanced malig- nant biliary tract diseases. Quantitative real-time re- verse transcription polymerase chain reaction was used to detect CK19 and hTERT mRNA in the peripheral blood of these patients. Overall survival was analyzed using the Kaplan-Meier method and Cox regression modeling.RESULTS: Positive CK19 and hTERT mRNA expression was detected in 45% and 60%, respectively, of the 40 patients. Univariable analysis indicated that positive CK19 mRNA expression was significantly associated with worse overall survival (P = 0.009). Multivariable analysis determined that positive CK19 mRNA expres- sion, patient's age and serum bilirubin were each inde- pendently associated with overall survival. CONCLUSION: CK19 mRNA expression levels in pe- ripheral blood appear to provide a valuable marker to predict the overall survival of patients with advanced malignant biliary tract obstruction.
基金Supported by The Research Special Fund for Public Welfare Industry of Health,No.201202007
文摘AIM: To gain a better understanding of biliary tract intraductal papillary mucinous neoplasm(BT-IPMN).METHODS: From January 2000 to December 2013, 19cases of BT-IPMN were retrospectively identified from a total of 343 biliary tract tumors resected in our single institution.Demographic characteristics, clinical data, pathology, surgical strategies, and long-term follow-up were analyzed.RESULTS: The mean age of the 19 BT-IPMN cases was 53.8 years(range: 25-74 years).The most common symptom was abdominal pain(15/19; 78.9%), followed by jaundice(7/19; 36.8%).Cholangitis was associated with most(16/19; 84.2%) of the BT-IPMN cases.Macroscopically visible mucin was detected in all 19 patients, based on original surgical reports.The most common abnormal preoperative imaging findings for BT-IPMN were bile duct dilation(19/19; 100%) and intraluminal masses(10/19; 52.6%).Thirteen(68.4%) cases involved the intrahepatic bile duct and hilum.We performed left hepatectomy in 11/19(57.9%), right hepatectomy in 2/19(10.5%), bile duct resection in 4/19(21.1%), and pancreatoduodenectomy in 1/19(5.3%) patients.One(5.3%) patient was biopsied and received a choledochojejunostomy because of multiple tumors involving the right extrahepatic and left intrahepatic bile ducts.Histology showed malignancy in 10/19(52.6%) patients.The overall median survival was 68 mo.The benign cases showed a non-significant trend towards improved survival compared to malignant cases(68 mo vs 48 mo, P = 0.347).The patient without tumor resection died of liver failure 22 mo after palliative surgery.CONCLUSION: BT-IPMN is a rare biliary entity.Complete resection of the tumor is associated with good survival, even in patients with malignant disease.
文摘Bile duct tumors are comprised of tumors that originate from both intrahepatic and extrahepatic bile ducts and gallbladder tumors.These are aggressive tumors and chemotherapy is still the main treatment for advanced-stage disease and most of these cases have a poor overall survival.Strategies are aimed at treatments with better outcomes and less toxicity which makes immunotherapy an area of significant importance.Recent Food and Drug Administration approvals of immune checkpoint inhibitors(ICI)for agnostic tumors based on biomarkers such as microsatellite instability-high and tumor mutation burden-high are important steps in the treatment of patients with advanced bile duct tumors.Despite limited responses with isolated checkpoint inhibitors in later lines of systemic treatment in advanced disease,drug combination strategies have been demonstrating encouraging results to enhance ICI efficacy.
文摘Advanced cholangiocarcinoma is associated with poor prognostic survival and has limited therapeutic options available at present. The importance of angiogenesis and expression of pro-angiogenic factors in intrahepatic forms of cholangiocarcinoma suggest that therapies targeting angiogenesis might be useful for the treatment of this disease. Here we report three cases of patients with advanced intrahepatic cholangiocarcinoma progressive after standard chemotherapy and treated with sunitinib 50 mg/d in 6-wk cycles of 4 wk on treatment followed by 2 wk off treatment(Schedule 4/2). In all three patients, sunitinib treatment was associated with a sustained disease control superior to 4 mo, patients achieving either a partial response or stable disease. A reduction in tumor size and density was observed in all cases, suggesting tumor necrosis as a result of sunitinib treatment in these patients. In addition, sunitinib was generally well tolerated and the occurrence of side effects was managed with standard medical interventions, as required. Our results suggest that sunitinib therapy maybe associated with favorable outcomes and tolerability in patients with advanced cholangiocarcinoma. Those observations contributed to launch a prospective phase Ⅱ multicenter trial investigating sunitinib in advanced intrahepatic cholangiocarcinoma(SUN-CK study; NCT01718327).
基金Supported by Studies of the authors Mayr C,Pichler M,Neureiter D and Kiesslich T in the research field of this review were supported by research grants of the Jubilaumsfonds derosterreichischen Nationalbank,No.12677 and No.14842the research fund of the Paracelsus Medical University Salzburg,No.08/07/037,No.A-12/02/006-KIE and No.R-16/03/083-MAY
文摘Management of biliary tract cancer remains challenging. Tumors show high recurrence rates and therapeutic resistance, leading to dismal prognosis and short survival. The cancer stem cell model states that a tumor is a heterogeneous conglomerate of cells, in which a certain subpopulation of cells-the cancer stem cells-possesses stem cell properties. Cancer stem cells have high clinical relevance due to their potential contributions to development, progression and aggressiveness as well as recurrence and metastasis of malignant tumors. Consequently, reliable identification of as well as pharmacological intervention with cancer stem cells is an intensively investigated and promising research field. The involvement of cancer stem cells in biliary tract cancer is likely as a number of studies demonstrated their existence and the obvious clinical relevance of several established cancer stem cell markers in biliary tract cancer models and tissues. In the present article, we review and discuss the currently available literature addressing the role of putative cancer stem cells in biliary tract cancer as well as the connection between known contributors of biliary tract tumorigenesis such as oncogenic signaling pathways, micro-RNAs and the tumor microenvironment with cancer stem cells.
基金This work was supported by Baoding Technology Program(project number:2041ZF084).
文摘Epidemiological data show that the incidence rate of cholangiocarcinoma(CCA)has been increasing over the past 20 years.Due to its concealment of clinical manifestations,most patients are diagnosed with CCA at a late stage.On this premise,this review not only discusses the research progress related to CCA diagnosis,but also focuses on the concept of circulating tumor cell(CTC),its evaluation value,application,and prospects for the early diagnosis of extrahepatic cholangiocarcinoma.
文摘Mucin-producing bile duct tumors (MPBTs) are characterized by intraductal papillary tumorsproducing large amounts of mucin. The tumor comprises macroscopically prominent intraductal papillary neoplastic epithelia and produces a large amount of viscid mucin, resulting in dilatation of the bile ducts.1 These tumors of the peripheral bile duct, which include benign and malignant lesions, have also been referred to as intraductal growth- type peripheral cholangiocarcinomas,2 mucin-producing cholangiocellular carcinomas,3 intraductal papillary neoplasms (IPNs) of the biliary tract,4 IPNs of the liver,5 or IPNs of the bile duct.6 MPBTs have been the subject of recent attention due to its peculiar histopathology, biological and clinical behavior, varied radiological manifestations, and good prognosis of the patients] Due to the rarity of this disease entity and the non-specific clinical presentation, MPBTs are not well characterized. The purpose of this study was to define the precise diagnosis and correct management of MPBTs with the help of nine clinical cases observed in the last 10 years. The preoperative differential diagnosis, surgical procedure, and postoperative course of these nine cases were retrospectively reviewed.