BACKGROUND: The frequency of isolated biliary candidiasis is increasing in cancer patients. The clinical signiifcance of isolated biliary candidiasis remains unclear. We analyzed the risk factors of biliary candidiasi...BACKGROUND: The frequency of isolated biliary candidiasis is increasing in cancer patients. The clinical signiifcance of isolated biliary candidiasis remains unclear. We analyzed the risk factors of biliary candidiasis and outcomes of the patients with unresectable cholangiocarcinoma after percutaneous transhepatic biliary drainage (PTBD). METHODS: Among 430 patients who underwent PTBD between January 2012 and March 2015, 121 patients had unresectable cholangiocarcinoma. Bile and blood samples were collected for consecutive fungal culture. RESULTS: The study cohort included 49 women and 72 men with a median age of 71 years. Multivariate analysis showed that cancer progression (P=0.013), concurrent presence of another microorganism (P=0.010), and previous long-term (>7 days) antibiotic use (P=0.011) were potential risk factors of biliary candidiasis. Chemotherapy was not associated with overall biliary candidiasis (P=0.196), but was signiifcantly related to repeated biliary candidiasis (P=0.011). Patients with isolated biliary candidiasis showed remarkably reduced survival compared with those without (median overall sur-vival (OS): 32 vs 62 days,P=0.011)Subgroup analysis was also performed. Patients with repeated candidiasis had markedly decreased survival compared with those with transient candi-diasis (median OS: 30 vs 49 days,P=0.046). Biliary candidiasis was identiifed as a poor prognostic factor by univariate and multivariate analyses (P=0.033). Four cases of repeated can-didiasis (4/19, 21%) showedCandida species in consecutive blood culture until the end of the study, but others showed no candidemia. CONCLUSIONS: Isolated biliary candidiasis may be associ-ated with poor prognosis in patients with unresectable chol-angiocarcinoma. Especially, repeated biliary candidiasis may have the possibility of progression to candidemia. We suggest that biliary dilatation treatment or antifungal agents might be helpful for patients with biliary candidiasis.展开更多
BACKGROUND A decline in serum carbohydrate antigen 19-9(CA19-9)levels during systemic chemotherapy is considered as a prognostic marker for patients with advanced pancreatic cancer.Neutrophil-to-lymphocyte ratio(NLR)h...BACKGROUND A decline in serum carbohydrate antigen 19-9(CA19-9)levels during systemic chemotherapy is considered as a prognostic marker for patients with advanced pancreatic cancer.Neutrophil-to-lymphocyte ratio(NLR)has been extensively studied as a simple and useful indicator of prognosis in various cancers including pancreatic cancer.AIM To assess the prognostic significance of NLR and CA19-9 in patients with advanced pancreatic adenocarcinoma received first-line chemotherapy according to CA19-9 positivity.METHODS We retrospectively analyzed patients diagnosed with advanced pancreatic cancer who received first-line chemotherapy between January 2010 and July 2017 at the Catholic University of Seoul St.Mary’s Hospital.Patients were divided according to CA19-9 positivity(CA19-9-positive vs-negative groups)and pre-and posttreatment NLR levels.To determine cut-off value of NLR and CA19-9 reduction,time-dependent receiver operating characteristic curve was applied.We evaluated overall survival(OS)and progression-free survival(PFS)for each group using Kaplan-Meier method,and we performed multivariate analyses on the entire cohort.RESULTS We included 271 patients in this study.Cut-off value of NLR and CA19-9 reduction was determined as 2.62 and 18%.Multivariate analysis showed that post-treatment NLR<2.62 and reduction of≥18%of baseline CA19-9 were significantly associated with OS and PFS.Post-treatment NLR≥2.62 showed hazard ratio(HR)of 2.47[95%confidence interval(CI):1.84-3.32,P<0.001]and CA19-9 decline(≥18%)showed HR of 0.51(95%CI:0.39-0.67,P<0.001)for OS.When CA19-9-positive patients were divided into groups according to CA19-9 response(responder vs non-responder)and post-treatment NLR(<2.62 vs≥2.62),CA19-9 responder and post-treatment NLR<2.62 group showed better survival than CA19-9 non-responder and post-treatment NLR≥2.62 group(OS 11.0 mo vs 3.9 mo,P<0.001;PFS 6.3 mo vs 2.0 mo,P<0.001).The combination of CA19-9 decline and post-treatment NLR showed a significant correlation with clinical response in CA 19-9 positive group.Within the CA19-9-negative group,the posttreatment NLR<2.62 group showed better survival than the post-treatment NLR≥2.62 group(OS 12.7 mo vs 7.7 mo,P<0.001;PFS 6.7 mo vs 2.1 mo,P<0.001),and post-treatment NLR showed correlation with clinical response.CONCLUSION In advanced pancreatic cancer patients positive for CA19-9 and treated with systemic chemotherapy,the combination of post-treatment NLR<2.62 and 18%decline of CA19-9 at the first response evaluation is a good prognostic marker.Post-treatment NLR<2.62 alone could be used as a prognostic marker and an adjunctive tool for response evaluation in CA19-9-negative patients.展开更多
BACKGROUND Owing to rarity of disease and lack of prospective studies, data supporting the role of adjuvant chemotherapy in ampulla of Vater(AoV) carcinoma is limited.AIM To evaluate whether adjuvant chemotherapy case...BACKGROUND Owing to rarity of disease and lack of prospective studies, data supporting the role of adjuvant chemotherapy in ampulla of Vater(AoV) carcinoma is limited.AIM To evaluate whether adjuvant chemotherapy cases for AoV carcinoma had better disease-free survival(DFS) rates than cases of observation following curative surgery.METHODS We retrospectively analyzed the association between adjuvant chemotherapy and DFS and overall survival(OS) in patients with stage IB-Ⅲ AoV carcinoma who underwent curative surgical resection. Fluorouracil-based adjuvant chemotherapy was administered after surgery at the discretion of the physician. Adjusted multivariate regression models were used to evaluate the association between adjuvant chemotherapy and survival outcomes.RESULTS Of the total 104 patients who underwent curative surgery, 52 received adjuvant chemotherapy. Multivariate analysis revealed that higher histologic grade [hazard ratio(HR) = 2.24, P = 0.046], advanced tumor stage(HR = 1.85, P = 0.030), and vascular invasion(HR = 2.14, P = 0.010) were associated with shorter DFS. Adjuvant chemotherapy improved DFS compared to the observation group(HR =0.50, P = 0.015) and tended to be associated with a longer OS, although the difference was not statistically significant(HR = 0.58, P = 0.098).CONCLUSION Among patients with resected AoV carcinoma, the adjuvant chemotherapy group was not associated with a significant survival benefit compared to the observation group. However, on multivariate analysis adjusting for prognostic factors, adjuvant chemotherapy following surgery was an independent prognostic factor for DFS in patients with resected AoV carcinoma. Further studies are needed to investigate the effectiveness of adjuvant chemotherapy according to histologic phenotype.展开更多
Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)pathway.Although c...Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)pathway.Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer(MIBC),it has a poor survival rate.Therefore,this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B(APOBEC3B)expressing MIBC.Methods:Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC.The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis.Western blot analysis was performed to confirm differences in phosphorylated Chk1(pChk1)expression according to the APOBEC3B expression.Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin.Results:There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC.Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels.Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression.Compared to cisplatin single treatment,combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression.Conclusion:Our study shows that APOBEC3B’s higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition.This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.展开更多
文摘BACKGROUND: The frequency of isolated biliary candidiasis is increasing in cancer patients. The clinical signiifcance of isolated biliary candidiasis remains unclear. We analyzed the risk factors of biliary candidiasis and outcomes of the patients with unresectable cholangiocarcinoma after percutaneous transhepatic biliary drainage (PTBD). METHODS: Among 430 patients who underwent PTBD between January 2012 and March 2015, 121 patients had unresectable cholangiocarcinoma. Bile and blood samples were collected for consecutive fungal culture. RESULTS: The study cohort included 49 women and 72 men with a median age of 71 years. Multivariate analysis showed that cancer progression (P=0.013), concurrent presence of another microorganism (P=0.010), and previous long-term (>7 days) antibiotic use (P=0.011) were potential risk factors of biliary candidiasis. Chemotherapy was not associated with overall biliary candidiasis (P=0.196), but was signiifcantly related to repeated biliary candidiasis (P=0.011). Patients with isolated biliary candidiasis showed remarkably reduced survival compared with those without (median overall sur-vival (OS): 32 vs 62 days,P=0.011)Subgroup analysis was also performed. Patients with repeated candidiasis had markedly decreased survival compared with those with transient candi-diasis (median OS: 30 vs 49 days,P=0.046). Biliary candidiasis was identiifed as a poor prognostic factor by univariate and multivariate analyses (P=0.033). Four cases of repeated can-didiasis (4/19, 21%) showedCandida species in consecutive blood culture until the end of the study, but others showed no candidemia. CONCLUSIONS: Isolated biliary candidiasis may be associ-ated with poor prognosis in patients with unresectable chol-angiocarcinoma. Especially, repeated biliary candidiasis may have the possibility of progression to candidemia. We suggest that biliary dilatation treatment or antifungal agents might be helpful for patients with biliary candidiasis.
基金This study was reviewed and approved by the Ethics Committees of The Institutional Review Board of the Catholic University of Seoul Saint Mary’s Hospital(approval No.KC20RASI0321).
文摘BACKGROUND A decline in serum carbohydrate antigen 19-9(CA19-9)levels during systemic chemotherapy is considered as a prognostic marker for patients with advanced pancreatic cancer.Neutrophil-to-lymphocyte ratio(NLR)has been extensively studied as a simple and useful indicator of prognosis in various cancers including pancreatic cancer.AIM To assess the prognostic significance of NLR and CA19-9 in patients with advanced pancreatic adenocarcinoma received first-line chemotherapy according to CA19-9 positivity.METHODS We retrospectively analyzed patients diagnosed with advanced pancreatic cancer who received first-line chemotherapy between January 2010 and July 2017 at the Catholic University of Seoul St.Mary’s Hospital.Patients were divided according to CA19-9 positivity(CA19-9-positive vs-negative groups)and pre-and posttreatment NLR levels.To determine cut-off value of NLR and CA19-9 reduction,time-dependent receiver operating characteristic curve was applied.We evaluated overall survival(OS)and progression-free survival(PFS)for each group using Kaplan-Meier method,and we performed multivariate analyses on the entire cohort.RESULTS We included 271 patients in this study.Cut-off value of NLR and CA19-9 reduction was determined as 2.62 and 18%.Multivariate analysis showed that post-treatment NLR<2.62 and reduction of≥18%of baseline CA19-9 were significantly associated with OS and PFS.Post-treatment NLR≥2.62 showed hazard ratio(HR)of 2.47[95%confidence interval(CI):1.84-3.32,P<0.001]and CA19-9 decline(≥18%)showed HR of 0.51(95%CI:0.39-0.67,P<0.001)for OS.When CA19-9-positive patients were divided into groups according to CA19-9 response(responder vs non-responder)and post-treatment NLR(<2.62 vs≥2.62),CA19-9 responder and post-treatment NLR<2.62 group showed better survival than CA19-9 non-responder and post-treatment NLR≥2.62 group(OS 11.0 mo vs 3.9 mo,P<0.001;PFS 6.3 mo vs 2.0 mo,P<0.001).The combination of CA19-9 decline and post-treatment NLR showed a significant correlation with clinical response in CA 19-9 positive group.Within the CA19-9-negative group,the posttreatment NLR<2.62 group showed better survival than the post-treatment NLR≥2.62 group(OS 12.7 mo vs 7.7 mo,P<0.001;PFS 6.7 mo vs 2.1 mo,P<0.001),and post-treatment NLR showed correlation with clinical response.CONCLUSION In advanced pancreatic cancer patients positive for CA19-9 and treated with systemic chemotherapy,the combination of post-treatment NLR<2.62 and 18%decline of CA19-9 at the first response evaluation is a good prognostic marker.Post-treatment NLR<2.62 alone could be used as a prognostic marker and an adjunctive tool for response evaluation in CA19-9-negative patients.
文摘BACKGROUND Owing to rarity of disease and lack of prospective studies, data supporting the role of adjuvant chemotherapy in ampulla of Vater(AoV) carcinoma is limited.AIM To evaluate whether adjuvant chemotherapy cases for AoV carcinoma had better disease-free survival(DFS) rates than cases of observation following curative surgery.METHODS We retrospectively analyzed the association between adjuvant chemotherapy and DFS and overall survival(OS) in patients with stage IB-Ⅲ AoV carcinoma who underwent curative surgical resection. Fluorouracil-based adjuvant chemotherapy was administered after surgery at the discretion of the physician. Adjusted multivariate regression models were used to evaluate the association between adjuvant chemotherapy and survival outcomes.RESULTS Of the total 104 patients who underwent curative surgery, 52 received adjuvant chemotherapy. Multivariate analysis revealed that higher histologic grade [hazard ratio(HR) = 2.24, P = 0.046], advanced tumor stage(HR = 1.85, P = 0.030), and vascular invasion(HR = 2.14, P = 0.010) were associated with shorter DFS. Adjuvant chemotherapy improved DFS compared to the observation group(HR =0.50, P = 0.015) and tended to be associated with a longer OS, although the difference was not statistically significant(HR = 0.58, P = 0.098).CONCLUSION Among patients with resected AoV carcinoma, the adjuvant chemotherapy group was not associated with a significant survival benefit compared to the observation group. However, on multivariate analysis adjusting for prognostic factors, adjuvant chemotherapy following surgery was an independent prognostic factor for DFS in patients with resected AoV carcinoma. Further studies are needed to investigate the effectiveness of adjuvant chemotherapy according to histologic phenotype.
基金supported by St.Vincent’s Hospital,the Research Institute of Medical Science(Grant Number:SVHR-2021-03).
文摘Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)pathway.Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer(MIBC),it has a poor survival rate.Therefore,this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B(APOBEC3B)expressing MIBC.Methods:Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC.The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis.Western blot analysis was performed to confirm differences in phosphorylated Chk1(pChk1)expression according to the APOBEC3B expression.Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin.Results:There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC.Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels.Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression.Compared to cisplatin single treatment,combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression.Conclusion:Our study shows that APOBEC3B’s higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition.This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.
