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
Background:Endoscopic papillectomy(EP)is an effective method to remove an ampulla of Vater(AoV)adenoma with minimal invasiveness.We reviewed the clinical outcomes and prognosis of patients undergoing EP,including tumo...Background:Endoscopic papillectomy(EP)is an effective method to remove an ampulla of Vater(AoV)adenoma with minimal invasiveness.We reviewed the clinical outcomes and prognosis of patients undergoing EP,including tumor recurrence and adverse events.Methods:A total of 196 patients who underwent EP from January 2004 to December 2017 were included.Clinical information was collected through electronic medical records,and risk factors to predict postprocedural bleeding were analyzed using a multivariate logistic regression model.Results:A total of 93.9%patients(184/196)underwent complete resection.During the follow-up period,14.7%patients(27/184)experienced tumor recurrence,and two of seven surgically resected tumors were malignant.A total of 45.4%patients(89/196)experienced adverse events related to EP.Delayed bleeding occurred in 16.3%of the patients(32/196),and they were all successfully treated with endoscopic hemostasis and conservative management.The most frequent site of delayed bleeding was the distal end of the papillary orifice,and 56.3%(18/32)patients of delayed bleeding were classified as having mild severity,the others had moderate severity.Familial adenomatous polyposis(FAP)[odds ratio(OR)=3.80,95%confidence interval(CI):1.01-14.29;P<0.05]and male sex(OR=2.82,95%CI:1.04-7.63;P=0.04)showed statistical significance in predicting delayed post-EP bleeding.Conclusions:EP for AoV adenoma was a highly effective and safe procedure.The risk of post-EP delayed bleeding was increased in patients with FAP syndrome and male patients,and post-EP bleeding occurred most commonly in the distal part of the AoV.展开更多
AIM: To identify clinical and pathological differences between serum immunoglobulin G4 (IgG4)-positive (SIP) and IgG4-negative (SIN) type 1 autoimmune pancreatitis (AIP) in South Korea. METHODS: AIP was diagnosed by t...AIM: To identify clinical and pathological differences between serum immunoglobulin G4 (IgG4)-positive (SIP) and IgG4-negative (SIN) type 1 autoimmune pancreatitis (AIP) in South Korea. METHODS: AIP was diagnosed by the international consensus diagnostic criteria. The medical records and pathology were retrospectively reviewed and IgG4-positive cells were counted in a high power field (HPF). Type I AIP was defined as a high serum level of IgG4or histological finding. SIN type 1 AIP was defined as a histological evidence of type 1 AIP and a normal serum IgG4 level. The clinical and pathological findings were compared between the two groups. The analysis was performed using Student's t test, Fischer's exact test and Mann-Whitney's U test. A P value of < 0.05 was considered statistically significant. As repeated com- parison was made, P values of less than 5% (P < 0.05) were considered significant. RESULTS: Twenty five patients with definite type 1 AIP (19 histologically and six serologically diagnosed cases) were enrolled. The mean tissue IgG4 concentrations were significantly higher in SIP than SIN group (40 cells per HPF vs 18 cells per HPF, P = 0.02). Among eight SIN patients, the tissue IgG4 concentrations were less than 15 cells per HPF in most of cases, except one. The sensitivity of serum IgG4 was 68% (17 SIP and eight SIN AIP). Other organ involvement was more frequent- ly associated with SIP than SIN AIP (59% vs 26%, P = 0.016). However, the relapse rate and diffuse swelling of the pancreas were not associated with serum IgG4 level. The concentrations of IgG4-positive cells per HPF were higher in SIP than SIN AIP (40 vs 18, P = 0.02). CONCLUSION: The sensitivity of serum IgG4 was 68% in type 1 AIP. High serum IgG4 level was associated with other organ involvement and tissue IgG4 concentration but did not affect the relapse rate in type 1 AIP.展开更多
AIM： To investigate differences in the effects of biliary drainage procedures in patients with inoperable Klatskin＇s tumor based on Bismuth type, considering endoscopic retrograde biliary drainage （ERBD）, external...AIM： To investigate differences in the effects of biliary drainage procedures in patients with inoperable Klatskin＇s tumor based on Bismuth type, considering endoscopic retrograde biliary drainage （ERBD）, external percutaneous transhepatic biliary drainage （EPTBD） and internal biliary stenting via the PTBD tract （IPTBD）. METHODS： The initial success rate, cumulative patency rate, and complication rate were compared retrospectively, according to the Bismuth type and ERBD, EPTBD, and IPTBD. Patency was defined as the duration for adequate initial bile drainage or to the point of the patient＇s death associated with inadequate drainage. RESULTS： One hundred thirty-four patients （93 men, 41 women; 21 Bismuth type Ⅱ, 47Ⅲ, 66 Ⅳ; 34 ERBD, 66 EPTBD, 34 IPTBD） were recruited. There were no differences in demographics among the groups. Adequate initial relief of jaundice was achieved in 91% of patients without a significant difference in the results among different procedures or Bismuth types. The cumulative patency rates for ERBD and IPTBD were better than those for EPTBD with Bismuth type Ⅲ. IPTBD provided an excellent response for Bismuth type IV. However, there was no difference in the patency rate among drainage procedures for Bismuth type Ⅱ. Procedure-related cholangitis occurred less frequently with EPTBD than with ERBD and IPTBD. CONCLUSION： ERBD is recommended as the firstline drainage procedure for the palliation of jaundice in patients with inoperable Klatskin＇s tumor of Bismuth type Ⅱ or Ⅲ, but IPTBD is the best option for Bismuth type Ⅳ.展开更多
AIM: To identify the risk factors for organ failure(OF) in cholangitis with bacteriobilia.METHODS: This study included 182 patients with acute cholangitis who underwent percutaneous transhepatic biliary drainage betwe...AIM: To identify the risk factors for organ failure(OF) in cholangitis with bacteriobilia.METHODS: This study included 182 patients with acute cholangitis who underwent percutaneous transhepatic biliary drainage between January 2005 and April 2013. We conducted a retrospective analysis of comprehensive clinical and laboratory data.RESULTS: There were 24 cases(13.2%) of OF and five deaths(2.7%). Bile culture was positive for microbial growth in 130 out of 138(94.2%) patients. In multivariate analysis of 130 patients with positivebile cultures, significant predictive factors for OF were the presence of extended-spectrum beta-lactamase(ESBL) organisms in blood cultures, pre-existing renal dysfunction, and choledocholithiasis as an etiology, with odds ratios of 15.376, 6.319, and 3.573, respectively. We developed a scoring system with a regression coefficient of each significant variable. The OF score was calculated using the following equation:(2.7 × ESBL organisms in blood cultures) +(1.8 × pre-existing renal dysfunction) +(1.3 × choledocholithiasis). This scoring system for predicting OF was highly specific(99.1%) and had a positive predictive value of 86.2%.CONCLUSION: ESBL organisms in blood cultures, preexisting renal dysfunction, and choledocholithiasis are risk factors for OF in cholangitis with bacteriobilia. The OF scoring system may aid clinicians to identify a poor prognosis group.展开更多
AIM: To investigate the prognostic factors determining the success rate of non-surgical treatment in the management of post-operative bile duct injuries (BDIs).
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Background:Endoscopic papillectomy(EP)is an effective method to remove an ampulla of Vater(AoV)adenoma with minimal invasiveness.We reviewed the clinical outcomes and prognosis of patients undergoing EP,including tumor recurrence and adverse events.Methods:A total of 196 patients who underwent EP from January 2004 to December 2017 were included.Clinical information was collected through electronic medical records,and risk factors to predict postprocedural bleeding were analyzed using a multivariate logistic regression model.Results:A total of 93.9%patients(184/196)underwent complete resection.During the follow-up period,14.7%patients(27/184)experienced tumor recurrence,and two of seven surgically resected tumors were malignant.A total of 45.4%patients(89/196)experienced adverse events related to EP.Delayed bleeding occurred in 16.3%of the patients(32/196),and they were all successfully treated with endoscopic hemostasis and conservative management.The most frequent site of delayed bleeding was the distal end of the papillary orifice,and 56.3%(18/32)patients of delayed bleeding were classified as having mild severity,the others had moderate severity.Familial adenomatous polyposis(FAP)[odds ratio(OR)=3.80,95%confidence interval(CI):1.01-14.29;P<0.05]and male sex(OR=2.82,95%CI:1.04-7.63;P=0.04)showed statistical significance in predicting delayed post-EP bleeding.Conclusions:EP for AoV adenoma was a highly effective and safe procedure.The risk of post-EP delayed bleeding was increased in patients with FAP syndrome and male patients,and post-EP bleeding occurred most commonly in the distal part of the AoV.
文摘AIM: To identify clinical and pathological differences between serum immunoglobulin G4 (IgG4)-positive (SIP) and IgG4-negative (SIN) type 1 autoimmune pancreatitis (AIP) in South Korea. METHODS: AIP was diagnosed by the international consensus diagnostic criteria. The medical records and pathology were retrospectively reviewed and IgG4-positive cells were counted in a high power field (HPF). Type I AIP was defined as a high serum level of IgG4or histological finding. SIN type 1 AIP was defined as a histological evidence of type 1 AIP and a normal serum IgG4 level. The clinical and pathological findings were compared between the two groups. The analysis was performed using Student's t test, Fischer's exact test and Mann-Whitney's U test. A P value of < 0.05 was considered statistically significant. As repeated com- parison was made, P values of less than 5% (P < 0.05) were considered significant. RESULTS: Twenty five patients with definite type 1 AIP (19 histologically and six serologically diagnosed cases) were enrolled. The mean tissue IgG4 concentrations were significantly higher in SIP than SIN group (40 cells per HPF vs 18 cells per HPF, P = 0.02). Among eight SIN patients, the tissue IgG4 concentrations were less than 15 cells per HPF in most of cases, except one. The sensitivity of serum IgG4 was 68% (17 SIP and eight SIN AIP). Other organ involvement was more frequent- ly associated with SIP than SIN AIP (59% vs 26%, P = 0.016). However, the relapse rate and diffuse swelling of the pancreas were not associated with serum IgG4 level. The concentrations of IgG4-positive cells per HPF were higher in SIP than SIN AIP (40 vs 18, P = 0.02). CONCLUSION: The sensitivity of serum IgG4 was 68% in type 1 AIP. High serum IgG4 level was associated with other organ involvement and tissue IgG4 concentration but did not affect the relapse rate in type 1 AIP.
基金Supported by a grant No. 2120040320 from the Seoul National University Hospital Research Fund
文摘AIM： To investigate differences in the effects of biliary drainage procedures in patients with inoperable Klatskin＇s tumor based on Bismuth type, considering endoscopic retrograde biliary drainage （ERBD）, external percutaneous transhepatic biliary drainage （EPTBD） and internal biliary stenting via the PTBD tract （IPTBD）. METHODS： The initial success rate, cumulative patency rate, and complication rate were compared retrospectively, according to the Bismuth type and ERBD, EPTBD, and IPTBD. Patency was defined as the duration for adequate initial bile drainage or to the point of the patient＇s death associated with inadequate drainage. RESULTS： One hundred thirty-four patients （93 men, 41 women; 21 Bismuth type Ⅱ, 47Ⅲ, 66 Ⅳ; 34 ERBD, 66 EPTBD, 34 IPTBD） were recruited. There were no differences in demographics among the groups. Adequate initial relief of jaundice was achieved in 91% of patients without a significant difference in the results among different procedures or Bismuth types. The cumulative patency rates for ERBD and IPTBD were better than those for EPTBD with Bismuth type Ⅲ. IPTBD provided an excellent response for Bismuth type IV. However, there was no difference in the patency rate among drainage procedures for Bismuth type Ⅱ. Procedure-related cholangitis occurred less frequently with EPTBD than with ERBD and IPTBD. CONCLUSION： ERBD is recommended as the firstline drainage procedure for the palliation of jaundice in patients with inoperable Klatskin＇s tumor of Bismuth type Ⅱ or Ⅲ, but IPTBD is the best option for Bismuth type Ⅳ.
文摘AIM: To identify the risk factors for organ failure(OF) in cholangitis with bacteriobilia.METHODS: This study included 182 patients with acute cholangitis who underwent percutaneous transhepatic biliary drainage between January 2005 and April 2013. We conducted a retrospective analysis of comprehensive clinical and laboratory data.RESULTS: There were 24 cases(13.2%) of OF and five deaths(2.7%). Bile culture was positive for microbial growth in 130 out of 138(94.2%) patients. In multivariate analysis of 130 patients with positivebile cultures, significant predictive factors for OF were the presence of extended-spectrum beta-lactamase(ESBL) organisms in blood cultures, pre-existing renal dysfunction, and choledocholithiasis as an etiology, with odds ratios of 15.376, 6.319, and 3.573, respectively. We developed a scoring system with a regression coefficient of each significant variable. The OF score was calculated using the following equation:(2.7 × ESBL organisms in blood cultures) +(1.8 × pre-existing renal dysfunction) +(1.3 × choledocholithiasis). This scoring system for predicting OF was highly specific(99.1%) and had a positive predictive value of 86.2%.CONCLUSION: ESBL organisms in blood cultures, preexisting renal dysfunction, and choledocholithiasis are risk factors for OF in cholangitis with bacteriobilia. The OF scoring system may aid clinicians to identify a poor prognosis group.
文摘AIM: To investigate the prognostic factors determining the success rate of non-surgical treatment in the management of post-operative bile duct injuries (BDIs).
