AIM： To estimate the incidence of catheter tract implantation metastasis among patients undergoing percutaneous transhepatic biliary drainage （PTBD） for extrahepatic cholangiocarcinoma, and to provide data regardin...AIM： To estimate the incidence of catheter tract implantation metastasis among patients undergoing percutaneous transhepatic biliary drainage （PTBD） for extrahepatic cholangiocarcinoma, and to provide data regarding the management of this unusual complication of PTBD by reviewing cases reported in the literature. METHODS： A retrospective analysis of 67 consecutive patients who underwent PTBD before the resection of extrahepatic cholangiocarcinoma was conducted. The median follow-up period after PTBD was 106 too. The English language literature （PubMed, National Library of Medicine, Bethesda, MD, USA）, from .lanuary 1966 through December 2004, was reviewed. RESULTS： Catheter tract implantation metastasis developed in three patients. The cumulative incidence of implantation metastasis reached a plateau （6%） at 20 mo after PTBD. All of the three patients with implantation metastasis died of tumor progression at 3, 9, and 20 mo after the detection of this complication. Among the 10 reported patients with catheter tract implantation metastasis from extrahepatic cholangiocarcinoma （including our three patients）, two survived for more than 5 years after the excision of isolated catheter tract metastases. CONCLUSION： Catheter tract implantation metastasis is not a rare complication following PTBD for extrahepatic cholangiocarcinoma. Although the prognosis for patients with this complication is generally poor, the excision of the catheter tract may enable survival in selected patients with isolated metastases along the catheter tract.展开更多
BACKGROUND Effective endoscopic management is fundamental for the treatment of extrahepatic cholangiocarcinoma(ECC).However,current biliary stents that are widely used in clinical practice showed no antitumor effect.D...BACKGROUND Effective endoscopic management is fundamental for the treatment of extrahepatic cholangiocarcinoma(ECC).However,current biliary stents that are widely used in clinical practice showed no antitumor effect.Drug-eluting stents(DESs)may achieve a combination of local chemotherapy and biliary drainage to prolong stent patency and improve prognosis.AIM To develop novel DESs coated with gemcitabine(GEM)and cisplatin(CIS)-coloaded nanofilms that can maintain the continuous and long-term release of antitumor agents in the bile duct to inhibit tumor growth and reduce systemic toxicity.METHODS Stents coated with different drug-eluting components were prepared by the mixed electrospinning method,with poly-L-lactide-caprolactone(PLCL)as the drug-loaded nanofiber membrane and GEM and/or CIS as the antitumor agents.Four different DESs were manufactured with four drug-loading ratios(5%,10%,15%,and 20%),including bare-loaded(PLCL-0),single-drug-loaded(PLCL-GEM and PLCL-CIS),and dual-drug-loaded(PLCL-GC)stents.The drug release property,antitumor activity,and biocompatibility were evaluated in vitro and in vivo to confirm the feasibility and efficacy of this novel DES for ECC.RESULTS The in vitro drug release study showed the stable,continuous release of both GEM and CIS,which was sustained for over 30 d without an obvious initial burst,and a higher drug-loaded content induced a lower release rate.The drug-loading ratio of 10%was used for further experiments due to its ideal inhibitory efficiency and relatively low toxicity.All drug-loaded nanofilms effectively inhibited the growth of EGI-1 cells in vitro and the tumor xenografts of nude mice in vivo;in addition,the dual-loaded nanofilm(PLCL-GC)had a significantly better effect than the single-drug-loaded nanofilms(P<0.05).No significant differences in the serological analysis(P>0.05)or histopathological changes were observed between the single-loaded and drug-loaded nanofilms after stent placement in the normal porcine biliary tract.CONCLUSION This novel PLCL-GEM and CIS-eluting stent maintains continuous,stable drug release locally and inhibits tumor growth effectively in vitro and in vivo.It can also be used safely in normal porcine bile ducts.We anticipate that it might be considered an alternative strategy for the palliative therapy of ECC patients.展开更多
BACKGROUND Hepatopancreatoduodenectomy(HPD)is the simultaneous combination of hepatic resection,pancreaticoduodenectomy,and resection of the entire extrahepatic biliary system.HPD is not a universally accepted due to ...BACKGROUND Hepatopancreatoduodenectomy(HPD)is the simultaneous combination of hepatic resection,pancreaticoduodenectomy,and resection of the entire extrahepatic biliary system.HPD is not a universally accepted due to high mortality and morbidity rates,as well as to controversial survival benefits.AIM To evaluate the current role of HPD for curative treatment of gallbladder cancer(GC)or extrahepatic cholangiocarcinoma(ECC)invading both the hepatic hilum and the intrapancreatic common bile duct.METHODS A systematic literature search using the PubMed,Web of Science,and Scopus databases was performed to identify studies reporting on HPD,using the following keywords:‘Hepatopancreaticoduodenectomy’,‘hepatopancreatoduodenectomy’,‘hepatopancreatectomy’,‘pancreaticoduodenectomy’,‘hepatectomy’,‘hepatic resection’,‘liver resection’,‘Whipple procedure’,‘bile duct cancer’,‘gallbladder cancer’,and‘cholangiocarcinoma’.RESULTS This updated systematic review,focusing on 13 papers published between 2015 and 2020,found that rates of morbidity for HPD have remained high,ranging between 37.0%and 97.4%,while liver failure and pancreatic fistula are the most serious complications.However,perioperative mortality for HPD has decreased compared to initial experiences,and varies between 0%and 26%,although in selected center it is well below 10%.Long term survival outcomes can be achieved in selected patients with R0 resection,although 5–year survival is better for ECC than GC.CONCLUSION The present review supports the role of HPD in patients with GC and ECC with horizontal spread involving the hepatic hilum and the intrapancreatic bile duct,provided that it is performed in centers with high experience in hepatobiliarypancreatic surgery.Extensive use of preoperative portal vein embolization,and preoperative biliary drainage in patients with obstructive jaundice,represent strategies for decreasing the occurrence and severity of postoperative complications.It is advisable to develop internationally-accepted protocols for patient selection,preoperative assessment,operative technique,and perioperative care,in order to better define which patients would benefit from HPD.展开更多
BACKGROUND Radical resection is the only indicator associated with survival in extrahepatic cholangiocarcinoma(EHCC).However,limited data are available regarding the implications of dysplasia at the resection margin f...BACKGROUND Radical resection is the only indicator associated with survival in extrahepatic cholangiocarcinoma(EHCC).However,limited data are available regarding the implications of dysplasia at the resection margin following surgery.AIM To evaluate the prognostic significance of dysplasia-positive margins in patients diagnosed with EHCC.METHODS We reviewed the records of patients who had undergone surgery for EHCC with curative intent between January 2013 and July 2017.We retrospectively analyzed the clinicopathological data of 116 patients followed for longer than 3 years.The status of resection margin was used to classify patients into negative low-grade dysplasia(LGD)and high-grade dysplasia(HGD)/carcinoma in situ(CIS)categories.RESULTS Based on postoperative status,72 patients underwent resection with negative margins,19 had LGD-positive margins,and 25 showed HGD/CIS-positive margins.The mean survival rates of the patients with negative margins,LGD margins,and HGD/CIS margins were 49.1±4.5,47.3±6.0,and 20.8±4.4 mo,respectively(P<0.001).No difference in survival was found between groups with LGD margins and negative margins(P=0.56).In the multivariate analysis,age>70 years and HGD/CIS-positive margins were significant independent factors for survival(hazard ratio=1.90 and 2.47,respectively).CONCLUSION HGD/CIS margin in resected EHCC is associated with a poor survival.However,the LGDpositive resection margin is not a significant indicator of survival in patients with EHCC.展开更多
Objective： To investigate the mRNA and protein expression of histone methyltransferase G9a and its clinical significance in extrahepatic cholangiocarcinoma. Methods： Using RT-PCR and Western Blotting to detect the e...Objective： To investigate the mRNA and protein expression of histone methyltransferase G9a and its clinical significance in extrahepatic cholangiocarcinoma. Methods： Using RT-PCR and Western Blotting to detect the expression of G9a at the level of mRNA and protein in 48 tumor samples and 39 control tissues. Results： The mRNA and protein expression of Gga in extrahepatic cholangiocarcinoma was higher than control statistically （P 〈 0.05） and positively correlated with lymph metastasis （P 〈 0.05） and TNM stage （P 〈 0.01）. Conclusion： The significant difference of Gga expression between tumors and control implicated that the important role of histone methylation disruption resulted from increased G9a expression in extrahepatic cholangiocarcinoma.展开更多
Background:Adjuvant(chemo)radiotherapy(A(C)RT)may be an important supplement to surgery for extrahepatic cholangiocarcinoma(EHCC).However,whether all patients would achieve benefits from A(C)RT and which adjuvant regi...Background:Adjuvant(chemo)radiotherapy(A(C)RT)may be an important supplement to surgery for extrahepatic cholangiocarcinoma(EHCC).However,whether all patients would achieve benefits from A(C)RT and which adjuvant regimen,adjuvant radiotherapy(ART)or adjuvant chemoradiotherapy(ACRT),would be preferred,are still undetermined.The low incidence of EHCC makes it difficult to carry out randomized controlled trials(RCTs);therefore,almost all clinical studies on radiotherapy are retrospective.We have conducted a meta-analysis of these retrospective studies.Methods:We conducted a meta-analysis of current retrospective studies using PubMed,Embase,and ClinicalTrials databases.All studies published in English that were related to A(C)RT and which analyzed overall survival(OS),disease-free survival(DFS),or locoregional recurrence-free survival(LRFS)were included.Estimated hazard ratios(HRs)were calculated for OS,DFS,and LRFS.Results:Data from eight studies including 685 patients were included.Our analysis showed that A(C)RT significantly improved OS(HR 0.69,95%confidence interval(CI)0.48–0.97,P=0.03),DFS(HR 0.60,95%CI 0.47–0.76,P<0.0001),and LRFS(HR 0.27,95%CI 0.17–0.41,P<0.00001)of EHCC overall.In subgroups,patients with microscopically positive resection margin(R1)could achieve a benefit from A(C)RT(HR 0.44,95%CI 0.27–0.72,P=0.001).No statistically OS difference was observed in negative resection margin(R0)subgroup(HR 0.98,95%CI 0.30–3.19,P=0.98).Significant OS benefit was found in patients who received concurrent ACRT(HR 0.40,95%CI 0.26–0.62,P<0.0001),while the result of ART without chemotherapy showed no significant benefit(HR 1.14,95%CI 0.29–4.50,P=0.85).In the distal cholangiocarcinoma subgroup,no significant difference was seen when ACRT and ART were included(HR 0.61,95%CI 0.14–2.72,P=0.52),but a significant difference was seen ewOshSpe,enDc iaFanlSla,yl yianzn iddn igsL ttRahlF ep Sca iotinne cEnutHrsr.C eCnt pAaCtieRnTt so,nelys p(eHcRi a0 ll.y2 i9 n,t9 h5 o%s eC Iw i0 t.h13 R–10 r.e6 s4 e,cPti=o0 n.0 m0 a2 r).g iCnso.n AclCusRioT nms:aAy(bCe)RsTu pmeraiyo ri tmop rAoRvTe .展开更多
The global morbimortality of biliary tract cancer(BTC)is steadily increasing and accounts for~10%of all primary liver cancer.Distinct anatomical locations of BTC have singularities in their etiopathogenesis,which are ...The global morbimortality of biliary tract cancer(BTC)is steadily increasing and accounts for~10%of all primary liver cancer.Distinct anatomical locations of BTC have singularities in their etiopathogenesis,which are translated into differences in their molecular fingerprints and the associated therapeutic approaches.Extrahepatic cholangiocarcinoma(eCCA),arising in the large and distal bile ducts,presents recurrent activating mutations of KRAS and loss-of-function alterations in TP53,SMAD4,and CDKN2A/B.Despite being highly prevalent,no targeted therapies are yet available for these oncogenic drivers.ERBB2 mutations and amplifications,on the other hand,are the most recurrent actionable alterations for eCCA,with several clinical trials aiming to provide benefits in biomarker-enriched populations.In addition,integrative multi-omics analysis of eCCA has allowed the identification of novel molecular classes of this disease that could be therapeutically exploited.Beyond that,the highly immunosuppressive tumor microenvironment of eCCA has prevented until now the success of immune checkpoint inhibitors,recently approved in combination with cytotoxic chemotherapy.Further characterization of eCCA at the molecular level would potentially foster treating patients based on a precision oncology approach in order to increase the clinical outcomes for this challenging disease.展开更多
Objective To evaluate th e validity of a serum carbohydrate antigen 19-9(CA19-9) determination in the dia gnosis of extrahepatic cholangiocarcinoma(EHCC). Methods Serum CA19-9 concentration and serum carcinoembr...Objective To evaluate th e validity of a serum carbohydrate antigen 19-9(CA19-9) determination in the dia gnosis of extrahepatic cholangiocarcinoma(EHCC). Methods Serum CA19-9 concentration and serum carcinoembryonic antigen(CEA) concentration wer e prospectively measured by an immunoradiometric assay without knowledge of the clinical diagnosis in patients with EHCC (n=51), benign biliary diseases ( n=42), and healthy individuals (n=15). Using a receiver operating characte ristic (ROC) curve define a new strategy for interpreting CA19-9 and CEA in EHC C. Results The sensitivity of CA19-9 and CEA in diagnosing E HCC were 86.3% (44/51) and 25.5%(13/51), respectively. When compared with the be nign biliary diseases group, the true negative rates of serum CA19-9 and serum CEA were 85.7% (36/42) and 95.2%(40/42), respectively. The false positive rates of serum CA19-9 and serum CEA were 14.3 %( 6/42) and 4.8 %( 2/42), whereas the accuracy of serum CA19-9 and serum CEA were 57.0%(53/93) and 86.0%(80/93), resp ectively. Serum CA19-9 concentration and serum CEA concentration were significa ntly elevated (P<0.01 and P<0.05) in patients with EHCC \[(489.6±150.2 )kU·L -1 and (22.0±2.4)μg·L -1)\] compared with patients with beni gn biliary diseases\[ (20.2±4.7) kU·L -1 and (14.8± 0.8)μg·L -1)\] and healthy individuals \[(12.8±3.7) kU·L -1 and (11.5±3.4μ g·L -1)\]. The ROC curves analysis showed that the area under the ROC cu rve(AUC)of serum CA19-9 and serum CEA were 0.942 (P<0.001) and 0.516 (P >05), respectively. In 22 patients undergoing curative resection of EHCC, the mean serum CA19-9 concentration decreased from preoperative level of (456.6±1 20.4) kU·L -1 to postoperative level (62.8±17.3) kU·L -1(P< 0. 001). The outcomes showed that serum CA19-9 had greater diagnosis performance s than serum CEA. Conclusion Serum CA19-9 is an effective tum or marker in diagnosing of cholangiocarcinoma, deciding whether the tumor has be en radically resected and monitoring effect of treatment展开更多
Gallbladder(GB)carcinoma,although relatively rare,is the most common biliary tree cholangiocarcinoma with aggressiveness and poor prognosis.It is closely associated with cholelithiasis and long-standing large(>3 cm...Gallbladder(GB)carcinoma,although relatively rare,is the most common biliary tree cholangiocarcinoma with aggressiveness and poor prognosis.It is closely associated with cholelithiasis and long-standing large(>3 cm)gallstones in up to 90%of cases.The other main predisposing factors for GB carcinoma include molecular factors such as mutated genes,GB wall calcification(porcelain)or mainly mucosal microcalcifications,and GB polyps≥1 cm in size.Diagnosis is made by ultrasound,computed tomography(CT),and,more precisely,magnetic resonance imaging(MRI).Preoperative staging is of great importance in decisionmaking regarding therapeutic management.Preoperative staging is based on MRI findings,the leading technique for liver metastasis imaging,enhanced three-phase CT angiography,or magnetic resonance angiography for major vessel assessment.It is also necessary to use positron emission tomography(PET)-CT or ^(18)F-FDG PET-MRI to more accurately detect metastases and any other occult deposits with active metabolic uptake.Staging laparoscopy may detect dissemination not otherwise found in 20%-28.6%of cases.Multimodality treatment is needed,including surgical resection,targeted therapy by biological agents according to molecular testing gene mapping,chemotherapy,radiation therapy,and immunotherapy.It is of great importance to understand the updated guidelines and current treatment options.The extent of surgical intervention depends on the disease stage,ranging from simple cholecystectomy(T1a)to extended resections and including extended cholecystectomy(T1b),with wide lymph node resection in every case or IV-V segmentectomy(T2),hepatic trisegmentectomy or major hepatectomy accompanied by hepaticojejunostomy Roux-Y,and adjacent organ resection if necessary(T3).Laparoscopic or robotic surgery shows fewer postoperative complications and equivalent oncological outcomes when compared to open surgery,but much attention must be paid to avoiding injuries.In addition to surgery,novel targeted treatment along with immunotherapy and recent improvements in radiotherapy and chemotherapy(neoadjuvant-adjuvant capecitabine,cisplatin,gemcitabine)have yielded promising results even in inoperable cases calling for palliation(T4).Thus,individualized treatment must be applied.展开更多
Pancreatobiliary intraductal papillary neoplasms(IPNs)represent precursors of pancreatic cancer or bile duct cholangiocarcinoma that can be detected and treated.Despite advances in diagnostic methods,identifying these...Pancreatobiliary intraductal papillary neoplasms(IPNs)represent precursors of pancreatic cancer or bile duct cholangiocarcinoma that can be detected and treated.Despite advances in diagnostic methods,identifying these premalignant lesions is still challenging for treatment providers.Modern imaging,biomarkers and molecular tests for genomic alterations can be used for diagnosis and follow-up.Surgical intervention in combination with new chemotherapeutic agents is considered the optimal treatment for malignant cases.The balance between the risk of malignancy and any risk of resection guides management policy;therefore,treatment should be individualized based on a meticulous preoperative assessment of high-risk stigmata.IPN of the bile duct is more aggressive;thus,early diagnosis and surgery are crucial.The conservative management of low-risk pancreatic branch-duct lesions is safe and effective.展开更多
Aim:We aimed to analyze temporal trends in mortality from intrahepatic(ICC)and extrahepatic(ECC)cholangiocarcinoma in selected countries worldwide.Methods:Official death certification data for ICC and ECC and populati...Aim:We aimed to analyze temporal trends in mortality from intrahepatic(ICC)and extrahepatic(ECC)cholangiocarcinoma in selected countries worldwide.Methods:Official death certification data for ICC and ECC and populations estimates for 29 countries worldwide(17 from Europe,8 from the Americas,and 4 from Australasia)and for Hong Kong Special Administrative Region of the People’s Republic of China(SAR),from 1995 to 2018,were extracted from the World Health Organization and the Pan American Health Organization databases.Age-standardized mortality rates were computed.A joinpoint regression analysis was performed.Results:In both sexes,ICC mortality rates increased in most countries considered,including the USA,the UK,and Australia;in some countries,including Italy and France,the increasing trends leveled off over the most recent years.In men,around 2016,the highest rates(1.7-2.3/100,000)were observed in Hong Kong SAR,Portugal,France,Spain,Australia,Austria,the UK,and Canada;Latin American countries and some eastern European countries had the lowest rates(0.2-0.8/100,000).A similar pattern was observed in women,but with lower rates(from 1.7/100,000 in Hong Kong SAR to 0.14/100,000 in Argentina).ECC mortality declined in most European and Australasian countries,but it tended to increase in Americas.In both sexes,rates were below 1/100,000 around 2016,with the only exceptions being Japan(2.6/100,000 men and 1.2/100,000 women)and Hungary(1.5/100,000 men and 1.1/100,000 women).Conclusion:ICC mortality increased in most areas of the world,likely due to increased prevalence of risk factors and improved cancer recognition and classification.ECC mortality fell in most countries,largely due to the widespread use of cholecystectomy.展开更多
文摘AIM： To estimate the incidence of catheter tract implantation metastasis among patients undergoing percutaneous transhepatic biliary drainage （PTBD） for extrahepatic cholangiocarcinoma, and to provide data regarding the management of this unusual complication of PTBD by reviewing cases reported in the literature. METHODS： A retrospective analysis of 67 consecutive patients who underwent PTBD before the resection of extrahepatic cholangiocarcinoma was conducted. The median follow-up period after PTBD was 106 too. The English language literature （PubMed, National Library of Medicine, Bethesda, MD, USA）, from .lanuary 1966 through December 2004, was reviewed. RESULTS： Catheter tract implantation metastasis developed in three patients. The cumulative incidence of implantation metastasis reached a plateau （6%） at 20 mo after PTBD. All of the three patients with implantation metastasis died of tumor progression at 3, 9, and 20 mo after the detection of this complication. Among the 10 reported patients with catheter tract implantation metastasis from extrahepatic cholangiocarcinoma （including our three patients）, two survived for more than 5 years after the excision of isolated catheter tract metastases. CONCLUSION： Catheter tract implantation metastasis is not a rare complication following PTBD for extrahepatic cholangiocarcinoma. Although the prognosis for patients with this complication is generally poor, the excision of the catheter tract may enable survival in selected patients with isolated metastases along the catheter tract.
基金Supported by the National Natural Science Foundation of China,No.81870452 and No.81470904Science and Technology Development Funds of Shanghai of China,No.16411952400.
文摘BACKGROUND Effective endoscopic management is fundamental for the treatment of extrahepatic cholangiocarcinoma(ECC).However,current biliary stents that are widely used in clinical practice showed no antitumor effect.Drug-eluting stents(DESs)may achieve a combination of local chemotherapy and biliary drainage to prolong stent patency and improve prognosis.AIM To develop novel DESs coated with gemcitabine(GEM)and cisplatin(CIS)-coloaded nanofilms that can maintain the continuous and long-term release of antitumor agents in the bile duct to inhibit tumor growth and reduce systemic toxicity.METHODS Stents coated with different drug-eluting components were prepared by the mixed electrospinning method,with poly-L-lactide-caprolactone(PLCL)as the drug-loaded nanofiber membrane and GEM and/or CIS as the antitumor agents.Four different DESs were manufactured with four drug-loading ratios(5%,10%,15%,and 20%),including bare-loaded(PLCL-0),single-drug-loaded(PLCL-GEM and PLCL-CIS),and dual-drug-loaded(PLCL-GC)stents.The drug release property,antitumor activity,and biocompatibility were evaluated in vitro and in vivo to confirm the feasibility and efficacy of this novel DES for ECC.RESULTS The in vitro drug release study showed the stable,continuous release of both GEM and CIS,which was sustained for over 30 d without an obvious initial burst,and a higher drug-loaded content induced a lower release rate.The drug-loading ratio of 10%was used for further experiments due to its ideal inhibitory efficiency and relatively low toxicity.All drug-loaded nanofilms effectively inhibited the growth of EGI-1 cells in vitro and the tumor xenografts of nude mice in vivo;in addition,the dual-loaded nanofilm(PLCL-GC)had a significantly better effect than the single-drug-loaded nanofilms(P<0.05).No significant differences in the serological analysis(P>0.05)or histopathological changes were observed between the single-loaded and drug-loaded nanofilms after stent placement in the normal porcine biliary tract.CONCLUSION This novel PLCL-GEM and CIS-eluting stent maintains continuous,stable drug release locally and inhibits tumor growth effectively in vitro and in vivo.It can also be used safely in normal porcine bile ducts.We anticipate that it might be considered an alternative strategy for the palliative therapy of ECC patients.
文摘BACKGROUND Hepatopancreatoduodenectomy(HPD)is the simultaneous combination of hepatic resection,pancreaticoduodenectomy,and resection of the entire extrahepatic biliary system.HPD is not a universally accepted due to high mortality and morbidity rates,as well as to controversial survival benefits.AIM To evaluate the current role of HPD for curative treatment of gallbladder cancer(GC)or extrahepatic cholangiocarcinoma(ECC)invading both the hepatic hilum and the intrapancreatic common bile duct.METHODS A systematic literature search using the PubMed,Web of Science,and Scopus databases was performed to identify studies reporting on HPD,using the following keywords:‘Hepatopancreaticoduodenectomy’,‘hepatopancreatoduodenectomy’,‘hepatopancreatectomy’,‘pancreaticoduodenectomy’,‘hepatectomy’,‘hepatic resection’,‘liver resection’,‘Whipple procedure’,‘bile duct cancer’,‘gallbladder cancer’,and‘cholangiocarcinoma’.RESULTS This updated systematic review,focusing on 13 papers published between 2015 and 2020,found that rates of morbidity for HPD have remained high,ranging between 37.0%and 97.4%,while liver failure and pancreatic fistula are the most serious complications.However,perioperative mortality for HPD has decreased compared to initial experiences,and varies between 0%and 26%,although in selected center it is well below 10%.Long term survival outcomes can be achieved in selected patients with R0 resection,although 5–year survival is better for ECC than GC.CONCLUSION The present review supports the role of HPD in patients with GC and ECC with horizontal spread involving the hepatic hilum and the intrapancreatic bile duct,provided that it is performed in centers with high experience in hepatobiliarypancreatic surgery.Extensive use of preoperative portal vein embolization,and preoperative biliary drainage in patients with obstructive jaundice,represent strategies for decreasing the occurrence and severity of postoperative complications.It is advisable to develop internationally-accepted protocols for patient selection,preoperative assessment,operative technique,and perioperative care,in order to better define which patients would benefit from HPD.
基金Supported by the National Research Foundation of Korea,No. 2019R1C1C1003661
文摘BACKGROUND Radical resection is the only indicator associated with survival in extrahepatic cholangiocarcinoma(EHCC).However,limited data are available regarding the implications of dysplasia at the resection margin following surgery.AIM To evaluate the prognostic significance of dysplasia-positive margins in patients diagnosed with EHCC.METHODS We reviewed the records of patients who had undergone surgery for EHCC with curative intent between January 2013 and July 2017.We retrospectively analyzed the clinicopathological data of 116 patients followed for longer than 3 years.The status of resection margin was used to classify patients into negative low-grade dysplasia(LGD)and high-grade dysplasia(HGD)/carcinoma in situ(CIS)categories.RESULTS Based on postoperative status,72 patients underwent resection with negative margins,19 had LGD-positive margins,and 25 showed HGD/CIS-positive margins.The mean survival rates of the patients with negative margins,LGD margins,and HGD/CIS margins were 49.1±4.5,47.3±6.0,and 20.8±4.4 mo,respectively(P<0.001).No difference in survival was found between groups with LGD margins and negative margins(P=0.56).In the multivariate analysis,age>70 years and HGD/CIS-positive margins were significant independent factors for survival(hazard ratio=1.90 and 2.47,respectively).CONCLUSION HGD/CIS margin in resected EHCC is associated with a poor survival.However,the LGDpositive resection margin is not a significant indicator of survival in patients with EHCC.
基金Supported by a grant from the National High Technology ResearchDevelopment Program of China (863 Program) (No. 2002AA214061)
文摘Objective： To investigate the mRNA and protein expression of histone methyltransferase G9a and its clinical significance in extrahepatic cholangiocarcinoma. Methods： Using RT-PCR and Western Blotting to detect the expression of G9a at the level of mRNA and protein in 48 tumor samples and 39 control tissues. Results： The mRNA and protein expression of Gga in extrahepatic cholangiocarcinoma was higher than control statistically （P 〈 0.05） and positively correlated with lymph metastasis （P 〈 0.05） and TNM stage （P 〈 0.01）. Conclusion： The significant difference of Gga expression between tumors and control implicated that the important role of histone methylation disruption resulted from increased G9a expression in extrahepatic cholangiocarcinoma.
基金Project supported by the National Natural Science Foundation of China(No.81402520)。
文摘Background:Adjuvant(chemo)radiotherapy(A(C)RT)may be an important supplement to surgery for extrahepatic cholangiocarcinoma(EHCC).However,whether all patients would achieve benefits from A(C)RT and which adjuvant regimen,adjuvant radiotherapy(ART)or adjuvant chemoradiotherapy(ACRT),would be preferred,are still undetermined.The low incidence of EHCC makes it difficult to carry out randomized controlled trials(RCTs);therefore,almost all clinical studies on radiotherapy are retrospective.We have conducted a meta-analysis of these retrospective studies.Methods:We conducted a meta-analysis of current retrospective studies using PubMed,Embase,and ClinicalTrials databases.All studies published in English that were related to A(C)RT and which analyzed overall survival(OS),disease-free survival(DFS),or locoregional recurrence-free survival(LRFS)were included.Estimated hazard ratios(HRs)were calculated for OS,DFS,and LRFS.Results:Data from eight studies including 685 patients were included.Our analysis showed that A(C)RT significantly improved OS(HR 0.69,95%confidence interval(CI)0.48–0.97,P=0.03),DFS(HR 0.60,95%CI 0.47–0.76,P<0.0001),and LRFS(HR 0.27,95%CI 0.17–0.41,P<0.00001)of EHCC overall.In subgroups,patients with microscopically positive resection margin(R1)could achieve a benefit from A(C)RT(HR 0.44,95%CI 0.27–0.72,P=0.001).No statistically OS difference was observed in negative resection margin(R0)subgroup(HR 0.98,95%CI 0.30–3.19,P=0.98).Significant OS benefit was found in patients who received concurrent ACRT(HR 0.40,95%CI 0.26–0.62,P<0.0001),while the result of ART without chemotherapy showed no significant benefit(HR 1.14,95%CI 0.29–4.50,P=0.85).In the distal cholangiocarcinoma subgroup,no significant difference was seen when ACRT and ART were included(HR 0.61,95%CI 0.14–2.72,P=0.52),but a significant difference was seen ewOshSpe,enDc iaFanlSla,yl yianzn iddn igsL ttRahlF ep Sca iotinne cEnutHrsr.C eCnt pAaCtieRnTt so,nelys p(eHcRi a0 ll.y2 i9 n,t9 h5 o%s eC Iw i0 t.h13 R–10 r.e6 s4 e,cPti=o0 n.0 m0 a2 r).g iCnso.n AclCusRioT nms:aAy(bCe)RsTu pmeraiyo ri tmop rAoRvTe .
基金RM acknowledges the support from ISCⅢ(PI21/01619 research project and Juan Rodés contract)SEOM(research project)+1 种基金TTD(research project)Fundación MERCK Salud(research project).
文摘The global morbimortality of biliary tract cancer(BTC)is steadily increasing and accounts for~10%of all primary liver cancer.Distinct anatomical locations of BTC have singularities in their etiopathogenesis,which are translated into differences in their molecular fingerprints and the associated therapeutic approaches.Extrahepatic cholangiocarcinoma(eCCA),arising in the large and distal bile ducts,presents recurrent activating mutations of KRAS and loss-of-function alterations in TP53,SMAD4,and CDKN2A/B.Despite being highly prevalent,no targeted therapies are yet available for these oncogenic drivers.ERBB2 mutations and amplifications,on the other hand,are the most recurrent actionable alterations for eCCA,with several clinical trials aiming to provide benefits in biomarker-enriched populations.In addition,integrative multi-omics analysis of eCCA has allowed the identification of novel molecular classes of this disease that could be therapeutically exploited.Beyond that,the highly immunosuppressive tumor microenvironment of eCCA has prevented until now the success of immune checkpoint inhibitors,recently approved in combination with cytotoxic chemotherapy.Further characterization of eCCA at the molecular level would potentially foster treating patients based on a precision oncology approach in order to increase the clinical outcomes for this challenging disease.
文摘Objective To evaluate th e validity of a serum carbohydrate antigen 19-9(CA19-9) determination in the dia gnosis of extrahepatic cholangiocarcinoma(EHCC). Methods Serum CA19-9 concentration and serum carcinoembryonic antigen(CEA) concentration wer e prospectively measured by an immunoradiometric assay without knowledge of the clinical diagnosis in patients with EHCC (n=51), benign biliary diseases ( n=42), and healthy individuals (n=15). Using a receiver operating characte ristic (ROC) curve define a new strategy for interpreting CA19-9 and CEA in EHC C. Results The sensitivity of CA19-9 and CEA in diagnosing E HCC were 86.3% (44/51) and 25.5%(13/51), respectively. When compared with the be nign biliary diseases group, the true negative rates of serum CA19-9 and serum CEA were 85.7% (36/42) and 95.2%(40/42), respectively. The false positive rates of serum CA19-9 and serum CEA were 14.3 %( 6/42) and 4.8 %( 2/42), whereas the accuracy of serum CA19-9 and serum CEA were 57.0%(53/93) and 86.0%(80/93), resp ectively. Serum CA19-9 concentration and serum CEA concentration were significa ntly elevated (P<0.01 and P<0.05) in patients with EHCC \[(489.6±150.2 )kU·L -1 and (22.0±2.4)μg·L -1)\] compared with patients with beni gn biliary diseases\[ (20.2±4.7) kU·L -1 and (14.8± 0.8)μg·L -1)\] and healthy individuals \[(12.8±3.7) kU·L -1 and (11.5±3.4μ g·L -1)\]. The ROC curves analysis showed that the area under the ROC cu rve(AUC)of serum CA19-9 and serum CEA were 0.942 (P<0.001) and 0.516 (P >05), respectively. In 22 patients undergoing curative resection of EHCC, the mean serum CA19-9 concentration decreased from preoperative level of (456.6±1 20.4) kU·L -1 to postoperative level (62.8±17.3) kU·L -1(P< 0. 001). The outcomes showed that serum CA19-9 had greater diagnosis performance s than serum CEA. Conclusion Serum CA19-9 is an effective tum or marker in diagnosing of cholangiocarcinoma, deciding whether the tumor has be en radically resected and monitoring effect of treatment
文摘Gallbladder(GB)carcinoma,although relatively rare,is the most common biliary tree cholangiocarcinoma with aggressiveness and poor prognosis.It is closely associated with cholelithiasis and long-standing large(>3 cm)gallstones in up to 90%of cases.The other main predisposing factors for GB carcinoma include molecular factors such as mutated genes,GB wall calcification(porcelain)or mainly mucosal microcalcifications,and GB polyps≥1 cm in size.Diagnosis is made by ultrasound,computed tomography(CT),and,more precisely,magnetic resonance imaging(MRI).Preoperative staging is of great importance in decisionmaking regarding therapeutic management.Preoperative staging is based on MRI findings,the leading technique for liver metastasis imaging,enhanced three-phase CT angiography,or magnetic resonance angiography for major vessel assessment.It is also necessary to use positron emission tomography(PET)-CT or ^(18)F-FDG PET-MRI to more accurately detect metastases and any other occult deposits with active metabolic uptake.Staging laparoscopy may detect dissemination not otherwise found in 20%-28.6%of cases.Multimodality treatment is needed,including surgical resection,targeted therapy by biological agents according to molecular testing gene mapping,chemotherapy,radiation therapy,and immunotherapy.It is of great importance to understand the updated guidelines and current treatment options.The extent of surgical intervention depends on the disease stage,ranging from simple cholecystectomy(T1a)to extended resections and including extended cholecystectomy(T1b),with wide lymph node resection in every case or IV-V segmentectomy(T2),hepatic trisegmentectomy or major hepatectomy accompanied by hepaticojejunostomy Roux-Y,and adjacent organ resection if necessary(T3).Laparoscopic or robotic surgery shows fewer postoperative complications and equivalent oncological outcomes when compared to open surgery,but much attention must be paid to avoiding injuries.In addition to surgery,novel targeted treatment along with immunotherapy and recent improvements in radiotherapy and chemotherapy(neoadjuvant-adjuvant capecitabine,cisplatin,gemcitabine)have yielded promising results even in inoperable cases calling for palliation(T4).Thus,individualized treatment must be applied.
文摘Pancreatobiliary intraductal papillary neoplasms(IPNs)represent precursors of pancreatic cancer or bile duct cholangiocarcinoma that can be detected and treated.Despite advances in diagnostic methods,identifying these premalignant lesions is still challenging for treatment providers.Modern imaging,biomarkers and molecular tests for genomic alterations can be used for diagnosis and follow-up.Surgical intervention in combination with new chemotherapeutic agents is considered the optimal treatment for malignant cases.The balance between the risk of malignancy and any risk of resection guides management policy;therefore,treatment should be individualized based on a meticulous preoperative assessment of high-risk stigmata.IPN of the bile duct is more aggressive;thus,early diagnosis and surgery are crucial.The conservative management of low-risk pancreatic branch-duct lesions is safe and effective.
基金conducted with the contribution of the Fondazione AIRC per la Ricerca sul Cancro(project No.22987).
文摘Aim:We aimed to analyze temporal trends in mortality from intrahepatic(ICC)and extrahepatic(ECC)cholangiocarcinoma in selected countries worldwide.Methods:Official death certification data for ICC and ECC and populations estimates for 29 countries worldwide(17 from Europe,8 from the Americas,and 4 from Australasia)and for Hong Kong Special Administrative Region of the People’s Republic of China(SAR),from 1995 to 2018,were extracted from the World Health Organization and the Pan American Health Organization databases.Age-standardized mortality rates were computed.A joinpoint regression analysis was performed.Results:In both sexes,ICC mortality rates increased in most countries considered,including the USA,the UK,and Australia;in some countries,including Italy and France,the increasing trends leveled off over the most recent years.In men,around 2016,the highest rates(1.7-2.3/100,000)were observed in Hong Kong SAR,Portugal,France,Spain,Australia,Austria,the UK,and Canada;Latin American countries and some eastern European countries had the lowest rates(0.2-0.8/100,000).A similar pattern was observed in women,but with lower rates(from 1.7/100,000 in Hong Kong SAR to 0.14/100,000 in Argentina).ECC mortality declined in most European and Australasian countries,but it tended to increase in Americas.In both sexes,rates were below 1/100,000 around 2016,with the only exceptions being Japan(2.6/100,000 men and 1.2/100,000 women)and Hungary(1.5/100,000 men and 1.1/100,000 women).Conclusion:ICC mortality increased in most areas of the world,likely due to increased prevalence of risk factors and improved cancer recognition and classification.ECC mortality fell in most countries,largely due to the widespread use of cholecystectomy.
