Wholly defined ex vivo expansion conditions for biliary tree stem cell(BTSC)organoids were established,consisting of a defined proliferative medium(DPM)used in combination with soft hyaluronan hydrogels.The DPM consis...Wholly defined ex vivo expansion conditions for biliary tree stem cell(BTSC)organoids were established,consisting of a defined proliferative medium(DPM)used in combination with soft hyaluronan hydrogels.The DPM consisted of commercially available Kubota's Medium(KM),to which a set of small molecules,particular paracrine signals,and heparan sulfate(HS)were added.The small molecules used were DNA methyltransferase inhibitor(RG108),TGF-βType I receptor inhibitor(A83-01),adenylate cyclase activator(Forskolin),and L-type Ca2+channel agonist(Bay K8644).A key paracrine signal proved to be R-spondin 1(RSPO1),a secreted protein that activates Wnts.Soluble hyaluronans,0.05%sodium hyaluronate,were used with DPM to expand monolayer cultures.Expansion of organoids was achieved by using DPM in combination with embedding organoids in Matrigel that was replaced with a defined thiol-hyaluronan triggered with PEGDA to form a hydrogel with a rheology[G*]of less than 100 Pa.The combination is called the BTSC-Expansion-Glycogel-System(BEX-gel system)for expanding BTSCs as a monolayer or as organoids.The BTSC organoids were expanded more than 3000-fold ex vivo in the BEX-gel system within 70 days while maintaining phenotypic traits indicative of stem/progenitors.Stem-cell-patch grafting of expanded BTSC organoids was performed on the livers of Fah-/-mice with tyrosinemia and resulted in the rescue of the mice and restoration of their normal liver functions.The BEX-gel system for BTSC organoid expansion provides a strategy to generate sufficient numbers of organoids for the therapeutic treatments of liver diseases.展开更多
BACKGROUND:Stenting of malignant hilar strictures remains a standard endoscopic treatment in patients with unresectable tumors.The aim of this two-center prospective study was to compare unilateral versus bilateral dr...BACKGROUND:Stenting of malignant hilar strictures remains a standard endoscopic treatment in patients with unresectable tumors.The aim of this two-center prospective study was to compare unilateral versus bilateral drainage in hilar malignant stenosis Bismuth-Corlette type II.METHODS:During a 3-year period,a total of 49 patients with hilar tumors(Bismuth-Corlette type II) were referred for endoscopic treatment,following the criteria of unresectability.Ultrasound,computed tomography scan and magnetic resonance cholangiopancreatography(MRCP) were previously performed in all patients in order to facilitate endoscopic retrograde cholangiopancreatography(ERCP).The stricture was first passed by the hydrophilic guide-wire and then contrast medium was injected.Mechanical bile duct dilation was performed,followed by plastic stent placement only in the liver lobe which was previously opacified.The procedures were performed under conscious sedation.The patients were followed up for the next 12 months with a stent exchange every 3 months.Primary outcome was assessed by patient survival in the first 12 months after the procedure.RESULTS:All 49 patients were treated with ERCP while 39(79.59%) had successful stent placement.Among these,32 had hilar cholangiocarcinoma(82%) and 7(18%) had gallbladder cancer.Two groups of patients had Bismuth II strictures:A,21 patients(54%) with unilateral contrast injection and drainage,and B,18(46%) with bilateral contrast injection and drainage.A total of 57 plastic stents were used(10 Fr,89%;11.5 Fr,11%).Group B showed a lower bilirubin level 7 days after the procedure(P=0.008).Early complications were cholangitis(3 patients,2 in group A and 1 in group B) and acute pancreatitis(2 patients,1 each in A and B) with no statistical difference between the groups.Late complications were stent migration(5 patients,1 in A and 4 in B) and stent clogging(6 patients,2 in A and 4 in B) showing a significant difference between the groups(P<0.01).The first stent replacement after 3 months was successful in 87% of patients(four died due to disease progression and one due to cardiopulmonary insufficiency) showing no statistical difference between the groups.At 6 months follow-up,72% patients survived,with no statistical difference between the groups.A final follow-up(12 months) showed the survival rate of 18%(4 patients from group A and 3 from group B)(P>0.05).CONCLUSIONS:A minimally invasive approach,based on the criterion that every bile duct being opacified needs to be drained,is associated with a lower incidence of early complications.Considering that the clinical outcome measured by bilirubin level was lower in patients with bilateral drainage 7 days after the procedure,we assumed that drainage of 50% or more of the liver volume leads to sufficient drainage effectiveness.展开更多
BACKGROUND:Endoscopic therapy has been successful in the management of biliary complications after both deceased donor liver transplantation(DDLT) and living donor liver transplantation(LDLT).LDLT is thought to be ass...BACKGROUND:Endoscopic therapy has been successful in the management of biliary complications after both deceased donor liver transplantation(DDLT) and living donor liver transplantation(LDLT).LDLT is thought to be associated with higher rates of biliary complications,but there are few studies comparing the success of endoscopic management of anastomotic strictures between the two groups.This study aims to compare our experience in the endoscopic management of anastomotic strictures in DDLT versus LDLT.METHODS:This is a retrospective database review of all liver transplant patients undergoing endoscopic retrograde cholangiopancreatography(ERCP) after liver transplantation.The frequency of anastomotic stricture and the time to develop and to resolve anastomotic stricture were compared between DDLT and LDLT.The response of anastomotic stricture to endoscopic therapy was also analyzed.RESULTS:A total of 362 patients underwent liver transplantation between 2003 and 2011,with 125 requiring ERCP to manage biliary complications.Thirty-three(9.9%) cases of DDLT and 8(27.6%) of LDLT(P=0.01) were found to have anastomotic stricture.When comparing DDLT and LDLT,there was no difference in the mean time to the development of anastomotic strictures(98±17 vs 172±65 days,P=0.11),likelihood of response to ERCP [22(66.7%) vs 6(75.0%),P=0.69],mean time to the resolution of anastomotic strictures(268±77 vs 125±37 days,P=0.34),and the number of ERCPs required to achieve resolution(3.9±0.4 vs 4.7±0.9,P=0.38).CONCLUSIONS:Endoscopic therapy is effective in the majority of biliary complications relating to liver transplantation.Anastomotic strictures occur more frequently in LDLT compared with DDLT,with equivalent endoscopic treatment response and outcomes for both groups.展开更多
AIM: To compare the value of endoscopic retrograde cholangiography (ERC) and standard T2-weighted magnetic resonance cholangiography (MRC) in the evaluation process as adult-to-adult right lobe living donor liver tran...AIM: To compare the value of endoscopic retrograde cholangiography (ERC) and standard T2-weighted magnetic resonance cholangiography (MRC) in the evaluation process as adult-to-adult right lobe living donor liver transplantation (LDLTx) demands a successful outcome, and exact knowledge of the biliary tree is implicated to avoid biliary complications, postoperatively.METHODS: After starting the LDLTx program, 18 liver transplant candidates were selected for LDLTx by a stepwise evaluation process. ERC and standard T2-weighted MRC were performed to evaluate the biliary system of the donor liver. The anatomical findings of ERC and MRC mapping were compared using the Ohkubo classification. RESULTS: ERC allowed mapping of the whole biliary system in 15/15 (100%) cases, including 14/15 (93.3%) with biliary variants while routine MRC was only accurate in 2/13 (15.4%) cases. MRC was limited in depicting the biliary system proximal of the hepatic bifurcation. Postoperative biliary complications occurred in 2 donors and 8 recipients. Biliary complications were associated with Ohkubo type C, E or G in 6/8 recipients, and 2/3 recipients with biliary leak received a graft with multiple (≥2) bile ducts. CONCLUSION: Pretransplant ERC is safe and superior over standard MRC for detection of biliary variations that occur with a high frequency. However, precise knowledge of biliary variants did not reduce the incidence of postoperative biliary complications.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
BACKGROUND:Carcinoid tumors of the extrahepatic biliary tree are extremely rare malignancies,accounting for 0.2%-2%of all gastrointestinal carcinoid tumors,while carcinoids of the cystic duct are an uncommon entity an...BACKGROUND:Carcinoid tumors of the extrahepatic biliary tree are extremely rare malignancies,accounting for 0.2%-2%of all gastrointestinal carcinoid tumors,while carcinoids of the cystic duct are an uncommon entity and an extremely unusual cause of bile duct obstruction.METHODS:After an extensive literature review,we retrospectively analysed 61 cases of carcinoid tumor of the biliary tree as well as one additional case of a 60-yearold female with symptoms and laboratory/imaging examination findings compatible with those of a malignant biliary tract obstruction.At laparotomy,resection of the gallbladder and common bile duct was performed.Histological study revealed a well-differentiated neuroendocrine carcinoma of the cystic duct.The patient remained disease-free at 16 months.RESULTS:Our presentation is the seventh case reported in the world literature.Compared to cholangiocarcinoma,analysis of the reviewed group indicates an increased incidence of extrahepatic carcinoid tumors in younger persons along with a slight female predominance.Statistically,the most common anatomic location is the common bile duct,followed by the perihilar region and the cystic duct.Jaundice is the most common finding.Curative surgery was realized in the majority of cases and longterm disease-free survival was achieved when surgery was curative.CONCLUSIONS:Carcinoid tumors obstructing the biliary tree are extremely difficult to diagnose preoperatively,and nearly impossible to differentiate from non-neuroendocrine tumors.As surgery offers the only potential cure for both biliary carcinoids and cholangiocarcinoma,we recommend aggressive surgical therapy as the treatment of choice in every case of potentially resectable biliary tumor.展开更多
BACKGROUND:Primary sclerosing cholangitis(PSC)is a chronic cholestatic liver disease characterized by destruction and fibrosis of the bile ducts.This study aimed to demonstrate the hepatic and extrahepatic characteris...BACKGROUND:Primary sclerosing cholangitis(PSC)is a chronic cholestatic liver disease characterized by destruction and fibrosis of the bile ducts.This study aimed to demonstrate the hepatic and extrahepatic characteristic findings and prognostic outcomes of Turkish patients with PSC. METHODS:The medical records of 35 consecutive patients with PSC from January 1988 to June 2007 were recorded prospectively.From the time of diagnosis,clinical features and laboratory data were collected. RESULTS:The mean age of the 35 patients was 41.69 years (range 15-80 years)at the time of diagnosis;14(40%)were female,and 21(60%)were male.The mean duration of follow-up was 58.86 months(1-180 months).Twenty(57.1%) of the patients with PSC were asymptomatic and 22(62.9%) had inflammatory bowel disease.At the time of diagnosis, 20(57.1%)of the patients had both intra-and extra-hepatic PSC.Twenty-one(60%)of the patients,who had undergone ERCP for stent placement,had dominant bile duct stenosis. Cholangiocarcinoma was found in 2(5.7%)of the patients and cirrhosis was detected in 7(20%);5(14.3%)underwent liver transplantation.The median follow-up time after liver transplantation was 23 months and all are still alive.Six (17.1%)patients died. CONCLUSIONS:PSC has a clinical course varied from advanced liver disease requiring liver transplantation within a short time to being asymptomatic for decades. The prognosis of Turkish patients with PSC is also disappointing as described in other studies.展开更多
We report a rare case of a 74-year-old man with metachronous gallbladder cancer and bile duct cancer who underwent curative resection twice, with the operations nine years apart. At the age of 65 years, the patient un...We report a rare case of a 74-year-old man with metachronous gallbladder cancer and bile duct cancer who underwent curative resection twice, with the operations nine years apart. At the age of 65 years, the patient underwent a cholecystectomy and resection of the liver bed for gallbladder cancer. This was a welldifferentiated adenocarcinoma, with negative resection margins （T2NOM0, stage Ⅰ B）. Nine years later, during a follow-up examination, abdominal computed tomography and MRCP showed an enhanced 1.7 cm mass in the hilum that extended to the second branch of the right intrahepatic bile duct. We diagnosed this lesion as a perihilar bile duct cancer, Bismuth type Ⅲ a, and performed bile duct excision, right hepatic Iobectomy and Roux-en-Y hepaticojejunostomy. The histological diagnosis was a well-differentiated adenocarcinoma with one regional lymph node metastasis （TINIM0, stage Ⅱ B）. Twelve months after the second operation, the patient is well, with no signs of recurrence. This case is compared with 11 other cases of metachronous biliary tract cancer published in the world medical literature.展开更多
Paraneoplastic syndromes are the symptoms or signs which result from damage to tissues that are distant from the site of malignancy,due to complex interactions between the body’s immune system and malignant neoplasm....Paraneoplastic syndromes are the symptoms or signs which result from damage to tissues that are distant from the site of malignancy,due to complex interactions between the body’s immune system and malignant neoplasm.Cholangiocarcinoma(CCA)is an aggressive epithelial malignancy of hepatobiliary tree and it is found to be associated with various paraneoplastic syndromes.These syndromes can present as dermatological,neurological,renal,hematological,or multi-systemic manifestations.Clinical suspicion and timely recognition of these syndromes can lead to early diagnosis of covert malignancies like CCA.The management plan remains the removal of the underlying cause which in this case is CCA.展开更多
Over the last two decades,substantial progress has been made in the scope of molecular targeted therapy,leading to transformative advancements in the treatment of various malignancies,including biliary tract cancer(BT...Over the last two decades,substantial progress has been made in the scope of molecular targeted therapy,leading to transformative advancements in the treatment of various malignancies,including biliary tract cancer(BTC).BTC represents a heterogeneous group of aggressive tumors with historically poor prognoses.However,recent discoveries of novel molecular alterations in BTC have provided new avenues for targeted therapeutic interventions,exemplified by the approval of pemigatinib,specifically designed for FGFR2 gene fusions or rearrangements in advanced BTC.Furthermore,subsequent regulatory approvals and ongoing clinical trials focusing on specific gene mutations have considerably expanded the array of treatment options available,augmenting the potential for personalized treatment strategies.In light of these developments,this review aims to furnish a comprehensive and up-to-date account of the molecular characteristics and potential targeted therapies in BTC.By presenting insights into novel therapeutic approaches and outlining prospective directions for translational and clinical investigations,this review seeks to contribute to the ongoing progress and optimization of therapeutic approaches in managing BTC.展开更多
基金Major Program of National Key Research and Development Project(2020YFA0112600,2019YFA0801502)National Natural Science Foundation of China(82173019,82270638,8220374,82300718)+1 种基金Project of Shanghai Science and Technology Commission(22ZR1451100,22Y11908500)Peak Disciplines(Type IV)of Institutions of Higher Learning in Shanghai,and Shanghai Engineering Research Center of Stem Cells Translational Medicine(20DZ2255100).
文摘Wholly defined ex vivo expansion conditions for biliary tree stem cell(BTSC)organoids were established,consisting of a defined proliferative medium(DPM)used in combination with soft hyaluronan hydrogels.The DPM consisted of commercially available Kubota's Medium(KM),to which a set of small molecules,particular paracrine signals,and heparan sulfate(HS)were added.The small molecules used were DNA methyltransferase inhibitor(RG108),TGF-βType I receptor inhibitor(A83-01),adenylate cyclase activator(Forskolin),and L-type Ca2+channel agonist(Bay K8644).A key paracrine signal proved to be R-spondin 1(RSPO1),a secreted protein that activates Wnts.Soluble hyaluronans,0.05%sodium hyaluronate,were used with DPM to expand monolayer cultures.Expansion of organoids was achieved by using DPM in combination with embedding organoids in Matrigel that was replaced with a defined thiol-hyaluronan triggered with PEGDA to form a hydrogel with a rheology[G*]of less than 100 Pa.The combination is called the BTSC-Expansion-Glycogel-System(BEX-gel system)for expanding BTSCs as a monolayer or as organoids.The BTSC organoids were expanded more than 3000-fold ex vivo in the BEX-gel system within 70 days while maintaining phenotypic traits indicative of stem/progenitors.Stem-cell-patch grafting of expanded BTSC organoids was performed on the livers of Fah-/-mice with tyrosinemia and resulted in the rescue of the mice and restoration of their normal liver functions.The BEX-gel system for BTSC organoid expansion provides a strategy to generate sufficient numbers of organoids for the therapeutic treatments of liver diseases.
基金supported by the Ministry of Education and Science of the Republic of Serbia(175054)
文摘BACKGROUND:Stenting of malignant hilar strictures remains a standard endoscopic treatment in patients with unresectable tumors.The aim of this two-center prospective study was to compare unilateral versus bilateral drainage in hilar malignant stenosis Bismuth-Corlette type II.METHODS:During a 3-year period,a total of 49 patients with hilar tumors(Bismuth-Corlette type II) were referred for endoscopic treatment,following the criteria of unresectability.Ultrasound,computed tomography scan and magnetic resonance cholangiopancreatography(MRCP) were previously performed in all patients in order to facilitate endoscopic retrograde cholangiopancreatography(ERCP).The stricture was first passed by the hydrophilic guide-wire and then contrast medium was injected.Mechanical bile duct dilation was performed,followed by plastic stent placement only in the liver lobe which was previously opacified.The procedures were performed under conscious sedation.The patients were followed up for the next 12 months with a stent exchange every 3 months.Primary outcome was assessed by patient survival in the first 12 months after the procedure.RESULTS:All 49 patients were treated with ERCP while 39(79.59%) had successful stent placement.Among these,32 had hilar cholangiocarcinoma(82%) and 7(18%) had gallbladder cancer.Two groups of patients had Bismuth II strictures:A,21 patients(54%) with unilateral contrast injection and drainage,and B,18(46%) with bilateral contrast injection and drainage.A total of 57 plastic stents were used(10 Fr,89%;11.5 Fr,11%).Group B showed a lower bilirubin level 7 days after the procedure(P=0.008).Early complications were cholangitis(3 patients,2 in group A and 1 in group B) and acute pancreatitis(2 patients,1 each in A and B) with no statistical difference between the groups.Late complications were stent migration(5 patients,1 in A and 4 in B) and stent clogging(6 patients,2 in A and 4 in B) showing a significant difference between the groups(P<0.01).The first stent replacement after 3 months was successful in 87% of patients(four died due to disease progression and one due to cardiopulmonary insufficiency) showing no statistical difference between the groups.At 6 months follow-up,72% patients survived,with no statistical difference between the groups.A final follow-up(12 months) showed the survival rate of 18%(4 patients from group A and 3 from group B)(P>0.05).CONCLUSIONS:A minimally invasive approach,based on the criterion that every bile duct being opacified needs to be drained,is associated with a lower incidence of early complications.Considering that the clinical outcome measured by bilirubin level was lower in patients with bilateral drainage 7 days after the procedure,we assumed that drainage of 50% or more of the liver volume leads to sufficient drainage effectiveness.
文摘BACKGROUND:Endoscopic therapy has been successful in the management of biliary complications after both deceased donor liver transplantation(DDLT) and living donor liver transplantation(LDLT).LDLT is thought to be associated with higher rates of biliary complications,but there are few studies comparing the success of endoscopic management of anastomotic strictures between the two groups.This study aims to compare our experience in the endoscopic management of anastomotic strictures in DDLT versus LDLT.METHODS:This is a retrospective database review of all liver transplant patients undergoing endoscopic retrograde cholangiopancreatography(ERCP) after liver transplantation.The frequency of anastomotic stricture and the time to develop and to resolve anastomotic stricture were compared between DDLT and LDLT.The response of anastomotic stricture to endoscopic therapy was also analyzed.RESULTS:A total of 362 patients underwent liver transplantation between 2003 and 2011,with 125 requiring ERCP to manage biliary complications.Thirty-three(9.9%) cases of DDLT and 8(27.6%) of LDLT(P=0.01) were found to have anastomotic stricture.When comparing DDLT and LDLT,there was no difference in the mean time to the development of anastomotic strictures(98±17 vs 172±65 days,P=0.11),likelihood of response to ERCP [22(66.7%) vs 6(75.0%),P=0.69],mean time to the resolution of anastomotic strictures(268±77 vs 125±37 days,P=0.34),and the number of ERCPs required to achieve resolution(3.9±0.4 vs 4.7±0.9,P=0.38).CONCLUSIONS:Endoscopic therapy is effective in the majority of biliary complications relating to liver transplantation.Anastomotic strictures occur more frequently in LDLT compared with DDLT,with equivalent endoscopic treatment response and outcomes for both groups.
文摘AIM: To compare the value of endoscopic retrograde cholangiography (ERC) and standard T2-weighted magnetic resonance cholangiography (MRC) in the evaluation process as adult-to-adult right lobe living donor liver transplantation (LDLTx) demands a successful outcome, and exact knowledge of the biliary tree is implicated to avoid biliary complications, postoperatively.METHODS: After starting the LDLTx program, 18 liver transplant candidates were selected for LDLTx by a stepwise evaluation process. ERC and standard T2-weighted MRC were performed to evaluate the biliary system of the donor liver. The anatomical findings of ERC and MRC mapping were compared using the Ohkubo classification. RESULTS: ERC allowed mapping of the whole biliary system in 15/15 (100%) cases, including 14/15 (93.3%) with biliary variants while routine MRC was only accurate in 2/13 (15.4%) cases. MRC was limited in depicting the biliary system proximal of the hepatic bifurcation. Postoperative biliary complications occurred in 2 donors and 8 recipients. Biliary complications were associated with Ohkubo type C, E or G in 6/8 recipients, and 2/3 recipients with biliary leak received a graft with multiple (≥2) bile ducts. CONCLUSION: Pretransplant ERC is safe and superior over standard MRC for detection of biliary variations that occur with a high frequency. However, precise knowledge of biliary variants did not reduce the incidence of postoperative biliary complications.
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.
文摘BACKGROUND:Carcinoid tumors of the extrahepatic biliary tree are extremely rare malignancies,accounting for 0.2%-2%of all gastrointestinal carcinoid tumors,while carcinoids of the cystic duct are an uncommon entity and an extremely unusual cause of bile duct obstruction.METHODS:After an extensive literature review,we retrospectively analysed 61 cases of carcinoid tumor of the biliary tree as well as one additional case of a 60-yearold female with symptoms and laboratory/imaging examination findings compatible with those of a malignant biliary tract obstruction.At laparotomy,resection of the gallbladder and common bile duct was performed.Histological study revealed a well-differentiated neuroendocrine carcinoma of the cystic duct.The patient remained disease-free at 16 months.RESULTS:Our presentation is the seventh case reported in the world literature.Compared to cholangiocarcinoma,analysis of the reviewed group indicates an increased incidence of extrahepatic carcinoid tumors in younger persons along with a slight female predominance.Statistically,the most common anatomic location is the common bile duct,followed by the perihilar region and the cystic duct.Jaundice is the most common finding.Curative surgery was realized in the majority of cases and longterm disease-free survival was achieved when surgery was curative.CONCLUSIONS:Carcinoid tumors obstructing the biliary tree are extremely difficult to diagnose preoperatively,and nearly impossible to differentiate from non-neuroendocrine tumors.As surgery offers the only potential cure for both biliary carcinoids and cholangiocarcinoma,we recommend aggressive surgical therapy as the treatment of choice in every case of potentially resectable biliary tumor.
文摘BACKGROUND:Primary sclerosing cholangitis(PSC)is a chronic cholestatic liver disease characterized by destruction and fibrosis of the bile ducts.This study aimed to demonstrate the hepatic and extrahepatic characteristic findings and prognostic outcomes of Turkish patients with PSC. METHODS:The medical records of 35 consecutive patients with PSC from January 1988 to June 2007 were recorded prospectively.From the time of diagnosis,clinical features and laboratory data were collected. RESULTS:The mean age of the 35 patients was 41.69 years (range 15-80 years)at the time of diagnosis;14(40%)were female,and 21(60%)were male.The mean duration of follow-up was 58.86 months(1-180 months).Twenty(57.1%) of the patients with PSC were asymptomatic and 22(62.9%) had inflammatory bowel disease.At the time of diagnosis, 20(57.1%)of the patients had both intra-and extra-hepatic PSC.Twenty-one(60%)of the patients,who had undergone ERCP for stent placement,had dominant bile duct stenosis. Cholangiocarcinoma was found in 2(5.7%)of the patients and cirrhosis was detected in 7(20%);5(14.3%)underwent liver transplantation.The median follow-up time after liver transplantation was 23 months and all are still alive.Six (17.1%)patients died. CONCLUSIONS:PSC has a clinical course varied from advanced liver disease requiring liver transplantation within a short time to being asymptomatic for decades. The prognosis of Turkish patients with PSC is also disappointing as described in other studies.
文摘We report a rare case of a 74-year-old man with metachronous gallbladder cancer and bile duct cancer who underwent curative resection twice, with the operations nine years apart. At the age of 65 years, the patient underwent a cholecystectomy and resection of the liver bed for gallbladder cancer. This was a welldifferentiated adenocarcinoma, with negative resection margins （T2NOM0, stage Ⅰ B）. Nine years later, during a follow-up examination, abdominal computed tomography and MRCP showed an enhanced 1.7 cm mass in the hilum that extended to the second branch of the right intrahepatic bile duct. We diagnosed this lesion as a perihilar bile duct cancer, Bismuth type Ⅲ a, and performed bile duct excision, right hepatic Iobectomy and Roux-en-Y hepaticojejunostomy. The histological diagnosis was a well-differentiated adenocarcinoma with one regional lymph node metastasis （TINIM0, stage Ⅱ B）. Twelve months after the second operation, the patient is well, with no signs of recurrence. This case is compared with 11 other cases of metachronous biliary tract cancer published in the world medical literature.
文摘Paraneoplastic syndromes are the symptoms or signs which result from damage to tissues that are distant from the site of malignancy,due to complex interactions between the body’s immune system and malignant neoplasm.Cholangiocarcinoma(CCA)is an aggressive epithelial malignancy of hepatobiliary tree and it is found to be associated with various paraneoplastic syndromes.These syndromes can present as dermatological,neurological,renal,hematological,or multi-systemic manifestations.Clinical suspicion and timely recognition of these syndromes can lead to early diagnosis of covert malignancies like CCA.The management plan remains the removal of the underlying cause which in this case is CCA.
文摘Over the last two decades,substantial progress has been made in the scope of molecular targeted therapy,leading to transformative advancements in the treatment of various malignancies,including biliary tract cancer(BTC).BTC represents a heterogeneous group of aggressive tumors with historically poor prognoses.However,recent discoveries of novel molecular alterations in BTC have provided new avenues for targeted therapeutic interventions,exemplified by the approval of pemigatinib,specifically designed for FGFR2 gene fusions or rearrangements in advanced BTC.Furthermore,subsequent regulatory approvals and ongoing clinical trials focusing on specific gene mutations have considerably expanded the array of treatment options available,augmenting the potential for personalized treatment strategies.In light of these developments,this review aims to furnish a comprehensive and up-to-date account of the molecular characteristics and potential targeted therapies in BTC.By presenting insights into novel therapeutic approaches and outlining prospective directions for translational and clinical investigations,this review seeks to contribute to the ongoing progress and optimization of therapeutic approaches in managing BTC.
