In 2010, a panel of Chinese pathologists reported the first expert consensus for the pathological diagnosis of primary liver cancers to address the many contradictions and inconsistencies in the pathological character...In 2010, a panel of Chinese pathologists reported the first expert consensus for the pathological diagnosis of primary liver cancers to address the many contradictions and inconsistencies in the pathological characteristics and diagnostic criteria for PLC. Since then considerable clinicopathological studies have been conducted globally, prompting us to update the practice guidelines for the pathological diagnosis of PLC. In April 18, 2014, a Guideline Committee consisting of 40 specialists from seven Chinese Societies(including Chinese Society of Liver Cancer, Chinese Anti-Cancer Association; Liver Cancer Study Group, Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Pathology, Chinese Anti-Cancer Association; Digestive Disease Group, Chinese Society of Pathology, Chinese Medical Association; Chinese Society of Surgery, Chinese Medical Association; Chinese Society of Clinical Oncology, Chinese Anti-Cancer Association; Pathological Group of Hepatobiliary Tumor and Liver Transplantation, Chinese Society of Pathology, Chinese Medical Association) was created for the formulation of the first guidelines for the standardization of the pathological diagnosis of PLC, mainly focusing on the following topics: gross specimen sampling, concepts and diagnostic criteria of small hepatocellular carcinoma(SHCC), microvascular invasion(MVI), satellite nodules,and immunohistochemical and molecular diagnosis. The present updated guidelines are reflective of current clinicopathological studies, and include a novel 7-point baseline sampling protocol, which stipulate that at least four tissue specimens should be sampled at the junction of the tumor and adjacent liver tissues in a 1:1 ratio at the 12, 3, 6 and 9 o'clock reference positions. For the purposes of molecular pathological examination, at least one specimen should be sampled at the intratumoral zone, but more specimens should be sampled for tumors harboring different textures or colors. Specimens should be sampled at both adjacent and distant peri展开更多
Several advances in diagnosis,treatment and palliation of cholangiocarcinoma(CC)have occurred in the last decades.A multidisciplinary approach to this disease is therefore recommended.CC is a relatively rare tumor and...Several advances in diagnosis,treatment and palliation of cholangiocarcinoma(CC)have occurred in the last decades.A multidisciplinary approach to this disease is therefore recommended.CC is a relatively rare tumor and the main risk factors are:chronic inflammation, genetic predisposition and congenital abnormalities of the biliary tree.While the incidence of intra-hepatic CC is increasing,the incidence of extra-hepatic CC is trending down.The only curative treatment for CC is surgical resection with negative margins.Liver transplantation has been proposed only for selected patients with hilar CC that cannot be resected who have no metastatic disease after a period of neoadjuvant chemo-radiation therapy.Magnetic resonance imaging/magnetic resonance cholangiopancreatography,positron emission tomography scan,endoscopic ultrasound and computed tomography scans are the most frequently used modalities for diagnosis and tumor staging.Adjuvant therapy,palliative chemotherapy and radiotherapy have been relatively ineffective for inoperable CC.For most of these patients biliary stenting provides effective palliation.Photodynamic therapy is an emerging palliative treatment that seems to provide pain relief,improve biliary patency and increase survival. The clinical utility of other emerging therapies such as transarterial chemoembolization,hepatic arterial chemoinfusion and high intensity intraductal ultrasound needs further study.展开更多
Although the incidence of hepatolithiasis is decreasing as the pattern of gallstone disease changes in Asia, the prevalence of hepatolithiasis is persistently high, especially in Far Eastern countries. Hepatolithiasis...Although the incidence of hepatolithiasis is decreasing as the pattern of gallstone disease changes in Asia, the prevalence of hepatolithiasis is persistently high, especially in Far Eastern countries. Hepatolithiasis is an established risk factor for cholangiocarcinoma(CCA), and chronic proliferative inflammation may be involved in biliary carcinogenesis and in inducing the upregulation of cell-proliferating factors. With the use of advanced imaging modalities, there has been much improvement in the management of hepatolithiasis and the diagnosis of hepatolithiasis-associated CCA(HLCCA). However, there are many problems in managing the strictures in hepatolithiasis and differentiating them from infiltrating types of CCA. Surgical resection is recommended in cases of single lobe hepatolithiasis with atrophy, uncontrolled stricture, symptom duration of more than 10 years, and long history of biliaryenteric anastomosis. Even after resection, patients should be followed with caution for development of HL-CCA, because HL-CCA is an independent prognostic factor for survival. It is not yet clear whether hepatic resection can reduce the occurrence of subsequent HL-CCA. Furthermore, there are no consistent findings regarding prediction of subsequent HL-CCA in patients with hepatolithiasis. In the management of hepatolithiasis, important factors are the reduction of recurrence of cholangitis and suspicion of unrecognized HL-CCA.展开更多
AIM: To carry out a hospital-based case-control study to investigate risk factors for intrahepatic cholangiocarcinoma (ICC) in China. METHODS: A total of 312 ICC cases and 438 matched controls were included in the stu...AIM: To carry out a hospital-based case-control study to investigate risk factors for intrahepatic cholangiocarcinoma (ICC) in China. METHODS: A total of 312 ICC cases and 438 matched controls were included in the study. The presence of diabetes mellitus,hypertention,hepatolithiasis,primary sclerosing cholangitis,liver fluke infection (Clonorchis sinensis ),was investigated through clinical records. Blood from all participants was tested for hepatitis B surface antigen (HBsAg) and anti-HCV antibodies. Odds ratios (OR) and 95% confi dence intervals (95% CI) were estimated using conditional logistic regression. RESULTS: Compared with controls,ICC patients had a higher prevalence of HBsAg seropositivity (48.4% vs 9.6%,P < 0.000),and hepatolithiasis (5.4% vs 1.1%,P = 0.001). By multivariate analysis,the signif icant risk factors for development of ICC were HBsAg seropositivity (adjusted OR,8.876,95% CI,5.973-13.192),and hepatolithiasis (adjusted OR,5.765,95% CI,1.972-16.851). The prevalence of anti-HCV seropositivity,diabetes mellitus,hypertention,cigarette smoking,and alcohol consumption were not significantly different between cases and controls. CONCLUSION: These findings suggest that HBV infection and hepatolithiasis are strong risk factors for development of ICC in China.展开更多
To perform a systematic review and meta-analysis on clinical outcomes of photodynamic therapy (PDT) in non-resectable cholangiocarcinoma.METHODSIncluded studies compared outcomes with photodynamic therapy and biliary ...To perform a systematic review and meta-analysis on clinical outcomes of photodynamic therapy (PDT) in non-resectable cholangiocarcinoma.METHODSIncluded studies compared outcomes with photodynamic therapy and biliary stenting (PDT group) vs biliary stenting only (BS group) in palliation of non-resectable cholangiocarcinoma. Articles were searched in MEDLINE, PubMed, and EMBASE. Pooled proportions were calculated using fixed and random effects model. Heterogeneity among studies was assessed using the I<sup>2</sup> statistic.RESULTSTen studies (n = 402) that met inclusion criteria were included in this analysis. The P for χ<sup>2</sup> heterogeneity for all the pooled accuracy estimates was > 0.10. Pooled odds ratio for successful biliary drainage (decrease in bilirubin level > 50% within 7days after stenting) in PDT vs BS group was 4.39 (95%CI: 2.35-8.19). Survival period in PDT and BS groups were 413.04 d (95%CI: 349.54-476.54) and 183.41 (95%CI: 136.81-230.02) respectively. The change in Karnofsky performance scores after intervention in PDT and BS groups were +6.99 (95%CI: 4.15-9.82) and -3.93 (95%CI: -8.63-0.77) respectively. Odds ratio for post-intervention cholangitis in PDT vs BS group was 0.57 (95%CI: 0.35-0.94). In PDT group, 10.51% (95%CI: 6.94-14.72) had photosensitivity reactions that were self-limiting. Subgroup analysis of prospective studies showed similar results, except the incidence of cholangitis was comparable in both groups.CONCLUSIONIn palliation of unresectable cholangiocarcinoma, PDT seems to be significantly superior to BS alone. PDT should be used as an adjunct to biliary stenting in these patients.展开更多
AIM: To evaluate the prognostic factors of hilar cholangiocarcinoma in a large series of patients in a single institution.METHODS: Eight hundred and fourteen patients with a diagnosis of hilar cholangiocarcinoma that ...AIM: To evaluate the prognostic factors of hilar cholangiocarcinoma in a large series of patients in a single institution.METHODS: Eight hundred and fourteen patients with a diagnosis of hilar cholangiocarcinoma that were evaluated and treated between 1990 and 2014, of which 381 patients underwent curative surgery, were included in this study. Potential factors associated with overall survival(OS) and disease-free survival(DFS) were evaluated by univariate and multivariate analyses.RESULTS: Curative surgery provided the best long-term survival with a median OS of 26.3 mo. The median DFS was 18.1 mo. Multivariate analysis showed that patients with tumor size > 3 cm [hazard ratio(HR) = 1.482, 95%CI: 1.127-1.949; P = 0.005], positive nodal disease(HR = 1.701, 95%CI: 1.346-2.149; P < 0.001), poor differentiation(HR = 2.535, 95%CI: 1.839-3.493; P < 0.001), vascular invasion(HR = 1.542, 95%CI: 1.082-2.197; P = 0.017), and positive margins(HR = 1.798, 95%CI: 1.314-2.461; P < 0.001) had poor OS outcome. The independent factors for DFS were positive nodal disease(HR = 3.383, 95%CI: 2.633-4.348; P < 0.001), poor differentiation(HR = 2.774, 95%CI: 2.012-3.823; P < 0.001), vascular invasion(HR = 2.136, 95%CI: 1.658-3.236; P < 0.001), and positive margins(HR = 1.835, 95%CI: 1.256-2.679; P < 0.001). Multiple logistic regression analysis showed that caudate lobectomy [odds ratio(OR) = 9.771, 95%CI: 4.672-20.433; P < 0.001], tumor diameter(OR = 3.772, 95%CI: 1.914-7.434; P < 0.001), surgical procedures(OR = 10.236, 95%CI: 4.738-22.116; P < 0.001), American Joint Committee On Cancer T stage(OR = 2.010, 95%CI: 1.043-3.870; P = 0.037), and vascular invasion(OR = 2.278, 95%CI: 0.997-5.207; P = 0.051) were independently associated with tumorfree margin, and surgical procedures could indirectly affect survival outcome by influencing the tumor resection margin. CONCLUSION: Tumor margin, tumor differentiation, vascular invasion, and lymph node status were independent factors for OS and DFS. Surgical procedures can indirectly affect surv展开更多
Intrahepatic cholangiocarcinoma (ICC) arises from the lining epithelium and peribiliary glands of the intrahepatic biliary tree and shows variable cholangiocytic dif-f-e-re-ntiation. To date-,ICC was large-ly classifi...Intrahepatic cholangiocarcinoma (ICC) arises from the lining epithelium and peribiliary glands of the intrahepatic biliary tree and shows variable cholangiocytic dif-f-e-re-ntiation. To date-,ICC was large-ly classifie-d into adenocarcinoma and rare variants. Herein,we propose to subclassify the former,based on recent progress in the-study of-ICC including the-gross classification and hepatic progenitor/stem cells and on the pathological similarities between biliary and pancreatic neoplasms. That is,ICC is classifiable into the conventional (bile duct) type,the bile ductular type,the intraductal neoplasm type and rare variants. The conventional type is further divided into the small duct type (peripheral type) and large bile duct type (perihilar type). The former is a tubular or micropapillary adenocarcinoma while the latter involves the intrahepatic large bile duct. Bile ductular type resembles proliferated bile ductules and shows a replacing growth of the hepatic parenchyma.Hepatic progenitor cell or stem cell phenotypes such as neural cell adhesion molecule expression are frequently expressed in the bile ductular type. Intraductal type includes papillary and tubular neoplasms of the bile duct (IPNBs and ITNBs) and a superficial spreading type. IPNB and ITNB show a spectrum from a preneoplastic borderline lesion to carcinoma and may have pancreatic counterparts. At invasive sites,IPNB is associated with the conventional bile duct ICC and mucinous carcinoma. Biliary mucinous cystic neoplasm with ovarian-like stroma in its wall is different from IPNB,particularly IPNB showing cystic dilatation of the affected ducts. Rare variants of ICC include squamous/adenosquamous cell carcinoma,mucinous/signet ring cell carcinoma,clear cell type,undifferentiated type,neuroendocrine carcinoma and so on. This classification of-ICC may ope-n up a ne-w fie-ld of-re-se-arch of-ICC and contribute-to the-clini cal approach to ICC.展开更多
AIM:To understand the clinicopathological characteristics and treatment selections and improve survival and provide valuable information for patients with intrahepatic cholangiocarcinoma(ICC). METHODS:We retrospective...AIM:To understand the clinicopathological characteristics and treatment selections and improve survival and provide valuable information for patients with intrahepatic cholangiocarcinoma(ICC). METHODS:We retrospectively evaluated 5311 liver cancer patients who received resection between October 1999 and December 2003.Of these,429(8.1%)patients were diagnosed with ICC,and their clinicopathological, surgical,and survival characteristics were analyzed. RESULTS:Upper abdominal discomfort or pain(65.0%), no symptoms(12.1%),and hypodynamia(8.2%)were the major causes for medical attention.Laboratory tests showed 198(46.4%)patients were HBsAg positive, 90(21.3%)hadα-fetoprotein>20μg/L,50(11.9%) carcinoembryonic antigen>10μg/L,and 242(57.5%) carbohydrate antigen 19-9(CA19-9)>37 U/mL.Survival data was available for 329(76.7%)patients and their mean survival time was 12.4 mo.The overall survival of the patients with R0,R1 resection and punching exploration were 18.3,6.6 and 5.6 mo,respectively. Additionally,CA19-9>37 U/mL was associated with lymph node metastases,but inversely associated withcirrhosis.Multivariate analysis indicated that radical resection,lymph node metastases,macroscopic tumor thrombi and size,and CA19-9 were associated with prognosis. CONCLUSION:Surgical radical resection is still the most effective means to cure ICC.Certain laboratory tests(such as CA19-9)can effectively predict the survival of the patients with ICC.展开更多
This paper reviews the epidemiological status and characteristics of clonorchiasis at global level and the etiological relationship between Clonorchis sinensis infection and cholangiocarcinoma(CCA).A conservative esti...This paper reviews the epidemiological status and characteristics of clonorchiasis at global level and the etiological relationship between Clonorchis sinensis infection and cholangiocarcinoma(CCA).A conservative estimation was made that 15 million people were infected in the world in 2004,of which over 85%distributed in China.The epidemiology of clonorchiasis is characterized by rising trend in its prevalence,variability among sexes and age,as well as endemicity in different regions.More data indicate that C.sinensis infection is carcinogenic to human,and it is predicted that nearly 5000 CCA cases attributed to C.sinensis infection may occur annually in the world decades later,with its overall odds ratio of 4.47.Clonorchiasis is becoming one major public health problem in east Asia,and it is worthwhile to carry out further epidemiological studies.展开更多
AIM: To assess the management and outcome of hilar cholangiocarcinoma (Klatskin tumor) in a single tertiary referral center.METHODS: The notes of all patients with a diagnosis of hilar cholangiocarcinoma referred to o...AIM: To assess the management and outcome of hilar cholangiocarcinoma (Klatskin tumor) in a single tertiary referral center.METHODS: The notes of all patients with a diagnosis of hilar cholangiocarcinoma referred to our unit for over an 8-year period were identified and retrospectively reviewed. Presentation, management and outcome were assessed.RESULTS: Seventy-five patients were identified. The median age was 64 years (range 34-84 years). Male to female ratio was 1:1. Eighty-nine percent of patients presented with jaundice. Most patients referred were under Bismuth classification 3a, 3b or 4. Seventy patients required biliary drainage, 65 patients required 152percutaneous drainage procedures, and 25 had other complications. Forty-one patients had 51 endoscopic drainage procedures performed (15 failed). Of these,36 subsequently required percutaneous drainage. The median number of drainage procedures for all patients was three, 18 patients underwent resection (24%), nine had major complications and three died post-operatively.The 5-year survival rate was 4.2% for all patients, 21%for resected patients and 0% for those who did not undergo resection (P = 0.0021). The median number of admissions after diagnosis in resected patients was two and three in non-resected patients (P＜0.05).Twelve patients had external-beam radiotherapy, seven brachytherapy, and eight chemotherapy. There was no significant benefit in terms of survival (P = 0.46) or hospital admissions.CONCLUSION: Resection increases survival but carries the risk of significant morbidity and mortality.Percutaneous biliary drainage is almost always necessary and endoscopic drainage should be avoided if possible.展开更多
Multidimensional analyses have demonstrated the presence of a unique tumor microenvironment(TME)in liver cancer.Tumor-associated macrophages(TAMs)are among the most abundant immune cells infiltrating the TME and are p...Multidimensional analyses have demonstrated the presence of a unique tumor microenvironment(TME)in liver cancer.Tumor-associated macrophages(TAMs)are among the most abundant immune cells infiltrating the TME and are present at all stages of liver cancer progression,and targeting TAMs has become one of the most favored immunotherapy strategies.In addition,macrophages and liver cancer cells have distinct origins.At the early stage of liver cancer,macrophages can provide a niche for the maintenance of liver cancer stem cells.In contrast,cancer stem cells(CSCs)or poorly differentiated tumor cells are key factors modulating macrophage activation.In the present review,we first propose the origin connection between precursor macrophages and liver cancer cells.Macrophages undergo dynamic phenotypic transition during carcinogenesis.In this course of such transition,it is critical to determine the appropriate timing for therapy and block specific markers to suppress protumoral TAMs.The present review provides a more detailed discussion of transition trends of such surface markers than previous reviews.Complex crosstalk occurs between TAMs and liver cancer cells.TAMs play indispensable roles in tumor progression,angiogenesis,and autophagy due to their heterogeneity and robust plasticity.In addition,macrophages in the TME interact with other immune cells by directing cell-to-cell contact or secreting various effector molecules.Similarly,tumor cells combined with other immune cells can drive macrophage recruitment and polarization.Despite the latest achievements and the advancements in treatment strategies following TAMs studies,comprehensive discussions on the communication between macrophages and cancer cells or immune cells in liver cancer are currently lacking.In this review,we discussed the interactions between TAMs and liver cancer cells(from cell origin to maturation),the latest therapeutic strategies(including chimeric antigen receptor macrophages),and critical clinical trials for hepatocellular carcinoma(HCC)and intr展开更多
AIM:To investigate the role of hepatocyte growth factor(HGF) in cholangiocarcinoma(CCA) cell invasiveness and the mechanisms underlying such cellular responses. METHODS:Effects of HGF on cell invasion and motility wer...AIM:To investigate the role of hepatocyte growth factor(HGF) in cholangiocarcinoma(CCA) cell invasiveness and the mechanisms underlying such cellular responses. METHODS:Effects of HGF on cell invasion and motility were investigated in two human CCA cell lines,HuCCA-1 and KKU-M213,using Transwell in vitro assay.Levels of proteins of interest and their phosphorylated forms were determined by Western blotting.Localization of E-cadherin was analyzed by immunofluorescence staining and visualized under confocal microscope. Activities of matrix degrading enzymes were determined by zymography. RESULTS:Both CCA cell lines expressed higher Met levels than the H69 immortalized cholangiocyte cell line.HGF induced invasion and motility of the cell lines and altered E-cadherin from membrane to cytoplasm localization,but did not affect the levels of secreted matrix metalloproteinase(MMP) -2,MMP-9 andurokinase plasminogen activator,key matrix degrading enzymes involved in cell invasion.Concomitantly,HGF stimulated Akt and extracellular signal-regulated kinase(ERK) 1/2 phosphorylation but with slightly different kinetic profiles in the two cell lines.Inhibition of the phosphoinositide 3-kinase(PI3K) /Akt pathway by the PI3K inhibitor,LY294002,markedly suppressed HGFstimulated invasion of both CCA cell lines,and inhibition of the ERK pathway by U0126 suppressed HGF-induced invasion of the KKU-M213 cell line but had a moderate effect on HuCCA-1 cells. CONCLUSION:These data indicate that HGF promotes CCA cell invasiveness through dys-localization of E-cadherin and induction of cell motility by distinct signaling pathways depending on cell line type.展开更多
Aberrant expression and signaling of epidermal growth factor receptor (ErbB) family receptor tyrosine kinases, most notably that of ErbB2 and ErbB1, have been implicated in the molecular pathogenesis of intrahepatic c...Aberrant expression and signaling of epidermal growth factor receptor (ErbB) family receptor tyrosine kinases, most notably that of ErbB2 and ErbB1, have been implicated in the molecular pathogenesis of intrahepatic cholangiocarcinoma. Constitutive overexpression of ErbB2 and/or ErbB1 in malignant cholangiocytes has raised interest in the possibility that agents which selectively target these receptors could potentially be effective in cholangiocarcinoma therapy. However, current experience with such ErbB-directed therapies have at best produced only modest responses in patients with biliary tract cancers. This review provides a comprehensive and critical analysis of both preclinical and clinical studies aimed at assessing the role of altered ErbB2 and/or ErbB1 expression, genetic modifications, and dysregulated signaling on cholangiocarcinoma development and progression. Specific limitations in experimental approaches that have been used to assess human cholangiocarcinoma specimens for ErbB2 and/or ErbB1 overexpression and gene amplification are discussed. In addition, current rodent models of intrahepatic cholangiocarcinogenesis associated with constitutive ErbB2 overexpression are reviewed. Select interactive relationships between ErbB2 or ErbB1 with other relevant molecular signaling pathways associated with intrahepatic cholangiocarcinoma development and progression are also detailed, including those linking ErbB receptors to bile acid, cyclooxygenase-2,interleukin-6/gp130, transmembrane mucins, hepatocyte growth factor/Met, and vascular endothelial growth factor signaling. Lastly, various factors that can limit therapeutic efficacy of ErbB-targeted agents against cholangiocarcinoma are considered.展开更多
基金Supported by the Innovative Research Groups of the National Natural Science Foundation of China No.81221061the National Natural Science Foundation of China No.81072026,No.81272662 and No.81472278
文摘In 2010, a panel of Chinese pathologists reported the first expert consensus for the pathological diagnosis of primary liver cancers to address the many contradictions and inconsistencies in the pathological characteristics and diagnostic criteria for PLC. Since then considerable clinicopathological studies have been conducted globally, prompting us to update the practice guidelines for the pathological diagnosis of PLC. In April 18, 2014, a Guideline Committee consisting of 40 specialists from seven Chinese Societies(including Chinese Society of Liver Cancer, Chinese Anti-Cancer Association; Liver Cancer Study Group, Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Pathology, Chinese Anti-Cancer Association; Digestive Disease Group, Chinese Society of Pathology, Chinese Medical Association; Chinese Society of Surgery, Chinese Medical Association; Chinese Society of Clinical Oncology, Chinese Anti-Cancer Association; Pathological Group of Hepatobiliary Tumor and Liver Transplantation, Chinese Society of Pathology, Chinese Medical Association) was created for the formulation of the first guidelines for the standardization of the pathological diagnosis of PLC, mainly focusing on the following topics: gross specimen sampling, concepts and diagnostic criteria of small hepatocellular carcinoma(SHCC), microvascular invasion(MVI), satellite nodules,and immunohistochemical and molecular diagnosis. The present updated guidelines are reflective of current clinicopathological studies, and include a novel 7-point baseline sampling protocol, which stipulate that at least four tissue specimens should be sampled at the junction of the tumor and adjacent liver tissues in a 1:1 ratio at the 12, 3, 6 and 9 o'clock reference positions. For the purposes of molecular pathological examination, at least one specimen should be sampled at the intratumoral zone, but more specimens should be sampled for tumors harboring different textures or colors. Specimens should be sampled at both adjacent and distant peri
文摘Several advances in diagnosis,treatment and palliation of cholangiocarcinoma(CC)have occurred in the last decades.A multidisciplinary approach to this disease is therefore recommended.CC is a relatively rare tumor and the main risk factors are:chronic inflammation, genetic predisposition and congenital abnormalities of the biliary tree.While the incidence of intra-hepatic CC is increasing,the incidence of extra-hepatic CC is trending down.The only curative treatment for CC is surgical resection with negative margins.Liver transplantation has been proposed only for selected patients with hilar CC that cannot be resected who have no metastatic disease after a period of neoadjuvant chemo-radiation therapy.Magnetic resonance imaging/magnetic resonance cholangiopancreatography,positron emission tomography scan,endoscopic ultrasound and computed tomography scans are the most frequently used modalities for diagnosis and tumor staging.Adjuvant therapy,palliative chemotherapy and radiotherapy have been relatively ineffective for inoperable CC.For most of these patients biliary stenting provides effective palliation.Photodynamic therapy is an emerging palliative treatment that seems to provide pain relief,improve biliary patency and increase survival. The clinical utility of other emerging therapies such as transarterial chemoembolization,hepatic arterial chemoinfusion and high intensity intraductal ultrasound needs further study.
文摘Although the incidence of hepatolithiasis is decreasing as the pattern of gallstone disease changes in Asia, the prevalence of hepatolithiasis is persistently high, especially in Far Eastern countries. Hepatolithiasis is an established risk factor for cholangiocarcinoma(CCA), and chronic proliferative inflammation may be involved in biliary carcinogenesis and in inducing the upregulation of cell-proliferating factors. With the use of advanced imaging modalities, there has been much improvement in the management of hepatolithiasis and the diagnosis of hepatolithiasis-associated CCA(HLCCA). However, there are many problems in managing the strictures in hepatolithiasis and differentiating them from infiltrating types of CCA. Surgical resection is recommended in cases of single lobe hepatolithiasis with atrophy, uncontrolled stricture, symptom duration of more than 10 years, and long history of biliaryenteric anastomosis. Even after resection, patients should be followed with caution for development of HL-CCA, because HL-CCA is an independent prognostic factor for survival. It is not yet clear whether hepatic resection can reduce the occurrence of subsequent HL-CCA. Furthermore, there are no consistent findings regarding prediction of subsequent HL-CCA in patients with hepatolithiasis. In the management of hepatolithiasis, important factors are the reduction of recurrence of cholangitis and suspicion of unrecognized HL-CCA.
文摘AIM: To carry out a hospital-based case-control study to investigate risk factors for intrahepatic cholangiocarcinoma (ICC) in China. METHODS: A total of 312 ICC cases and 438 matched controls were included in the study. The presence of diabetes mellitus,hypertention,hepatolithiasis,primary sclerosing cholangitis,liver fluke infection (Clonorchis sinensis ),was investigated through clinical records. Blood from all participants was tested for hepatitis B surface antigen (HBsAg) and anti-HCV antibodies. Odds ratios (OR) and 95% confi dence intervals (95% CI) were estimated using conditional logistic regression. RESULTS: Compared with controls,ICC patients had a higher prevalence of HBsAg seropositivity (48.4% vs 9.6%,P < 0.000),and hepatolithiasis (5.4% vs 1.1%,P = 0.001). By multivariate analysis,the signif icant risk factors for development of ICC were HBsAg seropositivity (adjusted OR,8.876,95% CI,5.973-13.192),and hepatolithiasis (adjusted OR,5.765,95% CI,1.972-16.851). The prevalence of anti-HCV seropositivity,diabetes mellitus,hypertention,cigarette smoking,and alcohol consumption were not significantly different between cases and controls. CONCLUSION: These findings suggest that HBV infection and hepatolithiasis are strong risk factors for development of ICC in China.
文摘To perform a systematic review and meta-analysis on clinical outcomes of photodynamic therapy (PDT) in non-resectable cholangiocarcinoma.METHODSIncluded studies compared outcomes with photodynamic therapy and biliary stenting (PDT group) vs biliary stenting only (BS group) in palliation of non-resectable cholangiocarcinoma. Articles were searched in MEDLINE, PubMed, and EMBASE. Pooled proportions were calculated using fixed and random effects model. Heterogeneity among studies was assessed using the I<sup>2</sup> statistic.RESULTSTen studies (n = 402) that met inclusion criteria were included in this analysis. The P for χ<sup>2</sup> heterogeneity for all the pooled accuracy estimates was > 0.10. Pooled odds ratio for successful biliary drainage (decrease in bilirubin level > 50% within 7days after stenting) in PDT vs BS group was 4.39 (95%CI: 2.35-8.19). Survival period in PDT and BS groups were 413.04 d (95%CI: 349.54-476.54) and 183.41 (95%CI: 136.81-230.02) respectively. The change in Karnofsky performance scores after intervention in PDT and BS groups were +6.99 (95%CI: 4.15-9.82) and -3.93 (95%CI: -8.63-0.77) respectively. Odds ratio for post-intervention cholangitis in PDT vs BS group was 0.57 (95%CI: 0.35-0.94). In PDT group, 10.51% (95%CI: 6.94-14.72) had photosensitivity reactions that were self-limiting. Subgroup analysis of prospective studies showed similar results, except the incidence of cholangitis was comparable in both groups.CONCLUSIONIn palliation of unresectable cholangiocarcinoma, PDT seems to be significantly superior to BS alone. PDT should be used as an adjunct to biliary stenting in these patients.
基金Supported by The National Nature Science of China, No. 3080111 and No. 30972923Science and Technology Support Project of Sichuan Province, No. 2014SZ0002-10
文摘AIM: To evaluate the prognostic factors of hilar cholangiocarcinoma in a large series of patients in a single institution.METHODS: Eight hundred and fourteen patients with a diagnosis of hilar cholangiocarcinoma that were evaluated and treated between 1990 and 2014, of which 381 patients underwent curative surgery, were included in this study. Potential factors associated with overall survival(OS) and disease-free survival(DFS) were evaluated by univariate and multivariate analyses.RESULTS: Curative surgery provided the best long-term survival with a median OS of 26.3 mo. The median DFS was 18.1 mo. Multivariate analysis showed that patients with tumor size > 3 cm [hazard ratio(HR) = 1.482, 95%CI: 1.127-1.949; P = 0.005], positive nodal disease(HR = 1.701, 95%CI: 1.346-2.149; P < 0.001), poor differentiation(HR = 2.535, 95%CI: 1.839-3.493; P < 0.001), vascular invasion(HR = 1.542, 95%CI: 1.082-2.197; P = 0.017), and positive margins(HR = 1.798, 95%CI: 1.314-2.461; P < 0.001) had poor OS outcome. The independent factors for DFS were positive nodal disease(HR = 3.383, 95%CI: 2.633-4.348; P < 0.001), poor differentiation(HR = 2.774, 95%CI: 2.012-3.823; P < 0.001), vascular invasion(HR = 2.136, 95%CI: 1.658-3.236; P < 0.001), and positive margins(HR = 1.835, 95%CI: 1.256-2.679; P < 0.001). Multiple logistic regression analysis showed that caudate lobectomy [odds ratio(OR) = 9.771, 95%CI: 4.672-20.433; P < 0.001], tumor diameter(OR = 3.772, 95%CI: 1.914-7.434; P < 0.001), surgical procedures(OR = 10.236, 95%CI: 4.738-22.116; P < 0.001), American Joint Committee On Cancer T stage(OR = 2.010, 95%CI: 1.043-3.870; P = 0.037), and vascular invasion(OR = 2.278, 95%CI: 0.997-5.207; P = 0.051) were independently associated with tumorfree margin, and surgical procedures could indirectly affect survival outcome by influencing the tumor resection margin. CONCLUSION: Tumor margin, tumor differentiation, vascular invasion, and lymph node status were independent factors for OS and DFS. Surgical procedures can indirectly affect surv
文摘Intrahepatic cholangiocarcinoma (ICC) arises from the lining epithelium and peribiliary glands of the intrahepatic biliary tree and shows variable cholangiocytic dif-f-e-re-ntiation. To date-,ICC was large-ly classifie-d into adenocarcinoma and rare variants. Herein,we propose to subclassify the former,based on recent progress in the-study of-ICC including the-gross classification and hepatic progenitor/stem cells and on the pathological similarities between biliary and pancreatic neoplasms. That is,ICC is classifiable into the conventional (bile duct) type,the bile ductular type,the intraductal neoplasm type and rare variants. The conventional type is further divided into the small duct type (peripheral type) and large bile duct type (perihilar type). The former is a tubular or micropapillary adenocarcinoma while the latter involves the intrahepatic large bile duct. Bile ductular type resembles proliferated bile ductules and shows a replacing growth of the hepatic parenchyma.Hepatic progenitor cell or stem cell phenotypes such as neural cell adhesion molecule expression are frequently expressed in the bile ductular type. Intraductal type includes papillary and tubular neoplasms of the bile duct (IPNBs and ITNBs) and a superficial spreading type. IPNB and ITNB show a spectrum from a preneoplastic borderline lesion to carcinoma and may have pancreatic counterparts. At invasive sites,IPNB is associated with the conventional bile duct ICC and mucinous carcinoma. Biliary mucinous cystic neoplasm with ovarian-like stroma in its wall is different from IPNB,particularly IPNB showing cystic dilatation of the affected ducts. Rare variants of ICC include squamous/adenosquamous cell carcinoma,mucinous/signet ring cell carcinoma,clear cell type,undifferentiated type,neuroendocrine carcinoma and so on. This classification of-ICC may ope-n up a ne-w fie-ld of-re-se-arch of-ICC and contribute-to the-clini cal approach to ICC.
基金Supported by The Shanghai Natural Science Foundation,No.09ZR1401100
文摘AIM:To understand the clinicopathological characteristics and treatment selections and improve survival and provide valuable information for patients with intrahepatic cholangiocarcinoma(ICC). METHODS:We retrospectively evaluated 5311 liver cancer patients who received resection between October 1999 and December 2003.Of these,429(8.1%)patients were diagnosed with ICC,and their clinicopathological, surgical,and survival characteristics were analyzed. RESULTS:Upper abdominal discomfort or pain(65.0%), no symptoms(12.1%),and hypodynamia(8.2%)were the major causes for medical attention.Laboratory tests showed 198(46.4%)patients were HBsAg positive, 90(21.3%)hadα-fetoprotein>20μg/L,50(11.9%) carcinoembryonic antigen>10μg/L,and 242(57.5%) carbohydrate antigen 19-9(CA19-9)>37 U/mL.Survival data was available for 329(76.7%)patients and their mean survival time was 12.4 mo.The overall survival of the patients with R0,R1 resection and punching exploration were 18.3,6.6 and 5.6 mo,respectively. Additionally,CA19-9>37 U/mL was associated with lymph node metastases,but inversely associated withcirrhosis.Multivariate analysis indicated that radical resection,lymph node metastases,macroscopic tumor thrombi and size,and CA19-9 were associated with prognosis. CONCLUSION:Surgical radical resection is still the most effective means to cure ICC.Certain laboratory tests(such as CA19-9)can effectively predict the survival of the patients with ICC.
基金This project is funded through a capacity building initiative for Ecohealth Research on Emerging Infectious Disease in Southeast Asia supported by the International Development Research Centre(IDRC),the Canadian International Development Agency(CIDA),and the Australian Agency for International Development(AusAID)in partnership with the Global Health Research Initiative(grant No.105509-00001002-023)as well as supported by the National S&T Major Program(grant No.2008ZX10004-011)+1 种基金by the National S&T Supporting Project(grant No.2007BAC03A02)Zhou XN was supported by Shanghai S&T Committee(grant No.11XD1405400).
文摘This paper reviews the epidemiological status and characteristics of clonorchiasis at global level and the etiological relationship between Clonorchis sinensis infection and cholangiocarcinoma(CCA).A conservative estimation was made that 15 million people were infected in the world in 2004,of which over 85%distributed in China.The epidemiology of clonorchiasis is characterized by rising trend in its prevalence,variability among sexes and age,as well as endemicity in different regions.More data indicate that C.sinensis infection is carcinogenic to human,and it is predicted that nearly 5000 CCA cases attributed to C.sinensis infection may occur annually in the world decades later,with its overall odds ratio of 4.47.Clonorchiasis is becoming one major public health problem in east Asia,and it is worthwhile to carry out further epidemiological studies.
文摘AIM: To assess the management and outcome of hilar cholangiocarcinoma (Klatskin tumor) in a single tertiary referral center.METHODS: The notes of all patients with a diagnosis of hilar cholangiocarcinoma referred to our unit for over an 8-year period were identified and retrospectively reviewed. Presentation, management and outcome were assessed.RESULTS: Seventy-five patients were identified. The median age was 64 years (range 34-84 years). Male to female ratio was 1:1. Eighty-nine percent of patients presented with jaundice. Most patients referred were under Bismuth classification 3a, 3b or 4. Seventy patients required biliary drainage, 65 patients required 152percutaneous drainage procedures, and 25 had other complications. Forty-one patients had 51 endoscopic drainage procedures performed (15 failed). Of these,36 subsequently required percutaneous drainage. The median number of drainage procedures for all patients was three, 18 patients underwent resection (24%), nine had major complications and three died post-operatively.The 5-year survival rate was 4.2% for all patients, 21%for resected patients and 0% for those who did not undergo resection (P = 0.0021). The median number of admissions after diagnosis in resected patients was two and three in non-resected patients (P＜0.05).Twelve patients had external-beam radiotherapy, seven brachytherapy, and eight chemotherapy. There was no significant benefit in terms of survival (P = 0.46) or hospital admissions.CONCLUSION: Resection increases survival but carries the risk of significant morbidity and mortality.Percutaneous biliary drainage is almost always necessary and endoscopic drainage should be avoided if possible.
基金National Natural Science Foundation of China,Grant/Award Numbers:8187111473,8217113337。
文摘Multidimensional analyses have demonstrated the presence of a unique tumor microenvironment(TME)in liver cancer.Tumor-associated macrophages(TAMs)are among the most abundant immune cells infiltrating the TME and are present at all stages of liver cancer progression,and targeting TAMs has become one of the most favored immunotherapy strategies.In addition,macrophages and liver cancer cells have distinct origins.At the early stage of liver cancer,macrophages can provide a niche for the maintenance of liver cancer stem cells.In contrast,cancer stem cells(CSCs)or poorly differentiated tumor cells are key factors modulating macrophage activation.In the present review,we first propose the origin connection between precursor macrophages and liver cancer cells.Macrophages undergo dynamic phenotypic transition during carcinogenesis.In this course of such transition,it is critical to determine the appropriate timing for therapy and block specific markers to suppress protumoral TAMs.The present review provides a more detailed discussion of transition trends of such surface markers than previous reviews.Complex crosstalk occurs between TAMs and liver cancer cells.TAMs play indispensable roles in tumor progression,angiogenesis,and autophagy due to their heterogeneity and robust plasticity.In addition,macrophages in the TME interact with other immune cells by directing cell-to-cell contact or secreting various effector molecules.Similarly,tumor cells combined with other immune cells can drive macrophage recruitment and polarization.Despite the latest achievements and the advancements in treatment strategies following TAMs studies,comprehensive discussions on the communication between macrophages and cancer cells or immune cells in liver cancer are currently lacking.In this review,we discussed the interactions between TAMs and liver cancer cells(from cell origin to maturation),the latest therapeutic strategies(including chimeric antigen receptor macrophages),and critical clinical trials for hepatocellular carcinoma(HCC)and intr
基金Supported by Mahidol University,Thailand and Thailand Research Fund(Suthiphongchai T)Strategic Consortia for Capacity Building of University Faculties and Staff Scholarship,Commission on Higher Education,Ministry of Education,Thailand(Menakongka A)
文摘AIM:To investigate the role of hepatocyte growth factor(HGF) in cholangiocarcinoma(CCA) cell invasiveness and the mechanisms underlying such cellular responses. METHODS:Effects of HGF on cell invasion and motility were investigated in two human CCA cell lines,HuCCA-1 and KKU-M213,using Transwell in vitro assay.Levels of proteins of interest and their phosphorylated forms were determined by Western blotting.Localization of E-cadherin was analyzed by immunofluorescence staining and visualized under confocal microscope. Activities of matrix degrading enzymes were determined by zymography. RESULTS:Both CCA cell lines expressed higher Met levels than the H69 immortalized cholangiocyte cell line.HGF induced invasion and motility of the cell lines and altered E-cadherin from membrane to cytoplasm localization,but did not affect the levels of secreted matrix metalloproteinase(MMP) -2,MMP-9 andurokinase plasminogen activator,key matrix degrading enzymes involved in cell invasion.Concomitantly,HGF stimulated Akt and extracellular signal-regulated kinase(ERK) 1/2 phosphorylation but with slightly different kinetic profiles in the two cell lines.Inhibition of the phosphoinositide 3-kinase(PI3K) /Akt pathway by the PI3K inhibitor,LY294002,markedly suppressed HGFstimulated invasion of both CCA cell lines,and inhibition of the ERK pathway by U0126 suppressed HGF-induced invasion of the KKU-M213 cell line but had a moderate effect on HuCCA-1 cells. CONCLUSION:These data indicate that HGF promotes CCA cell invasiveness through dys-localization of E-cadherin and induction of cell motility by distinct signaling pathways depending on cell line type.
基金National Institutes of Health Grants,R01 CA 83650 and R01 CA 39225 to A.E.S.
文摘Aberrant expression and signaling of epidermal growth factor receptor (ErbB) family receptor tyrosine kinases, most notably that of ErbB2 and ErbB1, have been implicated in the molecular pathogenesis of intrahepatic cholangiocarcinoma. Constitutive overexpression of ErbB2 and/or ErbB1 in malignant cholangiocytes has raised interest in the possibility that agents which selectively target these receptors could potentially be effective in cholangiocarcinoma therapy. However, current experience with such ErbB-directed therapies have at best produced only modest responses in patients with biliary tract cancers. This review provides a comprehensive and critical analysis of both preclinical and clinical studies aimed at assessing the role of altered ErbB2 and/or ErbB1 expression, genetic modifications, and dysregulated signaling on cholangiocarcinoma development and progression. Specific limitations in experimental approaches that have been used to assess human cholangiocarcinoma specimens for ErbB2 and/or ErbB1 overexpression and gene amplification are discussed. In addition, current rodent models of intrahepatic cholangiocarcinogenesis associated with constitutive ErbB2 overexpression are reviewed. Select interactive relationships between ErbB2 or ErbB1 with other relevant molecular signaling pathways associated with intrahepatic cholangiocarcinoma development and progression are also detailed, including those linking ErbB receptors to bile acid, cyclooxygenase-2,interleukin-6/gp130, transmembrane mucins, hepatocyte growth factor/Met, and vascular endothelial growth factor signaling. Lastly, various factors that can limit therapeutic efficacy of ErbB-targeted agents against cholangiocarcinoma are considered.
