关于肝炎后肝硬化(LC)患者胆系改变的系统了解较少,为此,我们采用超声显像方法(下称 B 超)对202例 LC 患者作了胆系检查、并与典型急性肝炎(AH)、慢性肝炎(CH)患者作对照,发现 LC 患者胆系 B 超检查有多种异常表现、包括胆囊壁增厚、胆...关于肝炎后肝硬化(LC)患者胆系改变的系统了解较少,为此,我们采用超声显像方法(下称 B 超)对202例 LC 患者作了胆系检查、并与典型急性肝炎(AH)、慢性肝炎(CH)患者作对照,发现 LC 患者胆系 B 超检查有多种异常表现、包括胆囊壁增厚、胆石、胆囊缩小或增大等、且其发生率明显高于 AH 和 CH患者。现将结果报告如下。展开更多
AIM:To examine the expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1(LFA-1)expression on canals of Hering (COH)and bile ductules associated with the autoimmun...AIM:To examine the expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1(LFA-1)expression on canals of Hering (COH)and bile ductules associated with the autoimmune process of bile duct destruction in primary biliary cirrhosis(PBC).METHODS:Ten wedged liver biopsies of PBC(five cases each of stages 2 and 3)were studied. The liver specimens were processed for transmission electron microscopy. Immunohistochemistry was performed using anti-ICAM-1 and anti-LFA-1 mouse mAbs.In situ hybridization was done to examine the messenger RNA expression of ICAM-1 in formalin-fixed.paraffin-embedded sections using peptide nucleic acid probes and the catalyzed signal amplification (CSA)technique.Immunogold-silver staining for electron microscopy was Derrormed using anti-ICAM and anti-LFA-1 mouse mAbs.The immunogold particles on epithelial cells of bileductules and cholangiocytes of CoH cells were counted and analyzed semi-quantitatively.Western blotting was performed to confirm ICAM-1 protein expression.RESULTS:In liver tissues of PBC patients.immunohi-stochemistry showed aberrant ICAM-1 expression on the plasma membrane of epithelial cells lining bile ductules,and also on mature cholangiocytes but not on hepatocytes in CoH.LFA-1-positive lymphocytes were closely associated with epithelial cells in bile ductules.ICAM-1 expression at protein level was confirmed by Western blot.In situ hybridization demonstrated ICAM-1 mRNA expression in bile ductules and LFA-1 mRNA in lymphocytes infiltrating the bileductules.By immunoelectron microscopy,ICAM-1 was demonstrated on the basal suface of epithelial cells in bile ductules and on the luminal surfaces of cholangiocytes in damaged COH.Cells with intermediate morphology resembling progenitor cells in Coil were not labeled with ICAM-1 and LFA-1.CONCLUSION:De novo expression of ICAM-1 both on mature cholangiocytes in COH and epithelial cells in bile ductules in PBC implies that lymphocyte-induced destruction through adhesion by ICAM-1 and binding of LFA-1-expressing activated lymphocytes takes place not only in bile ductules but also in the COH.展开更多
Gallbladder localization of heterotopic pancreas (HP) is uncommon and very rarely gives rise to symptoms. Herein we report a case of HP found in the gallbladder neck presented with signs and symptoms of cholecystiti...Gallbladder localization of heterotopic pancreas (HP) is uncommon and very rarely gives rise to symptoms. Herein we report a case of HP found in the gallbladder neck presented with signs and symptoms of cholecystitis. The patient was a 40-year old male, suffering from epigastric pain, abdominal fullness and fever. On physical examination, the right upper abdomen was tender with a positive Murphy's sign. Ultrasonographic examination showed a hydropic gallbladder without stones and he underwent a cholecystectomy. Pathological examination revealed an intramural nodule (9 ram) in the neck region which is consisted of acini, ducts and islet cells of an aberrant pancreatic tissue. Although HP is encountered rarely in the gallbladder and is found incidentally during pathological studies, this case emphasizes that HP might cause symptoms and present clinically as cholecystitis. For this reason, in patients presenting with symptomatic gallbladder diseases, including cholecystitis without any other pathology, HP should be taken into consideration before it is diagnosed as "idiopathic':展开更多
Cholangiocarcinomas arise from the epithelial cells of the bile ducts and are associated with poor prognosis. Despite new diagnostic approaches, the definite diagnosis of this malignancy continues to be challenging. C...Cholangiocarcinomas arise from the epithelial cells of the bile ducts and are associated with poor prognosis. Despite new diagnostic approaches, the definite diagnosis of this malignancy continues to be challenging. Cholangiocarcinomas often grow longitudinally along the bile duct rather than in a radial direction. Thus, large tumor masses are frequently absent and imaging techniques, including ultrasound, CT, and MRI have only limited sensitivity. Tissue collection during endoscopic (ERCP) and/or percutaneous transhepatic (PTC) procedures are usually used to confirm a definitive diagnosis of cholangiocarcinoma. However, forceps biopsy and brush cytology provide positive results for malignancy in about only 50% of patients. Percutaneous and peroral cholangioscopy using fiber-optic techniques were therefore developed for direct visualization of the biliary tree, yielding additional information about endoscopic appearance and tumor extension, as well as a guided biopsy acquistion. Finally, endoscopic ultrasonography (EUS) complements endoscopic and percutaneous approaches and may provide a tissue diagnosis of tumors in the biliary region through fine-needle aspiration. In the future, new techniques allowing for early detection, including molecular markers, should be developed to improve the diagnostic sensitivity in this increasing tumor entity.展开更多
Bile duct cancers are frequently diagnosed as advanced diseases. Over half of patients with advanced bile duct cancer present with unresectable malignancies and their prognosis has been very poor even after curative r...Bile duct cancers are frequently diagnosed as advanced diseases. Over half of patients with advanced bile duct cancer present with unresectable malignancies and their prognosis has been very poor even after curative resections. Although there has been a need to diagnose bile duct cancer at its eady stage, it has been a difficult goal to achieve due to our lack of knowledge regarding this disease entity. Early bile duct cancer may be defined as a carcinoma whose invasion is confined within the fibromuscular layer of the extrahepatic bile duct or intrahepatic large bile duct without distant metastasis irrespective of lymph node involvement. Approximately 3%-10% of resected bile duct cancers have been reported to be early cancers in the literature. The clinicopathological features of patients with early bile duct cancer differ from those of patients with advanced bile duct cancer, with more frequent asymptomatic presentation, characteristic histopathological findings, and excellent prognosis. This manuscript is organized to emphasize the need for convening an international consensus to develop the concept of early bile duct cancer.展开更多
AIM: To evaluate the sensitivity of brush cytology and forceps biopsy in a homogeneous patient group with hilar cholangiocarcinoma.METHODS: Brush cytology and forceps biopsy were routinely performed in patients with s...AIM: To evaluate the sensitivity of brush cytology and forceps biopsy in a homogeneous patient group with hilar cholangiocarcinoma.METHODS: Brush cytology and forceps biopsy were routinely performed in patients with suspected malignant biliary strictures. Fifty-eight consecutive patients undergoing endoscopic retrograde cholangio-pancreatography (ERCP) including forceps biopsy and brush cytology in patients with hilar cholangiocarcinoma between 1995-2005.RESULTS: Positive results for malignancy were obtained in 24/58 patients (41.4%) by brush cytology and in 31/58 patients (53.4%) by forceps biopsy. The combination of both techniques brush cytology and forceps biopsy resulted only in a minor increase in diagnostic sensitivity to 60.3% (35/58 patients). In 20/58 patients (34.5%), diagnosis were obtained by both positive cytology and positive histology, in 11/58 (19%) by positive histology (negative cytology) and only 4/58 patients (6.9%) were confirmed by positive cytology (negative histology).CONCLUSION: Brush cytology and forceps biopsy have only limited sensitivity for the diagnosis of malignant hilar tumors. In our eyes, additional diagnostic techniques should be evaluated and should become routine in patients with negative cytological and histological findings.展开更多
Intrahepatic cholangiocarcinomas (ICC) are neoplasms that originate from cholangiocytes and can occur at any level of the biliary tree. Surgical resection is the current therapy of choice for this highly aggressive ca...Intrahepatic cholangiocarcinomas (ICC) are neoplasms that originate from cholangiocytes and can occur at any level of the biliary tree. Surgical resection is the current therapy of choice for this highly aggressive cancer. However, the 5-year survival still is poor, with high recurrence rates. Due to the intrahepatic growth a signifi cant proportion of patients present with advanced disease and are not candidates for curative surgery or transplantation. The existing palliative options are of limited benefit and there is a great necessity for novel therapeutic options. In this article we review the role of the phosphoinositide 3-kinase(PI3K)/ AKT and extracellular regulated kinase (ERK) signaling pathways in ICC and present new data on the prognostic value of these protein kinases. Finally, we discuss future upcoming therapeutic options based on targeting these signaling pathways.展开更多
AIM:To investigate the role and clinicopathological significance of aberrant expression of Notch receptors and Delta-like ligand-4 (DLL4) in extrahepatic cholangiocarcinoma and gallbladder carcinoma.METHODS:One hundre...AIM:To investigate the role and clinicopathological significance of aberrant expression of Notch receptors and Delta-like ligand-4 (DLL4) in extrahepatic cholangiocarcinoma and gallbladder carcinoma.METHODS:One hundred and ten patients had surgically resected extrahepatic cholangiocarcinoma (CC) and gallbladder carcinoma specimens examined by immunohistochemistry of available paraffin blocks.Immunohistochemistry was performed using anti-Notch receptors 1-4 and anti-DLL4 antibodies.We scored the immunopositivity of Notch receptors and DLL4 expression by percentage of positive tumor cells with cytoplasmic expression and intensity of immunostaining.Coexistent nuclear localization was evaluated.Clinicopatho-logical parameters and survival data were compared with the expression of Notch receptors 1-4 and DLL4.RESULTS:Notch receptor proteins showed in the cytoplasm with or without nuclear expression in cancer cells,as well as showing weak cytoplasmic expression in non-neoplastic cells.By semiquantitative evaluation,positive immunostaining of Notch receptor 1 was detected in 96 cases (87.3%),Notch receptor 2 in 97 (88.2%),Notch receptor 3 in 97 (88.2%),Notch receptor 4 in 103 (93.6),and DLL4 in 84 (76.4%).In addition,coex- istent nuclear localization was noted [Notch receptor 1;18 cases (18.8%),Notch receptor 2;40 (41.2%),Notch receptor 3;32 (33.0%),Notch receptor 4;99 (96.1%),DLL4;48 (57.1%)].Notch receptor 1 expression was correlated with advanced tumor,node,metastasis (TNM) stage (P=0.043),Notch receptor 3 with advanced T stage (P=0.017),tendency to express in cases with nodal metastasis (P=0.065) and advanced TNM stage (P=0.052).DLL4 expression tended to be related to less histological differentiation (P=0.095).Coexistent nuclear localization of Notch receptor 3 was related to no nodal metastasis (P=0.027) and Notch receptor 4 with less histological differentiation (P=0.036),while DLL4 tended to be related inversely with T stage (P=0.053).Coexistent nuclear localization of DLL4 was related to poor survival (P=0.002).CONCLUSION:Aberrant expression of Notch receptors 1 and 3 play a role during cancer progression,and cytoplasmic nuclear coexistence of DLL4 expression correlates with poor survival in extrahepatic CC and gallbladder carcinoma.展开更多
AIM: To assess the hypercoagulability in PBC and its relationship with homocysteine (HCY) and various components of the haemostatic system. METHODS: We investigated 51 PBC patients (43F/8M; mean age: 63±13....AIM: To assess the hypercoagulability in PBC and its relationship with homocysteine (HCY) and various components of the haemostatic system. METHODS: We investigated 51 PBC patients (43F/8M; mean age: 63±13.9 yr) and 102 healthy subjects (86 women/16 men, 63±13 yr), and evaluated the haemostatic process in whole blood by the Sonoclot analysis and the platelet function by PFA-100 device. We then measured HCY (fasting and after methionine loading), tissue factor (TF), thrombin-antithrombin complexes (TAT), D-dimer (D-D), thrombomodulin (TH), folic acid, vitamin B6 and B12 plasma levels. C677T 5,10-methylenetetrahydrofolate reductase (HTHFR) polymorphism was analyzed. RESULTS: Sonoclot RATE values of patients were significantly (P〈 0.001) higher than those of controls. Sonoclot time to peak values and PFA-100 closure times were comparable in patients and controls. TAT, TF and HCY levels, both in the fasting and post-methionine loading, were significantly (P〈0.001) higher in patients than in controls. Vitamin deficiencies were detected in 45/51 patients (88.2%). The prevalence of the homozygous TT677 MTHFR genotype was significantly higher in patients (31.4%) than in controls (17.5%) (P〈 0.05). Sonodot RATE values correlated significantly with HCY levels and TF.CONCLUSION: In PBC, hyper-HCY is related to hypovitaminosis and genetic predisposing factors. Increased TF and HCY levels and signs of endothelial activation areassociated with hypercoagulability and may have an important role in blood clotting activation.展开更多
To investigate the association of the expression of estrogen receptor ct, estrogen receptor 13 in placenta with intrahepatic cholestasis of pregnancy (ICP) susceptibility. Methods: In 14 cases of mild ICP, 14 cases...To investigate the association of the expression of estrogen receptor ct, estrogen receptor 13 in placenta with intrahepatic cholestasis of pregnancy (ICP) susceptibility. Methods: In 14 cases of mild ICP, 14 cases of severe ICP and 14 cases of normal cases (control group) with corresponding age and gestation weeks, the expressions of ERa and ERD were detected by means of immunohistochemical method S-P. Results: The mean grey numbers of ERa in each group mentioned above were 151.684±3.76, 149.854±3.69, 153.184±3.18, without significant difference (P〉0.05) The mean grey numbers of ERβ in each group mentioned above were 146.51±3.81, 139.434±9.97, 149.87±4.17, with significant difference (P〉0.05); the expression of ERI3 of severe ICP group was significantly higher than that of the mild ICP group and the control group (P〈0.05). The expression of ERβ in every group was higher than that of ERa (P〈0.05). Conclusion: ERβ maybe play an important part in the etiology and development of ICP展开更多
Progressive familial intrahepatic cholestasis (PFIC) type 2 is caused by mutations in ABCB11, which encodes bile salt export pump (BSEP). We report a Thai female infant who presented with progressive cholestatic j...Progressive familial intrahepatic cholestasis (PFIC) type 2 is caused by mutations in ABCB11, which encodes bile salt export pump (BSEP). We report a Thai female infant who presented with progressive cholestatic jaundice since 1 mo of age, with normal serum y-glutamyltransferase. Immunohistochemical staining of the liver did not demonstrate BSEP along the canaliculi, while multidrug resistance protein 3 was expressed adequately. Novel mutations in ABCB11, a four-nucleotide deletion in exon 3, c.90_93delGAAA, and a single-nucleotide insertion in exon 5, c.249_250insT, were identified, with confirmation in her parents. These mutations were predicted to lead to synthesis of truncated forms of BSEP. Immunostaining and mutation analysis thus established the diagnosis of PFIC type展开更多
Hemobilia is a rare manifestation of hemophilia and is usually iatrogenic following liver biopsy. There are only few reports of spontaneous hemobilia in hemophilia patients. Cholangiocarcinoma is a well-established ca...Hemobilia is a rare manifestation of hemophilia and is usually iatrogenic following liver biopsy. There are only few reports of spontaneous hemobilia in hemophilia patients. Cholangiocarcinoma is a well-established cause of hemobilia. We describe a case of a 70-year-old male, with known haemophilia B and a past history of papillotomy, who presented with classical symptoms of hemobilia. The initial diagnostic work-up failed to demonstrate a potential cause of bleeding other than the coagulopathy. Three months later, he was readmitted to our hospital with a second episode of hemobilia. During the second work-up, a cholangiocarcinoma was diagnosed both by imaging studies and by a significant elevation of cancer antigen 19-9. Although hemobilia could be attributed to hemophilia, especially in a patient with previous papillotomy, an underlying malignancy of the biliary tree should be suspected.展开更多
AIM: To explore the mechanism of benign biliary stricture. METHODS: A model of trauma of bile duct was established in 28 dogs. The anastomosed tissues were resected and examined by light and electron microscopes on da...AIM: To explore the mechanism of benign biliary stricture. METHODS: A model of trauma of bile duct was established in 28 dogs. The anastomosed tissues were resected and examined by light and electron microscopes on day 3, in wk 1, 3 and mo 3, 6 after operation. CD68, TGF-β1 and α-SMA were examined by immunohistochemical staining, respectively. RESULTS: The mucosal epithelium of the bile duct was slowly recovered, chronic inflammation lasted for a long time, fibroblasts proliferated actively, extracellular matrix was over-deposited. Myofibroblasts functioned actively and lasted through the whole process. The expression of macrophages in lamina propria under mucosa, TGF-β1 in granulation tissue, fibroblasts and endothelial cells of blood vessels, oc-SMA in myofiroblasts were rather strong from the 1st wk to the 6th mo after operation. CONCLUSION: The type of healing occurring in bile duct belongs to overhealing. Myofibroblasts are the main cause for scar contracture and stricture of bile duct. High expressions of CD68, TGF-β1 and a-SMA are closely related to the active proliferation of fibroblasts, extracellular matrix over-deposition and scar contracture of bile duct.展开更多
AIM:To determine the role of CD133 in cholangiocarcinoma progression. METHODS:CD133 protein expression was evaluated by immunohistochemistry in 34 cholangiocarcinoma specimens.In addition,proliferation,chemoresistance...AIM:To determine the role of CD133 in cholangiocarcinoma progression. METHODS:CD133 protein expression was evaluated by immunohistochemistry in 34 cholangiocarcinoma specimens.In addition,proliferation,chemoresistance and invasive properties of CD133-enriched(CD133 + ) and CD133-depleted(CD133 )RMCCA1 cholangiocarcinoma cells were studied and compared. RESULTS:Strong CD133 expression was observed in 67.6%(23/34)of the cholangiocarcinoma specimens. Strong expression of CD133 was significantly associated with nodal metastasis(P=0.009)and positive surgical margin status(P=0.011).In the in vitro study, both the CD133 + and CD133 cells had similar proliferation abilities and resistance to chemotherapeutic drugs.However,the CD133 + cells had a higher invasive ability compared with CD133 cells. CONCLUSION:CD133+cells play an important role in the invasiveness of cholangiocarcinoma.Targeting of the CD133+cells may be a useful approach to improve treatment against cholangiocarcinoma.展开更多
AIM: To investigate the role of tumor inf iltrating lym-phocytes (TIL) in primary hepatocellular and cholangio-lar carcinomas of the liver.METHODS: Immunohistochemical analysis was per-formed including antibodies to C...AIM: To investigate the role of tumor inf iltrating lym-phocytes (TIL) in primary hepatocellular and cholangio-lar carcinomas of the liver.METHODS: Immunohistochemical analysis was per-formed including antibodies to CD3, CD4, CD8, CD20, CD56 and TIA-1 in formalin-f ixed and paraff in-embed-ded tissue of 35 liver resection specimens of hepatocel-lular or cholangiocellular carcinomas. Semiquantitative evaluation was performed with emphasis on the area of the tumor itself and of the tumor/liver interface.RESULTS: All hepatocellular carcinomas showed in-filtration of lymphocytes predominantly around the tumor in the tumor/liver interface consisting mainly of CD3+ CD4+ T lymphocytes [164.3/10 high power f ields (HPF)] and in the tumor itself of CD8+ cells (54.9/10 HPF). Cholangiocarcinomas contained a heterogeneous amount of TIL, composed mainly of CD3+ T cells with a predominance of CD8+ cells in the tumor tissue (52.6/10 HPF) and of CD4+ cells in the interface region (223.1/10 HPF). CD56+ cells of the innate immune system were scarce. There was no significant difference between hepatocellular or cholangiolar carcinoma. No correlation with the clinicopathological data was seen. CONCLUSION: Liver TIL consists of intratumoral CD8+ T cells and peritumoral CD4+ T cells indepen-dent of histogenetic origin. Different functions of lym-phocytes in these regions seem possible.展开更多
文摘AIM:To examine the expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1(LFA-1)expression on canals of Hering (COH)and bile ductules associated with the autoimmune process of bile duct destruction in primary biliary cirrhosis(PBC).METHODS:Ten wedged liver biopsies of PBC(five cases each of stages 2 and 3)were studied. The liver specimens were processed for transmission electron microscopy. Immunohistochemistry was performed using anti-ICAM-1 and anti-LFA-1 mouse mAbs.In situ hybridization was done to examine the messenger RNA expression of ICAM-1 in formalin-fixed.paraffin-embedded sections using peptide nucleic acid probes and the catalyzed signal amplification (CSA)technique.Immunogold-silver staining for electron microscopy was Derrormed using anti-ICAM and anti-LFA-1 mouse mAbs.The immunogold particles on epithelial cells of bileductules and cholangiocytes of CoH cells were counted and analyzed semi-quantitatively.Western blotting was performed to confirm ICAM-1 protein expression.RESULTS:In liver tissues of PBC patients.immunohi-stochemistry showed aberrant ICAM-1 expression on the plasma membrane of epithelial cells lining bile ductules,and also on mature cholangiocytes but not on hepatocytes in CoH.LFA-1-positive lymphocytes were closely associated with epithelial cells in bile ductules.ICAM-1 expression at protein level was confirmed by Western blot.In situ hybridization demonstrated ICAM-1 mRNA expression in bile ductules and LFA-1 mRNA in lymphocytes infiltrating the bileductules.By immunoelectron microscopy,ICAM-1 was demonstrated on the basal suface of epithelial cells in bile ductules and on the luminal surfaces of cholangiocytes in damaged COH.Cells with intermediate morphology resembling progenitor cells in Coil were not labeled with ICAM-1 and LFA-1.CONCLUSION:De novo expression of ICAM-1 both on mature cholangiocytes in COH and epithelial cells in bile ductules in PBC implies that lymphocyte-induced destruction through adhesion by ICAM-1 and binding of LFA-1-expressing activated lymphocytes takes place not only in bile ductules but also in the COH.
文摘Gallbladder localization of heterotopic pancreas (HP) is uncommon and very rarely gives rise to symptoms. Herein we report a case of HP found in the gallbladder neck presented with signs and symptoms of cholecystitis. The patient was a 40-year old male, suffering from epigastric pain, abdominal fullness and fever. On physical examination, the right upper abdomen was tender with a positive Murphy's sign. Ultrasonographic examination showed a hydropic gallbladder without stones and he underwent a cholecystectomy. Pathological examination revealed an intramural nodule (9 ram) in the neck region which is consisted of acini, ducts and islet cells of an aberrant pancreatic tissue. Although HP is encountered rarely in the gallbladder and is found incidentally during pathological studies, this case emphasizes that HP might cause symptoms and present clinically as cholecystitis. For this reason, in patients presenting with symptomatic gallbladder diseases, including cholecystitis without any other pathology, HP should be taken into consideration before it is diagnosed as "idiopathic':
文摘Cholangiocarcinomas arise from the epithelial cells of the bile ducts and are associated with poor prognosis. Despite new diagnostic approaches, the definite diagnosis of this malignancy continues to be challenging. Cholangiocarcinomas often grow longitudinally along the bile duct rather than in a radial direction. Thus, large tumor masses are frequently absent and imaging techniques, including ultrasound, CT, and MRI have only limited sensitivity. Tissue collection during endoscopic (ERCP) and/or percutaneous transhepatic (PTC) procedures are usually used to confirm a definitive diagnosis of cholangiocarcinoma. However, forceps biopsy and brush cytology provide positive results for malignancy in about only 50% of patients. Percutaneous and peroral cholangioscopy using fiber-optic techniques were therefore developed for direct visualization of the biliary tree, yielding additional information about endoscopic appearance and tumor extension, as well as a guided biopsy acquistion. Finally, endoscopic ultrasonography (EUS) complements endoscopic and percutaneous approaches and may provide a tissue diagnosis of tumors in the biliary region through fine-needle aspiration. In the future, new techniques allowing for early detection, including molecular markers, should be developed to improve the diagnostic sensitivity in this increasing tumor entity.
文摘Bile duct cancers are frequently diagnosed as advanced diseases. Over half of patients with advanced bile duct cancer present with unresectable malignancies and their prognosis has been very poor even after curative resections. Although there has been a need to diagnose bile duct cancer at its eady stage, it has been a difficult goal to achieve due to our lack of knowledge regarding this disease entity. Early bile duct cancer may be defined as a carcinoma whose invasion is confined within the fibromuscular layer of the extrahepatic bile duct or intrahepatic large bile duct without distant metastasis irrespective of lymph node involvement. Approximately 3%-10% of resected bile duct cancers have been reported to be early cancers in the literature. The clinicopathological features of patients with early bile duct cancer differ from those of patients with advanced bile duct cancer, with more frequent asymptomatic presentation, characteristic histopathological findings, and excellent prognosis. This manuscript is organized to emphasize the need for convening an international consensus to develop the concept of early bile duct cancer.
文摘AIM: To evaluate the sensitivity of brush cytology and forceps biopsy in a homogeneous patient group with hilar cholangiocarcinoma.METHODS: Brush cytology and forceps biopsy were routinely performed in patients with suspected malignant biliary strictures. Fifty-eight consecutive patients undergoing endoscopic retrograde cholangio-pancreatography (ERCP) including forceps biopsy and brush cytology in patients with hilar cholangiocarcinoma between 1995-2005.RESULTS: Positive results for malignancy were obtained in 24/58 patients (41.4%) by brush cytology and in 31/58 patients (53.4%) by forceps biopsy. The combination of both techniques brush cytology and forceps biopsy resulted only in a minor increase in diagnostic sensitivity to 60.3% (35/58 patients). In 20/58 patients (34.5%), diagnosis were obtained by both positive cytology and positive histology, in 11/58 (19%) by positive histology (negative cytology) and only 4/58 patients (6.9%) were confirmed by positive cytology (negative histology).CONCLUSION: Brush cytology and forceps biopsy have only limited sensitivity for the diagnosis of malignant hilar tumors. In our eyes, additional diagnostic techniques should be evaluated and should become routine in patients with negative cytological and histological findings.
文摘Intrahepatic cholangiocarcinomas (ICC) are neoplasms that originate from cholangiocytes and can occur at any level of the biliary tree. Surgical resection is the current therapy of choice for this highly aggressive cancer. However, the 5-year survival still is poor, with high recurrence rates. Due to the intrahepatic growth a signifi cant proportion of patients present with advanced disease and are not candidates for curative surgery or transplantation. The existing palliative options are of limited benefit and there is a great necessity for novel therapeutic options. In this article we review the role of the phosphoinositide 3-kinase(PI3K)/ AKT and extracellular regulated kinase (ERK) signaling pathways in ICC and present new data on the prognostic value of these protein kinases. Finally, we discuss future upcoming therapeutic options based on targeting these signaling pathways.
文摘AIM:To investigate the role and clinicopathological significance of aberrant expression of Notch receptors and Delta-like ligand-4 (DLL4) in extrahepatic cholangiocarcinoma and gallbladder carcinoma.METHODS:One hundred and ten patients had surgically resected extrahepatic cholangiocarcinoma (CC) and gallbladder carcinoma specimens examined by immunohistochemistry of available paraffin blocks.Immunohistochemistry was performed using anti-Notch receptors 1-4 and anti-DLL4 antibodies.We scored the immunopositivity of Notch receptors and DLL4 expression by percentage of positive tumor cells with cytoplasmic expression and intensity of immunostaining.Coexistent nuclear localization was evaluated.Clinicopatho-logical parameters and survival data were compared with the expression of Notch receptors 1-4 and DLL4.RESULTS:Notch receptor proteins showed in the cytoplasm with or without nuclear expression in cancer cells,as well as showing weak cytoplasmic expression in non-neoplastic cells.By semiquantitative evaluation,positive immunostaining of Notch receptor 1 was detected in 96 cases (87.3%),Notch receptor 2 in 97 (88.2%),Notch receptor 3 in 97 (88.2%),Notch receptor 4 in 103 (93.6),and DLL4 in 84 (76.4%).In addition,coex- istent nuclear localization was noted [Notch receptor 1;18 cases (18.8%),Notch receptor 2;40 (41.2%),Notch receptor 3;32 (33.0%),Notch receptor 4;99 (96.1%),DLL4;48 (57.1%)].Notch receptor 1 expression was correlated with advanced tumor,node,metastasis (TNM) stage (P=0.043),Notch receptor 3 with advanced T stage (P=0.017),tendency to express in cases with nodal metastasis (P=0.065) and advanced TNM stage (P=0.052).DLL4 expression tended to be related to less histological differentiation (P=0.095).Coexistent nuclear localization of Notch receptor 3 was related to no nodal metastasis (P=0.027) and Notch receptor 4 with less histological differentiation (P=0.036),while DLL4 tended to be related inversely with T stage (P=0.053).Coexistent nuclear localization of DLL4 was related to poor survival (P=0.002).CONCLUSION:Aberrant expression of Notch receptors 1 and 3 play a role during cancer progression,and cytoplasmic nuclear coexistence of DLL4 expression correlates with poor survival in extrahepatic CC and gallbladder carcinoma.
文摘AIM: To assess the hypercoagulability in PBC and its relationship with homocysteine (HCY) and various components of the haemostatic system. METHODS: We investigated 51 PBC patients (43F/8M; mean age: 63±13.9 yr) and 102 healthy subjects (86 women/16 men, 63±13 yr), and evaluated the haemostatic process in whole blood by the Sonoclot analysis and the platelet function by PFA-100 device. We then measured HCY (fasting and after methionine loading), tissue factor (TF), thrombin-antithrombin complexes (TAT), D-dimer (D-D), thrombomodulin (TH), folic acid, vitamin B6 and B12 plasma levels. C677T 5,10-methylenetetrahydrofolate reductase (HTHFR) polymorphism was analyzed. RESULTS: Sonoclot RATE values of patients were significantly (P〈 0.001) higher than those of controls. Sonoclot time to peak values and PFA-100 closure times were comparable in patients and controls. TAT, TF and HCY levels, both in the fasting and post-methionine loading, were significantly (P〈0.001) higher in patients than in controls. Vitamin deficiencies were detected in 45/51 patients (88.2%). The prevalence of the homozygous TT677 MTHFR genotype was significantly higher in patients (31.4%) than in controls (17.5%) (P〈 0.05). Sonodot RATE values correlated significantly with HCY levels and TF.CONCLUSION: In PBC, hyper-HCY is related to hypovitaminosis and genetic predisposing factors. Increased TF and HCY levels and signs of endothelial activation areassociated with hypercoagulability and may have an important role in blood clotting activation.
文摘To investigate the association of the expression of estrogen receptor ct, estrogen receptor 13 in placenta with intrahepatic cholestasis of pregnancy (ICP) susceptibility. Methods: In 14 cases of mild ICP, 14 cases of severe ICP and 14 cases of normal cases (control group) with corresponding age and gestation weeks, the expressions of ERa and ERD were detected by means of immunohistochemical method S-P. Results: The mean grey numbers of ERa in each group mentioned above were 151.684±3.76, 149.854±3.69, 153.184±3.18, without significant difference (P〉0.05) The mean grey numbers of ERβ in each group mentioned above were 146.51±3.81, 139.434±9.97, 149.87±4.17, with significant difference (P〉0.05); the expression of ERI3 of severe ICP group was significantly higher than that of the mild ICP group and the control group (P〈0.05). The expression of ERβ in every group was higher than that of ERa (P〈0.05). Conclusion: ERβ maybe play an important part in the etiology and development of ICP
文摘Progressive familial intrahepatic cholestasis (PFIC) type 2 is caused by mutations in ABCB11, which encodes bile salt export pump (BSEP). We report a Thai female infant who presented with progressive cholestatic jaundice since 1 mo of age, with normal serum y-glutamyltransferase. Immunohistochemical staining of the liver did not demonstrate BSEP along the canaliculi, while multidrug resistance protein 3 was expressed adequately. Novel mutations in ABCB11, a four-nucleotide deletion in exon 3, c.90_93delGAAA, and a single-nucleotide insertion in exon 5, c.249_250insT, were identified, with confirmation in her parents. These mutations were predicted to lead to synthesis of truncated forms of BSEP. Immunostaining and mutation analysis thus established the diagnosis of PFIC type
文摘Hemobilia is a rare manifestation of hemophilia and is usually iatrogenic following liver biopsy. There are only few reports of spontaneous hemobilia in hemophilia patients. Cholangiocarcinoma is a well-established cause of hemobilia. We describe a case of a 70-year-old male, with known haemophilia B and a past history of papillotomy, who presented with classical symptoms of hemobilia. The initial diagnostic work-up failed to demonstrate a potential cause of bleeding other than the coagulopathy. Three months later, he was readmitted to our hospital with a second episode of hemobilia. During the second work-up, a cholangiocarcinoma was diagnosed both by imaging studies and by a significant elevation of cancer antigen 19-9. Although hemobilia could be attributed to hemophilia, especially in a patient with previous papillotomy, an underlying malignancy of the biliary tree should be suspected.
文摘AIM: To explore the mechanism of benign biliary stricture. METHODS: A model of trauma of bile duct was established in 28 dogs. The anastomosed tissues were resected and examined by light and electron microscopes on day 3, in wk 1, 3 and mo 3, 6 after operation. CD68, TGF-β1 and α-SMA were examined by immunohistochemical staining, respectively. RESULTS: The mucosal epithelium of the bile duct was slowly recovered, chronic inflammation lasted for a long time, fibroblasts proliferated actively, extracellular matrix was over-deposited. Myofibroblasts functioned actively and lasted through the whole process. The expression of macrophages in lamina propria under mucosa, TGF-β1 in granulation tissue, fibroblasts and endothelial cells of blood vessels, oc-SMA in myofiroblasts were rather strong from the 1st wk to the 6th mo after operation. CONCLUSION: The type of healing occurring in bile duct belongs to overhealing. Myofibroblasts are the main cause for scar contracture and stricture of bile duct. High expressions of CD68, TGF-β1 and a-SMA are closely related to the active proliferation of fibroblasts, extracellular matrix over-deposition and scar contracture of bile duct.
基金Supported by Rajavithi Hospital Project Grant and Thailand Research Fund(RSA52)
文摘AIM:To determine the role of CD133 in cholangiocarcinoma progression. METHODS:CD133 protein expression was evaluated by immunohistochemistry in 34 cholangiocarcinoma specimens.In addition,proliferation,chemoresistance and invasive properties of CD133-enriched(CD133 + ) and CD133-depleted(CD133 )RMCCA1 cholangiocarcinoma cells were studied and compared. RESULTS:Strong CD133 expression was observed in 67.6%(23/34)of the cholangiocarcinoma specimens. Strong expression of CD133 was significantly associated with nodal metastasis(P=0.009)and positive surgical margin status(P=0.011).In the in vitro study, both the CD133 + and CD133 cells had similar proliferation abilities and resistance to chemotherapeutic drugs.However,the CD133 + cells had a higher invasive ability compared with CD133 cells. CONCLUSION:CD133+cells play an important role in the invasiveness of cholangiocarcinoma.Targeting of the CD133+cells may be a useful approach to improve treatment against cholangiocarcinoma.
基金Supported by Centre of Molecular Medicine Cologne (CMMC), Kln, Germany
文摘AIM: To investigate the role of tumor inf iltrating lym-phocytes (TIL) in primary hepatocellular and cholangio-lar carcinomas of the liver.METHODS: Immunohistochemical analysis was per-formed including antibodies to CD3, CD4, CD8, CD20, CD56 and TIA-1 in formalin-f ixed and paraff in-embed-ded tissue of 35 liver resection specimens of hepatocel-lular or cholangiocellular carcinomas. Semiquantitative evaluation was performed with emphasis on the area of the tumor itself and of the tumor/liver interface.RESULTS: All hepatocellular carcinomas showed in-filtration of lymphocytes predominantly around the tumor in the tumor/liver interface consisting mainly of CD3+ CD4+ T lymphocytes [164.3/10 high power f ields (HPF)] and in the tumor itself of CD8+ cells (54.9/10 HPF). Cholangiocarcinomas contained a heterogeneous amount of TIL, composed mainly of CD3+ T cells with a predominance of CD8+ cells in the tumor tissue (52.6/10 HPF) and of CD4+ cells in the interface region (223.1/10 HPF). CD56+ cells of the innate immune system were scarce. There was no significant difference between hepatocellular or cholangiolar carcinoma. No correlation with the clinicopathological data was seen. CONCLUSION: Liver TIL consists of intratumoral CD8+ T cells and peritumoral CD4+ T cells indepen-dent of histogenetic origin. Different functions of lym-phocytes in these regions seem possible.