Recent histological and molecular characterization of cholangiocarcinoma(CCA) highlights the heterogeneity of this cancer that may emerge at different sites of the biliary tree and with different macroscopic or morpho...Recent histological and molecular characterization of cholangiocarcinoma(CCA) highlights the heterogeneity of this cancer that may emerge at different sites of the biliary tree and with different macroscopic or morphological features.Furthermore,different stem cell niches have been recently described in the liver and biliarytree,suggesting this as the basis of the heterogeneity of intrahepatic(IH)-and extrahepatic(EH)-CCAs,which are two largely different tumors from both biological and epidemiological points of view.The complexity of the organization of the liver stem cell compartments could underlie the CCA clinical-pathological heterogeneity and the criticisms in classifying primitive liver tumors.These recent advances highlight a possible new classification of CCAs based on cells of origin and this responds to the need of generating homogenous diagnostic,prognostic and,hopefully,therapeutic categories of IH-and EH-CCAs.展开更多
the bile duct system and pancreas show many similarities due to their anatomical proximity and common embryological origin.Consequently,preneoplastic and neoplastic lesions of the bile duct and pancreas share analogie...the bile duct system and pancreas show many similarities due to their anatomical proximity and common embryological origin.Consequently,preneoplastic and neoplastic lesions of the bile duct and pancreas share analogies in terms of molecular,histological and pathophysiological features.Intraepithelial neoplasms are reported in biliary tract,as biliary intraepithelial neoplasm(BilIN),and in pancreas,as pancreatic intraepithelial neoplasm(PanIN).Both can evolve to invasive carcinomas,respectively cholangiocarcinoma(CCA)and pancreatic ductal adenocarcinoma(PDAC).Intraductal papillary neoplasms arise in biliary tract and pancreas.Intraductal papillary neoplasm of the biliary tract(IPNB)share common histologic and phenotypic features such as pancreatobiliary,gastric,intestinal and oncocytic types,and biological behavior with the pancreatic counterpart,the intraductal papillary mucinous neoplasm of the pancreas(IPMN).All these neoplastic lesions exhibit similar immunohistochemical phenotypes,suggesting a common carcinogenic process.Indeed,CCA and PDAC display similar clinic-pathological features as growth pattern,poor response to conventional chemotherapy and radiotherapy and,as a consequence,an unfavorable prognosis.The objective of this review is to discuss similarities and differences between the neoplastic lesions of the pancreas and biliary tract with potential implications on a common origin from similar stem/progenitor cells.展开更多
Over the last two decades, the rise in the prevalence rates of overweight and obesity explains the emergence of nonalcoholic fatty liver disease(NAFLD) as the leading cause of chronic liver disease worldwide. As descr...Over the last two decades, the rise in the prevalence rates of overweight and obesity explains the emergence of nonalcoholic fatty liver disease(NAFLD) as the leading cause of chronic liver disease worldwide. As described in adults, children and adolescents with fatty liver display insulin resistance, glucose intolerance, and dyslipidemia. Thus NAFLD has emerged as the hepatic component of the metabolic syndrome(MetS) and a strong cardiovascular risk factor even at a very early age. Several studies, including pediatric populations, have reported independent associations between NAFLD and markers of subclinical atherosclerosis including impaired flow-mediated vasodilation, increased carotid artery intima-media thickness, and arterial stiffness, after adjusting for cardiovascular risk factors and MetS. Also, it has been shown that NAFLD is associated with cardiac alterations, including abnormal left ventricular structure and impaired diastolic function. The duration of these subclinical abnormalities may be important, because treatment to reverse the process is most likely to be effective earlier in the disease. In the present review, we examine the current evidence on the association between NAFLD and atherosclerosis as well as between NAFLD and cardiac dysfunction in the pediatric population, and discuss briefly the possible biological mechanisms linking NAFLD and cardiovascular changes. We also address the approach to treatment for this increasingly prevalent disease, which is likely to have an important future global impact on the burden of ill health, to prevent not only end-stage liver disease but also cardiovascular disease.展开更多
Over the last years,cholangiocytes,the cells that line the biliary tree,have been considered an important object of study for their biological properties which involves bile formation,proliferation,injury repair,fibro...Over the last years,cholangiocytes,the cells that line the biliary tree,have been considered an important object of study for their biological properties which involves bile formation,proliferation,injury repair,fibrosis and angiogenesis.Cholangiocyte proliferation occurs in all pathologic conditions of liver injury where it is associated with inflammation and regeneration.During these processes,biliary cells start to secrete different cytokines,growth factors,neuropeptides and hormones which represent potential mechanisms for cross talk with other liver cells.Several studies suggest that hormones,and in particular,sex hormones,play a fundamental role in the modulation of the growth of this compartment in the injured liver which functionally conditions the progression of liver disease.Understanding the mechanisms of action and the intracellular pathways of these compounds on cholangiocyte pathophysiology will provide new potential strategies for the management of chronic liver diseases.The purpose of this review is to summarize the recent findings on the role of sex hormones in cholangiocyte proliferation and biology.展开更多
Histamine has long been known to be involved in inflammatory events.The discovery of antihistamines dates back to the first half of the 20th century when a Swiss-Italian pharmacologist,Daniel Bovet began his work.In 1...Histamine has long been known to be involved in inflammatory events.The discovery of antihistamines dates back to the first half of the 20th century when a Swiss-Italian pharmacologist,Daniel Bovet began his work.In 1957 he was awarded a Nobel Prize for his production of antihistamines for allergy relief.Since that time,histamine has been found to play a role in other events besides allergic reaction.Possiblyun believable to Bovet and his peers,histamine has now been marked as playing a role in liver pathologies including hepatobiliary diseases.展开更多
Anatomy of the thyroid has been extensively studied but the presence of pyramidal lobe varies in percentages from 15% to 75% of cases according to different authors. We therefore investigated systematically this pecul...Anatomy of the thyroid has been extensively studied but the presence of pyramidal lobe varies in percentages from 15% to 75% of cases according to different authors. We therefore investigated systematically this peculiar anatomical aspect. From January 2001 to December 2011, 1002 patients underwent total thyroidectomy in our Division of General Surgery. We analyzed the data collected on the latest 200 thyroidectomies: for all patients pyramidal lobe was measured at removal of the specimen then dimension of the pyramidal lobe after fixation was checked. We found the pyramidal lobe in all cases. In most cases, it was approximately 2 cm (range 1 - 8 cm on fresh specimen). At histology it was described in 72% of cases, after fixation size decreased by a third approximatively. This is the first systematic intraoperative study to verify the prevalence of the thyroid pyramidal lobe. In our experience, the pyramidal lobe is always present and the thyroglossal duct is identifiable.展开更多
Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies that could develop at any level from the biliary tree. CCA is currently classified into intrahepatic (iCCA), perihilar and distal on the basis of its a...Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies that could develop at any level from the biliary tree. CCA is currently classified into intrahepatic (iCCA), perihilar and distal on the basis of its anatomical location. Of note, these three CCA subtypes have common features but also important inter-tumor and intra-tumor differences that can affect the pathogenesis and outcome. A unique feature of iCCA is that it recognizes as origin tissues, the hepatic parenchyma or large intrahepatic and extrahepatic bile ducts, which are furnished by two distinct stem cell niches, the canals of Hering and the peribiliary glands, respectively. The complexity of iCCA pathogenesis highlights the need of a multidisciplinary, translational and systemic approach to this malignancy. This review will focus on the advances of iCCA epidemiology, histo-morphology, risk factors, molecular pathogenesis, revealing the existence of multiple subsets of iCCA.展开更多
基金Supported by Research Project Grant from the University "Sapienza" of RomeFIRB grant No. RBAP10Z7FS_001+3 种基金FIRB grant No. RBAP10Z7FS_004PRIN grant No. 2009X84L84_001 (to Gaudio E)PRIN grant No. 2009X84L84_002 (to Alvaro D)Consorzio Interuniversitario Trapianti d'Organo,Rome,Italy
文摘Recent histological and molecular characterization of cholangiocarcinoma(CCA) highlights the heterogeneity of this cancer that may emerge at different sites of the biliary tree and with different macroscopic or morphological features.Furthermore,different stem cell niches have been recently described in the liver and biliarytree,suggesting this as the basis of the heterogeneity of intrahepatic(IH)-and extrahepatic(EH)-CCAs,which are two largely different tumors from both biological and epidemiological points of view.The complexity of the organization of the liver stem cell compartments could underlie the CCA clinical-pathological heterogeneity and the criticisms in classifying primitive liver tumors.These recent advances highlight a possible new classification of CCAs based on cells of origin and this responds to the need of generating homogenous diagnostic,prognostic and,hopefully,therapeutic categories of IH-and EH-CCAs.
基金MIUR grants PRIN, No.2003060498_002 and No. 2005067975_002 to Dr. Alvaro and by a grant award from Scott & White Hospital and The Texas A&M University System Health Science Center, a VA Merit Award, a VA Research Scholar Award and the NIH grants DK58411 and DK062975 to Dr. Alpini
基金MIUR grants PRIN 2005 (prot. 2005067975_001) to E. Gaudio and Biomedicina, Cluster C04, Progetto n. 5 to E.Gaudio-P.Onori MIUR grants PRIN 2005 (prot.No: 2005067975_002) to D. Alvaro and a VA Research Scholar Award, a VA Merit Award and the NIH grants DK58411 and DK062975 to Gianfranco Alpini
基金Associazione Italiana Ricerca sul Cancro,Italy,No.AIRC:IG 17177 to Capurso G
文摘the bile duct system and pancreas show many similarities due to their anatomical proximity and common embryological origin.Consequently,preneoplastic and neoplastic lesions of the bile duct and pancreas share analogies in terms of molecular,histological and pathophysiological features.Intraepithelial neoplasms are reported in biliary tract,as biliary intraepithelial neoplasm(BilIN),and in pancreas,as pancreatic intraepithelial neoplasm(PanIN).Both can evolve to invasive carcinomas,respectively cholangiocarcinoma(CCA)and pancreatic ductal adenocarcinoma(PDAC).Intraductal papillary neoplasms arise in biliary tract and pancreas.Intraductal papillary neoplasm of the biliary tract(IPNB)share common histologic and phenotypic features such as pancreatobiliary,gastric,intestinal and oncocytic types,and biological behavior with the pancreatic counterpart,the intraductal papillary mucinous neoplasm of the pancreas(IPMN).All these neoplastic lesions exhibit similar immunohistochemical phenotypes,suggesting a common carcinogenic process.Indeed,CCA and PDAC display similar clinic-pathological features as growth pattern,poor response to conventional chemotherapy and radiotherapy and,as a consequence,an unfavorable prognosis.The objective of this review is to discuss similarities and differences between the neoplastic lesions of the pancreas and biliary tract with potential implications on a common origin from similar stem/progenitor cells.
文摘Over the last two decades, the rise in the prevalence rates of overweight and obesity explains the emergence of nonalcoholic fatty liver disease(NAFLD) as the leading cause of chronic liver disease worldwide. As described in adults, children and adolescents with fatty liver display insulin resistance, glucose intolerance, and dyslipidemia. Thus NAFLD has emerged as the hepatic component of the metabolic syndrome(MetS) and a strong cardiovascular risk factor even at a very early age. Several studies, including pediatric populations, have reported independent associations between NAFLD and markers of subclinical atherosclerosis including impaired flow-mediated vasodilation, increased carotid artery intima-media thickness, and arterial stiffness, after adjusting for cardiovascular risk factors and MetS. Also, it has been shown that NAFLD is associated with cardiac alterations, including abnormal left ventricular structure and impaired diastolic function. The duration of these subclinical abnormalities may be important, because treatment to reverse the process is most likely to be effective earlier in the disease. In the present review, we examine the current evidence on the association between NAFLD and atherosclerosis as well as between NAFLD and cardiac dysfunction in the pediatric population, and discuss briefly the possible biological mechanisms linking NAFLD and cardiovascular changes. We also address the approach to treatment for this increasingly prevalent disease, which is likely to have an important future global impact on the burden of ill health, to prevent not only end-stage liver disease but also cardiovascular disease.
基金Supported partly by the University Federate Athenaeum Funds from University of Rome "La Sapienza" and PRIN 2007 to Gaudio EUniversity Funds to Onori P,the Dr.Nicholas C Hightower Centennial Chair of Gastroenterology from Scott and White+3 种基金the VA Research Scholar Awarda VA Merit Awardand the NIH Grants DK58411,and DK76898 to Dr.Alpinia NIH RO1 Grant Award to Dr.Glaser(DK081442)a NIH K01Grant Award(DK078532)to Dr.DeMorrow
文摘Over the last years,cholangiocytes,the cells that line the biliary tree,have been considered an important object of study for their biological properties which involves bile formation,proliferation,injury repair,fibrosis and angiogenesis.Cholangiocyte proliferation occurs in all pathologic conditions of liver injury where it is associated with inflammation and regeneration.During these processes,biliary cells start to secrete different cytokines,growth factors,neuropeptides and hormones which represent potential mechanisms for cross talk with other liver cells.Several studies suggest that hormones,and in particular,sex hormones,play a fundamental role in the modulation of the growth of this compartment in the injured liver which functionally conditions the progression of liver disease.Understanding the mechanisms of action and the intracellular pathways of these compounds on cholangiocyte pathophysiology will provide new potential strategies for the management of chronic liver diseases.The purpose of this review is to summarize the recent findings on the role of sex hormones in cholangiocyte proliferation and biology.
基金Supported partly by Dr.Nicholas C Hightower Centennial Chair of Gastroenterology from Scott and White,the VA Research Scholar Award,a VA Merit Award,the NIH Grants DK58411,and DK76898 to Dr.AlpiniUniversity funds to Dr.OnoriPRIN 2007 and Federate Athenaeum Funds from University of Rome "La Sapienza" to Professor Gaudio
文摘Histamine has long been known to be involved in inflammatory events.The discovery of antihistamines dates back to the first half of the 20th century when a Swiss-Italian pharmacologist,Daniel Bovet began his work.In 1957 he was awarded a Nobel Prize for his production of antihistamines for allergy relief.Since that time,histamine has been found to play a role in other events besides allergic reaction.Possiblyun believable to Bovet and his peers,histamine has now been marked as playing a role in liver pathologies including hepatobiliary diseases.
文摘Anatomy of the thyroid has been extensively studied but the presence of pyramidal lobe varies in percentages from 15% to 75% of cases according to different authors. We therefore investigated systematically this peculiar anatomical aspect. From January 2001 to December 2011, 1002 patients underwent total thyroidectomy in our Division of General Surgery. We analyzed the data collected on the latest 200 thyroidectomies: for all patients pyramidal lobe was measured at removal of the specimen then dimension of the pyramidal lobe after fixation was checked. We found the pyramidal lobe in all cases. In most cases, it was approximately 2 cm (range 1 - 8 cm on fresh specimen). At histology it was described in 72% of cases, after fixation size decreased by a third approximatively. This is the first systematic intraoperative study to verify the prevalence of the thyroid pyramidal lobe. In our experience, the pyramidal lobe is always present and the thyroglossal duct is identifiable.
文摘Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies that could develop at any level from the biliary tree. CCA is currently classified into intrahepatic (iCCA), perihilar and distal on the basis of its anatomical location. Of note, these three CCA subtypes have common features but also important inter-tumor and intra-tumor differences that can affect the pathogenesis and outcome. A unique feature of iCCA is that it recognizes as origin tissues, the hepatic parenchyma or large intrahepatic and extrahepatic bile ducts, which are furnished by two distinct stem cell niches, the canals of Hering and the peribiliary glands, respectively. The complexity of iCCA pathogenesis highlights the need of a multidisciplinary, translational and systemic approach to this malignancy. This review will focus on the advances of iCCA epidemiology, histo-morphology, risk factors, molecular pathogenesis, revealing the existence of multiple subsets of iCCA.
