JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Clinicopathological characteristics of serum amyloid A -positive hepatocellular neoplasms/nodules arising in alcoholic cirrhosis.
Histopathology
PUBLISHED: 10-17-2014
Show Abstract
Hide Abstract
We characterized serum amyloid A (SAA)-positive hepatocellular neoplasm/nodules arising in alcoholic cirrhosis, which is detected as a hypervascular hepatocellular nodules resembling hepatocellular carcinoma on imaging.
Related JoVE Video
Cellular senescence in biliary pathology. Special emphasis on expression of a polycomb group protein EZH2 and a senescent marker p16INK4a in bile ductular tumors and lesions.
Histol. Histopathol.
PUBLISHED: 10-08-2014
Show Abstract
Hide Abstract
A subgroup of intrahepatic cholangiocarcinoma and combined hepatocellular- cholangiocarcinoma contain a component of cholangiolocellular carcinoma, which is composed of small bile ductular cells. Ductular reaction, a reactive lesion at the portal tract interface comprising increased bile ductules, is frequently seen in chronic advanced liver diseases. Bile duct adenoma, a benign tumor/tumorous lesion is also composed of bile ductular cells. Differential diagnosis among these bile ductular tumors/lesions is sometimes difficult. Given overexpression of a polycomb group protein EZH2 in intrahepatic cholangiocarcinoma and high expression of senescence-associated p16INK4a in ductular reactions, we plan to apply immunostaining for EZH2 and p16INK4a for differential diagnosis of these bile ductular tumors/lesions. The expression of EZH2 was seen in all cases of cholangiolocellular carcinomas, while it was not observed in bile duct adenomas or ductular reactions. In contrast, the expression of p16INK4a was seen in most bile duct adenomas and all ductular reactions, whereas it was barely seen in cholangiolocellular carcinomas. A borderline between cholangiolocellular carcinoma and the surrounding ductular reaction was clearly highlighted by the reverse expression pattern of EZH2 and p16INK4a. In conclusion, immunostaining for EZH2 and p16INK4a may be useful for differential diagnosis for bile ductular tumors/lesions.
Related JoVE Video
Cholangiocarcinoma in a middle-aged patient working at a printing plant.
Osaka City Med J
PUBLISHED: 10-03-2014
Show Abstract
Hide Abstract
A 39-year-old male with elevated serum transferases consulted our hospital in September 2010. Since 1999, he had worked at a printing company using organic solvents. Cholangiography revealed stenosis of the left hepatic duct with peripheral dilation, stricture of the right hepatic duct, and irregularity of the extrahepatic bile duct. As a preoperative diagnosis of sclerosing cholangitis and cholangiocarcinoma was made, extended left hepatectomy with resection of the extrahepatic bile duct and anastomosis of the anterior and posterior branches of the bile duct and the jejunum (Roux-en Y reconstruction) were performed. A histological examination showed papillary carcinoma of the medial hepatic bile duct with intraductal growth, and biliary intraepithelial neoplasia-2/3 lesions from the medial hepatic bile duct to the right hepatic and the common bile ducts. Chronic cholangitis was shown around the tumors. Postoperatively, the patient was treated with adjuvant chemo-radiation, and he is doing well 30 months after the operation, without recurrence. Unknown causes, including exposure to organic solvents, might have induced chronic bile duct injury and contributed to the development of cholangiocarcinoma.
Related JoVE Video
Hepatobiliary/Pancreas Pathology: SY11-2 RECENT PROGRESS IN BILIARY TRACT PATHOLOGY AND CHOLANGIOCARCINOMA.
Pathology
PUBLISHED: 09-05-2014
Show Abstract
Hide Abstract
The biliary tract and pancreas develop from the foregut at almost same time, and the morphology of the biliary tract and pancreatic ducts share several features. In addition, there are peribiliary glands around the biliary tract, which occasionally contain pancreatic acini and enzymes. Some pancreatic and biliary tract diseases share similar pathological features. For example, IgG4-related disease affects the pancreas (autoimmune pancreatitis) and the biliary tract (IgG4-related sclerosing cholangitis), and peribiliary cysts and pancreatic damages in chronic alcoholics show similar histologies. Interestingly, perihilar cholangiocarcinoma and pancreatic duct adenocarcinoma, and their precursor lesions such as biliary intraepithelial neoplasm (BilIN) and pancreatic intraepithelial neoplasm (PanIN), show similar histologies and phenotypes, suggesting that these carcinoma and precursor lesions share similar developmental processes. Based on the similarities between the pancreas and biliary tract, we would like to propose that several biliary diseases have their counterparts in the pancreas (pancreatic diseases with pancreatic counterparts).
Related JoVE Video
Hepatobiliary/Pancreas Pathology: SY11-2 CLINICOPATHOLOGICAL FEATURES AND PROGNOSIS OF MUCIN-PRODUCING BILE DUCT TUMOR AND MUCINOUS CYSTIC TUMOR OF THE LIVER: A MULTI-INSTITUTIONAL STUDY BY JAPAN BILIARY ASSOCIATION.
Pathology
PUBLISHED: 09-05-2014
Show Abstract
Hide Abstract
The aim of this study was to determine the clinicopathological features and surgical outcomes of mucinous cystic neoplasm of the liver (MCN) and mucinproducing intraductal papillary neoplasm of the intrahepatic bile duct (M-IPNB).
Related JoVE Video
Hepatobiliary/Pancreas Pathology: SY11-2 CHOLANGIOCARCINOMA WITH RESPECT TO IGG4 REACTION.
Pathology
PUBLISHED: 09-05-2014
Show Abstract
Hide Abstract
IgG4-related diseases including IgG4-related sclerosing cholangitis are characterized by the increased level of serum IgG4 and the marked infiltration of IgG4+ plasma cells in affected organs. However, several cases of extrahepatic biliary cancers often accompany the significant infiltration of IgG4+ cells. IL-10 is an important regulatory cytokine associated with the differentiation of IgG4-producing plasma cells and the IgG4 reaction in biliary cancers shows a negative correlation with CD8+ cytotoxic T cells, suggesting that the IgG4 reaction in biliary cancers is associated with the evasion of the tumor-related immune surveillance. Moreover, cancer cells could play a role of regulatory functions by themselves directly and indirectly via a production of IL-10. To clarify the association with IgG4 reaction in the carcinogenesis of cholangiocarcinoma, we examined the IgG4 reaction in its precursor lesion biliary intraepithelial neoplasia (BilIN). Consequently, although a few or none IgG4+ cells were found in BilIN1 and BilIN2 lesions, several or many positive cells were scattered around the large bile ducts showing BilIN3, irrespective of the degree of periductal inflammation. These findings suggest that IgG4 reaction reflects the regulatory cytokine milieu associated with the extrahepatic biliary cancers and also its carcinogenesis, especially the development from BilIN2 to BilIN3.
Related JoVE Video
[Multiple gastrointestinal stromal tumors during nilotinib treatment for chronic myelogenous leukemia in a patient with neurofibromatosis type 1].
Nihon Shokakibyo Gakkai Zasshi
PUBLISHED: 08-08-2014
Show Abstract
Hide Abstract
A 60-year-old woman with neurofibromatosis type 1 presented to our hospital with melena. She reported a 1-year history of treatment with nilotinib hydrochloride hydrate for chronic myelogenous leukemia. Contrast-enhanced abdominal computed tomography revealed multiple intestinal tumors that were subsequently diagnosed as gastrointestinal stromal tumors (GIST) using single-balloon enteroscopy. Although the tumors showed no significant change over 1 year, partial jejunal resection was performed to confirm the diagnosis. Immunohistochemically, the tumors were GIST.
Related JoVE Video
Characteristics of printing company workers newly diagnosed with occupational cholangiocarcinoma.
J Hepatobiliary Pancreat Sci
PUBLISHED: 08-03-2014
Show Abstract
Hide Abstract
Cholangiocarcinoma has been reported in workers exposed to chlorinated organic solvents and has consequently been classified as an occupational disease (occupational cholangiocarcinoma) by the Japanese Ministry of Health, Labour and Welfare. This study aimed to identify the characteristics of nine workers newly diagnosed with occupational cholangiocarcinoma.
Related JoVE Video
Cholangiocarcinoma with respect to IgG4 Reaction.
Int J Hepatol
PUBLISHED: 07-15-2014
Show Abstract
Hide Abstract
IgG4 reactions marked by infiltration of IgG4-positive plasma cells in affected organs occur in cancer patients and in patients with IgG4-related diseases. Extrahepatic cholangiocarcinomas including gall bladder cancer are often accompanied by significant IgG4 reactions; these reactions show a negative correlation with CD8-positive cytotoxic T cells, suggesting that the evasion of immune surveillance is associated with cytotoxic T cells. The regulatory cytokine IL-10 may induce IgG4-positive plasma cell differentiation or promote B cell switching to IgG4 in the presence of IL-4. Cholangiocarcinoma cells may function as nonprofessional antigen presenting cells that indirectly induce IgG4 reactions via the IL-10-producing cells and/or these may act as Foxp3-positive and IL-10-producing cells that directly induce IgG4 reactions. Moreover, IgG4-related disease is a high-risk factor for cancer development; IgG4-related sclerosing cholangitis (IgG4-SC) cases associated with cholangiocarcinoma or its precursor lesion biliary intraepithelial neoplasia (BilIN) have been reported. IgG4-positive cell infiltration is an important finding of IgG4-SC but is not a histological hallmark of IgG4-SC. For the diagnosis of IgG4-SC, its differentiation from cholangiocarcinoma remains important.
Related JoVE Video
Changes in Laboratory Test Results and Diagnostic Imaging Presentation before the Detection of Occupational Cholangiocarcinoma.
J Occup Health
PUBLISHED: 06-21-2014
Show Abstract
Hide Abstract
A cholangiocarcinoma outbreak among workers of an offset color proof-printing department in a printing company was recently reported. It is important to understand the clinical course leading to occupational cholangiocarcinoma development for investigation of the carcinogenesis process and for surveillance and early detection. We evaluated the changes in laboratory test results and diagnostic imaging presentation before the detection of cholangiocarcinoma.
Related JoVE Video
Overlap of IgG4-related sclerosing cholangitis and primary biliary cirrhosis.
Intern. Med.
PUBLISHED: 06-15-2014
Show Abstract
Hide Abstract
We herein present a case of an overlap of immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) and primary biliary cirrhosis (PBC). A 61-year-old man was diagnosed with PBC due to abnormal liver biochemical tests and positivity for serum anti-M2 antibody. However, his response to bezafibrate and ursodeoxycholic acid was insufficient. Five years later, his serum IgG4 level was found to increase. His liver biopsy specimens showed features of nonsuppurative destructive cholangitis in some portal tracts and periductal fibrosis with dense infiltration of IgG4-positive cells in other portal tracts. This case demonstrates that the serum IgG4 level may be worth measuring in patients with PBC refractory to conventional treatment.
Related JoVE Video
A condition closely mimicking IgG4-related disease despite the absence of serum IgG4 elevation and IgG4-positive plasma cell infiltration.
Mod Rheumatol
PUBLISHED: 06-03-2014
Show Abstract
Hide Abstract
We describe a 74-year-old Japanese man with systemic fibroinflammatory conditions closely resembling those of immunoglobulin G4-related disease (IgG4-RD). Radiology and histology showed characteristics of IgG4-related tubulointerstitial nephritis, despite normal serum IgG4 value and scanty IgG4-positive plasma cell infiltration in each organ. This case suggests that a condition closely mimicking IgG4-RD may develop without IgG4-positive plasma cells and those exceptional cases should also be taken into account in the differential diagnosis of IgG4-RD.
Related JoVE Video
Biochemical responses to bezafibrate improve long-term outcome in asymptomatic patients with primary biliary cirrhosis refractory to UDCA.
J. Gastroenterol.
PUBLISHED: 05-20-2014
Show Abstract
Hide Abstract
Bezafibrate is reported to have biochemical efficacy for patients with primary biliary cirrhosis (PBC) refractory to ursodeoxycholic acid (UDCA), yet the long-term effect is still unknown. In Japan, nationwide surveys of PBC have been performed since 1980. In the current study, we retrospectively examined whether response to bezafibrate treatment is associated with the long-term outcomes using this large-scale database.
Related JoVE Video
Hepatolithiasis: analysis of Japanese nationwide surveys over a period of 40 years.
J Hepatobiliary Pancreat Sci
PUBLISHED: 05-14-2014
Show Abstract
Hide Abstract
The aims of the present study are to clarify the changes in clinicopathologic features, diagnosis and treatment for hepatolithiasis, and propose an appropriate management strategy in Japan. The research group conducted nationwide surveys seven times in the past over a period of 40 years. Furthermore, a cohort was followed up in 2010. We analyzed the clinical features, diagnosis tools, treatment procedures, outcomes, and predictive factors for cholangiocarcinoma. Surgery was the primary method for hepatolithiasis up to 1998, and the frequency of its use has decreased since then. In 2011, 66.7% of hepatolithiasis patients were treated using nonsurgical approaches. In addition, endoscopic retrograde cholangiography (ERC) with stone extraction was the most frequently performed procedure (22.7%). However, the incidences of residual stone and recurrent stone after ERC with stone extraction were higher than those after percutaneous transhepatic cholangioscopic lithotomy and surgery. Bile duct stricture and dilatation during follow up were significant risk factors for stone recurrences. In the cohort study, stone removal only and age >65 years were significant factors for the development of cholangiocarcinoma. In patients without a history of cholangioenterostomy, left-lobe-type stones were a risk factor, and hepatectomy reduced the risk of the development of cholangiocarcinoma significantly. Nonsurgical treatment may be performed as the first-line treatment for hepatolithiasis. Surgery should be performed on patients who were treated incompletely after nonsurgical treatment. However, hepatectomy may be recommended for patients with left-lobe-type stones and without a history of cholangioenterostomy.
Related JoVE Video
[Three cases of hepatocellular carcinoma with nodules showing different signal intensities in the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI].
Nihon Shokakibyo Gakkai Zasshi
PUBLISHED: 05-09-2014
Show Abstract
Hide Abstract
We report three cases of resected hepatocellular carcinomas with nodules showing different signal intensities in the hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced MRI (EOB-MRI). One case involved a nodule-in-nodule type hepatocellular carcinoma that showed high signal intensity for the outer tumor and low intensity for the inner tumor in the hepatobiliary phase of EOB-MRI. The inner tumor was more dedifferentiated than the outer. The other two cases involved similar nodules, which showed different signal intensities in the hepatobiliary phase of EOB-MRI. In all three cases, the expression of OATP8 showed good correlation with high signal intensity in the hepatobiliary phase of EOB-MRI, whereas MRP2, MRP3, or both were also highly expressed. However, in the two nodules showing low intensities, the expression of one excreting transporter was independently high even though that of OATP8 was not high. The expression of excreting transporters is usually characterized by passive correspondence to OATP8 expression levels; nevertheless, it sometimes shows expression independent of OATP8.
Related JoVE Video
Clinicopathological study of primary biliary cirrhosis with interface hepatitis compared to autoimmune hepatitis.
World J. Gastroenterol.
PUBLISHED: 04-08-2014
Show Abstract
Hide Abstract
To investigate histological and immunohistochemical differences in hepatitis between autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) with AIH features.
Related JoVE Video
Clinicopathological significance of 'subtypes with stem-cell feature' in combined hepatocellular-cholangiocarcinoma.
Liver Int.
PUBLISHED: 04-01-2014
Show Abstract
Hide Abstract
Combined hepatocellular-cholangiocarcinoma (cHC-CC), a malignant liver tumour with poor prognosis, is composed of hepatocellular carcinoma (HCC), cholangiocarcinoma (CC) and diverse components with intermediate features between HCC and CC, which correspond to hepatic progenitor cells. According to the WHO classification 2010, we surveyed the prevalence and clinicopathological significance of each subtype with stem-cell features [SC subtype; typical subtype (TS), intermediate cell subtype (INT) and cholangiolocellular type (CLC)] in cHC-CC and HCC.
Related JoVE Video
Significance of oestrogen-related receptor ? on biliary epithelial cells in the pathogenesis of primary biliary cirrhosis.
J. Clin. Pathol.
PUBLISHED: 03-31-2014
Show Abstract
Hide Abstract
Oestrogen has been speculated to play an important role in the pathogenesis of primary biliary cirrhosis (PBC), which mainly affects middle-aged and old-aged females because biliary epithelial cells (BECs) are known to express oestrogen receptors (ERs). Oestrogen-related receptors (ERRs) are constitutively active without oestrogen and competitively inhibit the ER-dependent effects of oestrogen. We clarified the effects of oestrogen and the significance of ERRs along with their association with the pathogenesis of cholangiopathy in PBC.
Related JoVE Video
Long-term survival of patients with cholangiolocellular carcinoma after curative hepatectomy.
Ann. Surg. Oncol.
PUBLISHED: 03-17-2014
Show Abstract
Hide Abstract
Cholangiolocellular carcinoma (CoCC) has distinct pathological characteristics, and CoCC is considered to originate from hepatic progenitor or stem cells. However, the surgical outcome of CoCC has not been clarified in detail.
Related JoVE Video
Adenovirus pneumonia presenting with nodular shadows on chest X-ray in two unrelated allogeneic bone marrow transplant recipients.
Intern. Med.
PUBLISHED: 03-04-2014
Show Abstract
Hide Abstract
Adenoviruses are increasingly recognized as important pathogens following allogeneic stem cell transplantation. We herein report two cases of disseminated adenovirus infection that presented with nodular shadows on chest X-ray after allogeneic bone marrow transplantation from unrelated donors. Both patients died of respiratory failure. Autopsies revealed adenovirus infection of multiple organs. Adenovirus infection should be suspected when nodular lung lesions of unknown origin appear in allogeneic stem cell transplant recipients.
Related JoVE Video
Gd-EOB-DTPA-enhanced magnetic resonance imaging and alpha-fetoprotein predict prognosis of early-stage hepatocellular carcinoma.
Hepatology
PUBLISHED: 02-20-2014
Show Abstract
Hide Abstract
The survival of patients with hepatocellular carcinoma (HCC) is often individually different even after surgery for early-stage tumors. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) has been introduced recently to evaluate hepatic lesions with regard to vascularity and the activity of the organic anion transporter OATP1B3. Here we report that Gd-EOB-DTPA-enhanced MRI (EOB-MRI) in combination with serum alpha-fetoprotein (AFP) status reflects the stem/maturational status of HCC with distinct biology and prognostic information. Gd-EOB-DTPA uptake in the hepatobiliary phase was observed in ?15% of HCCs. This uptake correlated with low serum AFP levels, maintenance of hepatocyte function with the up-regulation of OATP1B3 and HNF4A expression, and good prognosis. By contrast, HCC showing reduced Gd-EOB-DTPA uptake with high serum AFP levels was associated with poor prognosis and the activation of the oncogene FOXM1. Knockdown of HNF4A in HCC cells showing Gd-EOB-DTPA uptake resulted in the increased expression of AFP and FOXM1 and the loss of OATP1B3 expression accompanied by morphological changes, enhanced tumorigenesis, and loss of Gd-EOB-DTPA uptake in vivo. HCC classification based on EOB-MRI and serum AFP levels predicted overall survival in a single-institution cohort (n?=?70), and its prognostic utility was validated independently in a multi-institution cohort of early-stage HCCs (n?=?109).
Related JoVE Video
Targeting interleukin-4 receptor alpha by hybrid Peptide for novel biliary tract cancer therapy.
Int J Hepatol
PUBLISHED: 02-07-2014
Show Abstract
Hide Abstract
It is known that the interleukin-4 receptor ? (IL-4R ? ) is highly expressed on the surface of various human solid tumors. We previously designed novel IL-4R ? -lytic hybrid peptide composed of binding peptide to IL-4R ? and cell-lytic peptide and reported that the designed IL-4R ? -lytic hybrid peptide exhibited cytotoxic and antitumor activity both in vitro and in vivo against the human pancreatic cancer cells expressing IL-4R ? . Here, we evaluated the antitumor activity of the IL-4R ? -lytic hybrid peptide as a novel molecular targeted therapy for human biliary tract cancer (BTC). The IL-4R ? -lytic hybrid peptide showed cytotoxic activity in six BTC cell lines with a concentration that killed 50% of all cells (IC50) as low as 5? ? M. We also showed that IL-4R ? -lytic hybrid peptide in combination with gemcitabine exhibited synergistic cytotoxic activity in vitro. In addition, intravenous administration of IL-4R ? -lytic hybrid peptide significantly inhibited tumor growth in a xenograft model of human BTC in vivo. Taken together, these results indicated that the IL-4R ? -lytic hybrid peptide is a potent agent that might provide a novel therapy for patients with BTC.
Related JoVE Video
Immunostaining for polycomb group protein EZH2 and senescent marker p16INK4a may be useful to differentiate cholangiolocellular carcinoma from ductular reaction and bile duct adenoma.
Am. J. Surg. Pathol.
PUBLISHED: 02-04-2014
Show Abstract
Hide Abstract
Intrahepatic cholangiocarcinoma arising in chronic advanced liver disease sometimes contains a component of cholangiolocellular carcinoma. Bile duct adenoma, a benign tumor/tumorous lesion and ductular reaction, is also composed of bile ductular cells, and the differential diagnosis is sometimes difficult. We have previously reported that cholangiolocellular carcinoma showed overexpression of a polycomb group protein EZH2, which participates in bypass/escape from cellular senescence during carcinogenesis. In contrast, the ductular reaction showed high expression of senescence-associated p16(INK4a). In this study, we examined whether immunostaining for EZH2 and p16(INK4a) is useful for differential diagnosis among cholangiolocellular carcinoma, bile duct adenoma, and ductular reactions. Subjects included 33 patients with intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma with components of cholangiolocellular carcinoma and 16 patients with bile duct adenoma. The expressions of EZH2 and p16(INK4a) were examined immunohistochemically. The expression of EZH2 was seen in all cases of cholangiolocellular carcinomas, but it was not observed in bile duct adenomas and ductular reactions, which were seen around carcinomas in 80% of cases. The extensive expression of p16(INK4a) was seen only in 4 cases of cholangiolocellular carcinomas (12%). In contrast, the expression of p16(INK4a) was seen in 13 cases (81%) of bile duct adenomas and in all cases of ductular reactions. The borderline between the component of cholangiolocellular carcinoma and the surrounding ductular reaction was clearly highlighted by the reverse expression pattern of EZH2 and p16(INK4a) in 69% of cases. In conclusion, immunostaining for EZH2 and p16(INK4a) may be useful for differential diagnosis among cholangiolocellular carcinomas, bile duct adenomas, and ductular reactions.
Related JoVE Video
Clinical course after corticosteroid therapy in IgG4-related aortitis/periaortitis and periarteritis: a retrospective multicenter study.
Arthritis Res. Ther.
PUBLISHED: 01-30-2014
Show Abstract
Hide Abstract
Immunoglobulin G4 (IgG4)-related aortitis/periaortitis and periarteritis are vascular manifestations of IgG4-related disease. In this disease, the affected aneurysmal lesion has been suspected to be at risk of rupture. In this study, we aimed to clarify the clinical course after corticosteroid therapy in IgG4-related aortitis/periaortitis and periarteritis.
Related JoVE Video
Hilar cholangiocarcinoma is pathologically similar to pancreatic duct adenocarcinoma: suggestions of similar background and development.
J Hepatobiliary Pancreat Sci
PUBLISHED: 01-21-2014
Show Abstract
Hide Abstract
Routine experiences suggest that cholangiocarcinomas (CCAs) show different clinicopathological behaviors along the biliary tree, and hilar CCA apparently resembles pancreatic duct adenocarcinoma (PDAC). Herein, the backgrounds for these similarities were reviewed. While all cases of PDAC, hilar CCA, intrahepatic CCA (ICCA) and CCA components of combined hepatocellular-cholangiocarcinoma (cHC-CCA) were adenocarcinomas, micropapillary patterns and columnar carcinoma cells were common in PDAC and hilar CCA, and trabecular components and cuboidal carcinoma cells were common in ICCA and CCA components of cHC-CCA. Anterior gradient protein-2 and S100P were frequently expressed in perihilar CCA and PDAC, while neural cell adhesion molecule and luminal epithelial membrane antigen were common in CCA components of c-HC-CCA. Pdx1 and Hes1 were frequently and markedly expressed aberrantly in PDAC and perihilar CCA, although their expression was rare and mild in CCA components in cHC-CCA and ICCA. Hilar CCA showed a similar postoperative prognosis to PDAC but differed from ICCA and cHC-CCA. Taken together, hilar CCA may differ from ICCA and CCA components of cHC-CCA but have a similar development to PDAC. These similarities may be explained by the unique anatomical, embryological and reactive nature of the pancreatobiliary tract. Further studies of these intractable malignancies are warranted.
Related JoVE Video
What are the precursor and early lesions of peripheral intrahepatic cholangiocarcinoma?
Int J Hepatol
PUBLISHED: 01-20-2014
Show Abstract
Hide Abstract
Cholangiocarcinoma (CC) is divided into distal, perihilar, and intrahepatic CCs (ICCS), and are further subdivided into large bile duct ICC and peripheral ICC. In distal and perihilar CC and large duct ICC, biliary intraepithelial neoplasm (BilIN) and intraductal papillary neoplasm (IPN) have been proposed as precursor lesions. Peripheral ICC, bile duct adenoma (BDA), biliary adenofibroma (BAF), and von Meyenburg complexes (VMCs) are reportedly followed by development of ICCs. Herein, we surveyed these candidate precursor lesions in the background liver of 37 cases of peripheral ICC and controls (perihilar CC, 34 cases; hepatocellular carcinoma, 34 cases and combined hepatocellular cholangiocarcinoma, 25 cases). In the background liver of peripheral ICC, BDA and BAF were not found, but there were not infrequently foci of BDA-like lesions and atypical bile duct lesions involving small bile ducts (32.4% and 10.8%, resp.). VMCs were equally found in peripheral CCs and also control CCs. In conclusion, BDA, BAF, and VMCs are a possible precursor lesion of a minority of peripheral CCs, and BDA-like lesions and atypical bile duct lesions involving small bile ducts may also be related to the development of peripheral ICC. Further pathologic studies on these lesions are warranted for analysis of development of peripheral ICCs.
Related JoVE Video
Histological Characterization of Biliary Intraepithelial Neoplasia with respect to Pancreatic Intraepithelial Neoplasia.
Int J Hepatol
PUBLISHED: 01-20-2014
Show Abstract
Hide Abstract
Biliary intraepithelial neoplasia (BilIN) is a precursor lesion of hilar/perihilar and extrahepatic cholangiocarcinoma. BilIN represents the process of multistep cholangiocarcinogenesis and is the biliary counterpart of pancreatic intraepithelial neoplasia (PanIN). This study was performed to clarify the histological characteristics of BilIN in relation to PanIN. Using paraffin-embedded tissue sections of surgically resected specimens of cholangiocarcinoma associated with BilIN and pancreatic ductal adenocarcinoma associated with PanIN, immunohistochemical staining was performed using primary antibodies against MUC1, MUC2, MUC5AC, cyclin D1, p21, p53, and S100P. For mucin staining, Alcian blue pH 2.5 was used. Most of the molecules examined here showed similar expression patterns in BilIN and PanIN, in which their expression tended to increase along with the increase in atypia of the epithelial lesions. Significant differences were observed in the increase in mucin production and the expression of S100P in PanIN-1 and the expression of p53 in PanIN-3, when compared with those in BilIN of a corresponding grade. These results suggest that cholangiocarcinoma and pancreatic ductal adenocarcinoma share, at least in part, a common carcinogenic process and further confirm that BilIN can be regarded as the biliary counterpart of PanIN.
Related JoVE Video
Case series of 17 patients with cholangiocarcinoma among young adult workers of a printing company in Japan.
J Hepatobiliary Pancreat Sci
PUBLISHED: 01-13-2014
Show Abstract
Hide Abstract
An outbreak of cholangiocarcinoma occurred among workers in the offset color proof-printing department at a printing company in Japan. The aim of this study was to clarify the characteristics of the patients with cholangiocarcinoma.
Related JoVE Video
Characteristics of hepatic fatty acid compositions in patients with nonalcoholic steatohepatitis.
Liver Int.
PUBLISHED: 01-09-2014
Show Abstract
Hide Abstract
Nonalcoholic fatty liver disease (NAFLD) is closely related to insulin resistance and lipid metabolism. Recent studies have suggested that the quality of fat accumulated in the liver is associated with the development of nonalcoholic steatohepatitis (NASH). In this study, we investigated the fatty acid composition in liver tissue and its association with the pathology in NAFLD patients.
Related JoVE Video
Infiltration of inflammatory cells expressing mitochondrial proteins around bile ducts and in biliary epithelial layer may be involved in the pathogenesis in primary biliary cirrhosis.
J. Clin. Pathol.
PUBLISHED: 01-09-2014
Show Abstract
Hide Abstract
Serum antimitochondrial antibodies are characteristic in most patients with primary biliary cirrhosis (PBC); however, the significance of antimitochondrial antibodies in the pathogenesis of PBC remains unclear. We examined the extent and types of mitochondrial protein-expressing inflammatory cells and its association with deregulated autophagy of mitochondria in biliary epithelial lesions in PBC.
Related JoVE Video
Pancreatic body adenocarcinoma with neuroendocrine tumor characteristics: A case report.
Oncol Lett
PUBLISHED: 01-03-2014
Show Abstract
Hide Abstract
A 61-year-old female with pancreatic body cancer underwent a distal pancreatectomy. The tumor was a moderately- to poorly-differentiated adenocarcinoma. Tumor growth filled the dilated main pancreatic duct (MPD) and infiltrated the surrounding area. Six months later, metastases to the left diaphragm and MPD of the remnant pancreatic head were detected. Chemoradiotherapy was administered, but the patient succumbed 22 months after surgery. An autopsy demonstrated that a moderately- to poorly-differentiated adenocarcinoma had arisen from the pancreatic head and infiltrated the duodenum and bile duct. Huge liver metastases and multiple peritoneal disseminations were also present. Microscopically, a portion of the tumor had a pseudo-rosette appearance in the adenocarcinoma component, while another section showed characteristics of a neuroendocrine tumor (NET) immunohistochemically. The original surgically-resected tumor also showed NET characteristics immunohistochemically. It is therefore necessary to search for NET components in pancreatic cancer with atypical growth and metastases, even when adenocarcinoma has been diagnosed histologically.
Related JoVE Video
Cystic and micropapillary epithelial changes of peribiliary glands might represent a precursor lesion of biliary epithelial neoplasms.
Virchows Arch.
PUBLISHED: 01-02-2014
Show Abstract
Hide Abstract
A tumorigenic role of peribiliary glands (PBGs) has been suggested recently. This study was performed to clarify the histological characteristics of PBGs showing cystic and micropapillary epithelial changes. From histological sections of a total of 938 autopsy livers, cases with cystic and micropapillary changes of the epithelial cells of intrahepatic PBGs were collected. PBGs with cystic change that lacked micropapillary epithelial changes were referred to as cystic lesion. Mucin staining and immunohistochemical analysis were performed, and the results were compared between cystic and micropapillary (C-P) lesions and cystic lesions. C-P and cystic lesions were observed in 9 (1 %) and 40 (4 %) , respectively. The atypia of micropapillary epithelium was usually mild, but in a single case, invasive adenocarcinoma accompanied a C-P lesion. Abundant mucin expression was observed in all cases of C-P lesion, which was similar to mucinous acini of normal PBGs rather than serous acini. Immunohistochemical analysis showed that MUC5AC was more frequently expressed in C-P lesions than in cystic lesions. Immunohistochemical expression of cyclin D1 and S100P was characteristically found in C-P lesions. Mean Ki-67 labeling index of C-P lesions was significantly higher than that of cystic lesions. The immunoprofile of C-P lesions was similar to that of the branch-type intraductal papillary mucinous neoplasm of the pancreas. These results suggest that C-P lesions may have neoplastic features and might represent a precursor of biliary epithelial neoplasms, including branch-type intraductal papillary neoplasm of the bile duct as well as mucin-producing cholangiocarcinoma, a concept that we have recently proposed.
Related JoVE Video
Autophagy may promote carcinoma cell invasion and correlate with poor prognosis in cholangiocarcinoma.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
The role of autophagy in cholangiocarcinoma is poorly understood. This study investigated its involvement in cholangiocarcinoma, focusing on carcinoma cell invasion and prognostic significance using cholangiocarcinoma cell lines, CCKS1 and HuCCT1, and human tissues of hilar and extrahepatic cholangiocarcinoma. Nutrient starvation induced the expression of LC3-II and the formation of LC3 puncta in both CCKS1 and HuCCT1, suggesting the occurrence of autophagy. The induction of autophagy was accompanied by the increased expression of an autophagy-related protein, Ambra1, in the cells. Under starvation conditions, the invasive activity of both cells was significantly increased, and a lysosomal inhibitor, chloroquine, attenuated this increased invasive activity. Transforming growth factor-?1 (TGF-?1), known as an inducer of epithelial-mesenchymal transition (EMT), increased the invasive activity of both cells, and chloroquine also significantly reduced TGF-?1-induced cell invasion. Immunohistochemical staining using cholangiocarcinoma tissues showed that the expression of Ambra1 positively correlated with the expression of Snail, one of the major transcriptional factors of EMT. In addition, overexpression of Ambra1 significantly correlated with lymph node metastasis and poor survival rate of the patients. These results suggest that the occurrence of autophagy may be associated with a malignant phenotype and poor prognosis in cholangiocarcinoma, and autophagy is possibly involved in EMT-related cholangiocarcinoma cell invasion.
Related JoVE Video
Different carcinogenic process in cholangiocarcinoma cases epidemically developing among workers of a printing company in Japan.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Recently, cholangiocarcinoma has epidemically developed among young adult workers of a printing company in Japan. Exposure to organic solvents including 1,2-dichloropropane and/or dichloromethane is supposed to be associated with the carcinoma development. The metabolism of dichloromethane proceeds through a Theta-class glutathione S-transferase (GST) T1-1-catalyzed pathway, where its reactive intermediates have been implicated in genotoxicity and carcinogenicity. This study examined features of the carcinogenic process of the cholangiocarcinoma developed in the printing company. Surgically resected specimens of the cholangiocarcinoma cases were analyzed, where all cases were associated with precursor lesions such as biliary intraepithelial neoplasia (BilIN) and/or intraductal papillary neoplasm of the bile duct (IPNB). Immunohistochemical analysis confirmed constitutional expression of GST T1-1 in normal hepatobiliary tract. Immunostaining of ?-H2AX, a marker of DNA double strand break, showed that its expression was significantly increased in foci of BilIN, IPNB and invasive carcinoma as well as in non-neoplastic biliary epithelial cells of the printing company cases when compared to that of control groups. In the printing company cases, immunohistochemical expression of p53 was observed in non-neoplastic biliary epithelial cells and BilIN-1. Mutations of KRAS and GNAS were detected in foci of BilIN in one out of 3 cases of the printing company. These results revealed different carcinogenic process of the printing company cases, suggesting that the exposed organic solvents might act as a carcinogen for biliary epithelial cells by causing DNA damage, thereby contributing to the carcinoma development.
Related JoVE Video
Clinicopathological characterization of so-called "cholangiocarcinoma with intraductal papillary growth" with respect to "intraductal papillary neoplasm of bile duct (IPNB)".
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Cholangiocarcinoma (CC) of the biliary tract occasionally presents a predominant intraductal papillary growth in the bile ducts, called as biliary tract carcinoma (BTC) of papillary growth (PG) and intrahepatic CC (ICC) of intraductal growth (IG) type. Recently, intraductal papillary neoplasm of bile duct (IPNB) has been proposed as a pre-invasive biliary neoplasm. This study was performed to characterize pathologically BTC of PG type and ICC of IG type with respect to IPNB. It was found that 126 of such 154 CCs (81.8%) fulfilled the criteria of IPNB, while the remaining 28 cases showed different histologies, such as tubular adenocarcinoma and carcinosarcoma. These IPNBs occurred in old aged patients with a male predominance, and the left lobe was rather frequently affected in the liver. A majority of these cases were high grade IPNB (43 cases) and invasive IPNB (77 cases), while low grade IPNB was rare (6 cases). Pancreatobiliary type was predominant (48 cases) followed by gastric (30 cases), intestinal (29 cases) and oncocytic (19 cases) types. Mucus hypersecretion was found in 45 cases, and this was frequent in IPNB at the intrahepatic large bile duct and hilar bile ducts but rare at the extrahepatic bile ducts. Interestingly, 36 cases of high grade and invasive IPNBs contained foci of moderately differentiated adenocacinoma within the intraductal papillary tumor. In conclusion, a majority of ICC of IG type and BTC of PG type could be regarded as a IPNB lineage, and clinically detectable IPNBs were already a malignant papillary lesion.
Related JoVE Video
Activation of the PI3K/mTOR pathway is involved in cystic proliferation of cholangiocytes of the PCK rat.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
The polycystic kidney (PCK) rat is an animal model of Caroli's disease as well as autosomal recessive polycystic kidney disease (ARPKD). The signaling pathways involving the mammalian target of rapamycin (mTOR) are aberrantly activated in ARPKD. This study investigated the effects of inhibitors for the cell signaling pathways including mTOR on cholangiocyte proliferation of the PCK rat. Cultured PCK cholangiocytes were treated with rapamycin and everolimus [inhibitors of mTOR complex 1 (mTOC1)], LY294002 [an inhibitor of phosphatidylinositol 3-kinase (PI3K)] and NVP-BEZ235 (an inhibitor of PI3K and mTORC1/2), and the cell proliferative activity was determined in relation to autophagy and apoptosis. The expression of phosphorylated (p)-mTOR, p-Akt, and PI3K was increased in PCK cholangiocytes compared to normal cholangiocytes. All inhibitors significantly inhibited the cell proliferative activity of PCK cholangiocytes, where NVP-BEZ235 had the most prominent effect. NVP-BEZ235, but not rapamycin and everolimus, further inhibited biliary cyst formation in the three-dimensional cell culture system. Rapamycin and everolimus induced apoptosis in PCK cholangiocytes, whereas NVP-BEZ235 inhibited cholangiocyte apoptosis. Notably, the autophagic response was significantly induced following the treatment with NVP-BEZ235, but not rapamycin and everolimus. Inhibition of autophagy using siRNA against protein-light chain3 and 3-methyladenine significantly increased the cell proliferative activity of PCK cholangiocytes treated with NVP-BEZ235. In vivo, treatment of the PCK rat with NVP-BEZ235 attenuated cystic dilatation of the intrahepatic bile ducts, whereas renal cyst development was unaffected. These results suggest that the aberrant activation of the PI3K/mTOR pathway is involved in cystic proliferation of cholangiocytes of the PCK rat, and inhibition of the pathway can reduce cholangiocyte proliferation via the mechanism involving apoptosis and/or autophagy.
Related JoVE Video
Alteration of energy metabolism in the pathogenesis of bile duct lesions in primary biliary cirrhosis.
J. Clin. Pathol.
PUBLISHED: 11-29-2013
Show Abstract
Hide Abstract
Primary biliary cirrhosis (PBC) is characterised by antimitochondrial antibody against the pyruvate dehydrogenase complex (PDC) and chronic non-suppurative destructive cholangitis (CNSDC). Pyruvate oxidation to acetyl-CoA by PDC is a key step in the glycolytic system. Oestrogen-related receptor-? (ERR?) is functionally activated by inducible coactivators such as peroxisome proliferator-activated receptor ? coactivator-1? (PGC-1?) and Bcl-3. Moreover, the PGC-1?-ERR? axis interrupts glycolytic metabolism through the upregulation of pyruvate dehydrogenase kinase, isozyme 4 (PDK4), which functionally inhibits PDC-E1? and stimulates fatty acid oxidation. In this study, we investigated the PGC-1?-ERR? axis to clarify PDC dysfunction in CNSDC of PBC.
Related JoVE Video
[Cholangiocarcinoma developing in printing company workers: a new type of occupational cancer].
Gan To Kagaku Ryoho
PUBLISHED: 11-16-2013
Show Abstract
Hide Abstract
The incidence of cholangiocarcinoma among the past or present workers in the department of offset color proof-printing at a printing company in Osaka was extremely high. The workers were relatively young and were exposed to several chemicals including organic solvents such as dichloromethane and 1,2-dichloropropane. Although the exact cause of cholangiocarcinoma in the patients remain unknown, it is likely that the development of cholangiocarcinoma was triggered during exposure to these chemicals. Some chemicals can act as environmental factors that lead to the development of cholangiocarcinoma. Therefore, we believe that cholangiocarcinoma is a new type of occupational cancer.
Related JoVE Video
Proposal of a new disease concept "biliary diseases with pancreatic counterparts". Anatomical and pathological bases.
Histol. Histopathol.
PUBLISHED: 10-10-2013
Show Abstract
Hide Abstract
The biliary tract and pancreas are located closely anatomically, and both develop from the endoderm foregut almost at the same time. Interestingly, the lining epithelia of the bile duct and main pancreatic duct show similar morphologies and phenotypes, and both are accompanied by periductal glands. Furthermore, the exocrine pancreatic acini are remnantly found in the peribiliary glands. Based on these findings, it seems plausible that the biliary tract has features of pancreatic elements in addition to the duct system, which is specialized for the drainage of bile secreted by hepatic parenchyma, particularly, hepatocytes. Interestingly, some pancreatic and biliary diseases show similar pathological features and even biological behaviors. For example, extrahepatic cholangiocarcinoma and ductal adenocarcinoma of the pancreas share many clinicopathological features. Both of them are hypothesized to arise from similar preneoplastic and early neoplastic intraepithelial lesions. Intraductal papillary tumors, with frequent mucin hyperproduction, develop in the pancreas (intraductal papillary mucinous neoplasm) and also in the biliary tract (intraductal papillary neoplasm of the bile duct). IgG4-related disease affects the biliary tract (IgG4-related sclerosing cholangitis) and the pancreas (autoimmune pancreatitis) in the same patients, with both showing similar morphologies. Herein, we propose that these non-neoplastic and neoplastic biliary diseases showing similarities to corresponding pancreatic diseases could be included in a new disease concept "biliary diseases with pancreatic counterparts". Based on this new concept, information obtained in biliary tract diseases could be applied to the analysis of pancreatic disease and vice versa, and also novel therapeutical strategies and molecular and genetic studies on pancreatic and biliary diseases may be developed with a unified approach.
Related JoVE Video
Hemodynamics and progression of a hypervascular focus in a borderline lesion of hepatocellular carcinoma: analysis by angiography-assisted CT and histopathology.
Jpn J Radiol
PUBLISHED: 10-03-2013
Show Abstract
Hide Abstract
To investigate the hemodynamics and progression of a hypervascular focus (HF) in a borderline lesion by dual-phase CT during hepatic arteriography (CTHA) and reveal the process of the transformation to hypervascular overt hepatocellular carcinoma (HCC).
Related JoVE Video
Clinicopathologic significance of combined hepatocellular-cholangiocarcinoma with stem cell subtype components with reference to the expression of putative stem cell markers.
Am. J. Clin. Pathol.
PUBLISHED: 08-20-2013
Show Abstract
Hide Abstract
To examine the clinicopathologic features of combined hepatocellular-cholangiocarcinoma (HC-CC), which the World Health Organization (WHO) proposed classifying into 2 types, and the expression of delta-like 1 homolog (DLK1), as well as putative stem cell markers, such as NCAM/CD56 and CD133.
Related JoVE Video
Clinicopathological features and prognosis of mucin-producing bile duct tumor and mucinous cystic tumor of the liver: a multi-institutional study by the Japan Biliary Association.
J Hepatobiliary Pancreat Sci
PUBLISHED: 08-01-2013
Show Abstract
Hide Abstract
The aim of this study was to determine the clinicopathological features and surgical outcomes of mucinous cystic neoplasm of the liver (MCN) and mucin-producing intraductal papillary neoplasm of the intrahepatic bile duct (M-IPNB).
Related JoVE Video
Prevalence and risk factors of hepatocellular carcinoma in Japanese patients with primary biliary cirrhosis.
Hepatol. Res.
PUBLISHED: 07-10-2013
Show Abstract
Hide Abstract
Primary biliary cirrhosis (PBC) tends to affect females more than males. PBC selectively damages intrahepatic small bile ducts, particularly interlobular bile ducts. The clinical presentation of PBC has changed according to recent advances in clinicobiological diagnosis and improvements in therapeutic effects and prognosis. In particular, we encounter PBC patients with hepatocellular carcinoma (HCC), and the number of these patients appears to have increased. The precise reason for the increased number of PBC patients with HCC in recent decades remains unknown, but recognizing the current status of carcinogenesis in PBC patients, identifying the associated clinicopathological risk factors, and understanding how the pathogenesis of PBC is directly associated with HCC, is important. In this review, we summarize the data from two nationwide surveys undertaken in Japan as well as recent data from Japanese and international studies.
Related JoVE Video
Incidence of and risk factors for hepatocellular carcinoma in primary biliary cirrhosis: national data from Japan.
Hepatology
PUBLISHED: 07-06-2013
Show Abstract
Hide Abstract
Primary biliary cirrhosis (PBC) primarily affects females and is rarely complicated by hepatocellular carcinoma (HCC). Although the HCC incidence in PBC patients is low, several characteristics and risk factors associated with its development have been reported. In this study, national data concerning the current status of carcinogenesis in PBC patients in Japan are reviewed. Using data from two national questionnaire surveys, we investigated the clinicopathological findings associated with HCC in PBC patients. According to the data of all reviewed PBC patients, the HCC incidence was 2.4% (71/2946). The HCC incidence by gender was 5.1% (19/370) in males and 2.0% (52/2576) in females, and the proportion of males was 26.7%. Prognosis was significantly poorer in the PBC patients with HCC than in those without. Multivariate analysis of risk factors associated with HCC by gender revealed histological stage at the time of PBC diagnosis as an independent risk factor associated with the development of HCC in females, but not in males. Furthermore, data from another national survey of 178 PBC patients with HCC (male/female = 49/129; proportion of males 27.5%) revealed that the duration between the diagnosis of PBC and that of HCC was significantly shorter in males than in females. In addition, histological stage at the time of HCC diagnosis was an independent risk factor for HCC in females, whereas no risk factors were identified in males. Conclusion: these data indicate that males are at risk of developing HCC at any histological stage of PBC. Therefore, male PBC patients in particular should be carefully screened for HCC from the early stages of PBC.
Related JoVE Video
Application and validation of a new histologic staging and grading system for primary biliary cirrhosis.
J. Clin. Gastroenterol.
PUBLISHED: 07-03-2013
Show Abstract
Hide Abstract
We proposed a new grading and staging system for primary biliary cirrhosis (PBC), which takes into account the degree of both chronic cholangitis activity (CA) and hepatitic activity (HA) for grading disease activity and that of fibrosis, bile duct loss, and chronic cholestasis for staging. In this study, we validated our new system.
Related JoVE Video
Serum amyloid A-positive hepatocellular neoplasms in the resected livers from 3 patients with alcoholic cirrhosis.
Histol. Histopathol.
PUBLISHED: 05-21-2013
Show Abstract
Hide Abstract
Twelve hepatocellular nodules were characterized in the resected livers from 3 patients (2 men and a woman) with alcoholic cirrhosis. Imaging techniques suggested that the nodules were hypervascular and may be hepatocellular carcinoma. Five nodules (4-31 mm in diameter) were serum amyloid A-positive hepatocellular neoplasm, which shares features with inflammatory hepatocellular adenoma. The remaining 7 nodules (5-8 mm) were focal nodular hyperplasia-like nodules showing focal or no immunostaining for serum amyloid A. The serum amyloid A-positive hepatocellular neoplasms showed increased cellular density, inflammatory infiltrate, sinusoidal dilatation, and ductular reaction to various degrees. These histologic features tended to be less extensive in focal nodular hyperplasia-like nodules. Three of 4 serum amyloid A-positive hepatocellular neoplasms showed slight hypointensity in the hepatobiliary phase on the magnetic resonance (MR) imaging with gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) enhancement. In contrast, 3 focal nodular hyperplasia-like nodules showed iso-intensity in the hepatobiliary phase. This study further confirms characteristics of serum amyloid A-positive hepatocellular neoplasm arising in alcoholic cirrhosis that share features with inflammatory hepatocellular adenomas. Serum amyloid A-positive hepatocellular neoplasms sometimes co-exist with focal nodular hyperplasia-like nodules and may show different findings on Gd-EOB-enhanced MR imaging.
Related JoVE Video
Participation of peribiliary glands in biliary tract pathophysiologies.
World J Hepatol
PUBLISHED: 05-02-2013
Show Abstract
Hide Abstract
To investigate the roles of peribiliary glands around the bile ducts in the pathophysiology of the biliary tract.
Related JoVE Video
Hyperplastic hepatocellular nodule with localized hemangiomatosis: A hither-to unrecognized type of hypervascular hepatic lesion.
Hepatol. Res.
PUBLISHED: 04-20-2013
Show Abstract
Hide Abstract
The differential diagnosis of hypervascular hepatocellular nodular lesion includes hepatocellular carcinoma and it is sometimes difficult to image. We report herein two patients with hyperplastic hepatocellular nodule associated with localized hemangiomatosis.
Related JoVE Video
Clinicopathological significance of S100 protein expression in cholangiocarcinoma.
J. Gastroenterol. Hepatol.
PUBLISHED: 04-15-2013
Show Abstract
Hide Abstract
Cholangiocarcinoma arising in the large bile ducts undergoes a multistep carcinogenesis process in chronic biliary diseases, and biliary intraepithelial neoplasia is known as a precursor lesion. This study examined the expression of S100 proteins in the multistep cholangiocarcinogenesis to clarify their clinicopathological significance.
Related JoVE Video
Tissue culture correlational study of genetic cholangiopathy of autosomal recessive polycystic kidney disease.
Methods Mol. Biol.
PUBLISHED: 03-30-2013
Show Abstract
Hide Abstract
Cholangiocytes are epithelial cells that line the biliary tract and are also known as biliary epithelial cells (BECs). In vitro culture studies of BECs in correlation with tissue section examination may give us a comprehensive analysis of biliary tract diseases. Herein, we discuss genetic cholangiopathy of autosomal recessive polycystic kidney disease (ARPKD), mainly using a polycystic kidney (PCK) rat, an animal model of ARPKD. The hepatobiliary lesions in ARPKD patients (Carolis disease and congenital hepatic fibrosis) and in PCK rats are speculated to be related to mutations to polycystic kidney and hepatic disease 1 (PKHD1) which have been recently demonstrated, though the exact causal relation between these mutations and hepatobiliary pathology remain to be clarified. Recently we clarified that BECs of PCK rat showed increased cell proliferation followed by irregular dilatation of intrahepatic bile ducts. We also identified the essential involvement of the MEK5-ERK5 pathway in the abnormal proliferation of BECs in the PCK rat. The degradation of laminin and type IV collagen (basal membrane components of bile ducts) was closely related to the biliary dysgenesis and cystogenesis in the PCK rats. BECs also showed mesenchymal phenotype followed by progressive portal tract fibrosis, indicating TGF-?1 may be involved in this acquisition of mesenchymal phenotype. Detailed tissue culture correlation studies of ARPKD and PCK rats are mandatory to evaluate the pathogenesis of this genetic cholangiopathy.
Related JoVE Video
Abundant nucleostemin expression supports the undifferentiated properties of germ cell tumors.
Am. J. Pathol.
PUBLISHED: 03-21-2013
Show Abstract
Hide Abstract
Nucleostemin (NS) is a nucleolar GTP-binding protein that is involved in ribosomal biogenesis and protection of telomeres. We investigated the expression of NS in human germ cell tumors and its function in a mouse germ cell tumor model. NS was abundantly expressed in undifferentiated, but not differentiated, types of human testicular germ cell tumors. NS was expressed concomitantly with OCT3/4, a critical regulator of the undifferentiated status of pluripotent stem cells in primordial germ cells and embryonal carcinomas. To investigate the roles of NS in tumor growth in vivo, we used a mouse teratoma model. Analysis of teratomas derived from embryonic stem cells in which the NS promoter drives GFP expression showed that cells highly expressing NS were actively proliferating and exhibited the characteristics of tumor-initiating cells, including the ability to initiate and propagate tumor cells in vivo. NS-expressing cells exhibited higher levels of GTP than non-NS-expressing cells. Because NS protein is stabilized by intracellular GTP, metabolic changes may contribute to abundant NS expression in the undifferentiated cells. OCT3/4 deficiency in teratomas led to loss of NS expression, resulting in growth retardation. Finally, we found that teratomas deficient in NS lost their undifferentiated characteristics, resulting in defective tumor proliferation. These data indicate that abundant expression of NS supports the undifferentiated properties of germ cell tumors.
Related JoVE Video
Evaluation of eligibility criteria in living donor liver transplantation for hepatocellular carcinoma by ?-SMA-positive cancer-associated fibroblasts.
Oncol. Rep.
PUBLISHED: 03-21-2013
Show Abstract
Hide Abstract
The eligibility criteria of liver transplantation (LT) for hepatocellular carcinoma (HCC) must clearly confirm the prognosis not only from pathological diagnosis but also from pre-operative imaging diagnosis. In the present study, we evaluated published eligibility criteria for LT based on both pre-operative imaging diagnosis and pathological diagnosis using living donor liver transplantation (LDLT) recipients at our hospital by ?-smooth muscle actin (SMA)-positive cancer-associated fibroblasts (CAFs) in HCC. The Up-to-seven (Up-to-7), Asan and Tokyo criteria were evaluated, in both overall survival and HCC disease-free survival, to be statistically significantly beneficial criteria to define post-LDLT prognosis. Recipients only within Up-to-7 criteria based on both pre-operative imaging diagnosis and pathological diagnosis survived without HCC recurrence. Recipients with proliferation of ?-SMA-positive CAFs in HCC had significantly poorer prognosis. All survival recipients without HCC recurrence, who were above the Up-to-7 criteria in pathological diagnosis, had no proliferation of ?-SMA-positive CAFs. As a result of multivariate analysis, the significant independent factors defining prognosis of recipients after LDLT for HCC were Up-to-7 criteria and proliferation of ?-SMA-positive CAFs. The ideal eligibility criteria for LDLT with HCC is Up-to-7 criteria and ?-SMA-positive CAFs was considered to be an important factor in HCC recurrence. LDLT should be limited to recipients within Up-to-7 criteria or without proliferation of ?-SMA-positive CAFs.
Related JoVE Video
Hypervascular hepatocellular carcinomas showing hyperintensity on hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance imaging: a possible subtype with mature hepatocyte nature.
Jpn J Radiol
PUBLISHED: 03-13-2013
Show Abstract
Hide Abstract
We evaluated molecular features of hypervascular hepatocellular carcinoma (HCC) that shows iso- or hyperintensity (hyperintense HCC) in the hepatobiliary phase (HB phase) of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI).
Related JoVE Video
Intraductal papillary neoplasm of the bile duct accompanying biliary mixed adenoneuroendocrine carcinoma.
World J. Gastroenterol.
PUBLISHED: 03-13-2013
Show Abstract
Hide Abstract
We present the first case of an intraductal papillary neoplasm of the bile duct (IPNB) accompanying a mixed adenoneuroendocrine carcinoma (MANEC). A 74-year-old woman presented with fever of unknown cause. Laboratory data revealed jaundice and liver injury. Contrast-enhanced computed tomography revealed a 20 mm polypoid tumor in the dilated distal bile duct, which exhibited early enhancement and papillary growth. Upper gastrointestinal endoscopy revealed mucus production from the papilla of Vater, characterized by its protruding and dilated orifice. Endoscopic ultrasonography visualized the polypoid tumor in the distal bile duct, but no invasive region was suggested by diagnostic imaging. Therefore, the initial diagnosis was IPNB. After endoscopic nasobiliary drainage, a pylorus-preserving pancreaticoduodenectomy was performed. Pathological examination of the resected bile duct revealed papillary proliferation of biliary-type cells with nuclear atypia, indicating pancreaticobiliary-type IPNB. In addition, solid portions comprised of tumor cells with characteristic salt-and-pepper nuclei were evident. Immunohistochemistry revealed expression of the neuroendocrine marker synaptophysin in this solid component, diagnosing it as a neuroendocrine tumor (NET). Furthermore, the MIB-1 proliferation index of NET was higher than that of IPNB, and microinvasion of the NET component was found, indicating neuroendocrine carcinoma (NET G3). This unique case of MANEC, comprising IPNB and NET, provides insight into the pathogenesis of biliary NET.
Related JoVE Video
Hepatic steatosis estimated microscopically versus digital image analysis.
Liver Int.
PUBLISHED: 03-10-2013
Show Abstract
Hide Abstract
Evaluate in liver biopsies: (i) interobserver agreement of estimates of fat proportionate area (eFPA) and steatosis grading, (ii) the relationship between steatosis grades and measured fat proportionate area (mFPA, digital image analysis), (iii) the accuracy of eFPA, (iv) to present images to aid standardization and accuracy of eFPA.
Related JoVE Video
Possible involvement of CCL1-CCR8 interaction in lymphocytic recruitment in IgG4-related sclerosing cholangitis.
J. Hepatol.
PUBLISHED: 02-25-2013
Show Abstract
Hide Abstract
IgG4-related sclerosing cholangitis and type 1 autoimmune pancreatitis (IgG4-SC/AIP) are characterized by massive lymphoplasmacytic infiltration including Th2 and regulatory T cells (Tregs). This study was conducted to address which chemotactic factors are involved in this condition.
Related JoVE Video
Molecular analysis of a recurrent glioblastoma treated with bevacizumab.
Brain Tumor Pathol
PUBLISHED: 02-24-2013
Show Abstract
Hide Abstract
We treated a case of recurrent glioblastoma (GBM) with bevacizumab and assessed its effect biologically. A 55-year-old man with a left frontal lobe GBM was experiencing recurrence 7 months postoperation. We administered bevacizumab concomitant with temozolomide (TMZ). Follow-up magnetic resonance imaging (MRI) showed dramatic but temporal tumor reduction; however, the patient died of re-recurrent disease 6 months after beginning bevacizumab. We obtained an autopsy and analyzed the detailed molecular change. In the autopsy specimen, the quantity of microvessels was significantly reduced. Vascular endothelial growth factor receptor (VEGFR) 1 and VEGFR2 were downregulated, most likely due to a negative feedback mechanism by blocking of VEGF signaling. Matrix metalloproteinase (MMP)-2 and membrane-type 1 MMP were upregulated, resulting in the higher activation of MMP-2 in the autopsy specimen. MIB-1 staining index and phosphorylation levels of p44/42-mitogen-activated protein kinase did not change, whereas phosphorylated protein kinase B (Akt) was decreased in the autopsy specimen, suggesting compensation and/or amplification of other proliferative signaling pathways such as suppression of apoptosis signaling. Consequently, bevacizumab might inhibit the VEGF autocrine loop, which then causes a change in molecular expression related not only to enhancement of tumor invasion but also maintenance of tumor proliferation.
Related JoVE Video
Pathological diagnosis of flat epithelial lesions of the biliary tract with emphasis on biliary intraepithelial neoplasia.
J. Gastroenterol.
PUBLISHED: 02-23-2013
Show Abstract
Hide Abstract
Flat epithelial lesions of the biliary tract cannot be detected by the image analysis, and the diagnosis entirely depends on pathological examination. The biliary tract is often affected by inflammatory conditions, and the resultant changes of the biliary epithelium make it difficult to differentiate them from neoplasia. Thus, the pathological diagnosis of biliary flat epithelial lesions can be challenging. In the biliary tract, there are several forms of intraepithelial neoplasia of the flat type, and biliary intraepithelial neoplasia (BilIN) is known as one of such lesions that represent the multistep cholangiocarcinogenesis. In this article, the diagnostic criteria and the differential diagnosis of biliary flat epithelial lesions, particularly focusing on BilIN, were presented and discussed to provide help to advance clinical and research applications of the BilIN system.
Related JoVE Video
Association of interleukin-28B genotype and hepatocellular carcinoma recurrence in patients with chronic hepatitis C.
Clin. Cancer Res.
PUBLISHED: 02-20-2013
Show Abstract
Hide Abstract
Several single-nucleotide polymorphisms (SNP) in the interleukin-28B (IL-28B) locus have recently been shown to be associated with antiviral treatment efficacy for chronic hepatitis C (CHC). However, such an association with hepatocellular carcinoma (HCC) is unkno3 we investigated the association between the IL-28B genotype and the biology and clinical outcome of patients with HCC receiving curative treatment.
Related JoVE Video
Notch1-Hes1 signalling axis in the tumourigenesis of biliary neuroendocrine tumours.
J. Clin. Pathol.
PUBLISHED: 02-19-2013
Show Abstract
Hide Abstract
Biliary neuroendocrine tumours (NETs) are rare and mostly exist as a component of mixed adenoneuroendocrine carcinomas (MANECs). Although the NET component in biliary MANECs is generally more malignant and clinically more important to the prognosis than the ordinary adenocarcinomatous component, the histogenesis of biliary NET has not been clarified. In this study, the role of the Notch1-Hes1 signalling axis in the histogenesis of biliary NETs was examined.
Related JoVE Video
Systemic and local expression levels of TNF-like ligand 1A and its decoy receptor 3 are increased in primary biliary cirrhosis.
Liver Int.
PUBLISHED: 02-15-2013
Show Abstract
Hide Abstract
Through a genome-wide association study of a Japanese population, we recently identified TNFSF15, a gene encoding TNF-like ligand 1A (TL1A), as a susceptibility gene for primary biliary cirrhosis (PBC). We investigated the clinical significance of TL1A and one of its receptors, decoy receptor 3 (DcR3), in PBC.
Related JoVE Video
Histological characteristics of biliary intraepithelial neoplasia-3 and intraepithelial spread of cholangiocarcinoma.
Virchows Arch.
PUBLISHED: 02-11-2013
Show Abstract
Hide Abstract
The increasing grades of biliary intraepithelial neoplasia (BilIN) reflect multistep carcinogenesis of cholangiocarcinoma, BilIN-3 representing the carcinoma in situ stage. A different form of in situ growth form of cancer cells is the intraepithelial spreading of cholangiocarcinoma cells. We examined the histological characteristics of carcinoma in situ in the biliary tract on 64 partial hepatectomy specimens with a diagnosis of hepatolithiasis. We distinguished two forms of carcinoma in situ: BilIN-3 and intraepithelial spread of carcinoma (IES). BilIN-3 is defined by epithelial atypia gradually decreasing towards the transition to adjacent normal biliary epithelium. In IES, the lesion shows an abrupt transition to normal biliary epithelium, in which the intraepithelial carcinoma then tends to spread. BilIN-3 and IES were observed in 17 (94 %) and seven (39 %), respectively, in cases of invasive cholangiocarcinoma (n?=?18), and neither of them was observed in cases without invasive cholangiocarcinoma (n?=?46). Most lesions of BilIN-3 and IES microscopically showed a flat or pseudopapillary pattern. The less frequent micropapillary configuration was noted more often in BilIN-3. BilIN-3 was not observed in septal and small intrahepatic bile ducts, while IES was regularly observed in such bile ducts. Immunohistochemical analysis showed p53 to be expressed significantly more frequently in IES (29 %) than in BilIN-3 (8 %). In conclusion, carcinoma in situ in the biliary tract is morphologically heterogeneous, and it is important to distinguish BilIN-3 and intraepithelial carcinoma spreading as distinct lesions, to better understand their biology.
Related JoVE Video
PPAR? ligand attenuates portal inflammation in the MRL-lpr mouse: a new strategy to restrain cholangiopathy in primary biliary cirrhosis.
Med Mol Morphol
PUBLISHED: 02-09-2013
Show Abstract
Hide Abstract
Primary biliary cirrhosis (PBC) is characterized by chronic destructive cholangitis, which is associated with the reduced expression of an anti-inflammatory molecule, peroxisome proliferator-activated receptor-? (PPAR?), in intrahepatic bile ducts. We previously demonstrated the anti-inflammatory effects of PPAR? ligands using cultured human biliary epithelial cells. In this study, we evaluated the effectiveness of PPAR? ligand against peribiliary inflammation in vivo. As an animal model of PBC, we used MRL/lpr mice in which a PBC-like cholangitis occurs naturally. Anti-inflammatory effects of the intraperitoneal administration of a PPAR? ligand, the prostaglandin D metabolite 15-deoxy-?(12,14)-prostaglandin J2 (15d-PGJ2), were evaluated. In untreated mice, portal inflammation including cholangitis was found to some degree in the majority of portal tracts. In mice given a high-dose group, the degree of portal inflammation was significantly reduced and mice mostly lacking portal inflammation and cholangitis were also found. T cell numbers in portal tracts were markedly decreased in the high-dose group, compared with controls, whereas there was no significant difference in terms of B cells and macrophages. This study is the first to assess the therapeutic potential of a PPAR? ligand against portal inflammation including cholangitis. Anti-inflammatory effects of PPAR? ligands may prevent the progression of cholangiopathy in PBC patients.
Related JoVE Video
Chemokine-Chemokine Receptor CCL2-CCR2 and CX3CL1-CX3CR1 Axis May Play a Role in the Aggravated Inflammation in Primary Biliary Cirrhosis.
Dig. Dis. Sci.
PUBLISHED: 01-18-2013
Show Abstract
Hide Abstract
Senescent cells can alter local tissue environments by secretion of various senescence-associated secretory phenotypes (SASP), such as cytokines and chemokines. Given senescent biliary epithelial cells (BECs) in damaged small bile ducts in primary biliary cirrhosis (PBC) show increased expression of chemokines CCL2 and CX3CL1 as SASP, we further examined an involvement of CCL2/CCR2 and CX3CL1/CX3CR1 systems in the pathogenesis of PBC.
Related JoVE Video
KRAS and GNAS mutations and p53 overexpression in biliary intraepithelial neoplasia and intrahepatic cholangiocarcinomas.
Cancer
PUBLISHED: 01-18-2013
Show Abstract
Hide Abstract
Similar to the pancreatic intraepithelial neoplasia (PanIN)-pancreatic carcinoma sequence model, intrahepatic cholangiocarcinoma (ICC) also reportedly follows a stepwise carcinogenesis process through the a precursor lesion: biliary intraepithelial neoplasia (BilIN). For this study, the authors investigated the status of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and GNAS complex locus (GNAS) mutations and tumor protein 53 (p53) overexpression in the stepwise process of cholangiocarcinogenesis.
Related JoVE Video
Roles of myofibroblasts and notch and hedgehog signaling pathways in the formation of intrahepatic bile duct lesions in polycystic kidney rats.
Pediatr. Dev. Pathol.
PUBLISHED: 01-18-2013
Show Abstract
Hide Abstract
Polycystic kidney (PCK) rats, an animal model of Carolis disease, show a dilatation of intrahepatic bile ducts (IHBD) called "ductal plate malformation." Mesenchymal cells and the Notch and Hedgehog signaling pathways in portal tracts are reportedly involved in the normal development of IHBD, although there have been no studies on the roles of these signaling pathways in PCK rats. We immunohistochemically examined the expression of the molecules related to these signaling pathways in portal tracts. All molecules related to these signaling pathways expressed in portal tracts in Sprague Dawley (SD) rats (control) were also expressed in PCK rats. Mesenchymal cells (myofibroblasts) were frequently found in the connective tissue of portal tracts of 20 embryonic-day-old (E20D), 1-day-old (1D), and 1-week-old (1W) SD and PCK rats and were abundant in PCK rats. Interestingly, myofibroblasts almost disappeared at in both strains of 3W rats. Jagged1 was expressed in mesenchymal cells in portal tracts and was abundant in PCK rats. Double immunostaining showed that Jagged1-positive cells were myofibroblasts. Notch2 and HES1 were expressed in cholangiocytes of the bile ducts of both rats. Sonic Hedgehog was similarly expressed in the bile ducts of both rats. A well-balanced and time-sequential expression of the Notch and Hedgehog family in portal tracts might be essential for the normal development of IHBD in E20D to 1W SD rats, and an imbalanced interaction of these molecules, particularly increased Jagged1 expression in periductal and periportal myofibroblasts and Notch2 expressed in cholangiocytes, may be involved in the formation of bile duct lesions in PCK rats.
Related JoVE Video
Spread of hilar cholangiocarcinomas via peribiliary gland network: a hither-to-unrecognized route of periductal infiltration.
Int J Clin Exp Pathol
PUBLISHED: 01-15-2013
Show Abstract
Hide Abstract
Cholangiocarcinomas (CCs) show intraluminal spread to bile ducts and periductal infiltration associated with vascular, lymphatic and perineural invasion in addition to direct penetration. Recently, the peribiliary gland networks located around the hilar and extrahepatic bile ducts have been reportedly to be involved in a variety of biliary diseases. However, the pathological features and roles of these networks in the carcinogenesis and progression of CCs remain to be explored. Recently, we experienced two cases of hilar CC showing a nodular sclerosing growth grossly and histologically well-differentiated adenocarcinomas, with an extensive involvement of the peribiliary gland networks. In situ like spread of carcinoma cells in the bile duct lumen was focal in one case and not identifiable in the other. In contrast, other 4 cases of ordinary hilar CC which were also well-differentiated adenocarcinomas, showed variable intraductal luminal spread and also extensive periductal infiltration irrespective of the peribiliary gland network. In conclusion, the present study showed a unique form of periductal spread of CCs with preferential and extensive involvement of the peribiliary gland networks.
Related JoVE Video
Evaluation of a new histologic staging and grading system for primary biliary cirrhosis in comparison with classical systems.
Hum. Pathol.
PUBLISHED: 01-11-2013
Show Abstract
Hide Abstract
Recently, our research team proposed a new histologic staging and grading system for primary biliary cirrhosis (PBC) that takes into account necroinflammatory activity and histologic heterogeneity. The present study aimed to confirm the usefulness of the new evaluation system. A total of 152 liver biopsy specimens and clinical data (including outcomes in patients with PBC before treatment with ursodeoxycholic acid) were analyzed with respect to the new system. Staging was evaluated on the basis of 3 histologic components (fibrosis, bile duct loss, and deposition of orcein-positive granules), and grading was assessed on the basis of chronic cholangitis activity and hepatitis activity. Concurrently, the classical systems, that is, the Scheuer and Ludwig staging systems, were also assessed and compared with our new system. PBC cases showed different distributions in each stage of the 3 systems. The new staging and grading system reflected liver dysfunctions before specific treatment. This was on a par with the results obtained using the classical systems. Development of cirrhosis-related conditions correlated well with the new staging system compared with the 2 classical staging systems, and in particular, the amount of deposition of orcein-positive granules could reflect development of cirrhosis-related conditions (scores 0-1 versus scores 2-3 groups, P < .0001). In conclusion, the new PBC staging system was demonstrated to reflect clinicolaboratory features, and its progression was associated with the development of cirrhosis-related conditions.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.