Magnetic resonance cholangiopancreatography and a problem in diagnosis of hepatopancreatoduodenal diseases

Based on the findings of 54 magnetic resonance studies, the authors used 19 of them authors to study the types of normalcy. A role of the new noninvasive technique magnetic resonance cholangiopancreatography (MRCPG) in the diagnosis of hepatopancreatoduodenal diseases is assessed. The potentialities of MRCPG in the detection of most common diseases and malformations of the biliary system are demonstrated. Comparative studies of MRCPG and endoscopic retrograde cholangiopancreatography (ERCPG) were conducted in 18 cases. The paper shows a methodological approach to MRCPG and analyzes the studies by describing the MR semiotics of major diseases. Emphasis is laid on how it is important to combine routine MRI and MRCPG in certain diagnostic situations. The authors consider that MRCPG is able to replace X-ray endoscopic studies and primarily ERCPG in diagnostic terms, by reserving their therapeutical functions for itself. MRCPG has great potentialities that, require further investigations and analysis.     

Radiodiagnosis of patients with primary sclerosing cholangitis

Among diseases of the hepatobiliary system, primary sclerosing cholangitis is an undetectable disorder of the biliary tract rather than a rare nosological entity, complex radiation study is of great importance in its preoperative diagnosis. Among direct methods for contrasting the biliary tract, the authors gave preference to percutaneous transhepatic cholangiography that allows the dilated biliary tract to be contrasted virtually in 100% of cases. The specific features of X-ray semiotics of primary sclerosing cholangitis were identified in 17 patients.     

Regulation of intrahepatic biliary duct morphogenesis by Claudin 15-like b

The intrahepatic biliary ducts transport bile produced by the hepatocytes out of the liver. Defects in biliary cell differentiation and biliary duct remodeling cause a variety of congenital diseases including Alagille Syndrome and polycystic liver disease. While the molecular pathways regulating biliary cell differentiation have received increasing attention (Lemaigre, 2010), less is known about the cellular behavior underlying biliary duct remodeling. Here, we have identified a novel gene, claudin 15-like b (cldn15lb), which exhibits a unique and dynamic expression pattern in the hepatocytes and biliary epithelial cells in zebrafish. Claudins are tight junction proteins that have been implicated in maintaining epithelial polarity, regulating paracellular transport, and providing barrier function. In zebrafish cldn15lb mutant livers, tight junctions are observed between hepatocytes, but these cells show polarization defects as well as canalicular malformations. Furthermore, cldn15lb mutants show abnormalities in biliary duct morphogenesis whereby biliary epithelial cells remain clustered together and form a disorganized network. Our data suggest that Cldn15lb plays an important role in the remodeling process during biliary duct morphogenesis. Thus, cldn15lb mutants provide a novel in vivo model to study the role of tight junction proteins in the remodeling of the biliary network and hereditary cholestasis.     

In vitro and in vivo hepatic transport of the magnetic resonance imaging contrast agent B22956/1: role of MRP proteins

The molecular mechanisms of the hepatic transport of B22956/1, a new gadolinium complex from the class of intravascular contrast agents for MRI, which undergoes extensive biliary elimination, were studied. Biliary and urinary elimination of B22956/1 were measured in normal and in mutant MRP2 lacking rats (TR(-)); cellular trafficking of the compound was assessed in wild and MRP1 or MRP2 transfected MDCKII cells. Eight hours after IV injection of B22956/1, 90+/-8% of the dose was recovered in the bile of normal rats. By contrast, in TR(-) rats, the biliary excretion was significantly lower (14+/-3%) while 55+/-9% of the compound was found in urine. In vitro, the cellular accumulation of B22956/1 was significantly lower in both MRP1 and MRP2 transfected cells as compared to wild type MDCKII cells, and the cellular efflux was prevented by the MRP inhibitor MK571, indicating the involvement of both MRP2 and MRP1 in the transport of B22956/1. Due to the distinct cellular localization of the proteins, MRP2 accounts for the biliary and urinary excretion of the compound, while MRP1 prevents cellular accumulation of the MRI agent. B22956/1 may be useful in clinical conditions where a defective biliary transport is present.     

Interaction of CD44 and hyaluronic acid enhances biliary epithelial proliferation in cholestatic livers

Biliary epithelia express high levels of CD44 in hepatobiliary diseases. The role of CD44-hyaluronic acid interaction in biliary pathology, however, is unclear. A rat model of hepatic cholestasis induced by bile duct ligation was employed for characterization of hepatic CD44 expression and extracellular hyaluronan distribution. Cell culture experiments were employed to determine whether hyaluronan can regulate cholangiocyte growth through interacting with adhesion molecule CD44. Biliary epithelial cells were found to express the highest level of CD44 mRNA among four major types of nonparenchymal liver cells, including Kupffer, hepatic stellate, and liver sinusoidal endothelial cells isolated from cholestatic livers. CD44-positive biliary epithelia lining the intrahepatic bile ducts were geographically associated with extracellular hyaluronan accumulated in the portal tracts of the livers, suggesting a role for CD44 and hyaluronan in the development of biliary proliferation. Cellular proliferation assays demonstrated that cholangiocyte propagation was accelerated by hyaluronan treatment and antagonized by small interfering RNA CD44 or anti-CD44 antibody. The study provides compelling evidence to suggest that proliferative biliary epithelia lining the intrahepatic bile ducts are a prime source of hepatic CD44. CD44-hyaluronan interaction, by enhancing biliary proliferation, may play a pathogenic role in the development of cholestatic liver diseases.     

Expression of neural cell adhesion molecule in human liver development and in congenital and acquired liver diseases

In the liver, neural cell adhesion molecule (NCAM) is a marker of immature cells committed to the biliary lineage and is expressed by reactive bile ductules in human liver diseases. We investigated the possible role of NCAM in the development of intrahepatic bile ducts and aimed at determining whether immature biliary cells can contribute to the repair of damaged bile ducts in chronic liver diseases. Therefore, we performed immunohistochemistry for NCAM and bile duct cell markers cytokeratin 7 and cytokeratin 19 on frozen sections of 85 liver specimens taken from 14 fetuses, 10 donor livers, 18 patients with congenital liver diseases characterized by ductal plate malformations (DPMs), and 43 cirrhotic explant livers. Duplicated ductal plates and incorporating bile ducts during development showed a patchy immunoreactivity for NCAM, while DPMs were continuously positive for NCAM. Bile ducts showing complete or patchy immunoreactivity for NCAM were found in cirrhotic livers, with higher frequency in biliary than in posthepatitic cirrhosis. Our results suggest that NCAM may have a function in the development of the intrahepatic bile ducts and that NCAM-positive immature biliary cells can contribute to the repair of damaged bile ducts in chronic liver diseases.     

Complex use of radiation diagnostic techniques in tumors of the pancreatoduodenal area

In the work are summarized the results of the examination of the 500 patients with tumors of pancreas (141), tumors of biliary ducts (9), tumor of duodenum (1), chronic pancreatitis (315), choledocholithiasis (12) and non-specific biliary dilatation (13). The are show the possibilities different methods of radiation diagnosis (ultrasonography, CT, MRI, MR cholangiopancreatography) in the differential diagnosis tumors of pancreatico-duodenal region, estimation of the localization, specification, degree of invasion into the neoplasms gathering round the cells. The paper presents algorithm, used in the Regional hospital of Chelyabinsk.     

Imaging multiple sclerosis and other neurodegenerative diseases

Although the prevalence of neurodegenerative diseases is increasing as a consequence of the growing aging population, the exact pathophysiological mechanisms leading to these diseases remains obscure. Multiple sclerosis (MS), an autoimmune disease of the central nervous system and the most frequent cause of disability among young people after traumatic brain injury, is characterized by inflammatory/demyelinating and neurodegenerative processes that occurr earlier in life. The ability to make an early diagnosis of MS with the support of conventional MRI techniques, provides the opportunity to study neurodegeneration and the underlying pathophysiological processes in earlier stages than in classical neurodegenerative diseases. This review summarizes mechanisms of neurodegeneration common to MS and to Alzheimer disease, Parkinson disease, and amiotrophic lateral sclerosis, and provides a brief overview of the neuroimaging studies employing MRI and PET techniques to investigate and monitor neurodegeneration in both MS and classical neurodegenerative diseases.     

Humoral Responses to Diverse Autoimmune Disease-Associated Antigens in Multiple Sclerosis

To compare frequencies of autoreactive antibody responses to endogenous disease-associated antigens in healthy controls (HC), relapsing and progressive MS and to assess their associations with clinical and MRI measures of MS disease progression.

Methods

The study analyzed 969 serum samples from 315 HC, 411 relapsing remitting MS (RR-MS), 128 secondary progressive MS (SP-MS), 33 primary progressive MS (PP-MS) and 82 patients with other neurological diseases for autoantibodies against two putative MS antigens CSF114(Glc) and KIR4.1a and KIR4.1b and against 24 key endogenous antigens linked to diseases such as vasculitis, systemic sclerosis, rheumatoid arthritis, Sjogren’s syndrome, systemic lupus erythematosus, polymyositis, scleroderma, polymyositis, dermatomyositis, mixed connective tissue disease and primary biliary cirrhosis. Associations with disability and MRI measures of lesional injury and neurodegeneration were assessed.

Results

The frequencies of anti-KIR4.1a and anti-KIR4.1b peptide IgG positivity were 9.8% and 11.4% in HC compared to 4.9% and 7.5% in RR-MS, 8.6% for both peptides in SP-MS and 6.1% for both peptides in PP-MS (p = 0.13 for KIR4.1a and p = 0.34 for KIR4.1b), respectively. Antibodies against CSF114(Glc), KIR4.1a and KIR4.1b peptides were not associated with MS compared to HC, or with MS disease progression. HLA DRB1*15:01 positivity and anti-Epstein Barr virus antibodies, which are MS risk factors, were not associated with these putative MS antibodies.

Conclusions

Antibody responses to KIR4.1a and KIR4.1b peptides are not increased in MS compared to HC nor associated with MS disease progression. The frequencies of the diverse autoreactive antibodies investigated are similar in MS and HC.     

Quantitative Measurements in the Human Hippocampus and Related Areas: Correspondence between Ex-Vivo MRI and Histological Preparations

The decrease of volume estimates in different structures of the medial temporal lobe related to memory correlate with the decline of cognitive functions in neurodegenerative diseases. This study presents data on the association between MRI quantitative parameters of medial temporal lobe structures and their quantitative estimate in microscopic examination. Twelve control cases had ex-vivo MRI, and thereafter, the temporal lobe of both hemispheres was sectioned from the pole as far as the level of the splenium of the corpus callosum. Nissl stain was used to establish anatomical boundaries between structures in the medial temporal lobe. The study included morphometrical and stereological estimates of the amygdaloid complex, hippocampus, and temporal horn of the lateral ventricle, as well as different regions of grey and white matter in the temporal lobe. Data showed a close association between morphometric MRI images values and those based on the histological determination of boundaries. Only values in perimeter and circularity of the piamater were different. This correspondence is also revealed by the stereological study, although irregular compartments resulted in a lesser agreement. Neither age (< 65 yr and > 65yr) nor hemisphere had any effect. Our results indicate that ex-vivo MRI is highly associated with quantitative information gathered by histological examination, and these data could be used as structural MRI biomarker in neurodegenerative diseases.     

Occurrence of various autoantibodies in autoimmune diseases

The study aimed at determining the incidence of autoantibodies occurrence in the course of autoimmunological diseases of the thyroid gland and in healthy population. Autoantibodies against various structures were assayed, including: cellular nuclei, smooth muscles, mitochondria, biliary tubules, parietal cells, reticular fibres, striated muscles as well as thyroglobulin and thyroid microsomes. The study involved 63 patients with autoimmunological diseases of the thyroid gland (35 patients with Graves-Basedow disease and 28 patients with Hashimoto's disease) and 30 healthy individuals. Thyroid antimicrosomal and antithyroglobulin antibodies were assayed with RIA in stable phase whereas the remaining antibodies--with multifunctional indirect immunofluorescence test. The obtained results are the following: antimicrosomal antibodies were present in 68.3% cases while antithyroglobulin antibodies in 76.2% of the examined patients with autoimmunological diseases of the thyroid gland. Immunofluorescence tests performed in the same group have shown antinuclear antibodies in 13% of cases, antibodies against smooth muscles in 28.6%, antimitochondrial antibodies in 1.6%, antibodies against biliary tubules in 3.4%, antibodies against parietal cells in 11.1%, antibodies against reticular fibres in 7.9%, and antibodies against striated muscles in 9.5% of cases. Antinuclear antibodies, antibodies against smooth muscles, and antibodies against both thyroidal microsome and thyroglobulin (in 3.3%) were the only antibodies found in the control group.     

Breast cancer resistance protein (BCRP/ABCG2) is expressed by progenitor cells/reactive ductules and hepatocytes and its expression pattern is influenced by disease etiology and species type: possible functional consequences.

Breast cancer resistance protein (BCRP/ABCG2) is an ATP-binding cassette transport protein that is expressed in several organs including the liver. Previous studies have shown that ABC transport proteins play an important pathophysiological role in several liver diseases. However, to date, expression pattern and possible role of BCRP in human liver diseases and animal models have not been studied in detail. Here we investigated the expression pattern of BCRP in normal liver, chronic parenchymal and biliary human liver diseases, and parallel in different rat models of liver diseases. Expression was studied by immunohistochemistry and additionally by RT-PCR analysis in Thy-1-positive rat oval cells. Bile ducts, hepatic progenitor cells, reactive bile ductules, and blood vessel endothelium were immunoreactive for BCRP in normal liver and all types of human liver diseases and in rat models. BCRP was expressed by the canalicular membrane of hepatocytes in normal and diseased human liver, but never in rat liver. Remarkably, there was also expression of BCRP at the basolateral pole of human hepatocytes, and this was most pronounced in chronic biliary diseases. In conclusion, BCRP positivity in the progenitor cells/reactive ductules could contribute to the resistance of these cells to cytotoxic agents and xenotoxins. Basolateral hepatocytic expression in chronic biliary diseases may be an adaptive mechanism to pump bile constituents back into the sinusoidal blood. Strong differences between human and rat liver must be taken into account in future studies with animal models.     

肝移植术后肝脏淋巴回流淤滞发生的影响因素初步临床分析

目的:分析肝移植术后肝脏淋巴回流淤滞(Intrahepatic lymphatic stasis,IHLS)的影响因素。方法:收集我院自2004~2012年期间行肝移植手术并经增强计算机断层扫描(Computed tomography,CT)和/或磁共振(Magnetic resonance imaging,MRI)确诊的IHLS病人,分析正常肝移植组IHLS阳性率与肝移植术后静脉并发症、胆道并发症、乙肝复发、肝癌复发、动脉并发症、移植排斥、药物性肝损害、转移瘤组IHLS阳性率的差异。结果:正常移植肝组术后IHLS的阳性率分别与术后胆道并发症、静脉并发症、乙肝复发组肝移植术后IHLS的阳性率差异有统计学意义(P0.05),与其他并发症组IHLS的阳性率差异无统计学意义(P0.05)。结论:肝移植术后静脉并发症、胆道并发症及乙肝复发可影响肝移植术后IHLS发生。     

Measurement of changes in amino acids related to total collagen in fibrotic human liver

In the liver, total collagen accumulation during the fibrotic or cirrhotic process was measured using a methodology based on the determination of collagen amino acids in liver biopsies from adults with alcoholic liver diseases or children with biliary atresia. The results obtained with this methodology were compared to histopathological findings. Thus, it was shown that generally the severity of hepatic injury was dependent on collagen accumulation. In biliary atresia, collagen accumulation increased with the children's age despite reconstructive surgery and restoration of biliary flow.     

Diagnostic Performance of a Rapid Magnetic Resonance Imaging Method of Measuring Hepatic Steatosis

Objectives

Hepatic steatosis is associated with an increased risk of developing serious liver disease and other clinical sequelae of the metabolic syndrome. However, visual estimates of steatosis from histological sections of biopsy samples are subjective and reliant on an invasive procedure with associated risks. The aim of this study was to test the ability of a rapid, routinely available, magnetic resonance imaging (MRI) method to diagnose clinically relevant grades of hepatic steatosis in a cohort of patients with diverse liver diseases.

Materials and Methods

Fifty-nine patients with a range of liver diseases underwent liver biopsy and MRI. Hepatic steatosis was quantified firstly using an opposed-phase, in-phase gradient echo, single breath-hold MRI methodology and secondly, using liver biopsy with visual estimation by a histopathologist and by computer-assisted morphometric image analysis. The area under the receiver operating characteristic (ROC) curve was used to assess the diagnostic performance of the MRI method against the biopsy observations.

Results

The MRI approach had high sensitivity and specificity at all hepatic steatosis thresholds. Areas under ROC curves were 0.962, 0.993, and 0.972 at thresholds of 5%, 33%, and 66% liver fat, respectively. MRI measurements were strongly associated with visual (r² = 0.83) and computer-assisted morphometric (r² = 0.84) estimates of hepatic steatosis from histological specimens.

Conclusions

This MRI approach, using a conventional, rapid, gradient echo method, has high sensitivity and specificity for diagnosing liver fat at all grades of steatosis in a cohort with a range of liver diseases.     

Role of new radiation techniques (ultrasonography, computed tomography, and magnetic resonance imaging) in the diagnosis of incidentally discovered adrenal masses

The authors analyze the current views of incidentally discovered adrenal masses and the potentialities of ultrasound study (US), computed tomography (CT), and magnetic resonance imaging (MRI) in their detection and presents the US, CT, and MRI symptoms of different incidentally discovered adrenal masses. Due to the availability and almost extensive application of US apparatuses, they define the importance of US screening of the adrenal region and emphasize the capacities of echographic differentiation of cystic and solid adrenal masses in patients with different diseases of the abdomen and retroperitoneal space. The authors also note the basic role of CT and MRI in the specified topical diagnosis of retroperitoneal space lesions and in the presumption of the morphological structure of some tumor and tumoroid (hyperplasia-type) adrenal changes.     

Immuno-isolation and culture of biliary epithelial cells from normal human liver

Summary Biliary epithelial cells (BEC) lining the intra-hepatic biliary ducts are the site of damage in several immunologically mediated liver diseases. BEC are difficult to isolate since they represent only 5% of the total cell number in normal liver. In this communication, a novel method for their isolation from normal liver is presented using a monoclonal antibody (HEA125) with specificity for an epithelial cell surface glyco-protein reported to be expressed in liver only by biliary epithelium. By combining differential density centrifugation and immuno-magnetic separation using HEA125 pure BEC (10⁵ cells/g fresh tissue) were prepared routinely. These cells were maintained in culture for up to 4 weeks with significant increases in cell numbers. The ability to prepare BEC from human liver offers an opportunity to develop In Vitro models to investigate the aetiology of diseases in intra-hepatic biliary epithelium. EDITOR’S STATEMENT This is a novel application to purification of specific liver cell types directly from tissue. It is well-suited for rapid communication because of its novelty and potential utility to investigators.     

Animal models of cholestasis: An update on inflammatory cholangiopathies

Cholestasis is a frequent clinical condition initiating or complicating chronic liver diseases, particularly cholangiopathies, where the biliary epithelium is the primary target of the pathogenetic sequence. Until a few decades ago, understanding of cholestasis relied mostly on the experimental model of bile duct ligation in rodents. However, a simple model of biliary obstruction cannot reproduce the complex mechanisms and networks leading to cholestasis in cholangiopathies. These networks are underpinned by an intricate dysregulation of pro-inflammatory and pro-fibrotic signals involving besides cholangiocytes, multiple cell elements of both innate and adaptive immunity. Therefore, in the last years, a wide range of animal models of biliary injury have been developed, mostly in mice, following three main approaches, chemical induction, immunization and genetic manipulation. In this review, we will give an update of the animal models of the two main cholangiopathies, primary sclerosing cholangitis and primary biliary cholangitis, which have provided us with the most relevant insights into the pathogenesis of these still controversial diseases.     

Magnetic resonance tomography in the diagnosis of nonorganic bulky masses of the retroperitoneal space. Part 1. Cysts,abscesses and flegmons

The paper considers the diagnostic capacities of magnetic resonance imaging (MRI) in detecting non-organic bulky masses of the retroperitoneal space. Based on the analysis of tomographic findings in 23 patients with non-organic cysts of the retroperitoneal space and 27 patients with its abscesses and phlegmons, the first part of the paper describes the MRI semiotics of these diseases in detail and proposes methodic approaches to their identification. Comparison of the data of MRI and pathomorphological analysis of operation materials has yielded the rates of sensitivity, specificity, and accuracy of the method, which are equal to 100, 88.5, and 94.2% for non-organic cysts and 100, 87.1, and 93.5%, respectively. The authors note the lower efficiency of MRI in recognizing hydatid cysts and foreign bodies than ultrasound study and X-ray computed tomography and show it necessary to take into account clinical information in making a radiological conclusion.