Perihilar Glissonian Approach for Anatomical Parenchymal Sparing Liver Resections: Technical Aspects: The Taping Game.

PubMed

Figueroa, Rodrigo; Laurenzi, Andrea; Laurent, Alexis; Cherqui, Daniel

2018-03-01

To present technical details for central hepatectomy and right anterior and posterior sectionectomies using perihilar Glissonian approach for anatomical delineation and selective inflow occlusion. Central tumors and those deeply located in the right liver may require extensive resections because of their proximity to major vascular structures. In such cases, anatomical more limited resections such as central hepatectomy or sectionectomies may provide an alternative to extensive surgery by assuring both parenchymal sparing and suitable oncologic resection. We present the global concept for performing a perihilar Glissonian approach and its application to each individual anatomical procedure. This includes detailed descriptions, illustrations, and videos demonstrating the technique. This technique was applied since 1991 for anatomical parenchymal resections including central hepatectomy (resection of segments 4, 5, and 8), right anterior sectionectomy (resection of segments 5 and 8), and right posterior sectionectomy (resection of segments 6 and 7). The feasibility rate of the Glissonian approach was 88%. Perihilar Glissonian approach is a safe and reproducible technique that enables anatomical parenchymal preserving liver resections for selected central and right-sided deeply located tumors.

Copper uptake and retention in liver parenchymal cells isolated from nutritionally copper-deficient rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van den Berg, G.J.; de Goeij, J.J.; Bock, I.

1991-08-01

Copper uptake and retention were studied in primary cultures of liver parenchymal cells isolated from copper-deficient rats. Male Sprague-Dawley rats were fed a copper-deficient diet (less than 1 mg Cu/kg) for 10 wk. Copper-deficient rats were characterized by low copper concentrations in plasma and liver, anemia, low plasma ceruloplasmin oxidase activity and increased 64Cu whole-body retention. Freshly isolated liver parenchymal cells from copper-deficient rats showed a higher 64Cu influx, which was associated with a higher apparent Vmax of 45 {plus minus} 4 pmol Cu.mg protein-1.min-1 as compared with 30 {plus minus} 3 pmol Cu.mg protein-1.min-1 for cells isolated from copper-sufficientmore » rats. No significant difference in the apparent Km (approximately 30 mumol/L) was observed. Relative 64Cu efflux from cells from copper-deficient rats was significantly smaller than the efflux from cells from copper-sufficient rats after prelabeling as determined by 2-h efflux experiments. Analysis of the medium after efflux from cells from copper-deficient rats showed elevated protein-associated 64Cu, suggesting a higher incorporation of radioactive copper during metalloprotein synthesis. Effects of copper deficiency persist in primary cultures of parenchymal cells derived from copper-deficient rats, and short-term cultures of these cells offer a prospect for the study of cell biological aspects of the metabolic adaptation of the liver to copper deficiency.« less

A systematic review on radiofrequency assisted laparoscopic liver resection: Challenges and window to excel.

PubMed

Reccia, Isabella; Kumar, Jayant; Kusano, Tomokazu; Zanellato, Artur; Draz, Ahmed; Spalding, Duncan; Habib, Nagy; Pai, Madhava

2017-09-01

Laparoscopic liver resection has progressively gained acceptance as a safe and effective procedure in the treatment of benign and malignant liver neoplasms. However, blood loss remains the major challenge in liver surgery. Several techniques and devices have been introduced in liver surgery in order to minimize intraoperative haemorrhage during parenchymal transection. Radiofrequency (RF)-assisted liver resection has been shown to be an effective method to minimize bleeding in open and laparoscopic liver resection. A number of RF devices for parenchymal transection have been designed to assist laparoscopic liver resections. Here we have reviewed the results of various RF devices in laparoscopic liver resection. A total 15 article were considered relevant for the evaluation of technical aspects and outcomes of RF-assisted liver resections in laparoscopic procedures. In these studies, 176 patients had laparoscopic liver resection using RF-assisted parenchymal coagulation. Two monopolar and three bipolar devices were employed. Blood loss was limited in most of the studies. The need of blood transfusions was limited to two cases in all the series. Conversion was necessary due to bleeding in 3 cases. Operative and transection times varied between studies. However, RF-assisted resection with bipolar devices appeared to have taken less time in comparison to other RF devices. RF-related complications were minimum, and only one case of in-hospital death due to hepatic failure was reported. Although RF has been used in a small minority of laparoscopic liver resections, laparoscopic RF-assisted liver resection for benign and malignant disease is a safe and feasible procedure associated with reduction in blood loss, low morbidity, and lower hospital mortality rates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of human patient plasma ex vivo treatment on gene expression and progenitor cell activation of primary human liver cells in multi-compartment 3D perfusion bioreactors for extra-corporeal liver support.

PubMed

Schmelzer, Eva; Mutig, Kerim; Schrade, Petra; Bachmann, Sebastian; Gerlach, Jörg C; Zeilinger, Katrin

2009-07-01

Cultivation of primary human liver cells in innovative 3D perfusion multi-compartment capillary membrane bioreactors using decentralized mass exchange and integral oxygenation provides in vitro conditions close to the physiologic environment in vivo. While a few scale-up bioreactors were used clinically, inoculated liver progenitors in these bioreactors were not investigated. Therefore, we characterized regenerative processes and expression patterns of auto- and paracrine mediators involved in liver regeneration in bioreactors after patient treatment. Primary human liver cells containing parenchymal and non-parenchymal cells co-cultivated in bioreactors were used for clinical extra-corporeal liver support to bridge to liver transplantation. 3D tissue re-structuring in bioreactors was studied; expression of proteins and genes related to regenerative processes and hepatic progenitors was analyzed. Formation of multiple bile ductular networks and colonies of putative progenitors were observed within parenchymal cell aggregates. HGF was detected in scattered cells located close to vascular-like structures, expression of HGFA and c-Met was assigned to biliary cells and hepatocytes. Increased expression of genes associated to hepatic progenitors was detected following clinical application. The results confirm auto- and paracrine interactions between co-cultured cells in the bioreactor. The 3D bioreactor provides a valuable tool to study mechanisms of progenitor activation and hepatic regeneration ex vivo under patient plasma treatment. (c) 2009 Wiley Periodicals, Inc.

The Linear ubiquitin chain assembly complex acts as a liver tumor suppressor and inhibits hepatocyte apoptosis and hepatitis.

PubMed

Shimizu, Yutaka; Peltzer, Nieves; Sevko, Alexandra; Lafont, Elodie; Sarr, Aida; Draberova, Helena; Walczak, Henning

2017-06-01

Linear ubiquitination is a key posttranslational modification that regulates immune signaling and cell death pathways, notably tumor necrosis factor receptor 1 (TNFR1) signaling. The only known enzyme complex capable of forming linear ubiquitin chains under native conditions to date is the linear ubiquitin chain assembly complex, of which the catalytic core component is heme-oxidized iron regulatory protein 2 ubiquitin ligase-1-interacting protein (HOIP). To understand the underlying mechanisms of maintenance of liver homeostasis and the role of linear ubiquitination specifically in liver parenchymal cells, we investigated the physiological role of HOIP in the liver parenchyma. To do so, we created mice harboring liver parenchymal cell-specific deletion of HOIP (Hoip Δhep mice) by crossing Hoip-floxed mice with albumin-Cre mice. HOIP deficiency in liver parenchymal cells triggered tumorigenesis at 18 months of age preceded by spontaneous hepatocyte apoptosis and liver inflammation within the first month of life. In line with the emergence of inflammation, Hoip Δhep mice displayed enhanced liver regeneration and DNA damage. In addition, consistent with increased apoptosis, HOIP-deficient hepatocytes showed enhanced caspase activation and endogenous formation of a death-inducing signaling complex which activated caspase-8. Unexpectedly, exacerbated caspase activation and apoptosis were not dependent on TNFR1, whereas ensuing liver inflammation and tumorigenesis were promoted by TNFR1 signaling. The linear ubiquitin chain assembly complex serves as a previously undescribed tumor suppressor in the liver, restraining TNFR1-independent apoptosis in hepatocytes which, in its absence, is causative of TNFR1-mediated inflammation, resulting in hepatocarcinogenesis. (Hepatology 2017;65:1963-1978). © 2017 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.

Liver transplantation in man: morphometric analysis of the parenchymal alterations following cold ischaemia and warm ischaemia/reperfusion

PubMed Central

VIZZOTTO, LAURA; VERTEMATI, MAURIZIO; DEGNA, CARLO TOMMASINI; ASENI, PAOLO

2001-01-01

Ischaemia and reperfusion phases represent critical events during liver transplantation. The purpose of this study was to describe morphological alterations of both vascular and parenchymal compartments after ischaemia and reperfusion and to evaluate the possible relationship between morphometric parameters and biochemical/clinical data. Three needle biopsies were drawn from 20 patients who underwent orthotopic liver transplantation. The first biopsy was taken before flushing with preservation solution, and the second and the third to evaluate respectively the effects of cold ischaemia and of warm ischaemia/reperfusion. Biopsies were examined by an image analyser and morphometric parameters related to the liver parenchyma were evaluated. At the second biopsy we observed a decrease of the endothelium volume fraction while the same parameter referred to the sinusoidal lumen achieved a peak value. The hepatocytes showed a lower surface parenchymal/vascular sides ratio. This parameter was reversed at the end of the reperfusion phase; furthermore the third biopsy revealed endothelial swelling and a decreased volume fraction of the sinusoidal lumen. The results quantify the damage to the sinusoidal bed which, as already known, is one of the main targets of cold ischaemia; warm ischaemia and reperfusion accentuate endothelial damage. The end of transplantation is characterised by damage chiefly to parenchymal cells. Hepatocytes show a rearrangement of their surface sides, probably related to the alterations of the sinusoidal bed. In addition, the fluctuations of morphometric parameters during ischaemia/reperfusion correlate positively with biochemical data and clinical course of the patients. PMID:11430699

Recent Advancements in Diagnosis and Therapy of Liver Cirrhosis.

PubMed

Romanelli, Roberto Giulio; Stasi, Cristina

2016-01-01

Cirrhosis is a diffuse pathophysiological state of the liver considered to be the final stage of various liver injuries, characterized by chronic necroinflammatory and fibrogenetic processes, with subsequent conversion of normal liver architecture into structurally abnormal nodules, dense fibrotic septa, concomitant parenchymal exaustment and collapse of the liver tissue. Alcoholic liver disease and chronic infections due to HBV and/or HCV constitute the main causes of liver cirrhosis worldwide. During a lag time of 15 to 30 years, chronic liver diseases can lead to liver cirrhosis and its complications. Active hepatic inflammation plays a pivotal role in the inflammation- necrosis-regeneration process, which eventually leads to liver cirrhosis and hepatocellular carcinoma. Prognosis of liver cirrhosis is highly variable and influenced by several variables, such as etiology, severity of liver disease, presence of complications and comorbidities. In advanced cirrhosis, survival decreases to one or two years. Correct advanced diagnosis and selected treatment with different molecules may help in understanding mechanisms of fibrogenesis, the driving forces of cirrhosis's pathogenesis, and the scrupulous approach to more effective therapeutic procedures. Prevention of fibrosis with further deterioration of liver function through specific treatments is always required, through the removal of the underlying causes of liver disease. Advanced liver disease, with subsequent complications, requires targeted treatment. Therefore, the aim of this review is to assess the diagnosis and treatment of liver cirrhosis on the pathophysiological bases, searching for relevant studies published in English using the PubMed database from 2011 to the present.

Pulmonary Hypertension in Parenchymal Lung Disease

PubMed Central

Tsangaris, Iraklis; Tsaknis, Georgios; Anthi, Anastasia; Orfanos, Stylianos E.

2012-01-01

Idiopathic pulmonary arterial hypertension (IPAH) has been extensively investigated, although it represents a less common form of the pulmonary hypertension (PH) family, as shown by international registries. Interestingly, in types of PH that are encountered in parenchymal lung diseases such as interstitial lung diseases (ILDs), chronic obstructive pulmonary disease (COPD), and many other diffuse parenchymal lung diseases, some of which are very common, the available data is limited. In this paper, we try to browse in the latest available data regarding the occurrence, pathogenesis, and treatment of PH in chronic parenchymal lung diseases. PMID:23094153

[A novel compound heterozygous mutation in ABCA3 gene in a child with diffuse parenchymal lung disease].

PubMed

Bao, Y M; Liu, X L; Liu, X L; Chen, J H; Zheng, Y J

2017-11-02

Objective: To summarize the clinical characteristics of the diffuse parenchymal lung diseases in a child caused by a novel compound heterozygous ABCA3 mutation and explore the association between the phenotype and ABCA3 mutation. Method: The clinical material of a patient diagnosed with diffuse parenchymal lung disease with ABCA3 mutation in December 2016 in Shenzhen Children's Hospital was analyzed. The information about ABCA3 gene mutation updated before April, 2017 was searched and collected from the gene databases (including 1000Genomes, HGMD, EXAC) and the literatures (including Wanfang Chinese database and Pubmed). Result: The girl was one year and nine months old. She presented with chronic cough, tachypnea, cyanosis and failure to thrive since she was one year and three months old. Her condition gradually deteriorated after she was empirically treated. Physical examination showed malnutrition, tachypnea and clubbed-fingers. Her high resolution computed tomography (HRCT) revealed diffused ground-glass opacities, thickened interlobular septum, and multiple subpleural small air-filled lung cysts. The second generation sequencing study identified a novel compound heterozygous mutation (c.1755delC+c.2890G>A) in her ABCA3 gene, which derived respectively from her parents and has not been reported in the database and the literatures mentioned above. Conclusion: c.1755delC+c.2890G>A is a new kind of compound heterozygous mutation in ABCA3, which can cause children's diffuse parenchymal lung disease. Its phenotype is related to its genotype.

Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME.

PubMed

Godoy, Patricio; Hewitt, Nicola J; Albrecht, Ute; Andersen, Melvin E; Ansari, Nariman; Bhattacharya, Sudin; Bode, Johannes Georg; Bolleyn, Jennifer; Borner, Christoph; Böttger, Jan; Braeuning, Albert; Budinsky, Robert A; Burkhardt, Britta; Cameron, Neil R; Camussi, Giovanni; Cho, Chong-Su; Choi, Yun-Jaie; Craig Rowlands, J; Dahmen, Uta; Damm, Georg; Dirsch, Olaf; Donato, María Teresa; Dong, Jian; Dooley, Steven; Drasdo, Dirk; Eakins, Rowena; Ferreira, Karine Sá; Fonsato, Valentina; Fraczek, Joanna; Gebhardt, Rolf; Gibson, Andrew; Glanemann, Matthias; Goldring, Chris E P; Gómez-Lechón, María José; Groothuis, Geny M M; Gustavsson, Lena; Guyot, Christelle; Hallifax, David; Hammad, Seddik; Hayward, Adam; Häussinger, Dieter; Hellerbrand, Claus; Hewitt, Philip; Hoehme, Stefan; Holzhütter, Hermann-Georg; Houston, J Brian; Hrach, Jens; Ito, Kiyomi; Jaeschke, Hartmut; Keitel, Verena; Kelm, Jens M; Kevin Park, B; Kordes, Claus; Kullak-Ublick, Gerd A; LeCluyse, Edward L; Lu, Peng; Luebke-Wheeler, Jennifer; Lutz, Anna; Maltman, Daniel J; Matz-Soja, Madlen; McMullen, Patrick; Merfort, Irmgard; Messner, Simon; Meyer, Christoph; Mwinyi, Jessica; Naisbitt, Dean J; Nussler, Andreas K; Olinga, Peter; Pampaloni, Francesco; Pi, Jingbo; Pluta, Linda; Przyborski, Stefan A; Ramachandran, Anup; Rogiers, Vera; Rowe, Cliff; Schelcher, Celine; Schmich, Kathrin; Schwarz, Michael; Singh, Bijay; Stelzer, Ernst H K; Stieger, Bruno; Stöber, Regina; Sugiyama, Yuichi; Tetta, Ciro; Thasler, Wolfgang E; Vanhaecke, Tamara; Vinken, Mathieu; Weiss, Thomas S; Widera, Agata; Woods, Courtney G; Xu, Jinghai James; Yarborough, Kathy M; Hengstler, Jan G

2013-08-01

This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a secondary phase that may dramatically aggravate the initial damage. Hepatotoxicity, as well as hepatic metabolism, is controlled by a set of nuclear receptors (including PXR, CAR, HNF-4α, FXR, LXR, SHP, VDR and PPAR) and signaling pathways. When isolating liver cells, some pathways are activated, e.g., the RAS/MEK/ERK pathway, whereas others are silenced (e.g. HNF-4α), resulting in up- and downregulation of hundreds of genes. An understanding of these changes is crucial for a correct interpretation of in vitro data. The possibilities and limitations of the most useful liver in vitro systems are summarized, including three-dimensional culture techniques, co-cultures with non-parenchymal cells, hepatospheres, precision cut liver slices and the isolated perfused liver. Also discussed is how closely hepatoma, stem cell and iPS cell-derived hepatocyte-like-cells resemble real hepatocytes. Finally, a summary is given of the state of the art of liver in vitro and mathematical modeling systems that are currently used in the pharmaceutical industry with an emphasis on drug metabolism, prediction of clearance, drug interaction, transporter studies and hepatotoxicity. One key message is that despite our enthusiasm for in vitro systems, we must never lose sight of the in vivo situation. Although hepatocytes have been isolated for decades, the hunt for relevant alternative systems has only just begun.

Rat liver endothelial and Kupffer cell-mediated mutagenicity and polycyclic aromatic hydrocarbons and aflatoxin B sub 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steinberg, P.; Schlemper, B.; Molitor, E.

The ability of isolated rat liver endothelial and Kupffer cells to activate benzo(a)pyrene (BP), trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene (DDBP), trans-1,2-dihydroxy-1,2-dihydrochrysene (DDCH), and aflatoxin B{sub 1} (AFB{sub 1}) to mutagenic metabolites was assessed by means of a cell-mediated bacterial mutagenicity assay and compared with the ability of parenchymal cells to activate these compounds. Endothelial and Kupffer cells from untreated rats were able to activate AFB{sub 1} and DDBP; DDBP was activated even in the absence of an NADPH-generating system. Pretreating the animals with Aroclor 1254 strongly enhanced the mutagenicity of the dihydrodiol, whereas the mutagenicity of AFB{sub 1} showed a slight increase. BP andmore » DDCH were only activated by endothelial and Kupffer cells isolated from Aroclor 1254-pretreated rats. Parenchymal cells form untreated animals activated all four carcinogens tested; Aroclor 1254 enhanced the parenchymal cell-mediated mutagenicity of BP and DDCH but did not affect that of DDBP and clearly reduced that of AFB{sub 1}. The reduced mutagenicity of AFB{sub 1} correlates with the decrease in the amount of 2{alpha}-hydroxytestosterone formed when testosterone was incubated with parenchymal cell microsomes from Aroclor 1254-pretreated rats (compared with microsomes from untreated animals): the formation of 2{alpha}-hydroxytestosterone is specifically catalyzed by cytochrome P-450h, a hemoprotein thought to be involved in the activation of AFB{sub 1}. These results show that not only rat liver parenchymal cells, but also endothelial and Kupffer cells, activated several carcinogens to mutagenic metabolites.« less

Protocol for Isolation of Primary Human Hepatocytes and Corresponding Major Populations of Non-parenchymal Liver Cells

PubMed Central

Pfeiffer, Elisa; Zeilinger, Katrin; Seehofer, Daniel; Damm, Georg

2016-01-01

Beside parenchymal hepatocytes, the liver consists of non-parenchymal cells (NPC) namely Kupffer cells (KC), liver endothelial cells (LEC) and hepatic Stellate cells (HSC). Two-dimensional (2D) culture of primary human hepatocyte (PHH) is still considered as the "gold standard" for in vitro testing of drug metabolism and hepatotoxicity. It is well-known that the 2D monoculture of PHH suffers from dedifferentiation and loss of function. Recently it was shown that hepatic NPC play a central role in liver (patho-) physiology and the maintenance of PHH functions. Current research focuses on the reconstruction of in vivo tissue architecture by 3D- and co-culture models to overcome the limitations of 2D monocultures. Previously we published a method to isolate human liver cells and investigated the suitability of these cells for their use in cell cultures in Experimental Biology and Medicine1. Based on the broad interest in this technique the aim of this article was to provide a more detailed protocol for the liver cell isolation process including a video, which will allow an easy reproduction of this technique. Human liver cells were isolated from human liver tissue samples of surgical interventions by a two-step EGTA/collagenase P perfusion technique. PHH were separated from the NPC by an initial centrifugation at 50 x g. Density gradient centrifugation steps were used for removal of dead cells. Individual liver cell populations were isolated from the enriched NPC fraction using specific cell properties and cell sorting procedures. Beside the PHH isolation we were able to separate KC, LEC and HSC for further cultivation. Taken together, the presented protocol allows the isolation of PHH and NPC in high quality and quantity from one donor tissue sample. The access to purified liver cell populations could allow the creation of in vivo like human liver models. PMID:27077489

Protocol for Isolation of Primary Human Hepatocytes and Corresponding Major Populations of Non-parenchymal Liver Cells.

PubMed

Kegel, Victoria; Deharde, Daniela; Pfeiffer, Elisa; Zeilinger, Katrin; Seehofer, Daniel; Damm, Georg

2016-03-30

Beside parenchymal hepatocytes, the liver consists of non-parenchymal cells (NPC) namely Kupffer cells (KC), liver endothelial cells (LEC) and hepatic Stellate cells (HSC). Two-dimensional (2D) culture of primary human hepatocyte (PHH) is still considered as the "gold standard" for in vitro testing of drug metabolism and hepatotoxicity. It is well-known that the 2D monoculture of PHH suffers from dedifferentiation and loss of function. Recently it was shown that hepatic NPC play a central role in liver (patho-) physiology and the maintenance of PHH functions. Current research focuses on the reconstruction of in vivo tissue architecture by 3D- and co-culture models to overcome the limitations of 2D monocultures. Previously we published a method to isolate human liver cells and investigated the suitability of these cells for their use in cell cultures in Experimental Biology and Medicine(1). Based on the broad interest in this technique the aim of this article was to provide a more detailed protocol for the liver cell isolation process including a video, which will allow an easy reproduction of this technique. Human liver cells were isolated from human liver tissue samples of surgical interventions by a two-step EGTA/collagenase P perfusion technique. PHH were separated from the NPC by an initial centrifugation at 50 x g. Density gradient centrifugation steps were used for removal of dead cells. Individual liver cell populations were isolated from the enriched NPC fraction using specific cell properties and cell sorting procedures. Beside the PHH isolation we were able to separate KC, LEC and HSC for further cultivation. Taken together, the presented protocol allows the isolation of PHH and NPC in high quality and quantity from one donor tissue sample. The access to purified liver cell populations could allow the creation of in vivo like human liver models.

The utility of uric acid assay in dogs as an indicator of functional hepatic mass.

PubMed

Hill, J M; Leisewitz, A L; Goddard, A

2011-06-01

Uric acid was used as a test for liver disease before the advent of enzymology. Three old studies criticised uric acid as a test of liver function. Uric acid, as an end-product of purine metabolism in the liver, deserved re-evaluation as a liver function test. Serum totalbile acids are widely accepted as the most reliable liver function test. This study compared the ability of serum uric acid concentration to assess liver function with that of serum pre-prandial bile acids in dogs. In addition, due to the renal excretion of uric acid the 2 assays were also compared in a renal disease group. Using a control group of healthy dogs, a group of dogs with congenital vascular liver disease, a group of dogs with non-vascular parenchymal liver diseases and a renal disease group, the ability of uric acid and pre-prandial bile acids was compared to detect reduced functional hepatic mass overall and in the vascular or parenchymal liver disease groups separately. Sensitivities, specificities and predictive value parameters were calculated for each test. The medians of uric acid concentration did not differ significantly between any of the groups, whereas pre-prandial bile acids medians were significantly higher in the liver disease groups compared with the normal and renal disease group of dogs. The sensitivity of uric acid in detecting liver disease overall was 65% while the specificity of uric acid in detecting liver disease overall was 59%. The sensitivity and specificity of uric acid in detecting congenital vascular liver disease was 68% and 59%, respectively. The sensitivity and specificity of uric acid in detecting parenchymal liver disease was 63% and 60%, respectively. The overall positive and negative predictive values for uric acid in detecting liver disease were poor and the data in this study indicated uric acid to be an unreliable test of liver function. In dogs suffering from renal compromise serum uric acid concentrations may increase into the abnormal range due to its renal route of excretion.

T-drain reduces the incidence of biliary leakage after liver resection.

PubMed

Eurich, Dennis; Henze, S; Boas-Knoop, S; Pratschke, J; Seehofer, D

2016-12-01

Biliary leakage is a serious complication after liver resection and represents the major cause of post-operative morbidity. In spite of already identified risk factors, little is known about the role of intra-biliary pressure following liver surgery in the development of biliary leakage. Biliary decompression may have a positive impact and reduce the incidence of biliary leakage at the parenchymal resection site. 397 patients undergoing liver resection without bilioenteric anastomosis were included in the retrospective analysis of the risk factors for the development of biliary leakage focusing on the intra-operative reduction of the biliary pressure by T-tube and liver histology. Among 397 analyzed patients after parenchymal resection, biliary leakage occurred in 39 cases (9.8 %). The extent of parenchymal resection was not associated with the total occurrence of biliary leak (p = 0.626). Lower incidence of biliary leakage from the resection surface was significantly associated with the use of T-tube (4.9 vs. 13.2 %; p = 0.006). In the subgroup analysis, insertion of a T-tube was not associated with a reduction of biliary leakage after anatomical hemihepatectomies (p = 0.103) and extraanatomical liver resection (p = 0.676). However, a high statistical significance could be detected in patients with extended hemihepatectomies (58.3 vs. 3.8 %; p < 0.001). Once biliary leak occurred without T-tube, median hospitalization duration significantly increased compared to patients with biliary decompression and without biliary leak (p < 0.001). The results of our retrospective data analysis suggest a significant beneficial impact of the T-tube on the development of biliary leakage in patients undergoing extended liver surgery.

Anatomy of Hepatic Resectional Surgery.

PubMed

Lowe, Michael C; D'Angelica, Michael I

2016-04-01

Liver anatomy can be variable, and understanding of anatomic variations is crucial to performing hepatic resections, particularly parenchymal-sparing resections. Anatomic knowledge is a critical prerequisite for effective hepatic resection with minimal blood loss, parenchymal preservation, and optimal oncologic outcome. Each anatomic resection has pitfalls, about which the operating surgeon should be aware and comfortable managing intraoperatively. Copyright © 2016 Elsevier Inc. All rights reserved.

Cellular localization of thrombopoietin mRNA in the liver by in situ hybridization.

PubMed

Nomura, S; Ogami, K; Kawamura, K; Tsukamoto, I; Kudo, Y; Kanakura, Y; Kitamura, Y; Miyazaki, H; Kato, T

1997-07-01

The expression of thrombopoietin (TPO) mRNA is observed in several tissues, including liver, kidney, brain, skeletal muscle, intestine, spleen, and bone marrow. Among these organs, the highest expression of TPO mRNA is detected in the liver. We identified cells producing TPO by means of in situ hybridization of adult rat liver using digoxigenin-11-UTP-labeled cRNA probes. We found that the cells expressing TPO mRNA also expressed serum albumin mRNA. TPO mRNA was detected in parenchymal cells (hepatocytes) but not in non-parenchymal cells (including endothelial cells, epithelial cells, and so forth). To determine the location of TPO expression in embryogenesis, sections of fetal mice were further analyzed by in situ hybridization. TPO mRNA was detected only in hepatocytes of fetal liver, which was also the major site of hematopoiesis. The expression of TPO mRNA in fetal liver was observed from 12.5 days postcoitus. Northern blot analysis showed that mouse liver transcribed the same size of TPO mRNA in the fetus and in the adult. These results clearly demonstrate that hepatocytes are the primary site of TPO production in the liver from fetus to adult.

Diffuse Parenchymal Diseases Associated With Aluminum Use and Primary Aluminum Production

PubMed Central

2014-01-01

Aluminum use and primary aluminum production results in the generation of various particles, fumes, gases, and airborne materials with the potential for inducing a wide range of lung pathology. Nevertheless, the presence of diffuse parenchymal or interstitial lung disease related to these processes remains controversial. The relatively uncommon occurrence of interstitial lung diseases in aluminum-exposed workers—despite the extensive industrial use of aluminum—the potential for concurrent exposure to other fibrogenic fibers, and the previous use of inhaled aluminum powder for the prevention of silicosis without apparent adverse respiratory effects are some of the reasons for this continuing controversy. Specific aluminum-induced parenchymal diseases described in the literature, including existing evidence of interstitial lung diseases, associated with primary aluminum production are reviewed. PMID:24806728

Pathogenesis of Nonalcoholic Steatohepatitis: Interactions between Liver Parenchymal and Nonparenchymal Cells

PubMed Central

Magee, Nancy; Zou, An

2016-01-01

Nonalcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease in the Western countries, affecting up to 25% of the general population and becoming a major health concern in both adults and children. NAFLD encompasses the entire spectrum of fatty liver disease in individuals without significant alcohol consumption, ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) and cirrhosis. NASH is a manifestation of the metabolic syndrome and hepatic disorders with the presence of steatosis, hepatocyte injury (ballooning), inflammation, and, in some patients, progressive fibrosis leading to cirrhosis. The pathogenesis of NASH is a complex process and implicates cell interactions between liver parenchymal and nonparenchymal cells as well as crosstalk between various immune cell populations in liver. Lipotoxicity appears to be the central driver of hepatic cellular injury via oxidative stress and endoplasmic reticulum (ER) stress. This review focuses on the contributions of hepatocytes and nonparenchymal cells to NASH, assessing their potential applications to the development of novel therapeutic agents. Currently, there are limited pharmacological treatments for NASH; therefore, an increased understanding of NASH pathogenesis is pertinent to improve disease interventions in the future. PMID:27822476

A retrospective histopathological survey on canine and feline liver diseases at the University of Tokyo between 2006 and 2012.

PubMed

Hirose, Naoki; Uchida, Kazuyuki; Kanemoto, Hideyuki; Ohno, Koichi; Chambers, James K; Nakayama, Hiroyuki

2014-07-01

To determine the incidence of hepatic diseases in dogs and cats in Japan, a retrospective study was performed using data of 463 canine and 71 feline liver biopsies at the Veterinary Medical Center of the University of Tokyo. The most common canine hepatic disease was microvascular dysplasia (MVD) and occupied 29.4% of all diagnoses. This terminology might contain "real" MVD and primary portal vein hypoplasia, because these two conditions were difficult to be clearly distinguished histopathologically. Parenchymal and interstitial hepatitis and primary hepatic tumors accounted for 23.5% and 21.0% of the diagnoses, respectively. Parenchymal and interstitial hepatitis occupied 34.1% of non-proliferative canine hepatic diseases, while hepatocellular adenoma and carcinoma were 26.6% and 24.5% of proliferative hepatic diseases, respectively. Breed-specificity was seen in MVD for Yorkshire terrier, Papillon and Toy poodle, in hepatitis for Doberman pinscher and Labrador retriever, in cholangiohepatitis for American cocker spaniel, Miniature schnauzer and Pomeranian, in hepatocellular adenoma for Golden retriever and Shiba and in hepatocellular carcinoma for Shih Tzu. The most common feline liver disease was parenchymal and interstitial hepatitis (45.1% of all diagnoses). Among feline hepatitis, neutrophilic cholangiohepatitis (23.9%), lymphocytic cholangiohepatitis (14.1%) and chronic hepatitis (5.6%) were recorded. Adult polycystic liver disease was 5.6%. Among proliferative diseases in the feline liver (11.3% of the all), lymphoma (4.2%) and primary epithelial tumors (4.2%) including hepatocellular carcinoma, cholangiocellular adenoma and cholangiocellular carcinoma were observed. Hepatic degeneration was 14.1%, and MVD was 12.7%, respectively.

Nor-Ursodeoxycholic Acid as a Novel Therapeutic Approach for Cholestatic and Metabolic Liver Diseases.

PubMed

Halilbasic, Emina; Steinacher, Daniel; Trauner, Michael

2017-01-01

Norursodeoxycholic acid (norUDCA) is a side-chain-shortened derivative of ursodeoxycholic acid with relative resistance to amidation, which enables its cholehepatic shunting. Based on its specific pharmacologic properties, norUDCA is a promising drug for a range of cholestatic liver and bile duct disorders. Recently, norUDCA has been successfully tested clinically in patients with primary sclerosing cholangitis (PSC) as first application in patients. Moreover, hepatic enrichment of norUDCA facilitates direct therapeutic effects on both parenchymal and non-parenchymal liver cells, thereby counteracting cholestasis, steatosis, hepatic inflammation and fibrosis, inhibiting hepatocellular proliferation, and promoting autophagy. This may open its therapeutic use to other non-cholestatic and metabolic liver diseases. This review article is a summary of a lecture given at the XXIV International Bile Acid Meeting (Falk Symposium 203) on "Bile Acids in Health and Disease" held in Düsseldorf, on June 17-18, 2016 and summarizes the recent progress of norUDCA as novel therapeutic approach in cholestatic and metabolic liver disorders with a specific focus on PSC. © 2017 S. Karger AG, Basel.

A New Technique of Radiofrequency-assisted Ultrasound-guided Needle-localized Laparoscopic Resection of Disappearing Colorectal Liver Metastases.

PubMed

Yigitbas, Hakan; Yazici, Pinar; Taskin, Halit E; Okoh, Alexis K; Dural, Cem; Aydin, Nail; Berber, Eren

2017-02-01

The management of disappearing colorectal liver metastases in the postadjuvant chemotherapy setting is challenging. We describe a novel technique that facilitates laparoscopic resection of disappearing metastatic liver lesions with great precision. Details of this new technique are described in 2 patients with colorectal cancer synchronously metastatic to the liver. Both patients had small indistinct intraparenchymal liver lesions after adjuvant chemotherapy. A video displays the steps of the procedure. Both patients presented with colorectal cancer with synchronous liver metastasis. They received FOLFOX regimen after resection of their primary. They both responded to adjuvant chemotherapy. On repeat posttreatment imaging, the liver lesions became smaller and indistinct. With laparoscopic ultrasound, subtle parenchymal heterogeneities were identified. The lesions were initially ablated with a wide radiofrequency ablation zone. Then, without removing the needle, the prongs were deployed to the borders of the parenchymal heterogeneity. Using an ultrasonic vessel sealer, the lesions were resected. Final pathology identified 1 viable focus of cancer in each patient. Both patients were discharged home uneventfully on their second postoperative day. There were no complications. We have described a novel technique that could facilitate precise resection of intraparenchymal small indistinct or disappearing liver metastases of colorectal origin. This option should be kept within the armamentarium of the laparoscopic liver surgeon managing patients with malignant liver tumors.

JNK1 induces hedgehog signaling from stellate cells to accelerate liver regeneration in mice.

PubMed

Langiewicz, Magda; Graf, Rolf; Humar, Bostjan; Clavien, Pierre A

2018-04-28

To improve outcomes of two-staged hepatectomies for large/multiple liver tumors, portal vein ligation (PVL) has been combined with parenchymal transection (associating liver partition and portal vein ligation for staged hepatectomy [coined ALPPS]) to greatly accelerate liver regeneration. In a novel ALPPS mouse model, we have reported paracrine Indian hedgehog (IHH) signaling from stellate cells as an early contributor to augmented regeneration. Here, we sought to identify upstream regulators of IHH. ALPPS in mice was compared against PVL and additional control surgeries. Potential IHH regulators were identified through in silico mining of transcriptomic data. c-Jun N-terminal kinase (JNK1 [Mapk8]) activity was reduced through SP600125 to evaluate its effects on IHH signaling. Recombinant IHH was injected after JNK1 diminution to substantiate their relationship during accelerated liver regeneration. Transcriptomic analysis linked Ihh to Mapk8. JNK1 upregulation after ALPPS was validated and preceded the IHH peak. On immunofluorescence, JNK1 and IHH co-localized in alpha-smooth muscle actin-positive non-parenchymal cells. Inhibition of JNK1 prior to ALPPS surgery reduced liver weight gain to PVL levels and was accompanied by downregulation of hepatocellular proliferation and the IHH-GLI1-CCND1 axis. In JNK1-inhibited mice, recombinant IHH restored ALPPS-like acceleration of regeneration and re-elevated JNK1 activity, suggesting the presence of a positive IHH-JNK1 feedback loop. JNK1-mediated induction of IHH paracrine signaling from hepatic stellate cells is essential for accelerated regeneration of parenchymal mass. The JNK1-IHH axis is a mechanism unique to ALPPS surgery and may point to therapeutic alternatives for patients with insufficient regenerative capacity. Associating liver partition and portal vein ligation for staged hepatectomy (so called ALPPS), is a new two-staged approach to hepatectomy, which induces an unprecedented acceleration of liver regeneration, enabling treatment of patients with liver tumors that would otherwise be considered unresectable. Herein, we demonstrate that JNK1-IHH signaling from stellate cells is a key mechanism underlying the regenerative acceleration that is induced by ALPPS. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Scavenger receptor B1, the HDL receptor, is expressed abundantly in liver sinusoidal endothelial cells

PubMed Central

Ganesan, Latha P.; Mates, Jessica M.; Cheplowitz, Alana M.; Avila, Christina L.; Zimmerer, Jason M.; Yao, Zhili; Maiseyeu, Andrei; Rajaram, Murugesan V. S.; Robinson, John M.; Anderson, Clark L.

2016-01-01

Cholesterol from peripheral tissue, carried by HDL, is metabolized in the liver after uptake by the HDL receptor, SR-B1. Hepatocytes have long been considered the only liver cells expressing SR-B1; however, in this study we describe two disparate immunofluorescence (IF) experiments that suggest otherwise. Using high-resolution confocal microscopy employing ultrathin (120 nm) sections of mouse liver, improving z-axis resolution, we identified the liver sinusoidal endothelial cells (LSEC), marked by FcγRIIb, as the cell within the liver expressing abundant SR-B1. In contrast, the hepatocyte, identified with β-catenin, expressed considerably weaker levels, although optical resolution of SR-B1 was inadequate. Thus, we moved to a different IF strategy, first separating dissociated liver cells by gradient centrifugation into two portions, hepatocytes (parenchymal cells) and LSEC (non-parenchymal cells). Characterizing both portions for the cellular expression of SR-B1 by flow cytometry, we found that LSEC expressed considerable amounts of SR-B1 while in hepatocytes SR-B1 expression was barely perceptible. Assessing mRNA of SR-B1 by real time PCR we found messenger expression in LSEC to be about 5 times higher than in hepatocytes. PMID:26865459

Systematic extrahepatic Glissonean pedicle isolation for anatomical liver resection based on Laennec's capsule: proposal of a novel comprehensive surgical anatomy of the liver

PubMed Central

Sugioka, Atsushi; Kato, Yutaro; Tanahashi, Yoshinao

2017-01-01

Abstract Anatomical liver resection with the Glissonean pedicle isolation is widely approved as an essential procedure for safety and curability. Especially, the extrahepatic Glissonean pedicle isolation without parenchymal destruction should be an ideal procedure. However, the surgical technique has not been standardized due to a lack of anatomical understanding. Herein, we proposed a novel comprehensive surgical anatomy of the liver based on Laennec's capsule that would give a theoretical background to the extrahepatic Glissonean pedicle isolation. Laennec's capsule is the proper membrane that covers not only the entire surface of the liver including the bare area but also the intrahepatic parenchyma surrounding the Glissonean pedicles. Consequently, there exists a gap between the Glissonean pedicle and Laennec's capsule that could be reached extrahepatically and allows us to isolate the extrahepatic Glissonean pedicle without parenchymal destruction systematically. For standardization, it is essential to approach the “six gates” indicated by the “four anatomical landmarks”: the Arantius plate, the umbilical plate, the cystic plate and the Glissonean pedicle of the caudate process (G1c). This novel anatomy would contribute to standardize the surgical techniques of the systematic extrahepatic Glissonean pedicle isolation for anatomical liver resection including laparoscopic or robotic liver resection and to bring innovative changes in hepatobiliary surgery for spreading safe and curable liver resection. PMID:28156078

CARDIAC-LIKE OSCILLATION IN LIVER STEM CELLS INDUCE THEIR ACQUISITION OF CARDIAC PHENOTYPE

EPA Science Inventory

We examined in a cardiac microenvironment the plasticity of a liver stem cell line (WB F344) generated from a cloned, single, non-parenchymal epithelial cell from a normal adult male rat. Our previous studies suggested that WB F344 cells acquire a cardiac phenotype in the absenc...

Histologic analysis of rabbit liver cancer treated by bulk ultrasound ablation

NASA Astrophysics Data System (ADS)

Karunakaran, Chandra Priya; Rudich, Steven M.; Alqadah, Amel; Burgess, Mark T.; Narmoneva, Daria A.; Mast, T. Douglas

2012-10-01

VX2 rabbit liver cancer, treated in vivo using bulk ultrasound ablation by miniaturized image-ablate arrays, was histologically analyzed using TTC vital stain and DAPI nucleic acid stain. VX2 cells were implanted into rabbit liver lobes and allowed to grow for 11-21 days. Liver lobes containing solid VX2 tumors were then treated with 4.8 MHz, 22.5-38.5 W/cm2 in situ intensity, unfocused ultrasound for exposure times of 20-120 s. After animal sacrifice, thermal lesions were bisected along the imaging/treatment plane, one face stained with TTC, and the other with DAPI. Levels of TTC uptake (no uptake, partial uptake, and complete uptake) in liver parenchyma corresponded to three discrete regions of tan, pink and red color. By processing images of DAPI-stained parenchymal tissue from these three regions, cellular damage was quantified. A viability index parameter incorporating the size and shape of DAPI-stained nuclei correlated significantly with levels of TTC uptake, and thus with local tissue viability. For ablation of normal liver, viability indices for parenchymal regions of no TTC uptake and partial TTC uptake were significantly different from those for viable tissue. For ablation of VX2 tumor, differences in viability index between regions of no TTC uptake and complete TTC uptake were smaller, but significant overall.

Fontan-associated liver disease: Spectrum of US findings.

PubMed

Bae, Jung Min; Jeon, Tae Yeon; Kim, Jung Sun; Kim, Seokhwi; Hwang, Sook Min; Yoo, So-Young; Kim, Ji Hye

2016-04-01

To describe ultrasonography (US) findings of Fontan-associated liver disease (FALD) and to determine whether screening US examinations can identify FALD before biochemical hepatic dysfunction. This retrospective study included 55 patients who underwent Fontan procedure over a 20-year period. Hepatobiliary US findings (n=55), CT or MRI findings (n=19), biochemical hepatic function tests (n=49), and histopathological results (n=4) were analyzed. Images were reviewed focusing on the hepatic parenchymal changes, presence of focal lesions, and signs of portal hypertension. Hepatic parenchymal changes (either heterogeneous echotexture or surface nodularity) evident on US were present in 67% (37/55) and showed positive correlation with the Fontan duration. Hyper-echoic lesions were noted in 35% (19/55) and showed a predilection for multiplicity, small size, right lobe location, and irregular margin on high-frequency transducer. These lesions were not demonstrated by CT or MRI or by low-frequency transducer. Histopathological results of targeted biopsy for hyper-echoic lesions revealed lesser degree of patchy sinusoidal and portal fibrosis than seen in cases with surface nodularity. Abnormal parenchymal enhancement was commonly seen with CT or MRI in 63% (12/19) and hypervascular nodules in 21% (4/19). Most patients (82%, 40/49) showed normal biochemical hepatic function tests, despite the presence of hepatic parenchymal changes on imaging. The common US findings of FALD included heterogeneous parenchymal echotexture, surface nodularity, and hyper-echoic lesions. We suggest that hyper-echoic lesions without surface nodularity detected by high-frequency transducer may represent the early stage of fibrosis. US examination may be useful for identifying the progression of FALD before biochemical hepatic dysfunction. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Imaging of irradiated liver with Tc-99m-sulfur colloid and Tc-99m-IDA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gelfand, M.J.; Saha, S.; Aron, B.S.

1981-09-01

In three cases, irradiated regions of liver failed to concentrate Tc-99m-sulfur colloid. In two of these three, imaging with Tc-99m-acetanilide iminodiacetic acid (IDA) agents within five days showed near normal hepatic uptake of this hepatobiliary imaging agent. The hepatic parenchymal cells may be imaged with Tc-99m-IDA in some irradiated regions of liver, despite loss of reticuloendothelial cell function.

Systematic extrahepatic Glissonean pedicle isolation for anatomical liver resection based on Laennec's capsule: proposal of a novel comprehensive surgical anatomy of the liver.

PubMed

Sugioka, Atsushi; Kato, Yutaro; Tanahashi, Yoshinao

2017-01-01

Anatomical liver resection with the Glissonean pedicle isolation is widely approved as an essential procedure for safety and curability. Especially, the extrahepatic Glissonean pedicle isolation without parenchymal destruction should be an ideal procedure. However, the surgical technique has not been standardized due to a lack of anatomical understanding. Herein, we proposed a novel comprehensive surgical anatomy of the liver based on Laennec's capsule that would give a theoretical background to the extrahepatic Glissonean pedicle isolation. Laennec's capsule is the proper membrane that covers not only the entire surface of the liver including the bare area but also the intrahepatic parenchyma surrounding the Glissonean pedicles. Consequently, there exists a gap between the Glissonean pedicle and Laennec's capsule that could be reached extrahepatically and allows us to isolate the extrahepatic Glissonean pedicle without parenchymal destruction systematically. For standardization, it is essential to approach the "six gates" indicated by the "four anatomical landmarks": the Arantius plate, the umbilical plate, the cystic plate and the Glissonean pedicle of the caudate process (G1c). This novel anatomy would contribute to standardize the surgical techniques of the systematic extrahepatic Glissonean pedicle isolation for anatomical liver resection including laparoscopic or robotic liver resection and to bring innovative changes in hepatobiliary surgery for spreading safe and curable liver resection. © 2017 The Authors. Journal of Hepato-Biliary-Pancreatic Sciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Evaluation of the Effects of Atorvastatin and Ischemic Postconditioning Preventing on the Ischemia and Reperfusion Injury: Experimental Study in Rats

PubMed Central

Pontes, Henrique Budib Dorsa; Pontes, José Carlos Dorsa Vieira; de Azevedo Neto, Euler; Vendas, Giovanna Serra da Cruz; Miranda, João Victor Cunha; Dias, Letícia do Espírito Santos; Oliva, João Victor Durães Gomes; de Almeida, Murilo Henrique Martins; Chaves, Ian de Oliveira; Sampaio, Tricia Luna; dos Santos, Carlos Henrique Marques; Dourado, Doroty Mesquita

2018-01-01

Introduction Reperfusion injury leads to systemic morphological and functional pathological alterations. Some techniques are already estabilished to attenuate the damage induced by reperfusion. Ischemic preconditioning is one of the standard procedures. In the last 20 years, several experimental trials demonstrated that the ischemic postconditioning presents similar effectiveness. Recently experimental trials demonstrated that statins could be used as pharmacological preconditioning. Methods 41 Wistar rats (Rattus norvegicus albinus) were distributed in 5 groups: Ischemia and Reperfusion (A), Ischemic Postconditioning (B), Statin (C), Ischemic Postconditioning + Statins (D) and SHAM (E). After euthanasia, lungs, liver, kidneys and ileum were resected and submitted to histopathological analysis. Results The average of lung parenchymal injury was A=3.6, B=1.6, C=1.2, D=1.2, E=1 (P=0.0029). The average of liver parenchymal injury was A=3, B=1.5, C=1.2, D=1.2, E = 0 (P<0.0001). The average of renal parenchymal injury was A=4, B=2.44, C=1.22, D=1.11, E=1 (P<0.0001). The average of intestinal parenchymal injury was A=2, B=0.66, C=0, D=0, E=0 (P=0.0006). The results were submitted to statistics applying Kruskal-Wallis test, estabilishing level of significance P<0.05. Conclusion Groups submitted to ischemic postconditioning, to pre-treatment with statins and both methods associated demonstrated less remote reperfusion injuries, compared to the group submitted to ischemia and reperfusion without protection. PMID:29617505

Reactive oxygen species mediate liver injury through parenchymal nuclear factor-kappaB inactivation in prolonged ischemia/reperfusion.

PubMed

Llacuna, Laura; Marí, Montserrat; Lluis, Josep M; García-Ruiz, Carmen; Fernández-Checa, José C; Morales, Albert

2009-05-01

Nuclear factor (NF)-kappaB participates in ischemia/reperfusion (I/R) hepatic signaling, stimulating both protective mechanisms and the generation of inflammatory cytokines. After analyzing NF-kappaB activation during increasing times of ischemia in murine I/R, we observed that the nuclear translocation of p65 paralleled Src and IkappaB tyrosine phosphorylation, which peaked after 60 minutes of ischemia. After extended ischemic periods (90 to 120 minutes) however, nuclear p65 levels were inversely correlated with the progressive induction of oxidative stress. Despite this profile of NF-kappaB activation, inflammatory genes, such as tumor necrosis factor (TNF) and interleukin (IL)-1beta, predominantly induced by Kupffer cells, increased throughout time during ischemia (30 to 120 minutes), whereas protective NF-kappaB-dependent genes, such as manganese superoxide dismutase (Mn-SOD), expressed in parenchymal cells, decreased. Consistent with this behavior, gadolinium chloride pretreatment abolished TNF/IL-1beta up-regulation during ischemia without affecting Mn-SOD levels. Interestingly, specific glutathione (GSH) up-regulation in hepatocytes by S-adenosylmethionine increased Mn-SOD expression and protected against I/R-mediated liver injury despite TNF/IL-1beta induction. Similar protection was achieved by administration of the SOD mimetic MnTBAP. In contrast, indiscriminate hepatic GSH depletion by buthionine-sulfoximine before I/R potentiated oxidative stress and decreased both nuclear p65 and Mn-SOD expression levels, increasing TNF/IL-1beta up-regulation and I/R-induced liver damage. Thus, the divergent role of NF-kappaB activation in selective liver cell populations underlies the dichotomy of NF-kappaB in hepatic I/R injury, illustrating the relevance of specifically maintaining NF-kappaB activation in parenchymal cells.

Dark adaptation in vitamin A-deficient adults awaiting liver transplantation: improvement with intramuscular vitamin A treatment.

PubMed

Abbott-Johnson, Winsome J; Kerlin, Paul; Abiad, Ghassan; Clague, Alan E; Cuneo, Ross C

2011-04-01

Although vitamin A deficiency is common in chronic liver disease, limited data exist on impairment of dark adaptation and response to therapy. The aims were (1) to assess dark adaptation in patients, (2) to assess the relationship between dark adaptation and vitamin A status, zinc and Child-Pugh score, (3) to compare perceived and measured dark adaptation and (4) to assess the dark adaptation response to intramuscular vitamin A. This was a prospective study of 20 patients (alcoholic liver disease 10, other parenchymal diseases six, cholestatic diseases four) awaiting liver transplantation. Selection was based on low serum retinol. There were 15 age-matched controls. Dark adaptation was measured with a SST-1 dark adaptometer and perception by questionnaire. Eight patients received 50, 000 IU of retinyl palmitate, and dark adaptation was repeated at 1 month. Forty per cent of patients had impaired dark adaptation. Patients with alcoholic liver disease were more impaired than those with other parenchymal diseases (p=0.015). No relationship was found between dark adaptation and the biochemical indicators or Child-Pugh score. Seventy-five per cent of patients with impairment did not perceive a problem. After intervention, light of half the previous intensity could be seen (p=0.05). Dark-adaptation impairment was common, was worse in alcoholic liver disease, was largely not appreciated by the patients and improved with vitamin A treatment.

Enhanced iron removal from liver parenchymal cells in experimental iron overload: liposome encapsulation of HBED and phenobarbital administration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rahman, Y.E.; Cerny, E.A.; Lau, E.H.

1983-07-01

The effectiveness of N,N'-bis(2-hydroxybenzyl)-ethylene-diamine-N,N'-diacetic acid (HBED) in removing radioiron introduced into the parenchymal cells of mouse liver as /sup 59/Fe-ferritin has been investigated. The effectiveness of HBED, an iron chelator of low water solubility, has also been compared with that of desferrioxamine (DF), an iron chelator of high water solubility and currently in clinical use for treatment of transfusional iron overload. Using the /sup 59/Fe excretion as the measure of effectiveness of chelation therapy and a standardized single chelator dose of 25 mg/kg, they have found that: (1) a saline suspension of HBED, prepared by sonication and given intraperitoneally tomore » mice, promotes a small but significant increase in excretion of radioiron compared to the untreated controls, whereas DF, in its free form, is ineffective; (2) HBED encapsulated in lipid bilayers of liposomes and given intravenously is superior to nonencapsulated HBED; (3) DF encapsulated in small unilamellar liposomes is ineffective in removing iron given in the form of ferritin; (4) administration of phenobarbital in drinking water, at a concentration of 1 g/liter, induces a 30%-55% increase of iron excretion from untreated control mice and also from mice given HBED either in liposome-encapsulated or nonencapsulated form. HBED is superior to DF for removal of storage iron from liver parenchymal cells and liposomes are useful carriers for iron chelators of low water solubility.« less

Comparison Between Various Color Spectra and Conventional Grayscale Imaging for Detection of Parenchymal Liver Lesions With B-Mode Sonography.

PubMed

Merkel, Daniel; Brinkmann, Eckard; Kämmer, Joerg C; Köhler, Miriam; Wiens, Daniel; Derwahl, Karl-Michael

2015-09-01

The electronic colorization of grayscale B-mode sonograms using various color schemes aims to enhance the adaptability and practicability of B-mode sonography in daylight conditions. The purpose of this study was to determine the diagnostic effectiveness and importance of colorized B-mode sonography. Fifty-three video sequences of sonographic examinations of the liver were digitized and subsequently colorized in 2 different color combinations (yellow-brown and blue-white). The set of 53 images consisted of 33 with isoechoic masses, 8 with obvious lesions of the liver (hypoechoic or hyperechoic), and 12 with inconspicuous reference images of the liver. The video sequences were combined in a random order and edited into half-hour video clips. Isoechoic liver lesions were successfully detected in 58% of the yellow-brown video sequences and in 57% of the grayscale video sequences (P = .74, not significant). Fifty percent of the isoechoic liver lesions were successfully detected in the blue-white video sequences, as opposed to a 55% detection rate in the corresponding grayscale video sequences (P= .11, not significant). In 2 subgroups, significantly more liver lesions were detected with grayscale sonography compared to blue-white sonography. Yellow-brown-colorized B-mode sonography appears to be similarly effective for detection of isoechoic parenchymal liver lesions as traditional grayscale sonography. Blue-white colorization in B-mode sonography is probably not as effective as grayscale sonography, although a statistically significant disadvantage was shown only in the subgroup of hyperechoic liver lesions. © 2015 by the American Institute of Ultrasound in Medicine.

Contradictory intrahepatic immune responses activated in high-load hepatitis C virus livers compared with low-load livers.

PubMed

Ishibashi, Mariko; Yamaguchi, Hiromi; Hirotani, Yukari; Sakurada, Akihisa; Endo, Toshihide; Sugitani, Masahiko; Takayama, Tadatoshi; Makishima, Makoto; Esumi, Mariko

2018-04-01

We found a HLA class II histocompatibility antigen gene, DQ alpha 1 chain (HLA-DQA1), that was expressed more than 9-fold higher in high-load hepatitis C virus (HCV) livers than low-load HCV livers using transcriptomics of chronic HCV-infected livers. To further investigate this finding, we examined which cells were positive for HLA-DQA1 and what liver immune responses were different between HCV-high and -low livers. HLA-DQA1-positive cells were significantly increased in the HCV-high group, and most positive cells were identified as non-parenchymal sinusoid cells and lymphocytic infiltrates in the portal area. Parenchymal hepatocytes were negative for HLA-DQA1. HLA-DQA1-positive cells in the liver sinusoid were positive for CD68 (macrophages or Kupffer cells); those in the lymphocytic infiltrates were positive for CD20 (B cells) or CD3 (T cells). mRNA levels of antigen-presenting cell (APC) markers such as CD68 and CD11c were significantly upregulated in the HCV-high group and were correlated with HLA-DQA mRNA levels. CD8B mRNA (CD8 + T cells) was upregulated in both HCV-positive livers compared with HCV-negative livers, whereas CD154 mRNA (CD4 + T helper cell) was upregulated in the HCV-high group compared with the HCV-low group. The immune regulatory molecules FOXP3 mRNA (regulatory T cell, T reg) and programmed cell death ligand-1 (PD-L1) mRNA were significantly increased in the HCV-high group. HCV-high livers had two molecular immune responses: increased APC numbers and adaptive immunity and the induction of immune tolerance. The local hepatic imbalance of contradictory immune responses might be responsible for high HCV loads.

Comparison of holding strength of suture anchors for hepatic and renal parenchyma.

PubMed

Ames, Caroline D; Perrone, Juan M; Frisella, Alison J; Morrissey, Kevin; Landman, Jaime

2005-12-01

Various laparoscopic devices have been described for suture anchoring during solidorgan parenchymal closure. Application of these devices expedites the closure of parenchymal defects and minimizes ischemia time. We compared different technologies as suture anchors for parenchymal closure. A tensometer was used to determine the amount of tension necessary to dislodge each of five different clips from Vicryl suture alone or against two different substrates (fresh pig kidney and liver) with and without an intervening pledget. The clips investigated were the Lapra-Ty (Ethicon), Endoclip II (US Surgical), small Horizon Ligating Clips (Weck), Hem-o-lok Medium Polymer Clips (Week), and a novel Suture-clip (Applied Medical). ANOVA and two-sided Fisher's exact test provided statistical analysis. The force required to dislodge the Lapra-Ty clip from bare suture for both 0 and 1 Vicryl (7.0 N) was approximately fourfold the force required to dislodge the Endoclips or the 5-mm or 10-mm Hem-o-lok clips (p<0.01). When clips were applied to suture running through renal or liver parenchyma, the novel Suture-clip required the greatest tension to dislodge (P<0.01), followed by the Horizon and Lapra-Ty clips. There were no statistically significant differences in the tension required to dislodge a given clip from the two parenchymal substrates or in the presence or absence of a pledget. In our experimental model, the Suture-clip, Lapra-Ty, and Horizon clips required significantly greater tension to dislodge than the Hem-o-lok and Endoclip clips. The addition of a pledget did not improve tension resistance.

Initial experience with a new articulating energy device for laparoscopic liver resection.

PubMed

Berber, Eren; Akyuz, Muhammet; Aucejo, Federico; Aliyev, Shamil; Aksoy, Erol; Birsen, Onur; Taskin, Eren

2014-03-01

Although significant advances have been made in laparoscopic liver resection (LLR), most techniques still rely on multiple energy devices and staplers, which increase operative costs. The aim of this study was to report the initial results of a new multifunctional energy device for hepatic parenchymal transection. Fourteen patients who underwent LLR using this new device were compared to 20 patients who had LLR using current laparoscopic techniques (CL). Data were collected prospectively. The groups were similar demographics and tumor type and size. Although the type of resection was similar between the groups, the parenchymal transection time was less in the Caiman group (32 ± 5 vs. 63 ± 4 min, respectively, p = 0.0001). The operative time was similar (194 ± 21 vs. 233 ± 16 min, respectively, p = 0.158). There was reduction of the number of advanced instrumentation used in the Caiman group, including the staplers. Estimated blood loss, size of surgical margin, and hospital stay were similar. There was no mortality, and morbidity was 7 % in the Caiman and 20 % in the CL group. This initial study shows that the new device is safe and efficient for LLR. Its main advantage is shortening of hepatic parenchymal transection time. This has implications for increasing efficiency and cost saving in LLR.

Electro-microscopic observations of liver lesions after intravenous inoculation of mouldy hay extracts.

PubMed

Shadmi, A; Griffel, B

1985-01-01

With the aid of the electron microscope, a number of histopathological changes in the liver of mice caused by mycotoxins from mouldy hay were examined and studied. These changes were observed in the mitochondria, the cell nucleus, and the cell membranes, and included fatty and parenchymal degeneration, plasma granulation, vacuolisation and vesiculation, glycogen secretion, incorporation into RNA, karyolysis and karyolaxis, and space of Disse constriction.

Dexamethasone-induced haptoglobin release by calf liver parenchymal cells.

PubMed

Higuchi, H; Katoh, N; Miyamoto, T; Uchida, E; Yuasa, A; Takahashi, K

1994-08-01

Parenchymal cells were isolated from the liver of male calves, and monolayer cultures formed were treated with glucocorticoids to examine whether haptoglobin, appearance of which is associated with hepatic lipidosis (fatty liver) in cattle, is induced by steroid hormones. Without addition of dexamethasone, only trace amounts of haptoglobin were detected in culture medium. With addition of dexamethasone (10(-12) to 10(-4) M), considerable amounts of haptoglobin were released into the medium. Maximal release was observed at concentrations of 10(-8) to 10(-6) M dexamethasone. Haptoglobin release was similarly induced by cortisol, although the effect was less potent than that of dexamethasone. Actinomycin D (a known protein synthesis inhibitor) dose-dependently reduced amounts of haptoglobin released in response to 10(-8) M dexamethasone. Dexamethasone also induced annexin I, which is known to be synthesized in response to glucocorticoids. Dexamethasone treatment resulted in reduced protein kinase C activity in the cell cytosol, which has been shown to be an early event in dexamethasone-treated cells. Other than glucocorticoids, estradiol induced haptoglobin release, whereas progesterone was less effective. The association of haptoglobin with hepatic lipidosis can be reasonably explained by the fact that haptoglobin production by the liver is induced by glucocorticoids and estradiol, and these steroid hormones are triggers for development of hepatic lipidosis in cattle.

Safety and Efficacy of a New Bipolar Energy Device for Parenchymal Dissection in Laparoscopic Liver Resection.

PubMed

Dural, Cem; Akyuz, Muhammet; Yazici, Pinar; Aksoy, Erol; Aucejo, Federico; Quintini, Cristiano; Miller, Charles; Fung, John; Berber, Eren

2016-02-01

Despite emerging technologies, parenchymal transection still remains challenging in liver resection. The aim of this study is to assess the safety and efficacy of a new articulating vessel sealer for laparoscopic hepatectomy. Our hypothesis was that this new device would facilitate parenchymal transection and reduce intraoperative costs in laparoscopic hepatectomy. Within 18 months, a 5 cm bipolar articulating vessel sealer was used in 32 laparoscopic liver resections (LLR). By excluding 4 patients who underwent concomitant colorectal resections, the outcomes of the remaining 28 patients (group 1) were compared with 28 patients who underwent LLR by the same surgical group using other energy devices (group 2). Tumor type was malignant in 71% of patients (n=20) in group 1 and 89% of the patients (n=25) in group 2 (P=0.360). The number and size of tumors were similar in both groups, as well as the type of resections performed. In group 1, there was a less number of adjunctive devices (ie, energy, clip appliers, staplers) used (median 2) compared with group 2 (median 3, P=0.032). Parenchymal transection time (mean±SEM 28.2±3.5 vs. 55.2±4.1 min, respectively, P<0.001) and total operative time (200.1±13.7 vs. 242.7±14.4 min, respectively, P=0.036) were shorter for group 1 versus group 2. Estimated blood loss, transfusion rate, margin status, and length of stay were similar between the groups. There was no mortality. Morbidity was 11% (n=3) in group 1 and 18% (n=5) in group 2 (P=NS). The overall intraoperative costs were an average of $3000 less in group 1 (95% confidence interval, $1090-$4930, P=0.0029) compared with group 2. This study demonstrates the safety and efficacy of a new energy device for LLR. Our experience suggested that this new device provided the functionality of both a vessel sealer and a stapler with its large jaw and articulation.

Targeting of asialofetuin sugar chain-bearing liposomes to liver lysosomes.

PubMed

Banno, Y; Ohki, K; Nozawa, Y

1983-10-01

Specific direction of liposomes bearing an asialofetuin sugar chain (AFSC) to liver parenchymal cells was examined both in vivo and in vitro. The AFSC-bearing liposomes were preferentially recovered in the liver within several minutes after an intravenous injection into mice and were found to be predominantly localized in mitochondrial-lysosomal fraction. The massive distribution of the AFSC-liposomes in this fraction was also confirmed by using a lysosomal protease inhibitor, E-64-d. In isolated rat hepatocytes, the uptake of AFSC-liposomes was increased 2-3-fold as compared with the control liposomes without AFSC. Thus liposomes bearing AFSC would be useful to target enzymes to liver lysosomes.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stampfl, S.; Stampfl, U.; Rehnitz, C.

Purpose. To evaluate trisacryl-gelatin microspheres (40-120 {mu}m) for acute and chronic tissue embolization in mini-pig livers. Methods. Thirteen animals were divided into four groups: group 1 (n = 3), total arterial bed occlusion with acute procedure; groups 2 to 4, chronic superselective embolization with follow-up of 1 week (group 2, n = 1), 4 weeks (group 3, n 4) or 14 weeks (group 4, n = 5). Key endpoints were homogeneity and particle distribution in acute embolizations (group 1) and necrosis and inflammation in chronic embolizations (groups 2-4) as assessed microscopically and angiographically. Results. After liver embolization, parenchymal necrosis didmore » not occur; only signs of vessel wall disintegration were evident. The bile ducts remained intact. A distinct foreign body reaction with sparse leukocytic infiltration and giant cells was found at 14 weeks, but no signs of major inflammation were found. Particles were seen at the presinusoidal level, but no particle transportation into the sinusoids was observed. Conclusions. Embolization in mini-pig livers, using small trisacryl-gelatin microspheres, results in vessel fibrosis without parenchymal or bile duct necrosis. The most likely explanation for preservation of the parenchyma is portal inflow. Small trisacryl-gelatin microspheres may be ideal as an adjunct for chemoembolization.« less

Transection Speed and Impact on Perioperative Inflammatory Response - A Randomized Controlled Trial Comparing Stapler Hepatectomy and CUSA Resection.

PubMed

Schwarz, Christoph; Klaus, Daniel A; Tudor, Bianca; Fleischmann, Edith; Wekerle, Thomas; Roth, Georg; Bodingbauer, Martin; Kaczirek, Klaus

2015-01-01

Parenchymal transection represents a crucial step during liver surgery and many different techniques have been described so far. Stapler resection is supposed to be faster than CUSA resection. However, whether speed impacts on the inflammatory response in patients undergoing liver resection (LR) remains unclear. This is a randomized controlled trial including 40 patients undergoing anatomical LR. Primary endpoint was transection speed (cm2/min). Secondary endpoints included the perioperative change of pro- and anti-inflammatory cytokines, overall surgery duration, length of hospital stay, morbidity and mortality. Mean transection speed was significantly higher in patients undergoing stapler hepatectomy compared to CUSA resection (CUSA: 1 (0.4) cm2/min vs. Stapler: 10.8 (6.1) cm2/min; p<0.0001). Analyzing the impact of surgery duration on inflammatory response revealed a significant correlation between IL-6 levels measured at the end of surgery and the overall length of surgery (p<0.0001, r = 0.6188). Patients undergoing CUSA LR had significantly higher increase of interleukin-6 (IL-6) after parenchymal transection compared to patients with stapler hepatectomy in the portal and hepatic veins, respectively (p = 0.028; p = 0.044). C-reactive protein levels on the first post-operative day were significantly lower in the stapler cohort (p = 0.010). There was a trend towards a reduced overall surgery time in patients with stapler LR, especially in the subgroup of patients undergoing minor hepatectomies (p = 0.020). Liver resection using staplers is fast, safe and suggests a diminished inflammatory response probably due to a decreased parenchymal transection time. ClinicalTrials.gov NCT01785212.

Transection Speed and Impact on Perioperative Inflammatory Response – A Randomized Controlled Trial Comparing Stapler Hepatectomy and CUSA Resection

PubMed Central

Schwarz, Christoph; Klaus, Daniel A.; Tudor, Bianca; Fleischmann, Edith; Wekerle, Thomas; Roth, Georg; Bodingbauer, Martin; Kaczirek, Klaus

2015-01-01

Background Parenchymal transection represents a crucial step during liver surgery and many different techniques have been described so far. Stapler resection is supposed to be faster than CUSA resection. However, whether speed impacts on the inflammatory response in patients undergoing liver resection (LR) remains unclear. Materials and Methods This is a randomized controlled trial including 40 patients undergoing anatomical LR. Primary endpoint was transection speed (cm2/min). Secondary endpoints included the perioperative change of pro- and anti-inflammatory cytokines, overall surgery duration, length of hospital stay, morbidity and mortality. Results Mean transection speed was significantly higher in patients undergoing stapler hepatectomy compared to CUSA resection (CUSA: 1 (0.4) cm2/min vs. Stapler: 10.8 (6.1) cm2/min; p<0.0001). Analyzing the impact of surgery duration on inflammatory response revealed a significant correlation between IL-6 levels measured at the end of surgery and the overall length of surgery (p<0.0001, r = 0.6188). Patients undergoing CUSA LR had significantly higher increase of interleukin-6 (IL-6) after parenchymal transection compared to patients with stapler hepatectomy in the portal and hepatic veins, respectively (p = 0.028; p = 0.044). C-reactive protein levels on the first post-operative day were significantly lower in the stapler cohort (p = 0.010). There was a trend towards a reduced overall surgery time in patients with stapler LR, especially in the subgroup of patients undergoing minor hepatectomies (p = 0.020). Conclusions Liver resection using staplers is fast, safe and suggests a diminished inflammatory response probably due to a decreased parenchymal transection time. Trial Registration ClinicalTrials.gov NCT01785212 PMID:26452162

Lymphocyte and macrophage phenotypes in chronic hepatitis C infection. Correlation with disease activity.

PubMed Central

Khakoo, S. I.; Soni, P. N.; Savage, K.; Brown, D.; Dhillon, A. P.; Poulter, L. W.; Dusheiko, G. M.

1997-01-01

The pathogenesis of chronic hepatitis C and the mechanisms underlying progressive liver disease in patients with chronic hepatitis C infection are poorly understood. To demonstrate which inflammatory cells might be responsible for the necroinflammatory damage in chronic hepatitis C infection, we have correlated the phenotype of the intrahepatic lymphocytes and macrophages with histological activity in liver biopsy and explant specimens from 19 patients with chronic hepatitis C infection. In all stages of disease, more CD8+ than CD4+ lymphocytes were found. However, histologically active versus histologically mild hepatitis was associated with a trend toward greater parenchymal concentrations of CD4+ lymphocytes (0.71 +/- 0.27 per 10(4) microns 2 versus 0.35 +/- 0.15; not significant), significantly less parenchymal CD8+ lymphocytes (0.90 +/- 0.1 versus 1.70 +/- 0.3; t = 2.32, P = 0.03) and a greater parenchymal CD4/CD8 ratio (4.1 +/- 2.8 versus 0.91 +/- 0.3; t = 1.65, P = 0.07). No difference was found in the number of cells containing cytotoxic granules between the two groups. Greater numbers of CD4+ lymphocytes were found in liver biopsy specimens with little or no staining for hepatitis C virus antigen (1.47 +/- 0.88 versus 0.27 +/- 0.27; t = 2.28, P < 0.05). No significant differences were found in the macrophage subsets between the three stages of disease. Our data suggest that active histological disease in chronic hepatitis C infection may be associated with an increase in CD4+ lymphocytes and suggest that CD4+ T cells may play an important role in the hepatic injury in these patients. Images Figure 2 PMID:9060834

Identification of an enhancer element of class Pi glutathione S-transferase gene required for expression by a co-planar polychlorinated biphenyl.

PubMed Central

Matsumoto, M; Imagawa, M; Aoki, Y

1999-01-01

3,3',4,4',5-Pentachlorobiphenyl (PenCB), one of the most toxic co-planar polychlorinated biphenyl congeners, specifically induces class Pi glutathione S-transferase (GSTP1) as well as cytochrome P-450 1A1 in primary cultured rat liver parenchymal cells [Aoki, Matsumoto and Suzuki (1993) FEBS Lett. 333, 114-118]. However, the 5'-flanking sequence of the GSTP1 gene does not contain a xenobiotic responsive element, to which arylhydrocarbon receptor binds. Using a chloramphenicol acetyltransferase assay we demonstrate here that the enhancer termed GSTP1 enhancer I (GPEI) is necessary for the stimulation by PenCB of GSTP1 gene expression in primary cultured rat liver parenchymal cells. GPEI is already known to contain a dyad of PMA responsive element-like elements oriented palindromically. It is suggested that a novel signal transduction pathway activated by PenCB contributes to the stimulation of GSTP1 expression. PMID:10051428

High Risk But Not Always Lethal: The Effect of Cirrhosis on Thermally Injured Adults

DTIC Science & Technology

2013-01-01

115 Cirrhosis is the final common pathway on the spec- trum of many types of chronic liver injury.1 In the United States, the two most common causes ... cirrhosis are bridg- ing fibrous septa, the formation of regenerative parenchymal nodules, and disruption to the entire hepatic architecture.3 This...extensive liver fibrosis is caused by the activation of the hepatic stellate cell, and this loss of hepatocellular function can lead to jaundice, edema

Rapid Liver Hypertrophy After Portal Vein Occlusion Correlates with the Degree of Collateralization Between Lobes-a Study in Pigs.

PubMed

Deal, Rebecca; Frederiks, Charles; Williams, Lauren; Olthof, Pim B; Dirscherl, Konstantin; Keutgen, Xavier; Chan, Edie; Deziel, Daniel; Hertl, Martin; Schadde, Erik

2018-02-01

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) induces more rapid liver growth than portal vein ligation (PVL). Transection of parenchyma in ALPPS may prevent the formation of collaterals between lobes. The aim of this study was to determine if abrogating the formation of collaterals through parenchymal transection impacted growth rate. Twelve Yorkshire Landrace pigs were randomized to undergo ALPPS, PVL, or "partial ALPPS" by varying degrees of parenchymal transection. Hepatic volume was measured after 7 days. Portal blood flow and pressure were measured. Portal vein collaterals were examined from epoxy casts. PVL, ALPPS, and partial ALPPS led to volume increases of the RLL by 15.5% (range 3-22), 64% (range 45-76), and 32% (range 18-77), respectively, with significant differences between PVL and ALPPS/partial ALPPS (p < 0.05). In PVL and partial ALPPS, substantial new portal vein collaterals were found. The number of collaterals correlated inversely with the growth rate (p = 0.039). Portal vein pressure was elevated in all models after ligation suggesting hyperflow to the portal vein-supplied lobe (p < 0.05). These data suggest that liver hypertrophy following PVL is inversely proportional to the development of collaterals. Hypertrophy after ALPPS is likely more rapid due to reduction of collaterals through transection.

Advances in hepatic stem/progenitor cell biology

PubMed Central

Verhulst, Stefaan; Best, Jan; van Grunsven, Leo A.; Dollé, Laurent

2015-01-01

The liver is famous for its strong regenerative capacity, employing different modes of regeneration according to type and extent of injury. Mature liver cells are able to proliferate in order to replace the damaged tissue allowing the recovery of the parenchymal function. In more severe scenarios hepatocytes are believed to arise also from a facultative liver progenitor cell compartment. In human, severe acute liver failure and liver cirrhosis are also both important clinical targets in which regeneration is impaired, where the role of this stem cell compartment seems more convincing. In animal models, the current state of ambiguity regarding the identity and role of liver progenitor cells in liver physiology dampens the enthusiasm for the potential use of these cells in regenerative medicine. The aim of this review is to give the basics of liver progenitor cell biology and discuss recent results vis-à-vis their identity and contribution to liver regeneration. PMID:26600740

Imaging of the transplant liver.

PubMed

Babyn, Paul Sheppard

2010-04-01

As the number of patients with liver transplants continues to increase, radiologists need to be aware of the normal post-operative appearance of the different liver transplants currently performed along with the wide variety of complications encountered. The complications commonly affect the biliar and vascular systems and can include anastomotic bile leakage and biliary stenosis along with stenosis or obstruction of the hepatic artery, portal or hepatic veins and IVC. Other complications include parenchymal abnormalities such as hepatic infarction, organ rejection, localized collections and post transplant lymphoproliferative disorder. This article reviews and illustrates the role of imaging for pediatric transplantation including the role of interventional radiology.

Quantitative imaging of fibrotic and morphological changes in liver of non-alcoholic steatohepatitis (NASH) model mice by second harmonic generation (SHG) and auto-fluorescence (AF) imaging using two-photon excitation microscopy (TPEM).

PubMed

Yamamoto, Shin; Oshima, Yusuke; Saitou, Takashi; Watanabe, Takao; Miyake, Teruki; Yoshida, Osamu; Tokumoto, Yoshio; Abe, Masanori; Matsuura, Bunzo; Hiasa, Yoichi; Imamura, Takeshi

2016-12-01

Non-alcoholic steatohepatitis (NASH) is a common liver disorder caused by fatty liver. Because NASH is associated with fibrotic and morphological changes in liver tissue, a direct imaging technique is required for accurate staging of liver tissue. For this purpose, in this study we took advantage of two label-free optical imaging techniques, second harmonic generation (SHG) and auto-fluorescence (AF), using two-photon excitation microscopy (TPEM). Three-dimensional ex vivo imaging of tissues from NASH model mice, followed by image processing, revealed that SHG and AF are sufficient to quantitatively characterize the hepatic capsule at an early stage and parenchymal morphologies associated with liver disease progression, respectively.

LIVER REGENERATION STUDIES WITH RAT HEPATOCYTES IN PRIMARY CULTURE

EPA Science Inventory

Adult rat parenchymal hepatocytes in primary culture can be induced to enter into DNA synthesis and mitosis. The optimal conditions for hepatocyte replication are low plating density (less than 10,000 cells/sq cm) and 50% serum from two-thirds partially hepatectomized rats (48 hr...

Cranial computed tomography and real-time sonography in full-term neonates and infants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Siegel, M.J.; Patel, J.; Gado, M.H.

1983-10-01

The results of cranial ultrasonography (US) and computed tomography (CT) were compared in 52 full-term neonates and young infants. The chief indications for examination included: increasing head size, dysmorphic features, myelomeningocele, inflammatory disease, and asphyxia. Disorders detected included hydrocephalus, parenchymal abnormalities, intracranial hemorrhage, extraparenchymal fluid collections, and vascular and other developmental malformations. CT and US essentially were equivalent in detecting hydrocephalus, moderate to large intraventricular hemorrhages or subdural collections, and large focal parenchymal lesions, although CT was somewhat better in determining the level and cause of obstruction in patients with hydrocephalus and characterizing parenchymal abnormalities. CT was more sensitive thanmore » ultrasound in detecting subarachnoid hemorrhage (100% vs. 0%), diffuse parenchymal abnormality (100% vs. 33%), and small intraventricular hemorrhages (100% vs. 0%) but these lesions often were not clinically significant. The results suggest that US should be used as the primary neuroradiological examination in term infants; CT probably should be reserved for further investigation after US in those patients with a history of hypoxia and progressive clinical deterioration.« less

Reversal of liver fibrosis: From fiction to reality.

PubMed

Zoubek, Miguel Eugenio; Trautwein, Christian; Strnad, Pavel

2017-04-01

In chronic liver diseases, an ongoing hepatocellular injury together with inflammatory reaction results in activation of hepatic stellate cells (HSCs) and increased deposition of extracellular matrix (ECM) termed as liver fibrosis. It can progress to cirrhosis that is characterized by parenchymal and vascular architectural changes together with the presence of regenerative nodules. Even at late stage, liver fibrosis is reversible and the underlying mechanisms include a switch in the inflammatory environment, elimination or regression of activated HSCs and degradation of ECM. While animal models have been indispensable for our understanding of liver fibrosis, they possess several important limitations and need to be further refined. A better insight into the liver fibrogenesis resulted in a large number of clinical trials aiming at reversing liver fibrosis, particularly in patients with non-alcoholic steatohepatitis. Collectively, the current developments demonstrate that reversal of liver fibrosis is turning from fiction to reality. Copyright © 2017. Published by Elsevier Ltd.

Hepatic progenitor cells in canine and feline medicine: potential for regenerative strategies

PubMed Central

2014-01-01

New curative therapies for severe liver disease are urgently needed in both the human and veterinary clinic. It is important to find new treatment modalities which aim to compensate for the loss of parenchymal tissue and to repopulate the liver with healthy hepatocytes. A prime focus in regenerative medicine of the liver is the use of adult liver stem cells, or hepatic progenitor cells (HPCs), for functional recovery of liver disease. This review describes recent developments in HPC research in dog and cat and compares these findings to experimental rodent studies and human pathology. Specifically, the role of HPCs in liver regeneration, key components of the HPC niche, and HPC activation in specific types of canine and feline liver disease will be reviewed. Finally, the potential applications of HPCs in regenerative medicine of the liver are discussed and a potential role is suggested for dogs as first target species for HPC-based trials. PMID:24946932

A long-term three dimensional liver co-culture system for improved prediction of clinically relevant drug-induced hepatotoxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kostadinova, Radina; Boess, Franziska; Applegate, Dawn

2013-04-01

Drug-induced liver injury (DILI) is the major cause for liver failure and post-marketing drug withdrawals. Due to species-specific differences in hepatocellular function, animal experiments to assess potential liabilities of drug candidates can predict hepatotoxicity in humans only to a certain extent. In addition to animal experimentation, primary hepatocytes from rat or human are widely used for pre-clinical safety assessment. However, as many toxic responses in vivo are mediated by a complex interplay among different cell types and often require chronic drug exposures, the predictive performance of hepatocytes is very limited. Here, we established and characterized human and rat in vitromore » three-dimensional (3D) liver co-culture systems containing primary parenchymal and non-parenchymal hepatic cells. Our data demonstrate that cells cultured on a 3D scaffold have a preserved composition of hepatocytes, stellate, Kupffer and endothelial cells and maintain liver function for up to 3 months, as measured by the production of albumin, fibrinogen, transferrin and urea. Additionally, 3D liver co-cultures maintain cytochrome P450 inducibility, form bile canaliculi-like structures and respond to inflammatory stimuli. Upon incubation with selected hepatotoxicants including drugs which have been shown to induce idiosyncratic toxicity, we demonstrated that this model better detected in vivo drug-induced toxicity, including species-specific drug effects, when compared to monolayer hepatocyte cultures. In conclusion, our results underline the importance of more complex and long lasting in vitro cell culture models that contain all liver cell types and allow repeated drug-treatments for detection of in vivo-relevant adverse drug effects. - Highlights: ► 3D liver co-cultures maintain liver specific functions for up to three months. ► Activities of Cytochrome P450s remain drug- inducible accross three months. ► 3D liver co-cultures recapitulate drug-induced liver toxicity observed in vivo. ► 3D liver co-cultures can detect species-specific drug toxicity observed in vivo. ► This in vitro model may improve assessment of human relevance of preclinical findings.« less

Infections Complicating Orthotopic Liver Transplantation

PubMed Central

Schröter, Gerhard P. J.; Hoelscher, Manfred; Putnam, Charles W.; Porter, Kendrick A.; Hansbrough, John F.; Starzl, Thomas E.

2011-01-01

In 93 recipients of 102 orthotopic liver homografts, the incidence of bacteremia or fungemia exceeded 70%. The graft itself was usually an entry site for systemic infection after both immunologic and nonimmunologic parenchymal injury, especially if there was defective biliary drainage. The role of the homograft itself as the special infectious risk factor has prompted increased use of defunctionalized jejunal Roux limbs to reduce graft contamination. It has also stimulated very aggressive postoperative diagnostic efforts to rule out remedial mechanical complications of the transplant. PMID:793568

Transbronchial cryobiopsy for diffuse parenchymal lung disease: a state-of-the-art review of procedural techniques, current evidence, and future challenges.

PubMed

Lentz, Robert J; Argento, A Christine; Colby, Thomas V; Rickman, Otis B; Maldonado, Fabien

2017-07-01

Transbronchial lung biopsy with a cryoprobe, or cryobiopsy, is a promising new bronchoscopic biopsy technique capable of obtaining larger and better-preserved samples than previously possible using traditional biopsy forceps. Over two dozen case series and several small randomized trials are now available describing experiences with this technique, largely for the diagnosis of diffuse parenchymal lung disease (DPLD), in which the reported diagnostic yield is typically 70% to 80%. Cryobiopsy technique varies widely between centers and this predominantly single center-based retrospective literature heterogeneously defines diagnostic yield and complications, limiting the degree to which this technique can be compared between centers or to surgical lung biopsy (SLB). This review explores the broad range of cryobiopsy techniques currently in use, their rationale, the current state of the literature, and suggestions for the direction of future study into this promising but unproven procedure.

Pulmonary hypertension in diffuse parenchymal lung diseases - is there any benefit of PAH-specific therapy?

PubMed

Szturmowicz, Monika; Kacprzak, Aneta; Kuś, Jan

2017-01-01

Pulmonary hypertension (PH) is diagnosed in 40-50% of the patients with end-stage diffuse parenchymal lung diseases (DPLD), and it is associated with significant worsening of life expectancy. Latest ERS/ESC guidelines recommend best available treatment of DPLD, and long-term oxygen therapy in the patients with PaO2 less than 60 mm Hg. Pulmonary arterial hypertension (PAH)-targeted drugs are not recommended in PH-DPLD patients, due to the risk of increasing the ventilation-perfusion mismatch, and consequently worsening of hypoxaemia. Nevertheless, PAH-oriented treatment may be beneficial to selected groups of patients. The authors try to find the answer to several important questions: is there any benefit of PAH-specific therapy in PH-DPLD, who should be the candidate for PAH-specific therapy, what class of drugs is most promising, and what outcome measures should be employed?

Quantitative Stratification of Diffuse Parenchymal Lung Diseases

PubMed Central

Raghunath, Sushravya; Rajagopalan, Srinivasan; Karwoski, Ronald A.; Maldonado, Fabien; Peikert, Tobias; Moua, Teng; Ryu, Jay H.; Bartholmai, Brian J.; Robb, Richard A.

2014-01-01

Diffuse parenchymal lung diseases (DPLDs) are characterized by widespread pathological changes within the pulmonary tissue that impair the elasticity and gas exchange properties of the lungs. Clinical-radiological diagnosis of these diseases remains challenging and their clinical course is characterized by variable disease progression. These challenges have hindered the introduction of robust objective biomarkers for patient-specific prediction based on specific phenotypes in clinical practice for patients with DPLD. Therefore, strategies facilitating individualized clinical management, staging and identification of specific phenotypes linked to clinical disease outcomes or therapeutic responses are urgently needed. A classification schema consistently reflecting the radiological, clinical (lung function and clinical outcomes) and pathological features of a disease represents a critical need in modern pulmonary medicine. Herein, we report a quantitative stratification paradigm to identify subsets of DPLD patients with characteristic radiologic patterns in an unsupervised manner and demonstrate significant correlation of these self-organized disease groups with clinically accepted surrogate endpoints. The proposed consistent and reproducible technique could potentially transform diagnostic staging, clinical management and prognostication of DPLD patients as well as facilitate patient selection for clinical trials beyond the ability of current radiological tools. In addition, the sequential quantitative stratification of the type and extent of parenchymal process may allow standardized and objective monitoring of disease, early assessment of treatment response and mortality prediction for DPLD patients. PMID:24676019

Modified liver hanging maneuver focusing on outflow control in pure laparoscopic left-sided hepatectomy.

PubMed

Kim, Ji Hoon

2018-04-01

Outflow control during laparoscopic liver resection necessitates the use of technically demanding procedures since the hepatic veins are fragile and vulnerable to damage during parenchymal transection. The liver hanging maneuver reduces venous backflow bleeding during deep parenchymal transection. The present report describes surgical outcomes and a technique to achieve outflow control during application of the modified liver hanging maneuver in patients undergoing laparoscopic left-sided hepatectomy. A retrospective review was performed of clinical data from 29 patients who underwent laparoscopic left-sided hepatectomy using the modified liver hanging maneuver between February 2013 and March 2017. For this hanging technique, the upper end of the hanging tape was placed on the lateral aspect of the left hepatic vein. The tape was then aligned with the ligamentum venosum. The position of the lower end of the hanging tape was determined according to left-sided hepatectomy type. The hanging tape gradually encircled either the left hepatic vein or the common trunk of the left hepatic vein and middle hepatic vein. The surgical procedures comprised: left lateral sectionectomy (n = 10); left hepatectomy (n = 17); and extended left hepatectomy including the middle hepatic vein (n = 2). Median operative time was 210 min (range 90-350 min). Median intraoperative blood loss was 200 ml (range 60-600 ml). Two intraoperative major hepatic vein injuries occurred during left hepatectomy. Neither patient developed massive bleeding or air embolism. Postoperative major complications occurred in one patient (3.4%). Median postoperative hospital stay was 7 days (range 4-15 days). No postoperative mortality occurred. The present modified liver hanging maneuver is a safe and effective method of outflow control during laparoscopic left-sided hepatectomy.

Randomized clinical trial of stapler versus clamp-crushing transection in elective liver resection.

PubMed

Rahbari, N N; Elbers, H; Koch, M; Vogler, P; Striebel, F; Bruckner, T; Mehrabi, A; Schemmer, P; Büchler, M W; Weitz, J

2014-02-01

Various devices have been developed to facilitate liver transection and reduce blood loss in liver resections. None of these has proven superiority compared with the classical clamp-crushing technique. This randomized clinical trial compared the effectiveness and safety of stapler transection with that of clamp-crushing during open liver resection. Patients admitted for elective open liver resection between January 2010 and October 2011 were assigned randomly to stapler transection or the clamp-crushing technique. The primary endpoint was the total amount of intraoperative blood loss. Secondary endpoints included transection time, duration of operation, complication rates and resection margins. A total of 130 patients were enrolled, 65 to clamp-crushing and 65 to stapler transection. There was no difference between groups in total intraoperative blood loss: median (i.q.r.) 1050 (525-1650) versus 925 (450-1425) ml respectively (P = 0·279). The difference in total intraoperative blood loss normalized to the transection surface area was not statistically significant (P = 0·092). Blood loss during parenchymal transection was significantly lower in the stapler transection group (P = 0·002), as were the parenchymal transection time (mean(s.d.) 30(21) versus 9(7) min for clamp-crushing and stapler transection groups respectively; P < 0·001) and total duration of operation (mean(s.d.) 221(86) versus 190(85) min; P = 0·047). There were no significant differences in postoperative morbidity (P = 0·863) or mortality (P = 0·684) between groups. Stapler transection is a safe technique but does not reduce intraoperative blood loss in elective liver resection compared with the clamp-crushing technique. NCT01049607 (http://www.clinicaltrials.gov). © 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.

Doppler ultrasonographic and scintigraphic assessment of an auxiliary heterotopic liver transplantation with portal vein arterialization in pigs.

PubMed

Fernández-Rodríguez, O M; Ríos, A; Navarro, J L; Pons, J A; Palenciano, C G; Mota, R; Berenguer, J J; Mulero, F; Contreras, J; Conesa, C; Ramírez, P; Fuente, T; Parrilla, P

2006-04-01

Our aim was to evaluate liver graft integrity and function using scintigraphy and ultrasonography in a porcine model of auxiliary heterotopic liver transplantation with portal vein arterialization (AHLT-PVA). Using Doppler ultrasonography we evaluated eight AHLT-PVA by parenchymal echogenicity, portal and arterial anatomy, and portal and biliary system flow. Two types of scintigraphy were performed: microaggregated human albumin colloid scintigraphy and diisopropyl iminodiacetic acid (DISIDA) scintigraphy, both labeled with 99mTc. The animals were distributed into two groups. The first group consisted of three animals with clinical suspicion of graft dysfunction, in which the ultrasonographic study revealed areas of parenchymal destructuring. In the scintigraphic study, heterogenous uptake was observed; there was no uptake in one animal. Necropsy of these three animals revealed areas of graft necrosis. The second group consisted of five animals with good clinical evolutions, in which the ultrasonographic study showed portal dilation, portal flow with arterial spiculations, and homogenous echogenicity of the hepatic parenchyma. The scintigraphic study revealed homogenous uptake by the graft and an elimination speed of the hepatobiliary agent similar to that of the native liver. An heterogenous echostructure of the graft provided a sign of poor prognosis indicating necrosis in the same way as heterogenous uptake or nonuptake of radioisotope upon scintigraphy. Scintigraphy is a good method to evaluate biliary function and bile elimination. In an AHLT-PVA, the main ultrasound findings derived from arterialization were dilation of the portal system and portal flow with arterial spiculations.

Advanced ultrasound applications in the assessment of renal transplants: contrast-enhanced ultrasound, elastography, and B-flow.

PubMed

Morgan, Tara A; Jha, Priyanka; Poder, Liina; Weinstein, Stefanie

2018-04-09

Ultrasound is routinely used as the first imaging exam for evaluation of renal transplants and can identify most major surgical complications and evaluate vascularity with color Doppler. Ultrasound is limited, however, in the detection of parenchymal disease processes and Doppler evaluation is also prone to technical errors. Multiple new ultrasound applications have been developed and are under ongoing investigation which could add additional diagnostic capability to the routine ultrasound exam with minimal additional time, cost, and patient risk. Contrast-enhanced ultrasound (CEUS) can be used off-label in the transplant kidney, and can assist in detection of infection, trauma, and vascular complications. CEUS also can demonstrate perfusion of the transplant assessed quantitatively with generation of time-intensity curves. Future directions of CEUS include monitoring treatment response and microbubble targeted medication delivery. Elastography is an ultrasound application that can detect changes in tissue elasticity, which is useful to diagnose diffuse parenchymal disease, such as fibrosis, otherwise unrecognizable with ultrasound. Elastography has been successfully applied in other organs including the liver, thyroid, and breast; however, it is still under development for use in the transplant kidney. Unique properties of the transplant kidney including its heterogeneity, anatomic location, and other technical factors present challenges in the development of reference standard measurements. Lastly, B-flow imaging is a flow application derived from B-mode. This application can show the true lumen size of a vessel which is useful to depict vascular anatomy and bypasses some of the pitfalls of color Doppler such as demonstration of slow flow.

Comparison of In-Vitro and In-Vivo Toxic Effects of Microcystin-LR in Fasted Rats

DTIC Science & Technology

1989-02-15

form: FASEB J. 2, A584 (1988); Conference on Natural Toxins from Aquatic arid Marine Environments, Woods Hole, MA, August 1987, in press. The views of...intramitochondrial granules. J. Cell ijiol. 20, 95-109. REYNOLDS, E. S. (1965) Liver parenchymal cell injury. Ill. The nature of calcium-associated

Cell growth and differentiation on feeder layers is predicted to be influenced by bioreactor geometry.

PubMed

Peng, C A; Palsson, B Ø

1996-06-05

Tissue function is comprised of a complex interplay between biological and physicochemical rate processes. The design of bioreactors for tissue engineering must account for these processes simultaneously in order to obtain a bioreactor that provides a uniform environment for tissue growth and development. In the present study we consider the effects of fluid flow and mass transfer on the growth of a tissue in a parallel-plate bioreactor configuration. The parenchymal cells grow on a preformed stromal (feeder) layer that secretes a growth factor that stimulates parenchymal stem cell replication and differentiation. The biological dynamics are described by a unilineage model that describes the replication and differentiation of the tissue stem cell. The physicochemical rates are described by the Navier-Stokes and convective-diffusion equations. The model equations are solved by a finite element method. Two dimensionless groups govern the behavior of the solution. One is the Graetz number (Gz) that describes the relative rates of convection and diffusion, and the other a new dimensionless ratio (designated by P) that describes the interplay of the growth factor production, diffusion, and stimulation. Four geometries (slab, gondola, diamond, and radial shapes) for the parallel-plate bioreactor are analyzed. The uniformity of cell growth is measured by a two-dimensional coefficient of variance. The concentration distribution of the stroma-derived growth factor was computed first based on fluid flow and bioreactor geometry. Then the concomitant cell density distribution was obtained by integrating the calculated growth factor concentration with the parenchymal cell growth and unilineage differentiation process. The spatiotemporal cell growth patterns in four different bioreactor configurations were investigated under a variety of combinations of Gz (10(-1), 10(0), and 10(1)) and P(10(-2), 10(-1), 10(0), 10(1), and 10(2)). The results indicate high cell density and uniformity can be achieved for parameter values of P = 0.01, ..., 0.1 and Gz = 0.1, ..., 1.0. Among the four geometries investigated the radial-flow-type bioreactor provides the most uniform environment in which parenchymal cells can grow and differentiate ex vivo due to the absence of walls that are parallel to the flow paths creating slow flowing regions.

Death receptor-independent FADD signalling triggers hepatitis and hepatocellular carcinoma in mice with liver parenchymal cell-specific NEMO knockout.

PubMed

Ehlken, H; Krishna-Subramanian, S; Ochoa-Callejero, L; Kondylis, V; Nadi, N E; Straub, B K; Schirmacher, P; Walczak, H; Kollias, G; Pasparakis, M

2014-11-01

Hepatocellular carcinoma (HCC) usually develops in the context of chronic hepatitis triggered by viruses or toxic substances causing hepatocyte death, inflammation and compensatory proliferation of liver cells. Death receptors of the TNFR superfamily regulate cell death and inflammation and are implicated in liver disease and cancer. Liver parenchymal cell-specific ablation of NEMO/IKKγ, a subunit of the IκB kinase (IKK) complex that is essential for the activation of canonical NF-κB signalling, sensitized hepatocytes to apoptosis and caused the spontaneous development of chronic hepatitis and HCC in mice. Here we show that hepatitis and HCC development in NEMO(LPC-KO) mice is triggered by death receptor-independent FADD-mediated hepatocyte apoptosis. TNF deficiency in all cells or conditional LPC-specific ablation of TNFR1, Fas or TRAIL-R did not prevent hepatocyte apoptosis, hepatitis and HCC development in NEMO(LPC-KO) mice. To address potential functional redundancies between death receptors we generated and analysed NEMO(LPC-KO) mice with combined LPC-specific deficiency of TNFR1, Fas and TRAIL-R and found that also simultaneous lack of all three death receptors did not prevent hepatocyte apoptosis, chronic hepatitis and HCC development. However, LPC-specific combined deficiency in TNFR1, Fas and TRAIL-R protected the NEMO-deficient liver from LPS-induced liver failure, showing that different mechanisms trigger spontaneous and LPS-induced hepatocyte apoptosis in NEMO(LPC-KO) mice. In addition, NK cell depletion did not prevent liver damage and hepatitis. Moreover, NEMO(LPC-KO) mice crossed into a RAG-1-deficient genetic background-developed hepatitis and HCC. Collectively, these results show that the spontaneous development of hepatocyte apoptosis, chronic hepatitis and HCC in NEMO(LPC-KO) mice occurs independently of death receptor signalling, NK cells and B and T lymphocytes, arguing against an immunological trigger as the critical stimulus driving hepatocarcinogenesis in this model.

Morphometric analysis of primary graft non-function in liver transplantation.

PubMed

Vertemati, M; Sabatella, G; Minola, E; Gambacorta, M; Goffredi, M; Vizzotto, L

2005-04-01

Primary graft non-function (PNF) is a life-threatening condition that is thought to be the consequence of microcirculation injury. The aim of the present study was to assess, with a computerized morphometric model, the morphological changes at reperfusion in liver biopsy specimens from patients who developed PNF after liver transplantation. Biopsy specimens were obtained at maximum ischaemia and at the end of reperfusion. Morphology included many stereological parameters, such as volumes of all parenchymal components, surface density, size distribution and mean diameter of hepatocytes. Other variables examined were intensive care unit stay, degree of steatosis, serum liver function tests and ischaemic time. In the postoperative period, the PNF group showed elevated serum levels of alanine transferase, decreased daily rate of bile production and prothrombin activity. Blood lactates were significantly higher in the PNF group than in a control group. When comparing groups, the volumetric parameters related to hepatocytes and sinusoids and the surface densities of the hepatic cells showed an inverse relationship. At the end of reperfusion, in PNF group the volume fraction of hepatocyte cytoplasm was decreased; in contrast, the volume fraction of sinusoidal lumen was markedly increased. The cell profiles showed the same inverse trend: the surface density of the parenchymal border of hepatocytes was decreased in PNF when compared with the control group, while the surface density of the vascular border was increased. In the PNF group, the surface density of the sinusoidal bed was directly correlated with alanine transferase, daily rate of bile production, prothrombin activity and cold ischaemic time. The alterations in hepatic architecture, as demonstrated by morphometric analysis in liver transplant recipients that developed PNF, provide additional information that may represent useful viability markers of the graft to complement conventional histological analysis.

The sites of catabolism of murine monomeric IgA.

PubMed

Moldoveanu, Z; Epps, J M; Thorpe, S R; Mestecky, J

1988-07-01

The tissue sites of monomeric IgA (mIgA) catabolism were determined in a BALB/c mouse model. Mouse mIgA myeloma proteins were labeled either by direct iodination or by coupling the residualizing label, dilactitol-125I-tyramine (125I-DLT) to the proteins; catabolites from protein labeled with 125I-DLT accumulate at the site of protein degradation, allowing identification of the tissue and cellular sites involved in catabolism of the protein. The circulating half-lives of 125I- and 125I-DLT-mIgA were the same. The distribution of radioactivity in tissues was measured at 1, 3, 24, and 96 h after iv. injection of 125I-DLT-labeled mIgA, dimeric IgA (dIgA), IgG, or mouse serum albumin. The greatest uptake of 125I-DLT-mIgA was attributable to the liver. This organ accounted for more internal catabolism of mIgA than all other tissues combined. In contrast, 125I-DLT-IgG was catabolized equally in skin, muscle, and liver. These data indicate that, in mice, the liver is the major site of mIgA catabolism. To determine the cell types involved, collagenase digestion was used to isolate parenchymal and non-parenchymal cells from perfused liver of animals injected with 125-DLT-mIgA. Most of the radioactivity was associated with the hepatocyte fraction, even though both cell types showed uptake of 125I-DLT-mIgA. Inhibition studies, with asialofetuin and mouse IgA demonstrated that the uptake of mIgA by liver cells was mediated primarily by the asialoglycoprotein receptor.

Transbronchial Lung Cryobiopsy and Video-assisted Thoracoscopic Lung Biopsy in the Diagnosis of Diffuse Parenchymal Lung Disease. A Meta-analysis of Diagnostic Test Accuracy.

PubMed

Iftikhar, Imran H; Alghothani, Lana; Sardi, Alejandro; Berkowitz, David; Musani, Ali I

2017-07-01

Transbronchial lung cryobiopsy is increasingly being used for the assessment of diffuse parenchymal lung diseases. Several studies have shown larger biopsy samples and higher yields compared with conventional transbronchial biopsies. However, the higher risk of bleeding and other complications has raised concerns for widespread use of this modality. To study the diagnostic accuracy and safety profile of transbronchial lung cryobiopsy and compare with video-assisted thoracoscopic surgery (VATS) by reviewing available evidence from the literature. Medline and PubMed were searched from inception until December 2016. Data on diagnostic performance were abstracted by constructing two-by-two contingency tables for each study. Data on a priori selected safety outcomes were collected. Risk of bias was assessed with the Quality Assessment of Diagnostic Accuracy Studies tool. Random effects meta-analyses were performed to obtain summary estimates of the diagnostic accuracy. The pooled diagnostic yield, pooled sensitivity, and pooled specificity of transbronchial lung cryobiopsy were 83.7% (76.9-88.8%), 87% (85-89%), and 57% (40-73%), respectively. The pooled diagnostic yield, pooled sensitivity, and pooled specificity of VATS were 92.7% (87.6-95.8%), 91.0% (89-92%), and 58% (31-81%), respectively. The incidence of grade 2 (moderate to severe) endobronchial bleeding after transbronchial lung cryobiopsy and of post-procedural pneumothorax was 4.9% (2.2-10.7%) and 9.5% (5.9-14.9%), respectively. Although the diagnostic test accuracy measures of transbronchial lung cryobiopsy lag behind those of VATS, with an acceptable safety profile and potential cost savings, the former could be considered as an alternative in the evaluation of patients with diffuse parenchymal lung diseases.

A novel method of mouse ex utero transplantation of hepatic progenitor cells into the fetal liver

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shikanai, Mima; Asahina, Kinji; Iseki, Sachiko

2009-04-03

Avoiding the limitations of the adult liver niche, transplantation of hepatic stem/progenitor cells into fetal liver is desirable to analyze immature cells in a hepatic developmental environment. Here, we established a new monitor tool for cell fate of hepatic progenitor cells transplanted into the mouse fetal liver by using ex utero surgery. When embryonic day (ED) 14.5 hepatoblasts were injected into the ED14.5 fetal liver, the transplanted cells expressed albumin abundantly or {alpha}-fetoprotein weakly, and contained glycogen in the neonatal liver, indicating that transplanted hepatoblasts can proliferate and differentiate in concord with surrounding recipient parenchymal cells. The transplanted cells becamemore » mature in the liver of 6-week-old mice. Furthermore, this method was applicable to transplantation of hepatoblast-like cells derived from mouse embryonic stem cells. These data indicate that this unique technique will provide a new in vivo experimental system for studying cell fate of hepatic stem/progenitor cells and liver organogenesis.« less

Postmortem Findings for 7 Neonates with Congenital Zika Virus Infection.

PubMed

Sousa, Anastácio Q; Cavalcante, Diane I M; Franco, Luciano M; Araújo, Fernanda M C; Sousa, Emília T; Valença-Junior, José Telmo; Rolim, Dionne B; Melo, Maria E L; Sindeaux, Pedro D T; Araújo, Marialva T F; Pearson, Richard D; Wilson, Mary E; Pompeu, Margarida M L

2017-07-01

Postmortem examination of 7 neonates with congenital Zika virus infection in Brazil revealed microcephaly, ventriculomegaly, dystrophic calcifications, and severe cortical neuronal depletion in all and arthrogryposis in 6. Other findings were leptomeningeal and brain parenchymal inflammation and pulmonary hypoplasia and lymphocytic infiltration in liver and lungs. Findings confirmed virus neurotropism and multiple organ infection.

Magnetic resonance imaging in central nervous system sarcoidosis.

PubMed

Miller, D H; Kendall, B E; Barter, S; Johnson, G; MacManus, D G; Logsdail, S J; Ormerod, I E; McDonald, W I

1988-03-01

We performed brain MRIs on 21 patients with CNS sarcoidosis. Brain CTs were performed in 18 of these. Parenchymal lesions were seen in 17 of 21 with MRI, compared with 9 of 18 with CT. MRI detected a greater number of parenchymal lesions in cases where both CT and MRI were positive, and some lesions appeared more extensive with MRI than with CT. The most common MRI pattern was one of periventricular and multifocal white matter lesions (14 cases). Such a pattern is not specific, and other recognized causes for it were identified in four cases. It is likely, however, that sarcoid tissue causes this pattern in some cases, and confirmation was obtained from cerebral biopsy in one. In six patients, the white matter changes were indistinguishable from those seen in multiple sclerosis. Contrast-enhanced CT in two patients showed diffuse meningeal involvement not seen with MRI. MRI is the investigation of choice in detecting parenchymal changes in the brain of patients with CNS sarcoidosis and may prove useful in monitoring treatment in such cases.

Nano-vectors for efficient liver specific gene transfer

PubMed Central

Pathak, Atul; Vyas, Suresh P; Gupta, Kailash C

2008-01-01

Recent progress in nanotechnology has triggered the site specific drug/gene delivery research and gained wide acknowledgment in contemporary DNA therapeutics. Amongst various organs, liver plays a crucial role in various body functions and in addition, the site is a primary location of metastatic tumor growth. In past few years, a plethora of nano-vectors have been developed and investigated to target liver associated cells through receptor mediated endocytosis. This emerging paradigm in cellular drug/gene delivery provides promising approach to eradicate genetic as well as acquired diseases affecting the liver. The present review provides a comprehensive overview of potential of various delivery systems, viz., lipoplexes, liposomes, polyplexes, nanoparticles and so forth to selectively relocate foreign therapeutic DNA into liver specific cell type via the receptor mediated endocytosis. Various receptors like asialoglycoprotein receptors (ASGP-R) provide unique opportunity to target liver parenchymal cells. The results obtained so far reveal tremendous promise and offer enormous options to develop novel DNA-based pharmaceuticals for liver disorders in near future. PMID:18488414

[Liver engineering as a new source of donor organs : A systematic review].

PubMed

Mußbach, F; Dahmen, U; Dirsch, O; Settmacher, U

2016-06-01

Organ engineering is a new strategy to cope with the shortage of donor organs. A functional scaffold from explanted organs is prepared by removing all cellular components (decellularization) and the reseeding (repopulation) of the organ scaffold to generate a functional organ in vitro for transplantation. This technique was also applied to the liver (liver engineering). Outline of the current state of the art and resulting approaches for future research strategies. Systematic review according to the PRISMA guidelines: a PubMed-based literature search (search terms liver, decellularization), selection of relevant articles based on predetermined criteria for relevance (e.g. decellularization, repopulation and transplantation), extraction and critical appraisal of data and results concerning the conditions for decellularization, repopulation and transplantation. Decellularization was successfully performed in small and large animal models. Hepatocytes as well as stem cells and hepatic cell lines were applied for repopulation and 7 publications could show the successful transplantation of acellular and repopulated organ scaffolds. The current scientific need for further studies concerning the source of donor organs, optimization of the decellularization process, the cell type for the reseeding process and the establishment of the optimal conditions for the repopulation of the scaffold is still tremendous. For successful recellularization of the liver three goals need to be achieved: (1) reseeding of the organ scaffold with a sufficient amount of parenchymal cells, (2) endothelialization of the vascular tree to ensure the supply of oxygen and nutrients to parenchymal cells and (3) an appropriate epithelialization of the biliary tree. In order to progress to clinical trials a suitable transplantation model to verify the function of the organ constructs must be established. Liver engineering using biological cell-free organ scaffolds represents a scientific and ethical challenge. The existing results emphasize the potential of this new and promising strategy to create organs for transplantation in the future.

Multicentre evaluation of multidisciplinary team meeting agreement on diagnosis in diffuse parenchymal lung disease: a case-cohort study.

PubMed

Walsh, Simon L F; Wells, Athol U; Desai, Sujal R; Poletti, Venerino; Piciucchi, Sara; Dubini, Alessandra; Nunes, Hilario; Valeyre, Dominique; Brillet, Pierre Y; Kambouchner, Marianne; Morais, António; Pereira, José M; Moura, Conceição Souto; Grutters, Jan C; van den Heuvel, Daniel A; van Es, Hendrik W; van Oosterhout, Matthijs F; Seldenrijk, Cornelis A; Bendstrup, Elisabeth; Rasmussen, Finn; Madsen, Line B; Gooptu, Bibek; Pomplun, Sabine; Taniguchi, Hiroyuki; Fukuoka, Junya; Johkoh, Takeshi; Nicholson, Andrew G; Sayer, Charlie; Edmunds, Lilian; Jacob, Joseph; Kokosi, Maria A; Myers, Jeffrey L; Flaherty, Kevin R; Hansell, David M

2016-07-01

Diffuse parenchymal lung disease represents a diverse and challenging group of pulmonary disorders. A consistent diagnostic approach to diffuse parenchymal lung disease is crucial if clinical trial data are to be applied to individual patients. We aimed to evaluate inter-multidisciplinary team agreement for the diagnosis of diffuse parenchymal lung disease. We did a multicentre evaluation of clinical data of patients who presented to the interstitial lung disease unit of the Royal Brompton and Harefield NHS Foundation Trust (London, UK; host institution) and required multidisciplinary team meeting (MDTM) characterisation between March 1, 2010, and Aug 31, 2010. Only patients whose baseline clinical, radiological, and, if biopsy was taken, pathological data were undertaken at the host institution were included. Seven MDTMs, consisting of at least one clinician, radiologist, and pathologist, from seven countries (Denmark, France, Italy, Japan, Netherlands, Portugal, and the UK) evaluated cases of diffuse parenchymal lung disease in a two-stage process between Jan 1, and Oct 15, 2015. First, the clinician, radiologist, and pathologist (if lung biopsy was completed) independently evaluated each case, selected up to five differential diagnoses from a choice of diffuse lung diseases, and chose likelihoods (censored at 5% and summing to 100% in each case) for each of their differential diagnoses, without inter-disciplinary consultation. Second, these specialists convened at an MDTM and reviewed all data, selected up to five differential diagnoses, and chose diagnosis likelihoods. We compared inter-observer and inter-MDTM agreements on patient first-choice diagnoses using Cohen's kappa coefficient (κ). We then estimated inter-observer and inter-MDTM agreement on the probability of diagnosis using weighted kappa coefficient (κw). We compared inter-observer and inter-MDTM confidence of patient first-choice diagnosis. Finally, we evaluated the prognostic significance of a first-choice diagnosis of idiopathic pulmonary fibrosis (IPF) versus not IPF for MDTMs, clinicians, and radiologists, using univariate Cox regression analysis. 70 patients were included in the final study cohort. Clinicians, radiologists, pathologists, and the MDTMs assigned their patient diagnoses between Jan 1, and Oct 15, 2015. IPF made up 88 (18%) of all 490 MDTM first-choice diagnoses. Inter-MDTM agreement for first-choice diagnoses overall was moderate (κ=0·50). Inter-MDTM agreement on diagnostic likelihoods was good for IPF (κw=0·71 [IQR 0·64-0·77]) and connective tissue disease-related interstitial lung disease (κw=0·73 [0·68-0·78]); moderate for non-specific interstitial pneumonia (NSIP; κw=0·42 [0·37-0·49]); and fair for hypersensitivity pneumonitis (κw=0·29 [0·24-0·40]). High-confidence diagnoses (>65% likelihood) of IPF were given in 68 (77%) of 88 cases by MDTMs, 62 (65%) of 96 cases by clinicians, and in 57 (66%) of 86 cases by radiologists. Greater prognostic separation was shown for an MDTM diagnosis of IPF than compared with individual clinician's diagnosis of this disease in five of seven MDTMs, and radiologist's diagnosis of IPF in four of seven MDTMs. Agreement between MDTMs for diagnosis in diffuse lung disease is acceptable and good for a diagnosis of IPF, as validated by the non-significant greater prognostic separation of an IPF diagnosis made by MDTMs than the separation of a diagnosis made by individual clinicians or radiologists. Furthermore, MDTMs made the diagnosis of IPF with higher confidence and more frequently than did clinicians or radiologists. This difference is of particular importance, because accurate and consistent diagnoses of IPF are needed if clinical outcomes are to be optimised. Inter-multidisciplinary team agreement for a diagnosis of hypersensitivity pneumonitis is low, highlighting an urgent need for standardised diagnostic guidelines for this disease. National Institute of Health Research, Imperial College London. Copyright © 2016 Elsevier Ltd. All rights reserved.

Quantitative consensus of supervised learners for diffuse lung parenchymal HRCT patterns

NASA Astrophysics Data System (ADS)

Raghunath, Sushravya; Rajagopalan, Srinivasan; Karwoski, Ronald A.; Bartholmai, Brian J.; Robb, Richard A.

2013-03-01

Automated lung parenchymal classification usually relies on supervised learning of expert chosen regions representative of the visually differentiable HRCT patterns specific to different pathologies (eg. emphysema, ground glass, honey combing, reticular and normal). Considering the elusiveness of a single most discriminating similarity measure, a plurality of weak learners can be combined to improve the machine learnability. Though a number of quantitative combination strategies exist, their efficacy is data and domain dependent. In this paper, we investigate multiple (N=12) quantitative consensus approaches to combine the clusters obtained with multiple (n=33) probability density-based similarity measures. Our study shows that hypergraph based meta-clustering and probabilistic clustering provides optimal expert-metric agreement.

Integration of technologies for hepatic tissue engineering.

PubMed

Nahmias, Yaakov; Berthiaume, Francois; Yarmush, Martin L

2007-01-01

The liver is the largest internal organ in the body, responsible for over 500 metabolic, regulatory, and immune functions. Loss of liver function leads to liver failure which causes over 25,000 deaths/year in the United States. Efforts in the field of hepatic tissue engineering include the design of bioartificial liver systems to prolong patient's lives during liver failure, for drug toxicity screening and for the study of liver regeneration, ischemia/reperfusion injury, fibrosis, viral infection, and inflammation. This chapter will overview the current state-of-the-art in hepatology including isolated perfused liver, culture of liver slices and tissue explants, hepatocyte culture on collagen "sandwich" and spheroids, coculture of hepatocytes with non-parenchymal cells, and the integration of these culture techniques with microfluidics and reactor design. This work will discuss the role of oxygen and medium composition in hepatocyte culture and present promising new technologies for hepatocyte proliferation and function. We will also discuss liver development, architecture, and function as they relate to these culture techniques. Finally, we will review current opportunities and major challenges in integrating cell culture, bioreactor design, and microtechnology to develop new systems for novel applications.

Surgical anatomy of the liver, hepatic vasculature and bile ducts in the rat.

PubMed

Martins, Paulo Ney Aguiar; Neuhaus, Peter

2007-04-01

The rat is the most used experimental model in surgical research. Virtually all procedures in clinical liver surgery can be performed in the rat. However, the use of the rat model in liver surgery is limited by its small size and limited knowledge of the liver anatomy. As in humans, the rat liver vasculature and biliary system have many anatomical variations. The development of surgical techniques, and the study of liver function and diseases require detailed knowledge of the regional anatomy. The objective of this study was to describe and illustrate systematically the surgical anatomy of the rat liver to facilitate the planning and performance of studies in this animal. Knowledge of the diameter and length of liver vessels is also important for the selection of catheters and perivascular devices. Twelve Wistar rat livers were dissected using a surgical microscope. Hepatic and extrahepatic anatomical structures were measured under magnification with a millimeter scale. In this study, we describe the rat liver topographical anatomy, compare it with the human liver and review the literature. Increased knowledge of the rat liver anatomy and microsurgical skills permit individualized dissection, parenchymal section, embolization and ligature of vascular and biliary branches.

Vascular liver anatomy and main variants: what the radiologist must know.

PubMed

Seco, M; Donato, P; Costa, J; Bernardes, A; Caseiro-Alves, F

2010-01-01

Advances in surgical techniques are extremely demanding regarding the accuracy and level of detail expected for display of the vascular anatomy of the liver. Precise knowledge of the arterial, portal and hepatic vein territories are mandatory whenever a liver intervention is planned. Sectional anatomy can now be routinely performed on multidetector computed tomography (MDCT) with volumetric data and isotropic voxel display, by means of sub-millimetric slice thickness acquisition. The relevant vascular information can thus be gathered, reviewed and post-processed with unprecedented clarity, obviating the need for digital subtraction angiography. The scope of the present paper is to review the normal vascular liver anatomy, its most relevant variants including additional sources of vascular inflow. Apart from providing the surgeon with a detailed vascular and parenchymal roadmap knowledge of imaging findings may avoid potential confusion with pathologic processes.

Increased parenchymal damage and steatohepatitis in Caucasian non-alcoholic fatty liver disease patients with common IL1B and IL6 polymorphisms.

PubMed

Nelson, J E; Handa, P; Aouizerat, B; Wilson, L; Vemulakonda, L A; Yeh, M M; Kowdley, K V

2016-12-01

Non-alcoholic fatty liver disease (NAFLD) is a complex, multifactorial disease affected by diet, lifestyle and genetics. Proinflammatory cytokines like IL-1β and IL-6 have been shown to be elevated in non-alcoholic steatohepatitis (NASH). To investigate the relationship between IL1B and IL6 gene polymorphisms and histological features of NAFLD in the NASH CRN cohort. A total of 604 adult (≥18 years) non-Hispanic Caucasians with biopsy-proven NAFLD were genotyped for the following SNPs: IL1B, rs16944, rs1143634; IL6, rs1800795, rs10499563. Logistic regression was used to examine the relationship between genotype and a definitive diagnosis and advanced histological features of NASH after controlling for the following variables selected a priori: age, sex, diabetes, obesity and HOMA-IR level. The IL6 rs10499563 C allele was independently associated with the presence of definitive NASH, and increased ballooning and Mallory bodies. The IL1B rs1143634 TT genotype was associated with advanced fibrosis and increased Mallory bodies. The IL6 rs1800795 C allele was associated with not only increased risk for severe steatosis, >66% but also decreased risk for advanced fibrosis and lobular inflammation and Mallory body formation. These results suggest that common variants in the IL6 and IL1B genes may increase susceptibility for NASH and confer a higher risk of hepatic parenchymal damage including increased ballooning, increased Mallory bodies, and bridging fibrosis or cirrhosis. In contrast, the IL6 rs1800795 C allele may confer a higher risk for steatosis, but less parenchymal damage. Our findings support the development of therapeutics aimed at IL-1β and IL-6 suppression. © 2016 John Wiley & Sons Ltd.

Increased Parenchymal Damage and Steatohepatitis in Caucasian Nonalcoholic Fatty Liver Disease Patients with Common IL1B and IL6 Polymorphisms

PubMed Central

Nelson, James E.; Handa, Priya; Aouizerat, Bradley; Wilson, Laura; Vemulakonda, L Akhila; Yeh, Matthew M.; Kowdley, Kris V.

2016-01-01

Background Nonalcoholic fatty liver disease (NAFLD) is a complex, multifactorial disease affected by diet, lifestyle and genetics. Proinflammatory cytokines like IL-1β and IL-6 have been shown to be elevated in nonalcoholic steatohepatitis (NASH). The goal of this study was to investigate the relationship between IL1B and IL6 gene polymorphisms and histologic features of NAFLD in the NASH CRN cohort. Methods 604 adult (≥18 yrs) non-Hispanic Caucasians with biopsy-proven NAFLD were genotyped for the following SNPs: IL1B, rs16944, rs1143634; IL6, rs1800795, rs10499563. Logistic regression was used to examine the relationship between genotype and a definitive diagnosis and advanced histological features of NASH after controlling for the following variables selected a priori: age, sex, diabetes, obesity and HOMA-IR level. Results The IL6 rs10499563 C allele was independently associated with the presence of definitive NASH, and increased ballooning and Mallory bodies. The IL1B rs1143634 TT genotype was associated with advanced fibrosis and increased Mallory bodies. The IL6 rs1800795 C allele was associated with increased risk for severe steatosis, >66% but also decreased risk for advanced fibrosis and lobular inflammation and Mallory body formation. Conclusions These results suggest that common variants in the IL6 and IL1B genes may increase susceptibility for NASH and confer a higher risk of hepatic parenchymal damage including increased ballooning, increased Mallory bodies, and bridging fibrosis or cirrhosis. In contrast, the IL6 rs1800795 C allele may confer a higher risk for steatosis, but less parenchymal damage. Our findings support the development of therapeutics aimed at IL-1β and IL-6 suppression. PMID:27730688

Sonographic assessment of petroleum-induced hepatotoxicity in Nigerians: does biochemical assessment underestimate liver damage?

PubMed

Anakwue, Angel-Mary; Anakwue, Raphael; Okeji, Mark; Idigo, Felicitas; Agwu, Kenneth; Nwogu, Uloma

2017-03-01

Exposure to petroleum products has been shown to have significant adverse effects on the liver which can manifest either as morphological or physiological changes. The aim of the study was to assess the effects of chronic exposure to some petroleum products on the liver of exposed workers using sonography and to determine whether biochemical assessments underestimated hepatotoxicity. Abdominal ultrasound was performed on 415 exposed workers in order to evaluate liver echogenicity and size. Also, biochemical assessment of the liver was done to evaluate its function. Statistically significant increase in the liver parenchymal echogenicity and the liver size was seen in the exposed workers compared with control (p ≤ 0.05). These increased as the exposure duration increased. It was also noted that out of 16.87% (N=70) exposed workers with abnormal liver echopattern, only 2.65% (N=11) had alanine aminotransferase above the reference range. The study revealed evidence of ultrasound detectable hepatotoxicity among the exposed subjects. Sonography appeared to detect petroleum products-induced hepatic toxicity more than biochemical assays suggesting that biochemical assessment may have underestimated toxicity.

Control of oxygen tension recapitulates zone-specific functions in human liver microphysiology systems.

PubMed

Lee-Montiel, Felipe T; George, Subin M; Gough, Albert H; Sharma, Anup D; Wu, Juanfang; DeBiasio, Richard; Vernetti, Lawrence A; Taylor, D Lansing

2017-10-01

This article describes our next generation human Liver Acinus MicroPhysiology System (LAMPS). The key demonstration of this study was that Zone 1 and Zone 3 microenvironments can be established by controlling the oxygen tension in individual devices over the range of ca. 3 to 13%. The oxygen tension was computationally modeled using input on the microfluidic device dimensions, numbers of cells, oxygen consumption rates of hepatocytes, the diffusion coefficients of oxygen in different materials and the flow rate of media in the MicroPhysiology System (MPS). In addition, the oxygen tension was measured using a ratiometric imaging method with the oxygen sensitive dye, Tris(2,2'-bipyridyl) dichlororuthenium(II) hexahydrate (RTDP) and the oxygen insensitive dye, Alexa 488. The Zone 1 biased functions of oxidative phosphorylation, albumin and urea secretion and Zone 3 biased functions of glycolysis, α1AT secretion, Cyp2E1 expression and acetaminophen toxicity were demonstrated in the respective Zone 1 and Zone 3 MicroPhysiology System. Further improvements in the Liver Acinus MicroPhysiology System included improved performance of selected nonparenchymal cells, the inclusion of a porcine liver extracellular matrix to model the Space of Disse, as well as an improved media to support both hepatocytes and non-parenchymal cells. In its current form, the Liver Acinus MicroPhysiology System is most amenable to low to medium throughput, acute through chronic studies, including liver disease models, prioritizing compounds for preclinical studies, optimizing chemistry in structure activity relationship (SAR) projects, as well as in rising dose studies for initial dose ranging. Impact statement Oxygen zonation is a critical aspect of liver functions. A human microphysiology system is needed to investigate the impact of zonation on a wide range of liver functions that can be experimentally manipulated. Because oxygen zonation has such diverse physiological effects in the liver, we developed and present a method for computationally modeling and measuring oxygen that can easily be implemented in all MPS models. We have applied this method in a liver MPS in which we are then able to control oxygenation in separate devices and demonstrate that zonation-dependent hepatocyte functions in the MPS recapitulate what is known about in vivo liver physiology. We believe that this advance allows a deep experimental investigation on the role of zonation in liver metabolism and disease. In addition, modeling and measuring oxygen tension will be required as investigators migrate from PDMS to plastic and glass devices.

Control of oxygen tension recapitulates zone-specific functions in human liver microphysiology systems

PubMed Central

Lee-Montiel, Felipe T; George, Subin M; Sharma, Anup D; Wu, Juanfang; DeBiasio, Richard; Vernetti, Lawrence A; Taylor, D Lansing

2017-01-01

This article describes our next generation human Liver Acinus MicroPhysiology System (LAMPS). The key demonstration of this study was that Zone 1 and Zone 3 microenvironments can be established by controlling the oxygen tension in individual devices over the range of ca. 3 to 13%. The oxygen tension was computationally modeled using input on the microfluidic device dimensions, numbers of cells, oxygen consumption rates of hepatocytes, the diffusion coefficients of oxygen in different materials and the flow rate of media in the MicroPhysiology System (MPS). In addition, the oxygen tension was measured using a ratiometric imaging method with the oxygen sensitive dye, Tris(2,2′-bipyridyl) dichlororuthenium(II) hexahydrate (RTDP) and the oxygen insensitive dye, Alexa 488. The Zone 1 biased functions of oxidative phosphorylation, albumin and urea secretion and Zone 3 biased functions of glycolysis, α1AT secretion, Cyp2E1 expression and acetaminophen toxicity were demonstrated in the respective Zone 1 and Zone 3 MicroPhysiology System. Further improvements in the Liver Acinus MicroPhysiology System included improved performance of selected nonparenchymal cells, the inclusion of a porcine liver extracellular matrix to model the Space of Disse, as well as an improved media to support both hepatocytes and non-parenchymal cells. In its current form, the Liver Acinus MicroPhysiology System is most amenable to low to medium throughput, acute through chronic studies, including liver disease models, prioritizing compounds for preclinical studies, optimizing chemistry in structure activity relationship (SAR) projects, as well as in rising dose studies for initial dose ranging. Impact statement Oxygen zonation is a critical aspect of liver functions. A human microphysiology system is needed to investigate the impact of zonation on a wide range of liver functions that can be experimentally manipulated. Because oxygen zonation has such diverse physiological effects in the liver, we developed and present a method for computationally modeling and measuring oxygen that can easily be implemented in all MPS models. We have applied this method in a liver MPS in which we are then able to control oxygenation in separate devices and demonstrate that zonation-dependent hepatocyte functions in the MPS recapitulate what is known about in vivo liver physiology. We believe that this advance allows a deep experimental investigation on the role of zonation in liver metabolism and disease. In addition, modeling and measuring oxygen tension will be required as investigators migrate from PDMS to plastic and glass devices. PMID:28409533

Generation of hepatocyte-like cells from human induced pluripotent stem (iPS) cells by co-culturing embryoid body cells with liver non-parenchymal cell line TWNT-1.

PubMed

Javed, M Shahid; Yaqoob, Naeem; Iwamuro, Masaya; Kobayashi, Naoya; Fujiwara, Toshiyoshi

2014-02-01

To generate a homogeneous population of patient-specific hepatocyte-like cells (HLCs) from human iPS cells those show the morphologic and phenotypic properties of primary human hepatocytes. An experimental study. Department of Surgery, Okayama University, Graduate School of Medicine, Japan, from April to December 2011. Human iPS cells were generated and maintained on ES qualified matrigel coated plates supplemented with mTeSR medium or alternatively on mitotically inactivated MEF feeder layer in DMEM/F12 medium containing 20% KOSR, 4ng/ml bFGF-2, 1 x 10-4 M 2-mercaptoethanol, 1 mmol/L NEAA, 2mM L-glutamine and 1% penicillin-streptomycin. iPS cells were differentiated to HLCs by sequential culture using a four step differentiation protocol: (I) Generation of embryoid bodies (EBs) in suspension culture; (II) Induction of definitive endoderm (DE) from 2 days old EBs by growth in human activin-A (100 ng/ml) and basic fibroblasts growth factor (bFGF2) (100 ng/ml) on matrigel coated plates; (III) Induction of hepatic progenitors by co-culture with non-parenchymal human hepatic stellate cell line (TWNT-1); and (IV) Maturation by culture in dexamethasone. Characterization was performed by RT-PCR and functional assays. The generated HLCs showed microscopically morphological phenotype of human hepatocytes, expressed liver-specific genes (ASGPR, Albumin, AFP, Sox17, Fox A2), secreted human liver-specific proteins such as albumin, synthesized urea and metabolized ammonia. Functional HLCs were generated from human iPS cells, which could be used for autologus hepatocyte transplantation for liver failure and as in vitro model for determining the metabolic and toxicological properties of drug compounds.

Cell expression patterns of CD147 in N-diethylnitrosamine/phenobarbital-induced mouse hepatocellular carcinoma.

PubMed

Lu, Meng; Wu, Jiao; He, Feng; Wang, Xi-Long; Li, Can; Chen, Zhi-Nan; Bian, Huijie

2015-02-01

Overexpression of CD147/basigin in hepatic cells promotes the progression of hepatocellular carcinoma (HCC). Whether CD147 also expressed in liver non-parenchymal cells and associated with HCC development was unknown. The aim of the study was to explore time-dependent cell expression patterns of CD147 in a widely accepted N-diethylnitrosamine/phenobarbital (DEN/PB)-induced HCC mouse model. Liver samples collected at month 1-12 of post-DEN/PB administration were assessed the localization of CD147 in hepatocytes, endothelial cells, hepatic stellate cells, and macrophages. Immunohistochemistry analysis showed that CD147 was upregulated in liver tumors during month 1-8 of DEN/PB induction. Expression of CD147 was positively correlated with cytokeratin 18, a hepatocyte marker (r = 0.7857, P = 0.0279), CD31 (r = 0.9048, P = 0.0046), an endothelial cell marker, and CD68, a macrophage marker (r = 0.7619, P = 0.0368). A significant correlation was also observed between CD147 and alpha-smooth muscle actin (r = 0.8857, P = 0.0333) at DEN/PB initiation and early stage of tumor formation. Immunofluorescence and fluorescence in situ hybridization showed that CD147 co-expressed with cytokeratin 18, CD31, alpha-smooth muscle actin, and CD68. Moreover, there existed positive correlations between CD147 and microvessel density (r = 0.7857, P = 0.0279), CD147 and Ki-67 (r = 0.9341, P = 0.0022) in the development of DEN/PB-induced HCC. In conclusion, our results demonstrated that CD147 was upregulated in the liver parenchymal and mesenchymal cells and involved in angiogenesis and tumor cell proliferation in the development of DEN/PB-induced HCC.

Alagille Syndrome Candidates for Liver Transplantation: Differentiation from End-Stage Biliary Atresia Using Preoperative CT.

PubMed

Hwang, Sook Min; Jeon, Tae Yeon; Yoo, So-Young; Kim, Ji Hye; Kang, Ben; Choe, Yon Ho; Cho, Haeyon; Kim, Jung Sun

2016-01-01

To compare preoperative CT findings before liver transplantation between patients with Alagille syndrome (AGS) and those with end-stage biliary atresia (BA). The institutional review board approved this retrospective study. Eleven children with AGS (median age, 19.0 ± 13.0 months; male to female ratio, 3:8) and 109 children with end-stage BA (median age, 17.9 ± 25.8 months; male to female ratio, 37:72) who underwent abdomen CT as candidates for liver transplant were included. CT images were reviewed focusing on hepatic parenchymal changes, vascular changes, presence of focal lesions, and signs of portal hypertension. Hepatic parenchymal changes were present in 27% (3/11) of AGS patients and 100% (109/109) of end-stage BA patients (P < .001). The hepatic artery diameter was significantly smaller (1.9 mm versus 3.6 mm, P = 008), whereas portal vein diameter was larger (6.8 mm versus 5.0 mm, P < .001) in patients with AGS compared with patients with end-stage BA. No focal lesion was seen in patients with AGS, whereas 44% (48/109) of patients with end-stage BA had intrahepatic biliary cysts (39%, 43/109) and hepatic tumors (8%, 9/109) (P = .008). Splenomegaly was commonly seen in both groups (P = .082), and ascites (9% [1/11] versus 50% [54/109], P = .010) and gastroesophageal varix (0% [0/11] versus 80% [87/109], P < .001) were less common in patients with AGS than in patients with end-stage BA. Fibrotic or cirrhotic changes of the liver, presence of focal lesions, and relevant portal hypertension were less common in patients with AGS than in patients with end-stage BA.

Preparation of Kupffer cell enriched non-parenchymal liver cells with high yield and reduced damage of surface markers by a modified method for flow cytometry.

PubMed

Xu, Fan; Zhen, Peng; Zheng, Yu; LIjuan, Feng; Aiting, Yang; Min, Cong; Hong, You; Jidong, Jia

2013-04-01

The aim of this study was to optimise a collagenase perfusion protocol for the isolation of a liver non-parenchymal cell (NPC) suspension enriched for Kupffer cells that reduced damage to F4/80 antigen cell surface expression to allow analysis by flow cytometry. Kupffer cell-enriched liver NPCs were isolated from C57BL/6 mice using different protocols. Flow cytometry was used to examine the effect of collagenase digestion on F4/80 expression on Kupffer cells, and results were represented by the percentage of F4/80 positive cells and by the F4/80 mean fluorescence intensity (MFI). The perfusion temperature, concentration of collagenase solution and total dosage of collagenase for liver perfusion influenced the effect of collagenase perfusion on the expression of F4/80 antigen on Kupffer cells. Collagenase perfusion at 28°C resulted in an increased percentage of F4/80 positive cells (P = 0.001) and MFI (P = 0.005) compared with 37°C. Perfusion with a total dose of 1.0 g/kg BW collagenase (using a 0.75 mg/mL solution) resulted in the highest percentage of F4/80 positive cells (P = 0.001) compared with 0.8 g/kg BW and 1.2 g/kg BW collagenase. Isolation of cells using the modified protocol resulted in a higher percentage of Kupffer cells (P < 0.001) and a higher MFI of F4/80 antigen (P < 0.001) compared with the common protocol. © 2013 International Federation for Cell Biology.

Liver macrophages: friend or foe during hepatitis B infection?

PubMed

Faure-Dupuy, Suzanne; Durantel, David; Lucifora, Julie

2018-05-17

The Hepatitis B virus chronically infects the liver of 250 million people worldwide. Over the past decades, major advances have been made in the understanding of Hepatitis B virus life cycle in hepatocytes. Beside these parenchymal cells, the liver also contains resident and infiltrating myeloid cells involved in immune responses to pathogens and much less is known about their interplay with Hepatitis B virus. In this review, we summarized and discussed the current knowledge of the role of liver macrophages (including Kupffer cells and liver monocyte-derived macrophages), in HBV infection. While it is still unclear if liver macrophages play a role in the establishment and persistence of HBV infection, several studies disclosed data suggesting that HBV would favour liver macrophage anti-inflammatory phenotypes and thereby increase liver tolerance. In addition, alternatively activated liver macrophages might also play in the long term a key role in hepatitis B associated pathogenesis, especially through the activation of hepatic stellate cells. Therapies aiming at a transient activation of pro-inflammatory liver macrophages should therefore be considered for the treatment of chronic HBV infection. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Pulmonary Abscess as a Complication of Transbronchial Lung Cryobiopsy.

PubMed

Skalski, Joseph H; Kern, Ryan M; Midthun, David E; Edell, Eric S; Maldonado, Fabien

2016-01-01

We present the case of a 49-year-old man who developed pulmonary abscess as a complication of transbronchial lung cryobiopsy. He had been receiving prednisone therapy, but otherwise had no specific risk factors for lung abscess. Cryobiopsy is a novel technique for obtaining peripheral lung parenchymal tissue for the evaluation of diffuse parenchymal lung diseases. Cryobiopsy is being increasingly proposed as an alternative to surgical lung biopsy or conventional bronchoscopic transbronchial forceps biopsy, but the safety profile of the procedure has not been fully appreciated. Pulmonary abscess has been rarely reported as a complication of other bronchoscopic procedures such as endobronchial ultrasound-guided needle biopsy, however, to our knowledge this is the first reported case of pulmonary abscess complicating peripheral lung cryobiopsy.

Multi-cellular 3D human primary liver cell culture elevates metabolic activity under fluidic flow.

PubMed

Esch, Mandy B; Prot, Jean-Matthieu; Wang, Ying I; Miller, Paula; Llamas-Vidales, Jose Ricardo; Naughton, Brian A; Applegate, Dawn R; Shuler, Michael L

2015-05-21

We have developed a low-cost liver cell culture device that creates fluidic flow over a 3D primary liver cell culture that consists of multiple liver cell types, including hepatocytes and non-parenchymal cells (fibroblasts, stellate cells, and Kupffer cells). We tested the performance of the cell culture under fluidic flow for 14 days, finding that hepatocytes produced albumin and urea at elevated levels compared to static cultures. Hepatocytes also responded with induction of P450 (CYP1A1 and CYP3A4) enzyme activity when challenged with P450 inducers, although we did not find significant differences between static and fluidic cultures. Non-parenchymal cells were similarly responsive, producing interleukin 8 (IL-8) when challenged with 10 μM bacterial lipoprotein (LPS). To create the fluidic flow in an inexpensive manner, we used a rocking platform that tilts the cell culture devices at angles between ±12°, resulting in a periodically changing hydrostatic pressure drop between reservoirs and the accompanying periodically changing fluidic flow (average flow rate of 650 μL min(-1), and a maximum shear stress of 0.64 dyne cm(-2)). The increase in metabolic activity is consistent with the hypothesis that, similar to unidirectional fluidic flow, primary liver cell cultures increase their metabolic activity in response to fluidic flow periodically changes direction. Since fluidic flow that changes direction periodically drastically changes the behavior of other cells types that are shear sensitive, our findings support the theory that the increase in hepatic metabolic activity associated with fluidic flow is either activated by mechanisms other than shear sensing (for example increased opportunities for gas and metabolite exchange), or that it follows a shear sensing mechanism that does not depend on the direction of shear. Our mode of device operation allows us to evaluate drugs under fluidic cell culture conditions and at low device manufacturing and operation costs.

Innate Immune Regulations and Liver Ischemia Reperfusion Injury

PubMed Central

Lu, Ling; Zhou, Haoming; Ni, Ming; Wang, Xuehao; Busuttil, Ronald; Kupiec-Weglinski, Jerzy; Zhai, Yuan

2016-01-01

Liver ischemia reperfusion activates innate immune system to drive the full development of inflammatory hepatocellular injury. Damage-associated molecular patterns (DAMPs) stimulate myeloid and dendritic cells via pattern recognition receptors (PRRs) to initiate the immune response. Complex intracellular signaling network transduces inflammatory signaling to regulate both innate immune cell activation and parenchymal cell death. Recent studies have revealed that DAMPs may trigger not only proinflammatory, but also immune regulatory responses by activating different PRRs or distinctive intracellular signaling pathways or in special cell populations. Additionally, tissue injury milieu activates PRR-independent receptors which also regulate inflammatory disease processes. Thus, the innate immune mechanism of liver IRI involves diverse molecular and cellular interactions, subjected to both endogenous and exogenous regulation in different cells. A better understanding of these complicated regulatory pathways/network is imperative for us in designing safe and effective therapeutic strategy to ameliorate liver IRI in patients. PMID:27861288

Endoscopic Ultrasound for the Hepatologist: A Comprehensive Review.

PubMed

Rimbaş, Mihai; Di Maurizio, Luca; Rizzatti, Gianenrico; Gasbarrini, Antonio; Costamagna, Guido; Larghi, Alberto

2018-05-01

In the last few years, the diagnostic and therapeutic utilization of endoscopic ultrasound (EUS) for a variety of liver conditions has exponentially grown. We performed a thorough search for all available studies on the performance of diagnostic and therapeutic EUS in the field of hepatology. This article reviews the indication of EUS in the evaluation and treatment of portal hypertension, portal vein pressure measurement, focal liver lesions, and parenchymal liver diseases, and presents all the clinical evidences available so far in this regard. All the review data suggest that EUS is becoming an increasingly important tool in the armamentarium of the hepatologists for the management of certain liver-related conditions. Implementation in the education of the hepatologists of means to become more familiar with both diagnostic and therapeutic capabilities of EUS is warranted. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Flow-cytometric separation and enrichment of hepatic progenitor cells in the developing mouse liver.

PubMed

Suzuki, A; Zheng, Y; Kondo, R; Kusakabe, M; Takada, Y; Fukao, K; Nakauchi, H; Taniguchi, H

2000-12-01

Stem cells responsible for tissue maintenance and repair are found in a number of organs. However, hepatic stem cells assumed to play a key role in liver development and regeneration remain to be well characterized. To address this issue, we set up a culture system in which primitive hepatic progenitor cells formed colonies. By combining this culture system with fluorescence-activated cell sorting (FACS), cells forming colonies containing distinct hepatocytes and cholangiocytes were identified in the fetal mouse liver. These cells express both CD49f and CD29 (alpha6 and beta1 integrin subunits), but do not mark for hematopoietic antigens such as CD45, TER119, and c-Kit. When transplanted into the spleen, these cells migrated to the recipient liver and differentiated into liver parenchymal cells. Our data demonstrate that hepatic progenitor cells are enriched by FACS and suggest approaches to supplanting organ allografting and improving artificial-organ hepatic support.

Multi-Cellular 3D Human Primary Liver Cell Cultures Elevate Metabolic Activity Under Fluidic Flow

PubMed Central

Esch, Mandy B.; Prot, Jean-Matthieu; Wang, Ying I.; Miller, Paula; Llamas-Vidales, Jose Ricardo; Naughton, Brian A.; Applegate, Dawn R.

2015-01-01

Predicting drug-induced liver injury with in vitro cell culture models more accurately would be of significant value to the pharmaceutical industry. To this end we have developed a low-cost liver cell culture device that creates fluidic flow over a 3D primary liver cell culture that consists of multiple liver cell types, including hepatocytes and non-parenchymal cells (fibroblasts, stellate cells, and Kupffer cells). We tested the performance of the cell culture under fluidic flow for 14 days, finding that hepatocytes produced albumin and urea at elevated levels compared to static cultures. Hepatocytes also responded with induction of P450 (CYP1A1 and CYP3A4) enzyme activity when challenged with P450 inducers, although we did not find significant differences between static and fluidic cultures. Non-parenchymal cells were similarly responsive, producing interleukin 8 (IL-8) when challenged with 10 μM bacterial lipoprotein (LPS). To create the fluidic flow in an inexpensive manner, we used a rocking platform that tilts the cell culture devices at angles between ±12°, resulting in a periodically changing hydrostatic pressure drop and bidirectional fluid flow (average flow rate of 650 μL/min, and a maximum shear stress of 0.64 dyne/cm2). The increase in metabolic activity is consistent with the hypothesis that, similar to unidirectional fluidic flow, primary liver cell cultures derived from human tissues increase their metabolic activity in response to bidirectional fluidic flow. Since bidirectional flow drastically changes the behavior of other cells types that are shear sensitive, the finding that bidirectional flow increases the metabolic activity of primary liver cells also supports the theory that this increase in metabolic activity is likely caused by increased levels of gas and metabolite exchange or by the accumulation of soluble growth factors rather than by shear sensing. Our results indicate that device operation with bi-directional gravity-driven medium flow supports the 14-day culture of a mix of primary human liver cells with the benefits of enhanced metabolic activity. Our mode of device operation allows us to evaluate drugs under fluidic cell culture conditions and at low device manufacturing and operation costs. PMID:25857666

Histochemical in situ identification of bovine embryonic blood cells reveals differences to the adult haematopoietic system and suggests a close relationship between haematopoietic stem cells and primordial germ cells.

PubMed

Kritzenberger, Michaela; Wrobel, Karl-Heinz

2004-04-01

Cryostat sections of bovine embryos of exactly known age (obtained from artificial insemination), ranging from 32 to 60 days post-insemination, were treated with a wide range of antibodies directed against cell surface antigens or lineage-specific factors in order to demonstrate different types of fetal blood cells and their precursors. An antibody specific to bovine c-kit (bk-1) stained not only presumptive haematopoietic stem cells in the dorsal aorta and the embryonic liver, but also a subpopulation of putative primordial germ cells in the gonadal anlage, the latter being further characterised by a positive labelling with the lectins STA, WFA and WGA and a histochemical reaction for alkaline phosphatase. The antibody against CD 45, commonly regarded as a pan-leukocyte marker, reacted in the bovine embryo with different types of blood cells, as well as with presumptive vasculogenetic cells and a subpopulation of putative primordial germ cells. CD 61 immunoreaction proved to be a useful tool for demonstrating megakaryocytopoiesis in the embryonic liver, in addition to the lumen of blood vessels and the mesonephros. Staining with BM-2 was restricted to a single population of medium-sized, round to oval cells, forming small groups within the parenchymal strands of the liver. Characterised furthermore by a U-shaped nucleus, this BM-2-positive cell type apparently represents a developmental stage in the granulopoietic lineage. B-lymphocytopoiesis in the bovine liver was detected with antibodies directed against WC-4 and IgM, but not until day 58 post-insemination. Using antibodies to CD 14, no positive results could be obtained in embryonic tissues, although anti-CD 14-positive macrophages were easily recognised in lymph nodes of adult bovines. The antibody against CD 68, however, identified two populations of primitive macrophages in our samples. One population was located in parenchymal strands of the embryonic liver, probably acting as nursing cells for haematopoietic foci, and the other was observed intravasally in the sinusoids of the liver, most probably representing primitive Kupffer cells.

Opportunistic use of a Foley catheter to provide a common electrocautery with a water-irrigating channel for hepatic parenchymal transection.

PubMed

Yamamoto, Yuzo; Yoshioka, Masato; Watanabe, Go; Uchinami, Hiroshi

2015-11-01

High-tech surgical energy devices that are used during a single surgery have increased in number and the expense for such disposable units is by no means negligible. We developed a handmade water-irrigating monopolar electrocautery using a Foley catheter to perform liver parenchymal transection. A commonly used 20-24 Fr Foley catheter was cut at a length of about 8 cm. The shaft of the 5 mm ball electrode measuring 13.5 cm in length was then inlaid into the urine drainage channel. The target tissues were cauterized without making an eschar, thereby preventing the adhesion of the electrode to the tissues. A ball electrode with our handmade water irrigation sheath can be made in only a few minutes at a very low cost, using common medical supplies and yielding satisfactory effects comparable to the use of specialized high-tech devices.

Synthesis of a novel galactosylated lipid and its application to the hepatocyte-selective targeting of liposomal doxorubicin.

PubMed

Wang, Shao-Ning; Deng, Yi-Hui; Xu, Hui; Wu, Hong-Bing; Qiu, Ying-Kun; Chen, Da-Wei

2006-01-01

This paper described the synthesis of a novel galactosylated lipid with mono-galactoside moiety, (5-Cholesten-3beta-yl) 4-oxo-4-[2-(lactobionyl amido) ethylamido] butanoate (CHS-ED-LA), and the targetability of doxorubicin (DOX), a model drug, in liposomes containing 10% mol/mol CHS-ED-LA (galactosylated liposomes, GalL) to the liver was studied. The weighted-average overall drug targeting efficiency (Te(*)) was used to evaluate the liver targetability of GalL DOX. The results showed that GalL DOX gave a relatively high (Te(*))(liver) value of 64.6%, while DOX in conventional liposome (CL DOX) only gave a (Te(*))(liver) value of 21.8%. In the liver, the GalL DOX was mainly taken up by parenchymal cells (88% of the total hepatic uptake). Moreover, preinjection of asialofetuin significantly inhibited the liver uptake of GalL DOX (from 70 to 12% of the total injected dose). It was suggested that liposomes containing such novel galactosylated lipid, CHS-ED-LA, had a great potential as drug delivery carriers for hepatocyte-selective targeting.

The Intersection of Pulmonary Hypertension and Solid Organ Transplantation.

PubMed

Frost, Adaani E

2016-01-01

Pulmonary hypertension (PH) is a complication and marker of disease severity in many parenchymal lung diseases. It also is a frequent complication of portal hypertension and negatively impacts survival with liver transplant. Pulmonary hypertension is frequently diagnosed in patients with end-stage renal disease who are undergoing dialysis, and it has recently been demonstrated to adversely affect posttransplant outcome in this patient population even though the mechanism of PH is substantially different from that associated with liver disease. The presence of PH in patients with heart failure is frequent, and the necessity for PH therapy prior to heart transplant has evolved in the last decade. We review the frequency of and risk factors for PH in recipients of and candidates for lung, liver, heart, and renal transplants as well as the impact of this diagnosis on posttransplant outcomes.

Identification and differentiation of hepatic stem cells during liver development.

PubMed

Kamiya, Akihide; Gonzalez, Frank J; Nakauchi, Hiromitsu

2006-05-01

Stem cells responsible for maintenance and repair of tissues are found in a number of organs. The liver's remarkable capacity to regenerate after hepatectomy or chemical-induced injury does not involve proliferation of stem cells. However, recent studies suggest that liver stem cells exist in both embryonic and adult livers. Using fluorescence-activated cell sorting and a culture system in which primitive hepatic progenitor cells form colonies, a novel class of cells with the marker profile c-Met(+)CD49f(+/low)c-Kit(-)CD45(-)TER119(-) was found in the developing liver. This class apparently represents the population of cells that form colonies containing distinct hepatocytes and cholangiocytes. When cells in this class are transplanted into the spleen or liver of mice subjected to liver injury, the cells migrate and differentiate into liver parenchymal cells and cholangiocytes that are morphologically and functionally indistinguishable from their native counterparts. During mid-gestation, hematopoietic cells migrate into the liver from a region bounded by aorta, gonad, and mesonephros and produce oncostatin M (OSM). In combination with glucocorticoid hormones, OSM induces maturation of liver stem and progenitor cells, including those of the c-Met(+)CD49f(+/low)c-Kit(-)CD45(-)TER119(-) class. The ability to manipulate the proliferation and differentiation of liver stem cells in vitro will greatly aid in analyzing mechanisms of liver development and offers promise in stem cell therapy of liver diseases.

Shrinking lung syndrome as a manifestation of pleuritis: a new model based on pulmonary physiological studies.

PubMed

Henderson, Lauren A; Loring, Stephen H; Gill, Ritu R; Liao, Katherine P; Ishizawar, Rumey; Kim, Susan; Perlmutter-Goldenson, Robin; Rothman, Deborah; Son, Mary Beth F; Stoll, Matthew L; Zemel, Lawrence S; Sandborg, Christy; Dellaripa, Paul F; Nigrovic, Peter A

2013-03-01

The pathophysiology of shrinking lung syndrome (SLS) is poorly understood. We sought to define the structural basis for this condition through the study of pulmonary mechanics in affected patients. Since 2007, most patients evaluated for SLS at our institutions have undergone standardized respiratory testing including esophageal manometry. We analyzed these studies to define the physiological abnormalities driving respiratory restriction. Chest computed tomography data were post-processed to quantify lung volume and parenchymal density. Six cases met criteria for SLS. All presented with dyspnea as well as pleurisy and/or transient pleural effusions. Chest imaging results were free of parenchymal disease and corrected diffusing capacities were normal. Total lung capacities were 39%-50% of predicted. Maximal inspiratory pressures were impaired at high lung volumes, but not low lung volumes, in 5 patients. Lung compliance was strikingly reduced in all patients, accompanied by increased parenchymal density. Patients with SLS exhibited symptomatic and/or radiographic pleuritis associated with 2 characteristic physiological abnormalities: (1) impaired respiratory force at high but not low lung volumes; and (2) markedly decreased pulmonary compliance in the absence of identifiable interstitial lung disease. These findings suggest a model in which pleural inflammation chronically impairs deep inspiration, for example through neural reflexes, leading to parenchymal reorganization that impairs lung compliance, a known complication of persistently low lung volumes. Together these processes could account for the association of SLS with pleuritis as well as the gradual symptomatic and functional progression that is a hallmark of this syndrome.

Cytoreduction of diaphragmatic metastasis from ovarian cancer with involvement of the liver using a ventral liver mobilization technique.

PubMed

Kato, Kazuyoshi; Katsuda, Takahiro; Takeshima, Nobuhiro

2016-03-01

Upper abdominal spreading of advanced-stage ovarian cancer often involves the diaphragm. In addition, bulky diaphragmatic tumors occasionally infiltrate the liver. Here, we describe our early experiences with a ventral liver mobilization technique to remove diaphragmatic tumors with liver involvement. Two patients with primary ovarian cancer and 1 patient with recurrent ovarian cancer underwent en bloc resections of a diaphragmatic tumor together with the full-thickness diaphragm and the liver tissue using a ventral liver mobilization technique. The surgical technique involved a full-thickness division of the diaphragm at the central tendon and a ventral mobilization of the right lobe of the liver, with entry into the pleural cavity. During the parenchymal transection of the liver, the posterior area of the right lobe of the liver was pressed using the surgeon's hand to reduce bleeding from the resection surface. After the completion of the en bloc resection, the diaphragmatic opening was closed using running sutures. All the diaphragmatic tumors were completely removed without severe bleeding in the current series. No intraoperative or postoperative complications occurred. Diaphragmatic tumors with involvement of the liver can be safely and effectively removed using a ventral liver mobilization technique. This surgical procedure may be suitable for the management of bulky diaphragmatic tumors in select patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Radiologic and clinical features of idiopathic granulomatous lobular mastitis mimicking advanced breast cancer.

PubMed

Lee, Jei Hee; Oh, Ki Keun; Kim, Eun-kyung; Kwack, Kyu Sung; Jung, Woo Hee; Lee, Han Kyung

2006-02-28

Idiopathic granulomatous lobular mastitis (IGLM), also known as idiopathic granulomatous mastitis, is a rare chronic inflammatory lesion of the breast that can clinically and radiographically mimic breast carcinoma. The aim of this study was to describe the radiological imaging and clinical features of IGLM in order to better differentiate this disorder from breast cancer. We performed a retrospective analysis of the clinical and radiographic features of 11 women with a total of 12 IGLM lesions. The ages of these women ranged between 29 and 42 years, with a mean age of 34.8 years. Ten patients were examined by both mammography and sonography and one by sonography alone. The sites that were the most frequently involved were the peripheral (6/12), diffuse, (3/12), and subareolar (3/12) regions of the breast. The patient mammograms showed irregular ill-defined masses (7/11), diffuse increased densities (3/11), and one oval obscured mass. In addition, patient sonograms showed irregular tubular lesions (7/12) or lobulated masses with minimal parenchymal distortion (2/12), parenchymal distortion without definite mass lesions (2/12), and one oval mass. Subcutaneous fat obliteration (12/12) and skin thickening (11/12) were also observed in these patients. Contrary to previous reports, skin changes and subareolar involvement were not rare occurrences in IGLM. In conclusion, the sonographic features of IGLM show irregular or tubular hypoechoic masses with minimal parenchymal distortion. Both clinical information and the description of radiographic features of IGLM may aid in the differentiation between IGLM and breast cancer, however histological confirmation is still required for the proper diagnosis and treatment of the disorder.

Radiologic and Clinical Features of Idiopathic Granulomatous Lobular Mastitis Mimicking Advanced Breast Cancer

PubMed Central

Lee, Jei Hee; Kim, Eun-kyung; Kwack, Kyu Sung; Jung, Woo Hee; Lee, Han Kyung

2006-01-01

Idiopathic granulomatous lobular mastitis (IGLM), also known as idiopathic granulomatous mastitis, is a rare chronic inflammatory lesion of the breast that can clinically and radiographically mimic breast carcinoma. The aim of this study was to describe the radiological imaging and clinical features of IGLM in order to better differentiate this disorder from breast cancer. We performed a retrospective analysis of the clinical and radiographic features of 11 women with a total of 12 IGLM lesions. The ages of these women ranged between 29 and 42 years, with a mean age of 34.8 years. Ten patients were examined by both mammography and sonography and one by sonography alone. The sites that were the most frequently involved were the peripheral (6/12), diffuse, (3/12), and subareolar (3/12) regions of the breast. The patient mammograms showed irregular ill-defined masses (7/11), diffuse increased densities (3/11), and one oval obscured mass. In addition, patient sonograms showed irregular tubular lesions (7/12) or lobulated masses with minimal parenchymal distortion (2/12), parenchymal distortion without definite mass lesions (2/12), and one oval mass. Subcutaneous fat obliteration (12/12) and skin thickening (11/12) were also observed in these patients. Contrary to previous reports, skin changes and subareolar involvement were not rare occurrences in IGLM. In conclusion, the sonographic features of IGLM show irregular or tubular hypoechoic masses with minimal parenchymal distortion. Both clinical information and the description of radiographic features of IGLM may aid in the differentiation between IGLM and breast cancer, however histological confirmation is still required for the proper diagnosis and treatment of the disorder. PMID:16502488

Effect of diffusion time on liver DWI: an experimental study of normal and fibrotic livers.

PubMed

Zhou, Iris Y; Gao, Darwin S; Chow, April M; Fan, Shujuan; Cheung, Matthew M; Ling, Changchun; Liu, Xiaobing; Cao, Peng; Guo, Hua; Man, Kwan; Wu, Ed X

2014-11-01

To investigate whether diffusion time (Δ) affects the diffusion measurements in liver and their sensitivity in detecting fibrosis. Liver fibrosis was induced in Sprague-Dawley rats (n = 12) by carbon tetrachloride (CCl(4)) injections. Diffusion-weighted MRI was performed longitudinally during 8-week CCl(4) administration at 7 Tesla (T) using single-shot stimulated-echo EPI with five b-values (0 to 1000 s/mm(2)) and three Δs. Apparent diffusion coefficient (ADC) and true diffusion coefficient (D(true)) were calculated by using all five b-values and large b-values, respectively. ADC and D(true) decreased with Δ for both normal and fibrotic liver at each time point. ADC and D(true) also generally decreased with the time after CCl(4) insult. The reductions in D(true) between 2-week and 4-week CCl(4) insult were larger than the ADC reductions at all Δs. At each time point, D(true) measured with long Δ (200 ms) detected the largest changes among the 3 Δs examined. Histology revealed gradual collagen deposition and presence of intracellular fat vacuoles after CCl(4) insult. Our results demonstrated the Δ dependent diffusion measurements, indicating restricted diffusion in both normal and fibrotic liver. D(true) measured with long Δ acted as a more sensitive index of the pathological alterations in liver microstructure during fibrogenesis. Copyright © 2013 Wiley Periodicals, Inc.

A polymeric nanoparticle formulation of curcumin (NanoCurc™) ameliorates CCl4-induced hepatic injury and fibrosis through reduction of pro-inflammatory cytokines and stellate cell activation

PubMed Central

Bisht, Savita; Khan, Mehtab A; Bekhit, Mena; Bai, Haibo; Cornish, Toby; Mizuma, Masamichi; Rudek, Michelle A; Zhao, Ming; Maitra, Amarnath; Ray, Balmiki; Lahiri, Debomoy; Maitra, Anirban; Anders, Robert A

2012-01-01

Plant-derived polyphenols such as curcumin hold promise as a therapeutic agent in the treatment of chronic liver diseases. However, its development is plagued by poor aqueous solubility resulting in poor bioavailability. To circumvent the suboptimal bioavailability of free curcumin, we have developed a polymeric nanoparticle formulation of curcumin (NanoCurc™) that overcomes this major pitfall of the free compound. In this study, we show that NanoCurc™ results in sustained intrahepatic curcumin levels that can be found in both hepatocytes and non-parenchymal cells. NanoCurc™ markedly inhibits carbon tetrachloride-induced liver injury, production of pro-inflammatory cytokines and fibrosis. It also enhances antioxidant levels in the liver and inhibits pro-fibrogenic transcripts associated with activated myofibroblasts. Finally, we show that NanoCurc™ directly induces stellate cell apoptosis in vitro. Our results suggest that NanoCurc™ might be an effective therapy for patients with chronic liver disease. PMID:21691262

A strain-hardening bi-power law for the nonlinear behaviour of biological soft tissues.

PubMed

Nicolle, S; Vezin, P; Palierne, J-F

2010-03-22

Biological soft tissues exhibit a strongly nonlinear viscoelastic behaviour. Among parenchymous tissues, kidney and liver remain less studied than brain, and a first goal of this study is to report additional material properties of kidney and liver tissues in oscillatory shear and constant shear rate tests. Results show that the liver tissue is more compliant but more strain hardening than kidney. A wealth of multi-parameter mathematical models has been proposed for describing the mechanical behaviour of soft tissues. A second purpose of this work is to develop a new constitutive law capable of predicting our experimental data in the both linear and nonlinear viscoelastic regime with as few parameters as possible. We propose a nonlinear strain-hardening fractional derivative model in which six parameters allow fitting the viscoelastic behaviour of kidney and liver tissues for strains ranging from 0.01 to 1 and strain rates from 0.0151 s(-1) to 0.7s(-1). Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Featured Article: Isolation, characterization, and cultivation of human hepatocytes and non-parenchymal liver cells

PubMed Central

Pfeiffer, Elisa; Kegel, Victoria; Zeilinger, Katrin; Hengstler, Jan G; Nüssler, Andreas K; Seehofer, Daniel

2015-01-01

Primary human hepatocytes (PHH) are considered to be the gold standard for in vitro testing of xenobiotic metabolism and hepatotoxicity. However, PHH cultivation in 2D mono-cultures leads to dedifferentiation and a loss of function. It is well known that hepatic non-parenchymal cells (NPC), such as Kupffer cells (KC), liver endothelial cells (LEC), and hepatic stellate cells (HSC), play a central role in the maintenance of PHH functions. The aims of the present study were to establish a protocol for the simultaneous isolation of human PHH and NPC from the same tissue specimen and to test their suitability for in vitro co-culture. Human PHH and NPC were isolated from tissue obtained by partial liver resection by a two-step EDTA/collagenase perfusion technique. The obtained cell fractions were purified by Percoll density gradient centrifugation. KC, LEC, and HSC contained in the NPC fraction were separated using specific adherence properties and magnetic activated cell sorting (MACS®). Identified NPC revealed a yield of 1.9 × 106 KC, 2.7 × 105 LEC and 4.7 × 105 HSC per gram liver tissue, showing viabilities >90%. Characterization of these NPC showed that all populations went through an activation process, which influenced the cell fate. The activation of KC strongly depended on the tissue quality and donor anamnesis. KC became activated in culture in association with a loss of viability within 4–5 days. LEC lost specific features during culture, while HSC went through a transformation process into myofibroblasts. The testing of different culture conditions for HSC demonstrated that they can attenuate, but not prevent dedifferentiation in vitro. In conclusion, the method described allows the isolation and separation of PHH and NPC in high quality and quantity from the same donor. PMID:25394621

Human scavenger receptor class B type I is expressed with cell-specific fashion in both initial and terminal site of reverse cholesterol transport.

PubMed

Nakagawa-Toyama, Yumiko; Hirano, Ken-ichi; Tsujii, Ken-ichi; Nishida, Makoto; Miyagawa, Jun-ichiro; Sakai, Naohiko; Yamashita, Shizuya

2005-11-01

The reverse cholesterol transport (RCT) is one of the major protective systems against atherosclerosis, in which high-density lipoprotein (HDL) removes cholesterol from lipid-laden cells and delivers it to the liver. Scavenger receptor class B type I (SR-BI) is a HDL receptor in the liver and adrenal glands and is involved in the selective uptake of cholesteryl ester from HDL, which has been extensively, analyzed using rodent models. However, the expression and regulation of the human homologue of this receptor are not known yet. We previously reported that this receptor is expressed in in vitro differentiated macrophages and its expression is up-regulated by the addition of modified lipoproteins into the medium [Hirano K, Yamashita S, Nakagawa Y, et al. Expression of human scavenger receptor class B type I in cultured human monocyte-derived macrophages and atherosclerotic lesions. Circ Res 1999;85:108-16]. In order to further investigate the physiological significance of this receptor in humans, we have performed extensive immunohistochemical analyses with specimens of the liver and adrenal glands as well as arteries with different stages of atherosclerotic lesions. In human liver and adrenal glands, a positive SR-BI immunoreactivity was detected in both hepatic and adrenal parenchymal cells as well as Kupffer cells. These parenchymal cells had a strong signal on the cell surface, whereas Kupffer cells showed a heterogeneous and punctate pattern. In human aorta and coronary arteries, SR-BI was highly expressed in atherosclerotic plaques, but not in non-atherosclerotic lesions. Double immunostaining revealed that SR-BI was expressed in a subpopulation of macrophages, of which staining pattern was similar to that observed in Kupffer cells. These data clearly demonstrated that SR-BI was expressed with cell-specific fashions in both the initial and terminal step of RCT in humans. Thus, SR-BI might be physiologically relevant and have distinct tissue-specific functions.

Use of C-Arm Cone Beam CT During Hepatic Radioembolization: Protocol Optimization for Extrahepatic Shunting and Parenchymal Enhancement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoven, Andor F. van den, E-mail: a.f.vandenhoven@umcutrecht.nl; Prince, Jip F.; Keizer, Bart de

PurposeTo optimize a C-arm computed tomography (CT) protocol for radioembolization (RE), specifically for extrahepatic shunting and parenchymal enhancement.Materials and MethodsA prospective development study was performed per IDEAL recommendations. A literature-based protocol was applied in patients with unresectable and chemorefractory liver malignancies undergoing an angiography before radioembolization. Contrast and scan settings were adjusted stepwise and repeatedly reviewed in a consensus meeting. Afterwards, two independent raters analyzed all scans. A third rater evaluated the SPECT/CT scans as a reference standard for extrahepatic shunting and lack of target segment perfusion.ResultsFifty scans were obtained in 29 procedures. The first protocol, using a 6 s delaymore » and 10 s scan, showed insufficient parenchymal enhancement. In the second protocol, the delay was determined by timing parenchymal enhancement on DSA power injection (median 8 s, range 4–10 s): enhancement improved, but breathing artifacts increased (from 0 to 27 %). Since the third protocol with a 5 s scan decremented subjective image quality, the second protocol was deemed optimal. Median CNR (range) was 1.7 (0.6–3.2), 2.2 (−1.4–4.0), and 2.1 (−0.3–3.0) for protocol 1, 2, and 3 (p = 0.80). Delineation of perfused segments was possible in 57, 73, and 44 % of scans (p = 0.13). In all C-arm CTs combined, the negative predictive value was 95 % for extrahepatic shunting and 83 % for lack of target segment perfusion.ConclusionAn optimized C-arm CT protocol was developed that can be used to detect extrahepatic shunts and non-perfusion of target segments during RE.« less

[Liver ultrasound: focal lesions and diffuse diseases].

PubMed

Segura Grau, A; Valero López, I; Díaz Rodríguez, N; Segura Cabral, J M

2016-01-01

Liver ultrasound is frequently used as a first-line technique for the detection and characterization of the most common liver lesions, especially those incidentally found focal liver lesions, and for monitoring of chronic liver diseases. Ultrasound is not only used in the Bmode, but also with Doppler and, more recently, contrast-enhanced ultrasound. It is mainly used in the diagnosis of diffuse liver diseases, such as steatosis or cirrhosis. This article presents a practical approach for diagnosis workup, in which the different characteristics of the main focal liver lesions and diffuse liver diseases are reviewed. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Hepatic Oval Cells Have the Side Population Phenotype Defined by Expression of ATP-Binding Cassette Transporter ABCG2/BCRP1

PubMed Central

Shimano, Koichi; Satake, Makoto; Okaya, Atsuhito; Kitanaka, Junichi; Kitanaka, Nobue; Takemura, Motohiko; Sakagami, Masafumi; Terada, Nobuyuki; Tsujimura, Tohru

2003-01-01

Organ-specific stem cells can be identified by the side population (SP) phenotype, which is defined by the property to effectively exclude the Hoechst 33342 dye. The ATP-binding cassette transporter ABCG2/BCRP1 mediates the SP phenotype. Because hepatic oval cells possess several characteristics of stem cells, we examined whether they have the SP phenotype using the 2-acetylaminofluorene/partial hepatectomy (PH) model. Fluorescence-activated cell sorting analysis showed that a population of non-parenchymal cells containing oval cells, prepared on day 7 after PH, carried a significant number of SP cells, whereas that of non-parenchymal cells without oval cells, prepared on day 0 after PH, did not. Northern blot analysis using total liver RNA obtained on various days after PH showed that the expression of ABCG2/BCRP1 mRNA increased after PH, reaching the highest level on day 7, and then gradually decreased. This pattern of changes in the ABCG2/BCRP1 mRNA level was well correlated to that in the number of oval cells. Furthermore, in situ hybridization revealed that oval cells were the sites of expression of ABCG2/BCRP1 mRNA. These results indicate that oval cells have the SP phenotype defined by expression of ABCG2/BCRP1, suggesting that oval cells may represent stem cells in the liver. PMID:12819005

Identification of cytosolic peroxisome proliferator binding protein as a member of the heat shock protein HSP70 family.

PubMed Central

Alvares, K; Carrillo, A; Yuan, P M; Kawano, H; Morimoto, R I; Reddy, J K

1990-01-01

Clofibrate and many of its structural analogues induce proliferation of peroxisomes in the hepatic parenchymal cells of rodents and certain nonrodent species including primates. This induction is tissue specific, occurring mainly in the liver parenchymal cells and to a lesser extent in the kidney cortical epithelium. The induction of peroxisomes is associated with a predictable pleiotropic response, characterized by hepatomegaly, and increased activities and mRNA levels of certain peroxisomal enzymes. Using affinity chromatography, we had previously isolated a protein that binds to clofibric acid. We now show that this protein is homologous with the heat shock protein HSP70 family by analysis of amino acid sequences of isolated peptides from trypsin-treated clofibric acid binding protein and by cross-reactivity with a monoclonal antibody raised against the conserved region of the 70-kDa heat shock proteins. The clofibric acid-Sepharose column could bind HSP70 proteins isolated from various species, which could then be eluted with either clofibric acid or ATP. Conversely, when a rat liver cytosol containing multiple members of the HSP70 family was passed through an ATP-agarose column, and eluted with clofibric acid, only P72 (HSC70) was eluted. These results suggest that clofibric acid, a peroxisome proliferator, preferentially interacts with P72 at or near the ATP binding site. Images PMID:2371272

Pediatric Liver Transplant: Techniques and Complications.

PubMed

Horvat, Natally; Marcelino, Antonio Sergio Zafred; Horvat, Joao Vicente; Yamanari, Tássia Regina; Batista Araújo-Filho, Jose de Arimateia; Panizza, Pedro; Seda-Neto, Joao; Antunes da Fonseca, Eduardo; Carnevale, Francisco Cesar; Mendes de Oliveira Cerri, Luciana; Chapchap, Paulo; Cerri, Giovanni Guido

2017-10-01

Liver transplant is considered to be the last-resort treatment approach for pediatric patients with end-stage liver disease. Despite the remarkable advance in survival rates, liver transplant remains an intricate surgery with significant morbidity and mortality. Early diagnosis of complications is crucial for patient survival but is challenging given the lack of specificity in clinical presentation. Knowledge of the liver and vascular anatomy of the donor and the recipient or recipients before surgery is also important to avoid complications. In this framework, radiologists play a pivotal role on the multidisciplinary team in both pre- and postoperative scenarios by providing a road map to guide the surgery and by assisting in diagnosis of complications. The most common complications after liver transplant are (a) vascular, including the hepatic artery, portal vein, hepatic veins, and inferior vena cava; (b) biliary; (c) parenchymal; (d) perihepatic; and (e) neoplastic. The authors review surgical techniques, the role of each imaging modality, normal posttransplant imaging features, types of complications after liver transplant, and information required in the radiology report that is critical to patient care. They present an algorithm for an imaging approach for pediatric patients after liver transplant and describe key points that should be included in radiologic reports in the pre- and postoperative settings. Online supplemental material is available for this article. © RSNA, 2017.

A microfluidically perfused three dimensional human liver model.

PubMed

Rennert, Knut; Steinborn, Sandra; Gröger, Marko; Ungerböck, Birgit; Jank, Anne-Marie; Ehgartner, Josef; Nietzsche, Sandor; Dinger, Julia; Kiehntopf, Michael; Funke, Harald; Peters, Frank T; Lupp, Amelie; Gärtner, Claudia; Mayr, Torsten; Bauer, Michael; Huber, Otmar; Mosig, Alexander S

2015-12-01

Within the liver, non-parenchymal cells (NPCs) are critically involved in the regulation of hepatocyte polarization and maintenance of metabolic function. We here report the establishment of a liver organoid that integrates NPCs in a vascular layer composed of endothelial cells and tissue macrophages and a hepatic layer comprising stellate cells co-cultured with hepatocytes. The three-dimensional liver organoid is embedded in a microfluidically perfused biochip that enables sufficient nutrition supply and resembles morphological aspects of the human liver sinusoid. It utilizes a suspended membrane as a cell substrate mimicking the space of Disse. Luminescence-based sensor spots were integrated into the chip to allow online measurement of cellular oxygen consumption. Application of microfluidic flow induces defined expression of ZO-1, transferrin, ASGPR-1 along with an increased expression of MRP-2 transporter protein within the liver organoids. Moreover, perfusion was accompanied by an increased hepatobiliary secretion of 5(6)-carboxy-2',7'-dichlorofluorescein and an enhanced formation of hepatocyte microvilli. From this we conclude that the perfused liver organoid shares relevant morphological and functional characteristics with the human liver and represents a new in vitro research tool to study human hepatocellular physiology at the cellular level under conditions close to the physiological situation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cholestasis-induced fibrosis is reduced by interferon alpha-2a and is associated with elevated liver metalloprotease activity.

PubMed

Bueno, M R; Daneri, A; Armendáriz-Borunda, J

2000-12-01

Several drugs have been tested for the treatment of hepatic cirrhosis induced by various etiologic agents. Although interferon (IFN)alpha-2a has mostly been used to treat viral hepatitis, its anti-fibrogenic properties remain to be established. An experimental model of cholestasis-induced cirrhosis was used to test the effect of IFNalpha-2a. Cirrhosis was induced in rats via ligation of the common bile duct. IFNalpha-2a (100,000 IU/rat, s.c.) was administered daily throughout the experiment. Collagens and TIMP-1 mRNA transcripts were determined by semi-quantitative reverse transcriptase-polymerase chain reaction in liver tissue samples. Activity of metalloproteases (MMPs) was measured using gelatin (denatured collagen) as substrate and the specific size of the enzymes was estimated by zymograms. Histology was performed using Sirius red as a specific stain for collagenous material, and computer-assisted morphometric analyses were carried out. A polyclonal mouse anti-plasminogen activator inhibitor (PAI-1) antibody was used to evaluate the distribution during treatment with IFNalpha-2a. MMP-activity was up-regulated in bile duct ligated rats treated with IFNalpha-2a. MMP-activity in homogenates of total liver was minimal as compared with activity in non-parenchymal cells isolated from the same parental perfused liver, indicating a cryptic MMP activity which was completely abolished by EDTA and 1,10 phenanthroline. Three bands of gelatin degradation were detected by zymography, corresponding to 95, 75 and 65 kDa. IFNalpha-2a decreased PAI-1 immunoreactivity in liver tissue slices as well as biochemical activity in non-parenchymal cell extracts (3.3+/-0.08 vs 7.4+/-1.1 U/mg protein). Procollagen alpha1 (III) and alpha1 (IV) genes expression were also down-regulated 1.5 and 4-fold, respectively. Interestingly, TIMP-1 gene expression did not change. Functional hepatic tests: alanine aminotransferase, aspartate aminotransferase, bilirubins and alkaline phosphatase were significantly lower in IFNalpha-2a treated animals. Analysis of histology demonstrated that IFNalpha-2a promoted resolution of fibrosis and decreased bile duct proliferation.

Non-parenchymal liver cells support the growth advantage in the first stages of hepatocarcinogenesis.

PubMed

Drucker, Claudia; Parzefall, Wolfram; Teufelhofer, Olga; Grusch, Michael; Ellinger, Adolf; Schulte-Hermann, Rolf; Grasl-Kraupp, Bettina

2006-01-01

Hepatocellular carcinoma almost always arises in chronically inflamed livers. We developed a culture model to study the role of non-parenchymal cells (NPCs) for inflammation-driven hepatocarcinogenesis. Rats were treated with the carcinogen N-nitrosomorpholine, which induced initiated hepatocytes expressing the marker placental glutathione-S-transferase (GSTp). After 21 days two preparations of hepatocytes were made: (i) conventional ones (Hep-conv) containing NPCs and (ii) hepatocytes purified of NPCs (Hep-pur). Initiated hepatocytes, being positive for GSTp (GSTp-pos) were present in both preparations and were cultured along with normal hepatocytes, being negative for GSTp (GSTp-neg). Under any culture condition DNA synthesis was approximately 4-fold higher in GSTp-pos than in GSTp-neg hepatocytes demonstrating the inherent growth advantage of the first stages of hepatocarcinogenesis. Hepatocytes showed approximately 3-fold lower rates of DNA synthesis in Hep-pur than in Hep-conv, which was elevated above Hep-conv levels by addition of NPC or NPC-supernatant. Pretreatment of NPCs with proinflammatory lipopolysaccharide (LPS) further increased DNA synthesis. Thus, NPCs release soluble growth stimulators. Next we investigated the effect of specific cytokines produced by NPCs. Tumour necrosis factor alpha and interleukin 6 barely altered DNA synthesis, whereas hepatocyte growth factor (HGF), keratinocyte growth factor (KGF) and the heparin-binding epidermal growth factor-like growth factor (HB-EGF) were potent inducers of DNA replication in both, GSTp-neg and GSTp-pos cells. In conclusion, DNA synthesis of hepatocytes is increased by factors released from NPCs, an effect augmented by LPS-stimulation. NPC-derived cytokines, such as KGF, HGF and HB-EGF, stimulate DNA synthesis preferentially in initiated hepatocytes, presumably resulting in tumour promotion. Similar mechanisms may contribute to carcinogenesis in human inflammatory liver diseases.

Simple and Reliable Method to Quantify the Hepatitis B Viral Load and Replicative Capacity in Liver Tissue and Blood Leukocytes

PubMed Central

Minosse, Claudia; Coen, Sabrina; Visco Comandini, Ubaldo; Lionetti, Raffaella; Montalbano, Marzia; Cerilli, Stefano; Vincenti, Donatella; Baiocchini, Andrea; Capobianchi, Maria R.; Menzo, Stefano

2016-01-01

Background A functional cure of chronic hepatitis B (CHB) is feasible, but a clear view of the intrahepatic viral dynamics in each patient is needed. Intrahepatic covalently closed circular DNA (cccDNA) is the stable form of the viral genome in infected cells, and represents the ideal marker of parenchymal colonization. Its relationships with easily accessible peripheral parameters need to be elucidated in order to avoid invasive procedures in patients. Objectives The goal of this study was to design, set up, and validate a reliable and straightforward method for the quantification of the cccDNA and total DNA of the hepatitis B virus (HBV) in a variety of clinical samples. Patients and Methods Clinical samples from a cohort of CHB patients, including liver biopsies in some, were collected for the analysis of intracellular HBV molecular markers using novel molecular assays. Results A plasmid construct, including sequences from the HBV genome and from the human gene hTERT, was generated as an isomolar multi-standard for HBV quantitation and normalization to the cellular contents. The specificity of the real-time assay for the cccDNA was assessed using Dane particles isolated on a density gradient. A comparison of liver tissue from 6 untreated and 6 treated patients showed that the treatment deeply reduced the replicative capacity (total DNA/cccDNA), but had limited impact on the parenchymal colonization. The peripheral blood mononuclear cells (PBMCs) and granulocytes from the treated and untreated patients were also analyzed. Conclusions A straightforward method for the quantification of intracellular HBV molecular parameters in clinical samples was developed and validated. The widespread use of such versatile assays could better define the prognosis of CHB, and allow a more rational approach to time-limited tailored treatment strategies. PMID:27882060

Liver function in cats with hyperthyroidism before and after 131I therapy.

PubMed

Berent, Allyson C; Drobatz, Kenneth J; Ziemer, Lisa; Johnson, Victoria S; Ward, Cynthia R

2007-01-01

The clinical significance of high serum concentration or activity of markers of liver damage in cats with hyperthyroidism is unknown. To evaluate serum markers of liver function and damage, and ultrasonographic changes in cats with hyperthyroidism and with high liver enzymes, and to determine if abnormalities resolve after treatment with 131I. Nineteen cats with hyperthyroidism (15 with high serum activities of liver enzymes) and 4 age-matched healthy control cats. Serum bile acids, albumin, ammonia, cholesterol, and blood urea nitrogen concentrations, and activities of liver-derived enzymes, and blood glucose concentrations were measured before and after 131I therapy. These values were compared with those of cats that were euthyroid. In addition, gross liver parenchymal changes detected by abdominal ultrasonographic examination, before and after 131I therapy were evaluated. High serum liver enzyme activities were not associated with abnormalities in hepatic parenchyma and liver functional variables, regardless of the degree of increase. Serum liver enzyme activities return to normal after control of hyperthyroidism with 131I therapy. Cats with hyperthyroidism have a significantly higher serum fasting ammonia concentration than cats who were euthyroid (P = .019). Cats with hyperthyroidism also have significantly lower serum cholesterol (P = .005) and glucose (P = .002) concentrations before compared with after 131I therapy. Nine of 19 cats with hyperthyroidism had trace ketonuria. These results demonstrate that extensive examination for hepatobiliary disease in most cats with hyperthyroidism is unnecessary.

Combining semiquantitative measures of fibrosis and qualitative features of parenchymal remodelling to identify fibrosis regression in hepatitis C: a multiple biopsy study.

PubMed

Pattullo, Venessa; Thein, Hla-Hla; Heathcote, Elizabeth Jenny; Guindi, Maha

2012-09-01

A fall in hepatic fibrosis stage may be observed in patients with chronic hepatitis C (CHC); however, parenchymal architectural changes may also signify hepatic remodelling associated with fibrosis regression. The aim of this study was to utilize semiquantitative and qualitative methods to report the prevalence and factors associated with fibrosis regression in CHC. Paired liver biopsies were scored for fibrosis (Ishak), and for the presence of eight qualitative features of parenchymal remodelling, to derive a qualitative regression score (QR score). Combined fibrosis regression was defined as ≥2-stage fall in Ishak stage (Reg-I) or <2-stage fall in Ishak stage with a rise in QR score (Reg-Qual). Among 159 patients (biopsy interval 5.4 ± 3.1 years), Reg-I was observed in 12 (7.5%) and Reg-Qual in 26 (16.4%) patients. The combined diagnostic criteria increased the diagnosis rate for fibrosis regression (38 patients, 23.9%) compared with use of Reg-I alone (P < 0.001). Combined fibrosis regression was observed in nine patients (50%) who achieved sustained virological response (SVR), and in 29 of 141 (21%) patients despite persistent viraemia. SVR was the only clinical factor associated independently with combined fibrosis regression (odds ratio 3.05). The combination of semiquantitative measures and qualitative features aids the identification of fibrosis regression in CHC. © 2012 Blackwell Publishing Ltd.

Diffusion-weighted MRI in intrahepatic bile duct adenoma arising from the cirrhotic liver.

PubMed

An, Chansik; Park, Sumi; Choi, Yoon Jung

2013-01-01

A 64-year-old male patient with liver cirrhosis underwent a CT study for hepatocellular carcinoma surveillance, which demonstrated a 1.4-cm hypervascular subcapsular tumor in the liver. On gadoxetic acid-enhanced MRI, the tumor showed brisk arterial enhancement and persistent hyperenhancement in the portal phase, but hypointensity in the hepatobiliary phase. On diffusion-weighted MRI, the tumor showed an apparent diffusion coefficient twofold greater than that of the background liver parenchyma, which suggested that the lesion was benign. The histologic diagnosis was intrahepatic bile duct adenoma with alcoholic liver cirrhosis.

In vivo assessment of liver fibrosis using diffuse reflectance and fluorescence spectroscopy: a proof of concept.

PubMed

Fabila, Diego; de la Rosa, José Manuel; Stolik, Suren; Moreno, Edgard; Suárez-Álvarez, Karina; López-Navarrete, Giuliana; Guzmán, Carolina; Aguirre-García, Jesús; Acevedo-García, Christian; Kershenobich, David; Escobedo, Galileo

2012-12-01

A novel application of diffuse reflectance and fluorescence spectroscopy in the assessment of liver fibrosis is here reported. To induce different stages of liver fibrosis, a sufficient number of male Wistar rats were differentially exposed to chronic administration with carbon tetrachloride. Then, diffuse reflectance and fluorescence spectra were in vivo measured from the liver surface of each animal by a minimal invasive laparoscopic procedure. The liver fibrosis degree was conventionally determined by means of histological examination using the Mason's Trichrome stain, accompanied by hepatic expression of α-sma, and evaluation of the ALT/AST serum levels. The liver from rats exhibiting higher grades of fibrosis showed a significant increase in diffuse reflectance and fluorescence intensity when compared with control animals. At 365 nm, the diffuse reflectance spectrum exhibited an increase of 4 and 3-fold in mild and advanced fibrotic rats, respectively, when compared to the control group. Similarly, the fluorescence emission at 493 nm was 2-fold higher in fibrotic animals than in controls. By using fluorescence intensity, discrimination algorithms indicated 73% sensitivity and 94% specificity for recognition of hepatic fibrosis, while for diffuse reflectance, these values increased up to 85% and 100%, respectively. Taking into consideration there is a special need for developing new diagnostic approaches focused on detecting different stages of liver fibrosis with minimal invasiveness, these results suggest that diffuse reflectance and fluorescence spectroscopy could be worthy of further exploration in patients with liver disease. Copyright © 2012 Elsevier B.V. All rights reserved.

DIFFUSION-WEIGHTED IMAGING OF THE LIVER: TECHNIQUES AND APPLICATIONS

PubMed Central

Lewis, Sara; Dyvorne, Hadrien; Cui, Yong; Taouli, Bachir

2014-01-01

SYNOPSIS Diffusion weighted MRI (DWI) is a technique that assesses the cellularity, tortuosity of the extracellular/extravascular space and cell membrane density based upon differences in water proton mobility in tissues. The strength of the diffusion weighting is reflected by the b-value. DWI using several b-values enables quantification of the apparent diffusion coefficient (ADC). DWI is increasingly employed in liver imaging for multiple reasons: it can add useful qualitative and quantitative information to conventional imaging sequences, it is acquired relatively quickly, it is easily incorporated into existing clinical protocols, and it is a non-contrast technique. DWI is useful for focal liver lesion detection and characterization, for the assessment of post-treatment tumor response and for evaluation of diffuse liver disease. ADC quantification can be used to characterize lesions as cystic/necrotic or solid and for predicting tumor response to therapy. Advanced diffusion methods such as IVIM (intravoxel incoherent motion) may have potential for detection, staging and evaluation of the progression of liver fibrosis and for liver lesion characterization. The lack of standardization of DWI technique including choice of b-values and sequence parameters has somewhat limited its widespread adoption. PMID:25086935

Hepatic Fibrosis, Inflammation, and Steatosis: Influence on the MR Viscoelastic and Diffusion Parameters in Patients with Chronic Liver Disease.

PubMed

Leitão, Helena S; Doblas, Sabrina; Garteiser, Philippe; d'Assignies, Gaspard; Paradis, Valérie; Mouri, Feryel; Geraldes, Carlos F G C; Ronot, Maxime; Van Beers, Bernard E

2017-04-01

Purpose To determine the relationship of liver fibrosis, inflammation, and steatosis with the magnetic resonance (MR) viscoelastic and diffusion parameters in patients with chronic liver disease and to compare the diagnostic accuracy of the imaging parameters in staging liver fibrosis. Materials and Methods Consecutive patients with chronic liver disease scheduled for liver biopsy were prospectively recruited from November 2010 to October 2012 for this institutional review board-approved study after they provided written informed consent. Sixty-eight patients underwent three-dimensional MR elastography and intravoxel incoherent motion diffusion-weighted MR imaging with a 1.5-T MR system. Fibrosis, inflammation, and steatosis were assessed with the METAVIR and steatosis, activity, and fibrosis (or SAF) scoring systems. Spearman correlation and multiple regression analyses were performed to determine the relationship between liver fibrosis, inflammation, steatosis, and alanine aminotransferase (ALT) levels and viscoelastic and diffusion parameters. The accuracy of three-dimensional MR elastography and diffusion-weighted MR imaging in the determination of fibrosis stage was assessed with Obuchowski measures. Results At multiple regression analysis, fibrosis was the only variable associated with viscoelastic parameters (β = 0.6, P < .001, R 2 = 0.33 for shear modulus; β = 0.6, P < .001, R 2 = 0.32 for elasticity). Fibrosis had a weaker independent association with the apparent diffusion coefficient (β = -0.3, P = .02, R 2 = 0.33) than did steatosis (β = -0.5, P < .001, R 2 = 0.33). Steatosis was the only factor independently associated with the pure diffusion coefficient (β = -0.4, P = .002, R 2 = 0.22). Inflammation and ALT level were not associated with the viscoelastic or diffusion parameters. The diagnostic accuracy of fibrosis staging was significantly higher when measuring the shear modulus rather than the apparent diffusion coefficient (Obuchowski measures, 0.82 ± 0.04 vs 0.30 ± 0.06; P < .001). Conclusion Fibrosis is independently associated with the MR viscoelastic parameters and is less associated with the diffusion parameters than is steatosis. These results and those of diagnostic accuracy suggest that MR elastography should be preferred over diffusion-weighted MR imaging in the staging of liver fibrosis. © RSNA, 2016.

Scaling down of a clinical three-dimensional perfusion multicompartment hollow fiber liver bioreactor developed for extracorporeal liver support to an analytical scale device useful for hepatic pharmacological in vitro studies.

PubMed

Zeilinger, Katrin; Schreiter, Thomas; Darnell, Malin; Söderdahl, Therese; Lübberstedt, Marc; Dillner, Birgitta; Knobeloch, Daniel; Nüssler, Andreas K; Gerlach, Jörg C; Andersson, Tommy B

2011-05-01

Within the scope of developing an in vitro culture model for pharmacological research on human liver functions, a three-dimensional multicompartment hollow fiber bioreactor proven to function as a clinical extracorporeal liver support system was scaled down in two steps from 800 mL to 8 mL and 2 mL bioreactors. Primary human liver cells cultured over 14 days in 800, 8, or 2 mL bioreactors exhibited comparable time-course profiles for most of the metabolic parameters in the different bioreactor size variants. Major drug-metabolizing cytochrome P450 activities analyzed in the 2 mL bioreactor were preserved over up to 23 days. Immunohistochemical studies revealed tissue-like structures of parenchymal and nonparenchymal cells in the miniaturized bioreactor, indicating physiological reorganization of the cells. Moreover, the canalicular transporters multidrug-resistance-associated protein 2, multidrug-resistance protein 1 (P-glycoprotein), and breast cancer resistance protein showed a similar distribution pattern to that found in human liver tissue. In conclusion, the down-scaled multicompartment hollow fiber technology allows stable maintenance of primary human liver cells and provides an innovative tool for pharmacological and kinetic studies of hepatic functions with small cell numbers.

Spontaneous rupture of a hepatic epithelioid angiomyolipoma: damage control surgery. A case report.

PubMed

Occhionorelli, S; Dellachiesa, L; Stano, R; Cappellari, L; Tartarini, D; Severi, S; Palini, G M; Pansini, G C; Vasquez, G

2013-01-01

Angiomyolipoma (AML) is a rare mesenchymal tumor composed by blood vessels, adipose tissue and smooth muscle cells in variable proportions. Although it is most often diagnosed in the kidney, this tumor may originate from any part of the liver. It is often misdiagnosed as hepatocellular carcinoma (HCC) or other benign liver tumor. We describe a case of spontaneous rupture of hepatic angiomyolipoma in a young woman, with evidence of internal hemorrhage and hemoperitoneum. Liver tumor rupture is a rare but real surgical emergency. In our case it has been managed according to the trauma principles of the damage control surgery. At the time of the observation, the patient presented an instable condition, so the decision-making was oriented toward a less invasive first step of liver packing instead of a more aggressive intervention such as one shot hepatic resection. Damage control surgery with deep parenchymal sutures of the liver and pro-coagulant tissue adhesives packing abbreviates surgical time before the development of critical and irreversible physiological endpoints and permits a more confident second time surgery. This surgical management concept helps to reduce the mortality rate and the incidence of complications not only in traumatic liver damages, it works very well in spontaneous liver ruptures as well.

Detection of Hepatic Fibrosis in Ex Vivo Liver Samples Using an Open-Photoacoustic-Cell Method: Feasibility Study

NASA Astrophysics Data System (ADS)

Stolik, S.; Fabila, D. A.; de la Rosa, J. M.; Escobedo, G.; Suárez-Álvarez, K.; Tomás, S. A.

2015-09-01

Design of non-invasive and accurate novel methods for liver fibrosis diagnosis has gained growing interest. Different stages of liver fibrosis were induced in Wistar rats by intraperitoneally administering different doses of carbon tetrachloride. The liver fibrosis degree was conventionally determined by means of histological examination. An open-photoacoustic-cell (OPC) technique for the assessment of liver fibrosis was developed and is reported here. The OPC technique is based on the fact that the thermal diffusivity can be accurately measured by photoacoustics taking into consideration the photoacoustic signal amplitude versus the modulation frequency. This technique measures directly the heat generated in a sample, due to non-radiative de-excitation processes, following the absorption of light. The thermal diffusivity was measured with a home-made open-photoacoustic-cell system that was specially designed to perform the measurement from ex vivo liver samples. The human liver tissue showed a significant increase in the thermal diffusivity depending on the fibrosis stage. Specifically, liver samples from rats exhibiting hepatic fibrosis showed a significantly higher value of the thermal diffusivity than for control animals.

Diffusion Lung Imaging with Hyperpolarized Gas MRI

PubMed Central

Yablonskiy, Dmitriy A; Sukstanskii, Alexander L; Quirk, James D

2015-01-01

Lung imaging using conventional 1H MRI presents great challenges due to low density of lung tissue, lung motion and very fast lung tissue transverse relaxation (typical T2* is about 1-2 ms). MRI with hyperpolarized gases (3He and 129Xe) provides a valuable alternative due to a very strong signal originated from inhaled gas residing in the lung airspaces and relatively slow gas T2* relaxation (typical T2* is about 20-30 ms). Though in vivo human experiments should be done very fast – usually during a single breath-hold. In this review we describe the recent developments in diffusion lung MRI with hyperpolarized gases. We show that a combination of modeling results of gas diffusion in lung airspaces and diffusion measurements with variable diffusion-sensitizing gradients allows extracting quantitative information on the lung microstructure at the alveolar level. This approach, called in vivo lung morphometry, allows from a less than 15-second MRI scan, providing quantitative values and spatial distributions of the same physiological parameters as are measured by means of the “standard” invasive stereology (mean linear intercept, surface-to-volume ratio, density of alveoli, etc.). Besides, the approach makes it possible to evaluate some advanced Weibel parameters characterizing lung microstructure - average radii of alveolar sacs and ducts, as well as the depth of their alveolar sleeves. Such measurements, providing in vivo information on the integrity of pulmonary acinar airways and their changes in different diseases, are of great importance and interest to a broad range of physiologists and clinicians. We also discuss a new type of experiments that are based on the in vivo lung morphometry technique combined with quantitative CT measurements as well as with the Gradient Echo MRI measurements of hyperpolarized gas transverse relaxation in the lung airspaces. Such experiments provide additional information on the blood vessel volume fraction, specific gas volume, the length of acinar airways, and allows evaluation of lung parenchymal and non-parenchymal tissue. PMID:26676342

Spontaneous liver fibrosis induced by long term dietary vitamin D deficiency in adult mice is related to chronic inflammation and enhanced apoptosis.

PubMed

Zhu, Longdong; Kong, Ming; Han, Yuan-Ping; Bai, Li; Zhang, Xiaohui; Chen, Yu; Zheng, Sujun; Yuan, Hong; Duan, Zhongping

2015-05-01

Epidemiological studies have revealed an association between vitamin D deficiency and various chronic liver diseases. However, it is not known whether lack of vitamin D can induce spontaneous liver fibrosis in an animal model. To study this, mice were fed either a control diet or a vitamin D deficient diet (VDD diet). For the positive control, liver fibrosis was induced with carbon tetrachloride. Here we show, for the first time, that liver fibrosis spontaneously developed in mice fed the VDD diet. Long-term administration of a VDD diet resulted in necro-inflammation and liver fibrosis. Inflammatory mediators including tumor necrosis factor-α, interleulin-1, interleukin-6, Toll-like-receptor 4, and monocyte chemotactic protein-1 were up-regulated in the livers of the mice fed the VDD diet. Conversely, the expression of Th2/M2 markers such as IL-10, IL-13, arginase 1, and heme oxygenase-1 were down-regulated in the livers of mice fed the VDD diet. Transforming growth factor-β1 and matrix metalloproteinase 13, which are important for fibrosis, were induced in the livers of mice fed the VDD diet. Moreover, the VDD diet triggered apoptosis in the parenchymal cells, in agreement with the increased levels of Fas and FasL, and decreased Bcl2 and Bclx. Thus, long-term vitamin D deficiency can provoke chronic inflammation that can induce liver apoptosis, which consequently activates hepatic stellate cells to initiate liver fibrosis.

PNPLA3 I148M polymorphism and progressive liver disease

PubMed Central

Dongiovanni, Paola; Donati, Benedetta; Fares, Roberta; Lombardi, Rosa; Mancina, Rosellina Margherita; Romeo, Stefano; Valenti, Luca

2013-01-01

The 148 Isoleucine to Methionine protein variant (I148M) of patatin-like phospholipase domain-containing 3 (PNPLA3), a protein is expressed in the liver and is involved in lipid metabolism, has recently been identified as a major determinant of liver fat content. Several studies confirmed that the I148M variant predisposes towards the full spectrum of liver damage associated with fatty liver: from simple steatosis to steatohepatitis and progressive fibrosis. Furthermore, the I148M variant represents a major determinant of progression of alcohol related steatohepatitis to cirrhosis, and to influence fibrogenesis and related clinical outcomes in chronic hepatitis C virus hepatitis, and possibly chronic hepatitis B virus hepatitis, hereditary hemochromatosis and primary sclerosing cholangitis. All in all, studies suggest that the I148M polymorphism may represent a general modifier of fibrogenesis in liver diseases. Remarkably, the effect of the I148M variant on fibrosis was independent of that on hepatic steatosis and inflammation, suggesting that it may affect both the quantity and quality of hepatic lipids and the biology of non-parenchymal liver cells besides hepatocytes, directly promoting fibrogenesis. Therefore, PNPLA3 is a key player in liver disease progression. Assessment of the I148M polymorphism will possibly inform clinical practice in the future, whereas the determination of the effect of the 148M variant will reveal mechanisms involved in hepatic fibrogenesis. PMID:24222941

Imaging of hepatic toxicity of systemic therapy in a tertiary cancer centre: chemotherapy, haematopoietic stem cell transplantation, molecular targeted therapies, and immune checkpoint inhibitors.

PubMed

Alessandrino, F; Tirumani, S H; Krajewski, K M; Shinagare, A B; Jagannathan, J P; Ramaiya, N H; Di Salvo, D N

2017-07-01

The purpose of this review is to familiarise radiologists with the spectrum of hepatic toxicity seen in the oncology setting, in view of the different systemic therapies used in cancer patients. Drug-induced liver injury can manifest in various forms, and anti-neoplastic agents are associated with different types of hepatotoxicity. Although chemotherapy-induced liver injury can present as hepatitis, steatosis, sinusoidal obstruction syndrome, and chronic parenchymal damages, molecular targeted therapy-associated liver toxicity ranges from mild liver function test elevation to fulminant life-threatening acute liver failure. The recent arrival of immune checkpoint inhibitors in oncology has introduced a new range of immune-related adverse events, with differing mechanisms of liver toxicity and varied imaging presentation of liver injury. High-dose chemotherapy regimens for haematopoietic stem cell transplantation are associated with sinusoidal obstruction syndrome. Management of hepatic toxicity depends on the clinical scenario, the drug in use, and the severity of the findings. In this article, we will (1) present the most common types of oncological drugs associated with hepatic toxicity and associated liver injuries; (2) illustrate imaging findings of hepatic toxicities and the possible differential diagnosis; and (3) provide a guide for management of these conditions. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Alcoholic pancreatitis: Lessons from the liver

PubMed Central

Clemens, Dahn L; Mahan, Katrina J

2010-01-01

The association between alcohol consumption and pancreatitis has been recognized for over 100 years. Despite the fact that this association is well recognized, the mechanisms by which alcohol abuse leads to pancreatic tissue damage are not entirely clear. Alcohol abuse is the major factor associated with pancreatitis in the Western world. Interestingly, although most cases of chronic pancreatitis and many cases of acute pancreatitis are associated with alcohol abuse, only a small percentage of individuals who abuse alcohol develop this disease. This situation is reminiscent of the association between alcohol abuse and the incidence of alcoholic liver disease. The liver and the pancreas are developmentally very closely related. Even though these two organs are quite different, they exhibit a number of general structural and functional similarities. Furthermore, the diseases mediated by alcohol abuse in these organs exhibit some striking similarities. The diseases in both organs are characterized by parenchymal cell damage, activation of stellate cells, aberrant wound healing, and fibrosis. Because of the similarities between the liver and the pancreas, and the alcohol-associated diseases of these organs, we may be able to apply much of the knowledge that we have gained regarding the effects of alcohol on the liver to the pancreas. PMID:20238397

The ischemic liver cirrhosis theory and its clinical implications.

PubMed

Mancuso, Andrea

2016-09-01

The canonical pathway theory of cirrhosis addresses inflammation as the main driver of hepatic fibrogenesis in hepatitis, so needing a further hypothesis for etiologies missing inflammation, for which parenchymal extinction is postulated. The present paper reports an alternative hypothesis suggesting a central role of micro-vascular ischemia in fibrogenesis and cirrhosis development, whatever is the aetiology of liver chronic injury. In fact, since chronic liver injury could finally result in endothelial damage and micro-vascular thrombosis, leading to a trigger of inappropriate hepatocyte proliferation and fibrosis, finally cirrhosis development could arise from chronic micro-vascular ischemia. Recently, some important confirmation of this hypothesis has been reported. In fact, in a murine experimental model of congestive hepatopathy, it was found that chronic hepatic congestion leads to sinusoidal thrombosis and strain, which in turn promote hepatic fibrosis. Furthermore, a study on a murine model of cirrhosis reported enoxaparin to reduce hepatic vascular resistance and portal pressure by having a protective role against fibrogenesis. In conclusion, the hypothesis giving a central role of micro-vascular ischemia in fibrogenesis and cirrhosis development could change the clinical scenario of chronic liver disease and have several main implications on management of various liver disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Apparent diffusion coefficient mapping using diffusion-weighted MRI: impact of background parenchymal enhancement, amount of fibroglandular tissue and menopausal status on breast cancer diagnosis.

PubMed

Horvat, Joao V; Durando, Manuela; Milans, Soledad; Patil, Sujata; Massler, Jessica; Gibbons, Girard; Giri, Dilip; Pinker, Katja; Morris, Elizabeth A; Thakur, Sunitha B

2018-06-01

To investigate the impact of background parenchymal enhancement (BPE), amount of fibroglandular tissue (FGT) and menopausal status on apparent diffusion coefficient (ADC) values in differentiation between malignant and benign lesions. In this HIPAA-compliant study, mean ADC values of 218 malignant and 130 benign lesions from 288 patients were retrospectively evaluated. The differences in mean ADC values between benign and malignant lesions were calculated within groups stratified by BPE level (high/low), amount of FGT (dense/non-dense) and menopausal status (premenopausal/postmenopausal). Sensitivities and specificities for distinguishing malignant from benign lesions within different groups were compared for statistical significance. The mean ADC value for malignant lesions was significantly lower compared to that for benign lesions (1.07±0.21 x 10 -3 mm 2 /s vs. 1.53±0.26 x 10 -3 mm 2 /s) (p<0.0001). Using the optimal cut-off point of 1.30 x 10 -3 mm 2 /s, an area under the curve of 0.918 was obtained, with sensitivity and specificity both of 87 %. There was no statistically significant difference in sensitivities and specificities of ADC values between different groups stratified by BPE level, amount of FGT or menopausal status. Differentiation between benign and malignant lesions on ADC values is not significantly affected by BPE level, amount of FGT or menopausal status. • ADC allows differentiation between benign and malignant lesions. • ADC is useful for breast cancer diagnosis despite different patient characteristics. • BPE, FGT or menopause do not significantly affect sensitivity and specificity.

Brain MRI in neuropsychiatric lupus: associations with the 1999 ACR case definitions.

PubMed

Jeong, Hae Woong; Her, Minyoung; Bae, Jong Seok; Kim, Seong-Kyu; Lee, Sung Won; Kim, Ho Kyun; Kim, Dongyook; Park, Nayoung; Chung, Won Tae; Lee, Sang Yeob; Choe, Jung-Yoon; Kim, In Joo

2015-05-01

The purpose of this study was to identify the characteristic magnetic resonance imaging (MRI) findings in neuropsychiatric systemic lupus erythematosus (NPSLE) and to investigate the association between MRI findings and neuropsychiatric manifestations in SLE. Brain MRIs with a diagnosis of SLE from 2002 to 2013 from three tertiary university hospitals were screened. All clinical manifestations evaluated by brain MRI were retrospectively reviewed. If the clinical manifestations were compatible with the 1999 NPSLE American College of Rheumatology (ACR) nomenclature and case definitions, the brain MRIs were assessed for the presence of white matter hyperintensities, gray matter hyperintensities, parenchymal defects, atrophy, enhancement, and abnormalities in diffusion-weighted images (DWI). The number, size, and location of each lesion were evaluated. The neuropsychiatric manifestation of each brain MRI was classified according to the 1999 ACR NPSLE case definitions. The associations between MRI findings and NPSLE manifestations were examined. In total, 219 brain MRIs with a diagnosis of SLE were screened, and 133 brain MRIs met the inclusion criteria for NPSLE. The most common MRI abnormality was white matter hyperintensities, which were observed in 76 MRIs (57.1 %). Gray matter hyperintensities were observed in 41 MRIs (30.8 %). Parenchymal defects were found in 31 MRIs (23.3 %), and atrophy was detected in 20 MRIs (15.0 %). Patients who had seizures were more associated with gray matter hyperintensities than patients with other neuropsychiatric manifestations. Patients with cerebrovascular disease were more associated with gray matter hyperintensity, parenchymal defects, and abnormal DWI than patients with other neuropsychiatric manifestations. In addition to white matter hyperintensities, which were previously known as SLE findings, we also noted the presence of gray matter hyperintensities, parenchymal defects, and abnormal DWI in a substantial portion of SLE patients, particularly in those with cerebrovascular disease or seizures.

In Vivo Stable Transduction of Humanized Liver Tissue in Chimeric Mice via High-Capacity Adenovirus–Lentivirus Hybrid Vector

PubMed Central

Kataoka, Miho; Tateno, Chise; Yoshizato, Katsutoshi; Kawasaki, Yoshiko; Kimura, Takahiro; Faure-Kumar, Emmanuelle; Palmer, Donna J.; Ng, Philip; Okamura, Haruki; Kasahara, Noriyuki

2010-01-01

Abstract We developed hybrid vectors employing high-capacity adenovirus as a first-stage carrier encoding all the components required for in situ production of a second-stage lentivirus, thereby achieving stable transgene expression in secondary target cells. Such vectors have never previously been tested in normal tissues, because of the scarcity of suitable in vivo systems permissive for second-stage lentivirus assembly. Here we employed a novel murine model in which endogenous liver tissue is extensively reconstituted with engrafted human hepatocytes, and successfully achieved stable transduction by the second-stage lentivirus produced in situ from first-stage adenovirus. This represents the first demonstration of the functionality of adenoviral-lentiviral hybrid vectors in a normal parenchymal organ in vivo. PMID:19725756

Little girl who conquered the "ALPPS''.

PubMed

Chan, Albert; Chung, Patrick H Y; Poon, Ronnie T P

2014-08-07

An insufficient future liver remnant (FLR) is associated with post-hepatectomy liver failure. Associating liver partition and portal vein ligation for stage hepatectomy (ALPPS) has been shown to be effective for the induction of rapid FLR hypertrophy so as to improve the resectability in patients with insufficient FLR. We hereby report our experience of this novel approach for a 6-year-old patient with hepatoblastoma. Computed tomography showed a hepatoblastoma measuring 12.5 cm × 9.9 cm × 11.7 cm in the right liver (Couinaud segment IV, V and VIII). Volumetric assessment of the FLR i.e., left lateral section was 112.6 mL i.e., 21.2% of the estimated total liver volume. In view of the small-for-size FLR, ALPPS was contemplated. An anterior approach was adopted for the in-situ parenchymal split without mobilisation of the right liver. FLR volumetry on the seventh postoperative day was 160.7 mL, which represented a 46.1% gain in volume, and a FLR/ESLV ratio of 30.2%. A right trisectionectomy was performed on the eighth postoperative day. Postoperative recovery was uneventful. Patient was discharged on day 16 after the first operation. To our knowledge, this was the first report that showed the applicability of ALPPS to a paediatric patient.

Emergency strategies and trends in the management of liver trauma.

PubMed

Jiang, Hongchi; Wang, Jizhou

2012-09-01

The liver is the most frequently injured organ during abdominal trauma. The management of hepatic trauma has undergone a paradigm shift over the past several decades, with mandatory operation giving way to nonoperative treatment. Better understanding of the mechanisms and grade of liver injury aids in the initial assessment and establishment of a management strategy. Hemodynamically unstable patients should undergo focused abdominal sonography for trauma, whereas stable patients may undergo computed tomography, the standard examination protocol. The grade of liver injury alone does not accurately predict the need for operation, and nonoperative management is rapidly becoming popular for high-grade injuries. Hemodynamic instability with positive focused abdominal sonography for trauma and peritonitis is an indicator of the need for emergent operative intervention. The damage control concept is appropriate for the treatment of major liver injuries and is associated with significant survival advantages compared with traditional prolonged surgical techniques. Although surgical intervention for hepatic trauma is not as common now as it was in the past, current trauma surgeons should be familiar with the emergency surgical skills necessary to manage complex hepatic injuries, such as packing, Pringle maneuver, selective vessel ligation, resectional debridement, and parenchymal sutures. The present review presents emergency strategies and trends in the management of liver trauma.

Association between consumption of Herbalife nutritional supplements and acute hepatotoxicity.

PubMed

Elinav, Eran; Pinsker, Galia; Safadi, Rifaat; Pappo, Orit; Bromberg, Michal; Anis, Emilia; Keinan-Boker, Lital; Broide, Efrat; Ackerman, Zvi; Kaluski, Dorit Nitzan; Lev, Boaz; Shouval, Daniel

2007-10-01

Nutritional supplements are frequently considered to be harmless but indiscriminate use of unlabelled ingredients may lead to significant adverse reactions. In 2004, identification of four index cases of acute hepatitis associated with Herbalife intake led to a ministry of health investigation in all Israeli hospitals. Twelve patients with acute idiopathic liver injury in association with consumption of Herbalife products were investigated. Eleven of the patients were females, aged 49.5+/-13.4 y. One patient had stage I primary biliary cirrhosis and another had hepatitis B. Acute liver injury was diagnosed after 11.9+/-11.1 months of initiation of Herbalife consumption. Liver biopsies demonstrated active hepatitis, portal inflammation rich with eosinophils, ductular reaction and parenchymal inflammation with peri-central accentuation. One patient developed sub-fulminant and two fulminant episodes of hepatic failure. Hepatitis resolved in eleven patients, while one patient succumbed to complications following liver transplantation. Three patients resumed consumption of Herbalife products following normalization of liver enzymes, resulting in a second bout of hepatitis. An association between intake of Herbalife products and acute hepatitis was identified in Israel. We call for prospective evaluation of Herbalife products for possible hepatotoxicity. Until then, caution should be exercised by consumers, especially among individuals suffering from underlying liver disease.

Mesenchymal stem cells support hepatocyte function in engineered liver grafts.

PubMed

Kadota, Yoshie; Yagi, Hiroshi; Inomata, Kenta; Matsubara, Kentaro; Hibi, Taizo; Abe, Yuta; Kitago, Minoru; Shinoda, Masahiro; Obara, Hideaki; Itano, Osamu; Kitagawa, Yuko

2014-01-01

Recent studies suggest that organ decellularization is a promising approach to facilitate the clinical application of regenerative therapy by providing a platform for organ engineering. This unique strategy uses native matrices to act as a reservoir for the functional cells which may show therapeutic potential when implanted into the body. Appropriate cell sources for artificial livers have been debated for some time. The desired cell type in artificial livers is primary hepatocytes, but in addition, other supportive cells may facilitate this stem cell technology. In this context, the use of mesenchymal stem cells (MSC) is an option meeting the criteria for therapeutic organ engineering. Ideally, supportive cells are required to (1) reduce the hepatic cell mass needed in an engineered liver by enhancing hepatocyte function, (2) modulate hepatic regeneration in a paracrine fashion or by direct contact, and (3) enhance the preservability of parenchymal cells during storage. Here, we describe enhanced hepatic function achieved using a strategy of sequential infusion of cells and illustrate the advantages of co-cultivating bone marrow-derived MSCs with primary hepatocytes in the engineered whole-liver scaffold. These co-recellularized liver scaffolds colonized by MSCs and hepatocytes were transplanted into live animals. After blood flow was established, we show that expression of adhesion molecules and proangiogenic factors was upregulated in the graft.

Color-Coded Imaging of Breast Cancer Metastatic Niche Formation in Nude Mice.

PubMed

Suetsugu, Atsushi; Momiyama, Masashi; Hiroshima, Yukihiko; Shimizu, Masahito; Saji, Shigetoyo; Moriwaki, Hisataka; Bouvet, Michael; Hoffman, Robert M

2015-12-01

We report here a color-coded imaging model in which metastatic niches in the lung and liver of breast cancer can be identified. The transgenic green fluorescent protein (GFP)-expressing nude mouse was used as the host. The GFP nude mouse expresses GFP in all organs. However, GFP expression is dim in the liver parenchymal cells. Mouse mammary tumor cells (MMT 060562) (MMT), expressing red fluorescent protein (RFP), were injected in the tail vein of GFP nude mice to produce experimental lung metastasis and in the spleen of GFP nude mice to establish a liver metastasis model. Niche formation in the lung and liver metastasis was observed using very high resolution imaging systems. In the lung, GFP host-mouse cells accumulated around as few as a single MMT-RFP cell. In addition, GFP host cells were observed to form circle-shaped niches in the lung even without RFP cancer cells, which was possibly a niche in which future metastasis could be formed. In the liver, as with the lung, GFP host cells could form circle-shaped niches. Liver and lung metastases were removed surgically and cultured in vitro. MMT-RFP cells and GFP host cells resembling cancer-associated fibroblasts (CAFs) were observed interacting, suggesting that CAFs could serve as a metastatic niche. © 2015 Wiley Periodicals, Inc.

Liver recurrence in endometrial cancer: a multi-institutional analysis of factors predictive of postrecurrence survival.

PubMed

Toptas, Tayfun; Karalok, Alper; Ureyen, Isin; Tasci, Tolga; Erol, Onur; Bozkurt, Selen; Tulunay, Gokhan; Simsek, Tayup; Turan, Taner

2016-10-01

Predictive factors for survival following liver metastasis in endometrial cancer (EC) have not been studied to date. It is expected that patients who initially presented with liver metastasis or developed liver metastasis as the subsequent metastatic site of progressive disease are likely to have poor outcomes. However, patients developing liver metastasis as the first site of recurrence may have a chance of benefiting from the salvage therapies. Therefore, we aimed to determine factors influencing postrecurrence survival in EC patients who developed liver metastasis as the first site of recurrence. Patients with EC who underwent primary surgery at three centers between 1993 and 2013 were reviewed. Liver recurrence was defined as documentation of parenchymal liver metastasis either by radiologically or biopsy, after a disease-free interval of ≥3 months. Patients with liver metastasis at presentation, or liver metastasis as the subsequent metastatic site of progressive disease were excluded. Forty-six patients were identified. Median time to liver recurrence was 12 months, with 91.3 % of recurrences detected within 3 years. Most patients (73.9 %) had liver recurrence concomitant with extra-hepatic disease. Median survival after the diagnosis of liver recurrence was 9 months. While in univariate analysis, time to liver recurrence (p < 0.001) and presence of concomitant extra-hepatic metastasis (p = 0.048) were potential predictors of survival, multivariate analysis revealed that time to liver recurrence (p < 0.001) was the only independent predictor. This criterion may be used as a marker for stratifying patients into different prognostic risk groups and for selection of patients for salvage therapies.

Correlation of B-Lines on Ultrasonography With Interstitial Lung Disease on Chest Radiography and CT Imaging.

PubMed

Dubinsky, Theodore J; Shah, Hardik; Sonneborn, Rachelle; Hippe, Daniel S

2017-11-01

We prospectively identified B-lines in patients undergoing ultrasonographic (US) examinations following liver transplantation who also had chest radiography (CXR) or chest CT imaging, or both, on the same day to determine if an association between the presence of B-lines from the thorax on US images correlates with the presence of lung abnormalities on CXR. Following institutional review board (IRB) approval, patients who received liver transplants and underwent routine US examinations and chest radiography or CT imaging, or both, on the same day between January 1, 2015 through July 1, 2016 were prospectively identified. Two readers who were blinded to chest films and CT images and reports independently reviewed the US interreader agreement for the presence or absence of B-lines and performed an evaluation for the presence or absence of diffuse parenchymal lung disease (DPLD) on chest films and CT images as well as from clinical evaluation. Receiver operating characteristic (ROC) curves were constructed. There was good agreement between the two readers on the presence of absence of B-lines (kappa = 0.94). The area under the ROC curve for discriminating between positive DPLD and negative DPLD for both readers was 0.79 (95% CI, 0.71-0.87). There is an association between the presence of extensive B-lines to the point of confluence and "dirty shadowing" on US examinations of the chest and associated findings on chest radiographs and CT scans of DPLD. Conversely, isolated B-lines do not always correlate with abnormalities on chest films and in fact sometimes appear to be a normal variant. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Hepatic microvascular dysfunction and increased advanced glycation end products are components of non-alcoholic fatty liver disease.

PubMed

Pereira, Evelyn Nunes Goulart da Silva; Silvares, Raquel Rangel; Flores, Edgar Eduardo Ilaquita; Rodrigues, Karine Lino; Ramos, Isalira Peroba; da Silva, Igor José; Machado, Marcelo Pelajo; Miranda, Rosiane Aparecida; Pazos-Moura, Carmen Cabanelas; Gonçalves-de-Albuquerque, Cassiano F; Faria-Neto, Hugo Caire de Castro; Tibiriça, Eduardo; Daliry, Anissa

2017-01-01

This study aimed to investigate the pathophysiology of hepatic microcirculatory dysfunction in non-alcoholic fatty liver disease (NAFLD). In Wistar rats, NAFLD model was induced by 20 weeks of high-fat diet (HFD) feeding. Rolling and adhesion of leukocytes and tissue perfusion in hepatic microcirculation were examined using in vivo microscopic and laser speckle contrast imaging (LSCI), respectively. Oxidative stress and inflamatory parameters were analysed by TBARs, catalase enzyme activity, RT-PCR and ELISA. The participation of advanced glycation end-products (AGE) and its receptor RAGE was evaluated by the measurement of gene and protein expression of RAGE by RT-PCR and Western-blot, respectively and by liver and serum quantification of fluorescent AGEs. Wistar rats fed high-fat diet (HFD) showed increase in epididymal and abdominal fat content, systolic arterial blood pressure, fasting blood glucose levels, hepatic triglycerides and cholesterol, and impairment of glucose and insulin metabolisms. Liver histology confirmed the presence of steatosis and ultrasound analysis revealed increased liver size and parenchymal echogenicity in HFD-fed rats. HFD causes significant increases in leukocyte rolling and adhesion on hepatic microcirculation and decrease in liver microvascular blood flow. Liver tissue presented increase in oxidative stress and inflammtion. At 20 weeks, there was a significantly increase in AGE content in the liver and serum of HFD-fed rats and an increase in RAGE gene expression in the liver. The increase in liver AGE levels and microcirculatory disturbances could play a role in the pathogenesis of liver injury and are key components of NAFLD.

Effect of cryopreservation on the appearance and liver function of hepatocyte-like cells in cultures of cirrhotic liver of biliary atresia.

PubMed

Yamazaki, Taisuke; Enosawa, Shin; Tokiwa, Takayoshi

2018-06-01

Previously, we reported that non-parenchymal cell (NPC) fractions from cirrhotic liver of biliary atresia (BA) may contain stem/progenitor cells, and clusters of hepatocyte-like cells appear via hepatocyte growth factor/c-Met signaling in primary cultures of NPCs. BA is a rare and serious liver disease, and procurement of BA cells is difficult. Therefore, cryopreservation of BA liver cells is an unavoidable challenge. In this study, we examined the appearance and liver function of hepatocyte-like cells in cultures of BA liver-derived NPC fractions after cryopreservation for 1 or 6 mo using a chemically defined cryopreservation solution, STEM-CELLBANKER. Although a decrease in cell viability was observed in recovered cells after 1 mo of cryopreservation, clusters of hepatocyte-like cells appeared in the culture of cells that had been cryopreserved for 1 or 6 mo, similar to non-cryopreserved cells. In addition, these hepatocyte-like cells expressed hepatocyte-related mRNAs and demonstrated albumin production and glycogen storage. The present results suggest that hepatic stem/progenitor cells in NPC fractions may be efficiently cryopreserved, as demonstrated by the appearance of hepatocyte-like cells that show various hepatic functions even after cryopreservation. This study may lead to future BA cell therapy using the patient's own cells.

Foetal hepatic progenitor cells assume a cholangiocytic cell phenotype during two-dimensional pre-culture.

PubMed

Anzai, Kazuya; Chikada, Hiromi; Tsuruya, Kota; Ida, Kinuyo; Kagawa, Tatehiro; Inagaki, Yutaka; Mine, Tesuya; Kamiya, Akihide

2016-06-23

Liver consists of parenchymal hepatocytes and other cells. Liver progenitor cell (LPC) is the origin of both hepatocytes and cholangiocytic cells. The analyses of mechanism regulating differentiation of LPCs into these functional cells are important for liver regenerative therapy using progenitor cells. LPCs in adult livers were found to form cysts with cholangiocytic characteristics in 3D culture. In contrast, foetal LPCs cannot form these cholangiocytic cysts in the same culture. Thus, the transition of foetal LPCs into cholangiocytic progenitor cells might occur during liver development. Primary CD45(-)Ter119(-)Dlk1(+) LPCs derived from murine foetal livers formed ALBUMIN (ALB)(+)CYTOKERATIN (CK)19(-) non-cholangiocytic cysts within 3D culture. In contrast, when foetal LPCs were pre-cultured on gelatine-coated dishes, they formed ALB(-)CK19(+) cholangiocytic cysts. When hepatocyte growth factor or oncostatin M, which are inducers of hepatocytic differentiation, was added to pre-culture, LPCs did not form cholangiocytic cysts. These results suggest that the pre-culture on gelatine-coated dishes changed the characteristics of foetal LPCs into cholangiocytic cells. Furthermore, neonatal liver progenitor cells were able to form cholangiocytic cysts in 3D culture without pre-culture. It is therefore possible that the pre-culture of mid-foetal LPCs in vitro functioned as a substitute for the late-foetal maturation step in vivo.

The impact of cortisol in steatotic and non-steatotic liver surgery.

PubMed

Cornide-Petronio, María Eugenia; Bujaldon, Esther; Mendes-Braz, Mariana; Avalos de León, Cindy G; Jiménez-Castro, Mónica B; Álvarez-Mercado, Ana I; Gracia-Sancho, Jordi; Rodés, Juan; Peralta, Carmen

2017-10-01

The intent of this study was to examine the effects of regulating cortisol levels on damage and regeneration in livers with and without steatosis subjected to partial hepatectomy under ischaemia-reperfusion. Ultimately, we found that lean animals undergoing liver resection displayed no changes in cortisol, whereas cortisol levels in plasma, liver and adipose tissue were elevated in obese animals undergoing such surgery. Such elevations were attributed to enzymatic upregulation, ensuring cortisol production, and downregulation of enzymes controlling cortisol clearance. In the absence of steatosis, exogenous cortisol administration boosted circulating cortisol, while inducing clearance of hepatic cortisol, thus maintaining low cortisol levels and preventing related hepatocellular harm. In the presence of steatosis, cortisol administration was marked by a substantial rise in intrahepatic availability, thereby exacerbating tissue damage and regenerative failure. The injurious effects of cortisol were linked to high hepatic acethylcholine levels. Upon administering an α7 nicotinic acethylcholine receptor antagonist, no changes in terms of tissue damage or regenerative lapse were apparent in steatotic livers. However, exposure to an M3 muscarinic acetylcholine receptor antagonist protected livers against damage, enhancing parenchymal regeneration and survival rate. These outcomes for the first time provide new mechanistic insight into surgically altered steatotic livers, underscoring the compelling therapeutic potential of cortisol-acetylcholine-M3 muscarinic receptors. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Dynamic contrast-enhanced magnetic resonance imaging of abdominal solid organ and major vessel: comparison of enhancement effect between Gd-EOB-DTPA and Gd-DTPA.

PubMed

Tamada, Tsutomu; Ito, Katsuyoshi; Sone, Teruki; Yamamoto, Akira; Yoshida, Koji; Kakuba, Koki; Tanimoto, Daigo; Higashi, Hiroki; Yamashita, Takenori

2009-03-01

To evaluate the differences in enhancement of the abdominal solid organ and the major vessel on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) obtained with gadolinium ethoxybenzyldiethylenetriamine pentaacetic acid (Gd-EOB-DTPA: EOB) and gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) in the same patients. A total of 13 healthy volunteers underwent repeat assessments of abdominal MR examinations with DCE-MRI using either Gd-DTPA at a dose of 0.1 mmol/kg body weight or EOB at a dose of 0.025 mmol/kg body weight. DCE images were obtained at precontrast injection and in the arterial phase (AP: 25 seconds), portal phase (PP: 70 seconds), and equilibrium phase (EP: 3 minutes). The signal intensities (SIs) of liver at AP, PP, and EP; the SIs of spleen, renal cortex, renal medulla, pancreas, adrenal gland, aorta at AP; and the SIs of portal vein and inferior vena cava (IVC) at PP were defined using region-of-interest measurements, and were used for calculation of signal intensity ratio (SIR). The mean SIRs of liver (0.195+/-0.140), spleen (1.35+/-0.353), renal cortex (1.58+/-0.517), renal medulla (0.548+/-0.259), pancreas (0.540+/-0.183), adrenal gland (1.04+/-0.405), and aorta (2.44+/-0.648) at AP as well as the mean SIRs of portal vein (1.85+/-0.477) and IVC (1.16+/-0.187) at PP in the EOB images were significantly lower than those (0.337+/-0.200, 1.99+/-0.443, 2.01+/-0.474, 0.742+/-0.336, 0.771+/-0.227, 1.26+/-0.442, 3.22+/-1.20, 2.73+/-0.429, and 1.68+/-0.366, respectively) in the Gd-DTPA images (P<0.05 each). There was no significant difference in mean SIR of liver at PP between EOB (0.529+/-0.124) and Gd-DTPA (0.564+/-0.139). Conversely, the mean SIR of liver at EP was significantly higher with EOB (0.576+/-0.167) than with Gd-DTPA (0.396+/-0.093) (P<0.001). Lower arterial vascular and parenchymal enhancement with Gd-EOB, as compared with Gd-DTPA, may require reassessment of its dose, despite the higher late venous phase liver parenchymal enhancement. Copyright (c) 2009 Wiley-Liss, Inc.

Utility of Diffusion-Weighted MRI to Detect Changes in Liver Diffusion in Benign and Malignant Distal Bile Duct Obstruction: The Influence of Choice of b-Values.

PubMed

Karan, Belgin; Erbay, Gurcan; Koc, Zafer; Pourbagher, Aysin; Yildirim, Sedat; Agildere, Ahmet Muhtesem

2016-11-01

The study sought to evaluate the potential of diffusion-weighted magnetic resonance imaging to detect changes in liver diffusion in benign and malignant distal bile duct obstruction and to investigate the effect of the choice of b-values on apparent diffusion coefficient (ADC). Diffusion-weighted imaging was acquired with b-values of 200, 600, 800, and 1000 s/mm 2 . ADC values were obtained in 4 segments of the liver. The mean ADC values of 16 patients with malignant distal bile duct obstruction, 14 patients with benign distal bile duct obstruction, and a control group of 16 healthy patients were compared. Mean ADC values for 4 liver segments were lower in the malignant obstruction group than in the benign obstruction and control groups using b = 200 s/mm 2 (P < .05). Mean ADC values of the left lobe medial and lateral segments were lower in the malignant obstruction group than in the benign obstructive and control groups using b = 600 s/mm 2 (P < .05). Mean ADC values of the right lobe posterior segment were lower in the malignant and benign obstruction groups than in the control group using b = 1000 s/mm 2 (P < .05). Using b = 800 s/mm 2 , ADC values of all 4 liver segments in each group were not significantly different (P > .05). There were no correlations between the ADC values of liver segments and liver function tests. Measurement of ADC shows good potential for detecting changes in liver diffusion in patients with distal bile duct obstruction. Calculated ADC values were affected by the choice of b-values. Copyright © 2016 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

Challenge of liver disease in systemic lupus erythematosus: Clues for diagnosis and hints for pathogenesis

PubMed Central

Bessone, Fernando; Poles, Natalia; Roma, Marcelo G

2014-01-01

Systemic lupus erythematosus (SLE) encompass a broad spectrum of liver diseases. We propose here to classify them as follows: (1) immunological comorbilities (overlap syndromes); (2) non-immunological comorbilities associated to SLE; and (3) a putative liver damage induced by SLE itself, referred to as “lupus hepatitis”. In the first group, liver injury can be ascribed to overlapping hepatopathies triggered by autoimmune mechanisms other than SLE occurring with higher incidence in the context of lupus (e.g., autoimmune hepatitis, primary biliary cirrhosis). The second group includes non-autoimmune liver diseases, such as esteatosis, hepatitis C, hypercoagulation state-related liver lesions, hyperplasic parenchymal and vascular lesions, porphyria cutanea tarda, and drug-induced hepatotoxicity. Finally, the data in the literature to support the existence of a hepatic disease produced by SLE itself, or the occurrence of a SLE-associated prone condition that increases susceptibility to acquire other liver diseases, is critically discussed. The pathological mechanisms underlying each of these liver disorders are also reviewed. Despite the high heterogeneity in the literature regarding the prevalence of SLE-associated liver diseases and, in most cases, lack of histopathological evidence or clinical studies large enough to support their existence, it is becoming increasingly apparent that liver is an important target of SLE. Consequently, biochemical liver tests should be routinely carried out in SLE patients to discard liver disorders, particularly in those patients chronically exposed to potentially hepatotoxic drugs. Diagnosing liver disease in SLE patients is always challenging, and the systematization of the current information carried out in this review is expected to be of help both to attain a better understanding of pathogenesis and to build an appropriate work-up for diagnosis. PMID:25018850

TWEAK induces liver progenitor cell proliferation

PubMed Central

Jakubowski, Aniela; Ambrose, Christine; Parr, Michael; Lincecum, John M.; Wang, Monica Z.; Zheng, Timothy S.; Browning, Beth; Michaelson, Jennifer S.; Baestcher, Manfred; Wang, Bruce; Bissell, D. Montgomery; Burkly, Linda C.

2005-01-01

Progenitor (“oval”) cell expansion accompanies many forms of liver injury, including alcohol toxicity and submassive parenchymal necrosis as well as experimental injury models featuring blocked hepatocyte replication. Oval cells can potentially become either hepatocytes or biliary epithelial cells and may be critical to liver regeneration, particularly when hepatocyte replication is impaired. The regulation of oval cell proliferation is incompletely understood. Herein we present evidence that a TNF family member called TWEAK (TNF-like weak inducer of apoptosis) stimulates oval cell proliferation in mouse liver through its receptor Fn14. TWEAK has no effect on mature hepatocytes and thus appears to be selective for oval cells. Transgenic mice overexpressing TWEAK in hepatocytes exhibit periportal oval cell hyperplasia. A similar phenotype was obtained in adult wild-type mice, but not Fn14-null mice, by administering TWEAK-expressing adenovirus. Oval cell expansion induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) was significantly reduced in Fn14-null mice as well as in adult wild-type mice with a blocking anti-TWEAK mAb. Importantly, TWEAK stimulated the proliferation of an oval cell culture model. Finally, we show increased Fn14 expression in chronic hepatitis C and other human liver diseases relative to its expression in normal liver, which suggests a role for the TWEAK/Fn14 pathway in human liver injury. We conclude that TWEAK has a selective mitogenic effect for liver oval cells that distinguishes it from other previously described growth factors. PMID:16110324

Bmp6 Expression in Murine Liver Non Parenchymal Cells: A Mechanism to Control their High Iron Exporter Activity and Protect Hepatocytes from Iron Overload?

PubMed Central

Rausa, Marco; Pagani, Alessia; Nai, Antonella; Campanella, Alessandro; Gilberti, Maria Enrica; Apostoli, Pietro; Camaschella, Clara; Silvestri, Laura

2015-01-01

Bmp6 is the main activator of hepcidin, the liver hormone that negatively regulates plasma iron influx by degrading the sole iron exporter ferroportin in enterocytes and macrophages. Bmp6 expression is modulated by iron but the molecular mechanisms are unknown. Although hepcidin is expressed almost exclusively by hepatocytes (HCs), Bmp6 is produced also by non-parenchymal cells (NPCs), mainly sinusoidal endothelial cells (LSECs). To investigate the regulation of Bmp6 in HCs and NPCs, liver cells were isolated from adult wild type mice whose diet was modified in iron content in acute or chronic manner and in disease models of iron deficiency (Tmprss6 KO mouse) and overload (Hjv KO mouse). With manipulation of dietary iron in wild-type mice, Bmp6 and Tfr1 expression in both HCs and NPCs was inversely related, as expected. When hepcidin expression is abnormal in murine models of iron overload (Hjv KO mice) and deficiency (Tmprss6 KO mice), Bmp6 expression in NPCs was not related to Tfr1. Despite the low Bmp6 in NPCs from Tmprss6 KO mice, Tfr1 mRNA was also low. Conversely, despite body iron overload and high expression of Bmp6 in NPCs from Hjv KO mice, Tfr1 mRNA and protein were increased. However, in the same cells ferritin L was only slightly increased, but the iron content was not, suggesting that Bmp6 in these cells reflects the high intracellular iron import and export. We propose that NPCs, sensing the iron flux, not only increase hepcidin through Bmp6 with a paracrine mechanism to control systemic iron homeostasis but, controlling hepcidin, they regulate their own ferroportin, inducing iron retention or release and further modulating Bmp6 production in an autocrine manner. This mechanism, that contributes to protect HC from iron loading or deficiency, is lost in disease models of hepcidin production. PMID:25860887

Growth and Development Symposium: Development, characterization, and use of a porcine epiblast-derived liver stem cell line: ARS-PICM-19.

PubMed

Talbot, N C; Caperna, T J; Garrett, W M

2013-01-01

Totipotent embryonic stem cell lines have not been established from ungulates; however, we have developed a somatic stem cell line from the in vitro culture of pig epiblast cells. The cell line, ARS-PICM-19, was isolated via colony cloning and was found to spontaneously differentiate into hepatic parenchymal epithelial cell types, namely hepatocytes and bile duct cells. Hepatocytes form as monolayers and bile duct cells as 3-dimensional bile ductules. Transmission electron microscopy revealed that the ductules were composed of radially arranged, monociliated cells with their cilia projecting into the lumen of the ductule whereas hepatocytes were arranged in monolayers with lateral canalicular structures containing numerous microvilli and connected by tight junctions and desmosomes. Extensive Golgi and rough endoplasmic reticulum networks were also present, indicative of active protein synthesis. Analysis of conditioned medium by 2-dimensional electrophoresis and mass spectrometry indicated a spectrum of serum-protein secretion by the hepatocytes. The PICM-19 cell line maintains a range of inducible cytochrome P450 activities and, most notably, is the only nontransformed cell line that synthesizes urea in response to ammonia challenge. The PICM-19 cell line has been used for several biomedical- and agricultural-related purposes, such as the in vitro replication of hepatitis E virus, a zoonotic virus of pigs, and a spaceflight experiment to evaluate somatic stem cell differentiation and liver cell function in microgravity. The cell line was also evaluated as a platform for toxicity testing and has been used in a commercial artificial liver rescue device bioreactor. A PICM-19 subclone, PICM-19H, which only differentiates into hepatocytes, was isolated and methods are currently under development to grow PICM-19 cells without feeder cells. Feeder-cell-independent growth will facilitate the study of mesenchymal-parenchymal interactions that influence the divergent differentiation of the PICM-19 cells, enhance our ability to genetically modify the cells, and provide a better model system to investigate porcine hepatic metabolism.

Pure laparoscopic right hepatectomy for giant hemangioma using anterior approach.

PubMed

Kim, Seok-Hwan; Kim, Ki-Hun; Kirchner, Varvara A; Lee, Sang-Kyung

2017-05-01

Laparoscopic major hepatectomy remains a challenging procedure [1, 2]. In the case of giant tumors in the right liver, conventional approach (complete mobilization of the right liver before parenchymal transection) could be dangerous during mobilization because of large volume and weight [3, 4]. We present the case of a pure laparoscopic right hepatectomy for a giant hemangioma using an anterior approach. We achieved the informed consent with this patient and approved by the Ethics Committee of the Asan Medical Center. Giant hemangioma (13 × 11 × 14 cm) was located in right liver. After glissonean approach [5], Pringle maneuver was performed during the hepatic parenchymal transection. For the transection, the Cavitron Ultrasonic Surgical Aspirator was used. Small hepatic vein branches along the middle hepatic vein and small glissonean pedicles were sealed and divided with a THUNDERBEATTM (Olympus), which is the device with integration of both bipolar and ultrasonic energies delivered simultaneously. iDriveTM Ultra Powered Stapling device (Medtronic) was used for division of right glissonean pedicle and large hepatic veins. Hemangioma was removed through the lower abdominal transverse incision using the endo-bag. This technique has the advantage of avoiding excessive bleeding caused by avulsion of the hepatic vein and caval branches, iatrogenic tumor rupture [3]. By means of the anterior approach, pure laparoscopic right hepatectomy was performed successfully without intraoperative complications and transfusions. The operation time was 202 min, and the estimated blood loss was less than 150 ml. On postoperative day 3, computed tomographic scan showed no pathological findings. The patient was discharged on postoperative day 5 without complications. Laparoscopic approach has good results because of the view with magnification enabling meticulous hemostasis and the small wounds that give patients less pain [6, 7]. The authors recommend that the laparoscopic anterior approach is safe and feasible for right hepatectomy, even for giant tumors.

Nitrogen and sulphur mustard induced histopathological observations in mouse visceral organs.

PubMed

Sharma, Manoj; Pant, S C; Pant, J C; Vijayaraghavan, R

2010-11-01

Nitrogen mustards (HN) and sulphur mustard (SM) are potent alkylating blister inducing chemical warfare agents. Single 1.0 LD50 dose produced a progressive fall in body weight from second day onwards in all groups of mustard agents exposed animals. Histological examination of spleen, liver skin and kidney revealed significant histopathological lesions in nitrogen mustards and sulphur mustard. These lesions include granulovascular degeneration with perinuclear clumping of the cytoplasm of hepatocytes and renal parenchymal cells. Renal lesions were characterized by congestion and hemorrhage. The maximum toxic manifestation were noted in spleen and skin of HN-3 exposed mice while sulphur mustard reported maximum toxicity in liver and kidneys. The study suggests both nitrogen mustards and sulphur mustard to be extremely toxic by percutaneous route based on histopathological observation and can contributed to earlier reported free radical generation by these toxicants.

Brain tissue oxygen tension is more indicative of oxygen diffusion than oxygen delivery and metabolism in patients with traumatic brain injury.

PubMed

Rosenthal, Guy; Hemphill, J Claude; Sorani, Marco; Martin, Christine; Morabito, Diane; Obrist, Walter D; Manley, Geoffrey T

2008-06-01

Despite the growing clinical use of brain tissue oxygen monitoring, the specific determinants of low brain tissue oxygen tension (P(bt)O2) following severe traumatic brain injury (TBI) remain poorly defined. The objective of this study was to evaluate whether P(bt)O2 more closely reflects variables related to cerebral oxygen diffusion or reflects cerebral oxygen delivery and metabolism. Prospective observational study. Level I trauma center. Fourteen TBI patients with advanced neuromonitoring underwent an oxygen challenge (increase in FiO2 to 1.0) to assess tissue oxygen reactivity, pressure challenge (increase in mean arterial pressure) to assess autoregulation, and CO2 challenge (hyperventilation) to assess cerebral vasoreactivity. None. P(bt)O2 was measured directly with a parenchymal probe in the least-injured hemisphere. Local cerebral blood flow (CBF) was measured with a parenchymal thermal diffusion probe. Cerebral venous blood gases were drawn from a jugular bulb venous catheter. We performed 119 measurements of PaO2, arterial oxygen content (CaO2), jugular bulb venous oxygen tension (PVO2), venous oxygen content (CVO2), arteriovenous oxygen content difference (AVDO2), and local cerebral metabolic rate of oxygen (locCMRO2). In multivariable analysis adjusting for various variables of cerebral oxygen delivery and metabolism, the only statistically significant relationship was that between P(bt)O2 and the product of CBF and cerebral arteriovenous oxygen tension difference (AVTO2), suggesting a strong association between brain tissue oxygen tension and diffusion of dissolved plasma oxygen across the blood-brain barrier. Measurements of P(bt)O2 represent the product of CBF and the cerebral AVTO2 rather than a direct measurement of total oxygen delivery or cerebral oxygen metabolism. This improved understanding of the cerebral physiology of P(bt)O2 should enhance the clinical utility of brain tissue oxygen monitoring in patients with TBI.

[Contralateral hepatic hypertrophy following unilateral yttrium-90 radioembolization : Implications for liver surgery].

PubMed

Garlipp, B; Seidensticker, M; Jechorek, D; Ptok, H; Bruns, C J; Ricke, J

2016-05-01

Preservation of an adequate future liver remnant (FLR) is the principal limitation to liver surgery in patients with primary or secondary liver malignancies. Hence, methods to increase the volume of the FLR in preparation for liver resection are gaining in importance. In addition to the traditional methods for induction of FLR hypertrophy, such as portal vein embolization (PVE) or portal vein ligation (PVL) with or without parenchymal dissection (ALPPS, in situ split), radioembolization (RE) using yttrium-90 microspheres also leads to a volume increase of non-embolized liver parenchyma. This review outlines its potential role as an alternative procedure for induction of liver hypertrophy. Synopsis and critical discussion of the available literature on the mechanisms of induction of liver hypertrophy, the advantages and drawbacks of the traditional methods, and current research on volume changes associated with RE as well as their implications for possible clinical use in preparation for liver surgery. Both PVE and PVL can achieve a substantial contralateral volume gain of up to 70 %. The development of contralateral hypertrophy can be accelerated by dissecting the liver parenchyma along the intended plane of resection in addition to PVL (in situ split). Compared to these methods, RE achieves less contralateral liver hypertrophy; however, this effect should not be disregarded as RE provides effective treatment of ipsilateral liver tumors along with induction of hypertrophy and may be associated with a reduced risk of tumor progression compared to PVE and PVL. The available data suggest that RE can complement the armamentarium of methods for induction of FLR hypertrophy in specific situations. Further studies are needed to establish its definitive role for this indication and are in preparation.

Alterations of parenchymal microstructure, neuronal connectivity and cerebrovascular resistance at adolescence following mild to moderate traumatic brain injury in early development.

PubMed

Parent, Maxime; Li, Ying; Santhakumar, Vijayalakshmi; Hyder, Fahmeed; Sanganahalli, Basavaraju G; Kannurpatti, Sridhar

2018-06-01

TBI is a leading cause of morbidity in children. To investigate outcome of early developmental TBI during adolescence, a rat model of fluid percussion injury was developed, where previous work reported deficits in sensorimotor behavior and cortical blood flow at adolescence. 1 Based on the non-localized outcome, we hypothesized that multiple neurophysiological components of brain function, namely neuronal connectivity, synapse/axonal microstructural integrity and neurovascular function are altered and magnetic resonance imaging (MRI) methods could be used to determine regional alterations. Adolescent outcomes of developmental TBI were studied 2-months after injury, using functional MRI (fMRI) and Diffusion Tensor Imaging (DTI). fMRI based resting state functional connectivity (RSFC), representing neural connectivity, was significantly altered between sham and TBI. RSFC strength decreased in the cortex, hippocampus and thalamus accompanied by decrease in the spatial extent of their corresponding RSFC networks and inter-hemispheric asymmetry. Cerebrovascular reactivity to arterial CO2 changes diminished after TBI across both hemispheres, with a more pronounced decrease in the ipsilateral hippocampus, thalamus and motor cortex. DTI measures of fractional anisotropy (FA) and apparent diffusion coefficient (ADC), reporting on axonal and microstructural integrity of the brain, indicated similar inter-hemispheric asymmetry, with highest change in the ipsilateral hippocampus and regions adjoining the ipsilateral thalamus, hypothalamus and amygdala. TBI-induced corpus callosal microstructural alterations indicated measurable changes in inter-hemispheric structural connectivity. Hippocampus, thalamus and select cortical regions were most consistently affected in multiple imaging markers. The multi-modal MRI results demonstrate cortical and subcortical alterations in neural connectivity, cerebrovascular resistance and parenchymal microstructure in the adolescent brain, indicating the highly diffuse and persistent nature of the lateral fluid percussion TBI early in development.

Effect of the herbal medicine Dai-kenchu-to for serum ammonia in hepatectomized patients.

PubMed

Kaiho, Takashi; Tanaka, Toshikazu; Tsuchiya, Shunichi; Yanagisawa, Shnji; Takeuchi, Osamu; Miura, Masami; Saigusa, Naoki; Miyazaki, Masaru

2005-01-01

Prolonged paralytic ileus occurring in hepatectomized patients may induce hyperammonemia or bacterial translocation, which injures the remnant liver function and sometimes causes post-resection liver failure. We examined the effectiveness of the herbal medicine, Dai-kenchu-to (DKT), on postoperative serum ammonia levels in patients with liver resection and compared it with lactulose. Patients with liver resection were divided into three groups. Lactulose group (n=31), 16g of lactulose was administered orally three times a day from the first postoperative day. DKT group (n=27), 5g of DKT was administered in the same fashion. Control group (n=26), neither lactulose nor DKT was administered. In all three groups, 16g of lactulose was administered three times a day for three days preoperatively. There was no significant difference among the groups in age, gender and preoperative hepatic functional values, such as ICG-R15 or galactose tolerance test. There was also no difference in parenchymal hepatic resection rate, operative time and amount of intraoperative bleeding volume. Postoperative serum ammonia levels were significantly lower in the DKT group than control and lactulose groups. Instances of delayed flatulence and occurrence of diarrhea were also fewer in the DKT group. DKT may become a more effective and safe agent than lactulose in postoperative management of liver resection.

Iron Overload and Heart Fibrosis in Mice Deficient for Both β2-Microglobulin and Rag1

PubMed Central

Santos, Manuela M.; de Sousa, Maria; Rademakers, Luke H. P. M.; Clevers, Hans; Marx, J. J. M.; Schilham, Marco W.

2000-01-01

Genetic causes of hereditary hemochromatosis (HH) include mutations in the HFE gene, a β2-microglobulin (β2m)-associated major histocompatibility complex class I-like protein. Accordingly, mutant β2m−/− mice have increased intestinal iron absorption and develop parenchymal iron overload in the liver. In humans, other genetic and environmental factors have been suggested to influence the pathology and severity of HH. Previously, an association has been reported between low numbers of lymphocytes and the severity of clinical expression of the iron overload in HH. In the present study, the effect of a total absence of lymphocytes on iron overload was investigated by crossing β2m−/− mice (which develop iron overload resembling human disease) with mice deficient in recombinase activator gene 1 (Rag1), which is required for normal B and T lymphocyte development. Iron overload was more severe in β2mRag1 double-deficient mice than in each of the single deficient mice, with iron accumulation in parenchymal cells of the liver, in acinar cells of the pancreas, and in heart myocytes. With increasing age β2mRag1−/− mice develop extensive heart fibrosis, which could be prevented by reconstitution with normal hematopoietic cells. Thus, the development of iron-mediated cellular damage is substantially enhanced when a Rag1 mutation, which causes a lack of mature lymphocytes, is introduced into β2m−/− mice. Mice deficient in β2m and Rag1 thus offer a new experimental model of iron-related cardiomyopathy. PMID:11106561

Quantitative MRI of kidneys in renal disease.

PubMed

Kline, Timothy L; Edwards, Marie E; Garg, Ishan; Irazabal, Maria V; Korfiatis, Panagiotis; Harris, Peter C; King, Bernard F; Torres, Vicente E; Venkatesh, Sudhakar K; Erickson, Bradley J

2018-03-01

To evaluate the reproducibility and utility of quantitative magnetic resonance imaging (MRI) sequences for the assessment of kidneys in young adults with normal renal function (eGFR ranged from 90 to 130 mL/min/1.73 m 2 ) and patients with early renal disease (autosomal dominant polycystic kidney disease). This prospective case-control study was performed on ten normal young adults (18-30 years old) and ten age- and sex-matched patients with early renal parenchymal disease (autosomal dominant polycystic kidney disease). All subjects underwent a comprehensive kidney MRI protocol, including qualitative imaging: T1w, T2w, FIESTA, and quantitative imaging: 2D cine phase contrast of the renal arteries, and parenchymal diffusion weighted imaging (DWI), magnetization transfer imaging (MTI), blood oxygen level dependent (BOLD) imaging, and magnetic resonance elastography (MRE). The normal controls were imaged on two separate occasions ≥24 h apart (range 24-210 h) to assess reproducibility of the measurements. Quantitative MR imaging sequences were found to be reproducible. The mean ± SD absolute percent difference between quantitative parameters measured ≥24 h apart were: MTI-derived ratio = 4.5 ± 3.6%, DWI-derived apparent diffusion coefficient (ADC) = 6.5 ± 3.4%, BOLD-derived R2* = 7.4 ± 5.9%, and MRE-derived tissue stiffness = 7.6 ± 3.3%. Compared with controls, the ADPKD patient's non-cystic renal parenchyma (NCRP) had statistically significant differences with regard to quantitative parenchymal measures: lower MTI percent ratios (16.3 ± 4.4 vs. 23.8 ± 1.2, p < 0.05), higher ADCs (2.46 ± 0.20 vs. 2.18 ± 0.10 × 10 -3  mm 2 /s, p < 0.05), lower R2*s (14.9 ± 1.7 vs. 18.1 ± 1.6 s -1 , p < 0.05), and lower tissue stiffness (3.2 ± 0.3 vs. 3.8 ± 0.5 kPa, p < 0.05). Excellent reproducibility of the quantitative measurements was obtained in all cases. Significantly different quantitative MR parenchymal measurement parameters between ADPKD patients and normal controls were obtained by MT, DWI, BOLD, and MRE indicating the potential for detecting and following renal disease at an earlier stage than the conventional qualitative imaging techniques.

Fibrinolytic preflush upon liver retrieval from non-heart beating donors to enhance postpreservation viability and energetic recovery upon reperfusion.

PubMed

Minor, T; Hachenberg, A; Tolba, R; Pauleit, D; Akbar, S

2001-06-27

Our objective was to evaluate graft equilibration with high viscosity (University of Wisconsin solution [UW]) or low viscosity (Bretschneider's histidine-tryptophan-ketoglutarate [HTK]) during liver procurement from non-heart beating donors (NHBD) and the potential impact of a preceding fibrinolysis with streptokinase on postpreservation viability. After 60 min of cardiac arrest, rat livers were perfused by gravity (60 cm H2O) via the portal vein with either 60 ml of HTK, 20 ml of UW, or 20 ml of Ringer's solution (22 degrees C including 7500U of streptokinase) and, subsequently, 20 ml of UW. After 24 h of storage at 4 degrees C, viability of the livers was assessed upon isolated reperfusion in vitro. Magnetic resonance imaging revealed severe perfusion deficits, which were mildly attenuated with HTK, upon flush-out with UW. After preflush with streptokinase, a mostly homogenous distribution of the preservation solution was observed throughout the liver tissue. The choice of the flush-out solution (UW or HTK) had no influence on parenchymal enzyme leakage, hepatic bile production, or tissue levels of ATP after reperfusion of the livers. Fibrinolytic preflush, however, resulted in a relevant and significant improvement of structural integrity as well as functional and metabolic recovery. Compromised vascular tissue perfusion upon organ harvest in NHBD triggers graft dysfunction after cold storage and can easily be circumvented by temporary fibrinolysis before graft retrieval.

Tumour necrosis factor α (TNF)–TNF receptor 1-inducible cytoprotective proteins in the mouse liver: relevance of suppressors of cytokine signalling

PubMed Central

Sass, Gabriele; Shembade, Noula D.; Tiegs, Gisa

2004-01-01

TNF (tumour necrosis factor α) induces tolerance towards itself in experimental liver injury. Tolerance induction has been shown to be dependent on TNFR1 (TNF receptor 1) signalling, but mechanisms and mediators of TNF-induced hepatic tolerance are unknown. We investigated the TNF-inducible gene-expression profile in livers of TNFR2−/− mice, using cDNA array technology. We found that, out of 793 investigated genes involved in inflammation, cell cycle and signal transduction, 282 were expressed in the mouse liver in response to TNF via TNFR1. Among those, expression of 78 genes was induced, while expression of 60 genes was reduced. We investigated further the cellular expression of the 27 most prominently induced genes, and found that 20 of these genes were up-regulated directly in parenchymal liver cells, representing potentially protective proteins and possible mediators of TNF tolerance. In vitro experiments revealed that overexpression of SOCS1 (silencer of cytokine signalling 1), a member of the SOCS family of proteins, as well as of HO-1 (haem oxygenase-1), but not of SOCS2 or SOCS3, protected isolated primary mouse hepatocytes from TNF-induced apoptosis. The identification of protective genes in hepatocytes is the prerequisite for future development of gene therapies for immune-mediated liver diseases. PMID:15554901

Receptor-mediated transfer of pSV2CAT DNA to mouse liver cells using asialofetuin-labeled liposomes.

PubMed

Hara, T; Aramaki, Y; Takada, S; Koike, K; Tsuchiya, S

1995-12-01

Asialofetuin-labeled liposomes (AF-liposomes) were developed as a nonviral vector having high transfection activity for receptor-mediated gene transfer to hepatocytes by systemic administration. Initially, the majority of pSV2CAT, a chloramphenicol acetyltransferase (CAT) gene expression plasmid, was associated with AF-liposomes (AF-liposome-pSV2CAT), and they were injected into the portal vein of an adult mouse. Significantly high CAT activity was observed in the liver. The CAT activity in the liver was further increased two-fold by using AF-liposomes completely encapsulating pSV2CAT. Nonlabeled control liposomes, on the other hand, showed lower CAT activity in the liver than in the spleen or lung. The level of CAT mRNA reflected the CAT activity obtained by each liposome preparation in each tissue. Immunohistochemical staining showed that CAT was produced in a large number of parenchymal cells localizing in the periportal area. The plasmid encapsulated in the internal aqueous layer of the liposomes was effectively protected from environmental degradation. Thus, by administration into the blood circulation, AF-liposomes would be successfully incorporated into hepatocytes through receptor-mediated endocytosis, and the encapsulated plasmid would be transferred to the intracellular pathway.

Type 1 neurofibromatosis and pulmonary hypertension: a report of two cases and a review

PubMed Central

Malviya, Amit; Mishra, Sundeep; Kothari, Shyam S

2012-01-01

Pulmonary hypertension in type 1 neurofibromatosis is not well known and was previously attributed to diffuse fibrosing alveolitis and parenchymal tumours. More recently, cases of severe pulmonary hypertension due to pulmonary vasculopathy have been described. Involvement of vascular beds, both large and medium calibre vessels, but not pulmonary vasculature, in type 1 neurofibromatosis is well known. The authors describe two such cases and briefly review the literature. Pulmonary arterial hypertension in neurofibromatosis warrants further studies. PMID:27326022

Hepatic reaction dose for parenchymal changes on Gd-EOB-DTPA-enhanced magnetic resonance images after stereotactic body radiation therapy for hepatocellular carcinoma.

PubMed

Jung, Jinhong; Yoon, Sang Min; Cho, Byungchul; Choi, Young Eun; Kwak, Jungwon; Kim, So Yeon; Lee, Sang-Wook; Ahn, Seung Do; Choi, Eun Kyung; Kim, Jong Hoon

2016-02-01

The present study evaluated the threshold dose for hepatic parenchymal changes on gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance (MR) images after stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC). Twenty patients with available data of follow-up MR images acquired 2-4 months after completion of SBRT were selected among the registered patients. SBRT was performed using multiple coplanar and non-coplanar beams with energies of 6 or 15 MV. All patients were treated with doses of 45 Gy administered in three fractions over 3 consecutive days. For image registration between planning computed tomography (CT) and MR images, landmark-based rigid body registration was performed using MIM software. Seventeen patients were included in the analysis. The median discrepancies between planning CT and MR images in the left-right, anterior-posterior and superior-inferior directions were 1.38 mm, 1.24 mm and 1.72 mm, respectively. The median D50 value for the defect in the hepatobiliary phase of Gd-EOB-DTPA-enhanced MR images after SBRT was 19.8 Gy (range, 14.2-28.7 Gy), with R(2) values ranging from 0.76 to 0.99. The threshold dose for parenchymal changes in the hepatobiliary phase of Gd-EOB-DTPA-enhanced MR images performed 2-4 months after 45 Gy of SBRT in three fractions was approximately 20 Gy. Our results provide the basis for further research on the functional loss of liver parenchyma after SBRT. © 2015 The Royal Australian and New Zealand College of Radiologists.

Gut Microbiota and the Liver: A Tale of 2 Cities: A Narrative View in 2 Acts.

PubMed

Koch, Maurizio

Microbes are mostly important for the digestion of food, the absorption of some micronutrients, and the production of vitamins. The microbiota stimulates lymphoid structures in the gastrointestinal mucosa and decrease pathogens by competing for nutrients and space. Bacterial translocation is defined as the escape of gut bacteria and their products through the intestinal mucosa to the outside of the intestine as portovenous or systemic circulation. This is induced by a leaky gut barrier. There is evidence for a role of intestinal permeability in the pathogenesis of nonalcoholic fatty liver disease. In the liver, bacterial products can bind to their specific pathogen recognition receptors on parenchymal and nonparenchymal cells, producing an inflammatory response and enhancing disease progression. When binding, bacterial products bind to their receptors, initiating intracellular signalling and inducing an inflammatory cascade, thus accelerating liver cell damage and fibrosis. However, the liver can also increase gut permeability, producing proinflammatory cytokines, and reversing them into the blood stream. Modification of the gut microbiota could lead to benefit in patients with liver disease. Nonabsorbable antibiotics (rifaximin) prevent and relieve overt encephalopathy. Probiotics alone are not capable of turning back overt encephalopathy, but could prevent its development. There is some evidence that probiotics could relent the progression of nonalcoholic liver disease, and possibly reverse steatosis. Antibiotics, such as fluoroquinolones, reduce the risk of development of the first episode of spontaneous bacterial peritonitis and mortality in cirrhotic patients.

Diffusion MRI with Semi-Automated Segmentation Can Serve as a Restricted Predictive Biomarker of the Therapeutic Response of Liver Metastasis

PubMed Central

Stephen, Renu M.; Jha, Abhinav K.; Roe, Denise J.; Trouard, Theodore P.; Galons, Jean-Philippe; Kupinski, Matthew A.; Frey, Georgette; Cui, Haiyan; Squire, Scott; Pagel, Mark D.; Rodriguez, Jeffrey J.; Gillies, Robert J.; Stopeck, Alison T.

2015-01-01

Purpose To assess the value of semi-automated segmentation applied to diffusion MRI for predicting the therapeutic response of liver metastasis. Methods Conventional diffusion weighted magnetic resonance imaging (MRI) was performed using b-values of 0, 150, 300 and 450 s/mm2 at baseline and days 4, 11 and 39 following initiation of a new chemotherapy regimen in a pilot study with 18 women with 37 liver metastases from primary breast cancer. A semi-automated segmentation approach was used to identify liver metastases. Linear regression analysis was used to assess the relationship between baseline values of the apparent diffusion coefficient (ADC) and change in tumor size by day 39. Results A semi-automated segmentation scheme was critical for obtaining the most reliable ADC measurements. A statistically significant relationship between baseline ADC values and change in tumor size at day 39 was observed for minimally treated patients with metastatic liver lesions measuring 2–5 cm in size (p = 0.002), but not for heavily treated patients with the same tumor size range (p = 0.29), or for tumors of smaller or larger sizes. ROC analysis identified a baseline threshold ADC value of 1.33 μm2/ms as 75% sensitive and 83% specific for identifying non-responding metastases in minimally treated patients with 2–5 cm liver lesions. Conclusion Quantitative imaging can substantially benefit from a semi-automated segmentation scheme. Quantitative diffusion MRI results can be predictive of therapeutic outcome in selected patients with liver metastases, but not for all liver metastases, and therefore should be considered to be a restricted biomarker. PMID:26284600

Diffusion MRI with Semi-Automated Segmentation Can Serve as a Restricted Predictive Biomarker of the Therapeutic Response of Liver Metastasis.

PubMed

Stephen, Renu M; Jha, Abhinav K; Roe, Denise J; Trouard, Theodore P; Galons, Jean-Philippe; Kupinski, Matthew A; Frey, Georgette; Cui, Haiyan; Squire, Scott; Pagel, Mark D; Rodriguez, Jeffrey J; Gillies, Robert J; Stopeck, Alison T

2015-12-01

To assess the value of semi-automated segmentation applied to diffusion MRI for predicting the therapeutic response of liver metastasis. Conventional diffusion weighted magnetic resonance imaging (MRI) was performed using b-values of 0, 150, 300 and 450s/mm(2) at baseline and days 4, 11 and 39 following initiation of a new chemotherapy regimen in a pilot study with 18 women with 37 liver metastases from primary breast cancer. A semi-automated segmentation approach was used to identify liver metastases. Linear regression analysis was used to assess the relationship between baseline values of the apparent diffusion coefficient (ADC) and change in tumor size by day 39. A semi-automated segmentation scheme was critical for obtaining the most reliable ADC measurements. A statistically significant relationship between baseline ADC values and change in tumor size at day 39 was observed for minimally treated patients with metastatic liver lesions measuring 2-5cm in size (p=0.002), but not for heavily treated patients with the same tumor size range (p=0.29), or for tumors of smaller or larger sizes. ROC analysis identified a baseline threshold ADC value of 1.33μm(2)/ms as 75% sensitive and 83% specific for identifying non-responding metastases in minimally treated patients with 2-5cm liver lesions. Quantitative imaging can substantially benefit from a semi-automated segmentation scheme. Quantitative diffusion MRI results can be predictive of therapeutic outcome in selected patients with liver metastases, but not for all liver metastases, and therefore should be considered to be a restricted biomarker. Copyright © 2015 Elsevier Inc. All rights reserved.

[Circulating endothelial cells--markers of blood vessel lesions in patients with diffuse liver disease].

PubMed

Dynnik, O B

2006-01-01

The increased level of the circulating endothelial cells (CEC) is in direct dependance with a degree of an endothelial trauma. We defined CEC in blood (cells x 104/L) of 67 adults and children with acute and chronic viral hepatitis (A and B) and healthy volontiars. The author obtained reliable results of increased CEC in all groups consisting of patients with diffuse liver deseases (17,4+/-6,5 and 19,8+/-8,4) in comparison with control groups (3,8+/-1,9 and 3,8+/-1,2) thus CEC can be of practical value as a marker of microvessel lesions of the liver. Endotheliocytemia testifies to be a factor during endothelial trauma in pathogenesis of diffuse liver disease.

Dysregulation of autophagy in rat liver with mitochondrial DNA depletion induced by the nucleoside analogue zidovudine.

PubMed

Santos-Llamas, Ana; Monte, Maria J; Marin, Jose J G; Perez, Maria J

2018-03-28

The nucleoside reverse transcriptase inhibitor zidovudine (AZT), used in HIV infection treatment, induces mitochondrial DNA (mtDNA) depletion. A cause-effect relationship between mtDNA status alterations and autophagy has been reported. Both events are common in several liver diseases, including hepatocellular carcinoma. Here, we have studied autophagy activation in rat liver with mtDNA depletion induced by AZT administration in drinking water for 35 days. AZT at a concentration of 1 mg/ml, but not 0.5 mg/ml in the drinking water, decreased mtDNA levels in rat liver and extrahepatic tissues. In liver, mtDNA-encoded cytochrome c oxidase 1 protein levels were decreased. Although serum biomarkers of liver and kidney toxicity remained unaltered, β-hydroxybutyrate levels were increased in liver of AZT-treated rats. Moreover, autophagy was dysregulated at two levels: (i) decreased induction signalling of this process as indicated by increases in autophagy inhibitors activity (AKT/mTOR), and absence of changes (Beclin-1, Atg5, Atg7) or decreases (AMPK/ULK1) in the expression/activity of pro-autophagy proteins; and (ii) reduced autophagosome degradation as indicated by decreases in the lysosome abundance (LAMP2 marker) and the transcription factor TFEB controlling lysosome biogenesis. This resulted in increased autophagosome abundance (LC3-II marker) and accumulation of the protein selectively degraded by autophagy p62, and the transcription factor Nrf2 in liver of AZT-treated rats. Nrf2 was activated as indicated by the up-regulation of antioxidant target genes Nqo1 and Hmox-1. In conclusion, rat liver with AZT-induced mtDNA depletion presented dysregulations in autophagosome formation and degradation balance, which results in accumulation of these structures in parenchymal liver cells, favouring hepatocarcinogenesis.

Extended hepatectomy using the bipolar tissue sealer: an experimental model of small-for-size syndrome in pigs.

PubMed

Athanasiou, Antonios; Kontos, Michael; Pikoulis, Emmanouil; Griniatsos, John; Papalois, Apostolos; Spartalis, Eleftherios; Moris, Demetrios; Felekouras, Evangelos; Liakakos, Theodoros

2016-01-01

After liver transplantation with a small-for-size liver graft or after extensive hepatectomy for liver malignancies or other non malignant conditions with an insufficient liver volume, the survival of patients depends on liver regeneration. This study was carried out in order to create a new porcine model for the study of small-for-size syndrome (SFSS) after extensive hepatectomy. In the present study we used 23 domestic Landrace pigs weighing 28.3±3 kg and aged 19-21 weeks. We describe our detailed surgical procedure for 75% partial hepatectomy a in porcine model, using the saline-coupled bipolar sealing device (Aquamantys®) for hepatectomy. The Aquamantis 2.3 bipolar sealer was connected to the Aquamantis generator and was adjusted to produce 150 watts at a medium flow rate of 20 ml/min. The device temperature was programmed to remain at approximately 100° C and, as a consequence, it produced a tissue ablation without charring. The mean operating time was 153.8 min and the mean blood loss 81.9 ml. The estimated residual liver weight (ERL) was 177 g, whereas the mean proportion of ERL was 24.5%. There was no perioperative mortality. A large animal model, such as pig, is extremely useful in order to reproduce and understand the SFSS. Our simple technique for successful resection of 75% of the liver in pigs, using the Aquamantys system, achieves effective and safe liver parenchymal transection with significant decrease of intraoperative blood loss and can provide useful information for researchers.

Diffuse reflectance spectroscopy of liver tissue

NASA Astrophysics Data System (ADS)

Reistad, Nina; Nilsson, Jan; Vilhelmsson Timmermand, Oskar; Sturesson, Christian; Andersson-Engels, Stefan

2015-06-01

Diffuse reflectance spectroscopy (DRS) with a fiber-optic contact probe is a cost-effective, rapid, and non-invasive optical method used to extract diagnosis information of tissue. By combining commercially available VIS- and NIR-spectrometers with various fiber-optic contact-probes, we have access to the full wavelength range from around 400 to 1600 nm. Using this flexible and portable spectroscopy system, we have acquired ex-vivo DRS-spectra from murine, porcine, and human liver tissue. For extracting the tissue optical properties from the measured spectra, we have employed and compared predictions from two models for light propagation in tissue, diffusion theory model (DT) and Monte Carlo simulations (MC). The focus in this work is on the capacity of this DRS-technique in discriminating metastatic tumor tissue from normal liver tissue as well as in assessing and characterizing damage to non-malignant liver tissue induced by preoperative chemotherapy for colorectal liver metastases.

Multiparametric or practical quantitative liver MRI: towards millisecond, fat fraction, kilopascal and function era.

PubMed

Unal, Emre; Idilman, Ilkay Sedakat; Karçaaltıncaba, Muşturay

2017-02-01

New advances in liver magnetic resonance imaging (MRI) may enable diagnosis of unseen pathologies by conventional techniques. Normal T1 (550-620 ms for 1.5 T and 700-850 ms for 3 T), T2, T2* (>20 ms), T1rho (40-50 ms) mapping, proton density fat fraction (PDFF) (≤5%) and stiffness (2-3kPa) values can enable differentiation of a normal liver from chronic liver and diffuse diseases. Gd-EOB-DTPA can enable assessment of liver function by using postcontrast hepatobiliary phase or T1 reduction rate (normally above 60%). T1 mapping can be important for the assessment of fibrosis, amyloidosis and copper overload. T1rho mapping is promising for the assessment of liver collagen deposition. PDFF can allow objective treatment assessment in NAFLD and NASH patients. T2 and T2* are used for iron overload determination. MR fingerprinting may enable single slice acquisition and easy implementation of multiparametric MRI and follow-up of patients. Areas covered: T1, T2, T2*, PDFF and stiffness, diffusion weighted imaging, intravoxel incoherent motion imaging (ADC, D, D* and f values) and function analysis are reviewed. Expert commentary: Multiparametric MRI can enable biopsyless diagnosis and more objective staging of diffuse liver disease, cirrhosis and predisposing diseases. A comprehensive approach is needed to understand and overcome the effects of iron, fat, fibrosis, edema, inflammation and copper on MR relaxometry values in diffuse liver disease.

Optimization and Clinical Feasibility of Free-breathing Diffusion-weighted Imaging of the Liver: Comparison with Respiratory-Triggered Diffusion-weighted Imaging.

PubMed

Takayama, Yukihisa; Nishie, Akihiro; Asayama, Yoshiki; Ishigami, Kousei; Kakihara, Daisuke; Ushijima, Yasuhiro; Fujita, Nobuhiro; Yoshiura, Takashi; Takemura, Atsushi; Obara, Makoto; Takahara, Taro; Honda, Hiroshi

2015-01-01

We compared the image quality of free-breathing diffusion-weighted imaging (FB-DWI) to that of respiratory-triggered DWI (RT-DWI) after proper optimization. Three healthy subjects were scanned to optimize magnetic resonance (MR) parameters of FB-DWI to improve image quality, including spatial resolution, image noise, and chemical shift artifacts. After this optimization, we scanned 32 patients with liver disease to assess the clinical feasibility of the optimized FB-DWI. Of the 32 patients, 14 had a total of 28 hepatocellular carcinomas (HCCs), four had a total of 15 metastatic liver tumors, and the other 14 had no tumor. Qualitatively, we compared the image quality scores of FB-DWI with those of RT-DWI with the Wilcoxon signed-rank test. Quantitatively, we compared the signal-to-noise ratios (SNRs) of the liver parenchyma, lesion-to-nonlesion contrast-to-noise ratios (CNRs) and apparent diffusion coefficient (ADC) values of the liver parenchyma and liver tumor by the paired t-test. The average scores of image quality for sharpness of liver contour, image noise, and chemical shift artifacts were significantly higher for FB-DWI than RT-DWI (P < 0.05). SNRs, CNRs, and ADC values of the liver parenchyma and tumors did not differ significantly between the 2 DWI methods. Compared with RT-DWI, the optimized FB-DWI provided better spatial resolution, fewer artifacts, and comparable SNRs, lesion-to-nonlesion CNRs, and ADC values.

A Microfabricated Platform for Generating Physiologically-Relevant Hepatocyte Zonation

NASA Astrophysics Data System (ADS)

McCarty, William J.; Usta, O. Berk; Yarmush, Martin L.

2016-05-01

In vitro liver models have been important tools for more than 40 years for academic research and preclinical toxicity screening by the pharmaceutical industry. Hepatocytes, the highly metabolic parenchymal cells of the liver, are efficient at different metabolic chemistries depending on their relative spatial location along the sinusoid from the portal triad to the central vein. Although replicating hepatocyte metabolic zonation is vitally important for physiologically-relevant in vitro liver tissue and organ models, it is most often completely overlooked. Here, we demonstrate the creation of spatially-controlled zonation across multiple hepatocyte metabolism levels through the application of precise concentration gradients of exogenous hormone (insulin and glucagon) and chemical (3-methylcholanthrene) induction agents in a microfluidic device. Observed gradients in glycogen storage via periodic acid-Schiff staining, urea production via carbamoyl phosphatase synthetase I staining, and cell viability after exposure to allyl alcohol and acetaminophen demonstrated the in vitro creation of hepatocyte carbohydrate, nitrogen, alcohol degradation, and drug conjugation metabolic zonation. This type of advanced control system will be crucial for studies evaluating drug metabolism and toxicology using in vitro constructs.

Hepatic parenchymal atrophy induction for intractable segmental bile duct injury after liver resection.

PubMed

Hwang, Shin; Park, Gil-Chun; Ha, Tae-Yong; Ko, Gi-Young; Gwon, Dong-Il; Choi, Young-Il; Song, Gi-Won; Lee, Sung-Gyu

2012-05-01

Liver resection can result in various types of bile duct injuries but their treatment is usually difficult and often leads to intractable clinical course. We present an unusual case of hepatic segment III duct (B3) injury, which occurred after left medial sectionectomy for large hepatocellular carcinoma and was incidentally detected 1 week later due to bile leak. Since the pattern of this B3 injury was not adequate for operative biliary reconstruction, atrophy induction of the involved hepatic parenchyma was attempted. This treatment consisted of embolization of the segment III portal branch to inhibit bile production, induction of heavy adhesion at the bile leak site and clamping of the percutaneous transhepatic biliary drainage (PTBD) tube to accelerate segment III atrophy. This entire procedure, from liver resection to PTBD tube removal took 4 months. This patient has shown no other complication or tumor recurrence for 4 years to date. These findings suggest that percutaneous segmental portal vein embolization, followed by intentional clamping of external biliary drainage, can effectively control intractable bile leak from segmental bile duct injury.

Computer-Aided Characterization and Diagnosis of Diffuse Liver Diseases Based on Ultrasound Imaging: A Review.

PubMed

Bharti, Puja; Mittal, Deepti; Ananthasivan, Rupa

2016-04-19

Diffuse liver diseases, such as hepatitis, fatty liver, and cirrhosis, are becoming a leading cause of fatality and disability all over the world. Early detection and diagnosis of these diseases is extremely important to save lives and improve effectiveness of treatment. Ultrasound imaging, a noninvasive diagnostic technique, is the most commonly used modality for examining liver abnormalities. However, the accuracy of ultrasound-based diagnosis depends highly on expertise of radiologists. Computer-aided diagnosis systems based on ultrasound imaging assist in fast diagnosis, provide a reliable "second opinion" for experts, and act as an effective tool to measure response of treatment on patients undergoing clinical trials. In this review, we first describe appearance of liver abnormalities in ultrasound images and state the practical issues encountered in characterization of diffuse liver diseases that can be addressed by software algorithms. We then discuss computer-aided diagnosis in general with features and classifiers relevant to diffuse liver diseases. In later sections of this paper, we review the published studies and describe the key findings of those studies. A concise tabular summary comparing image database, features extraction, feature selection, and classification algorithms presented in the published studies is also exhibited. Finally, we conclude with a summary of key findings and directions for further improvements in the areas of accuracy and objectiveness of computer-aided diagnosis. © The Author(s) 2016.

Novel algorithm to identify and differentiate specific digital signature of breath sound in patients with diffuse parenchymal lung disease.

PubMed

Bhattacharyya, Parthasarathi; Mondal, Ashok; Dey, Rana; Saha, Dipanjan; Saha, Goutam

2015-05-01

Auscultation is an important part of the clinical examination of different lung diseases. Objective analysis of lung sounds based on underlying characteristics and its subsequent automatic interpretations may help a clinical practice. We collected the breath sounds from 8 normal subjects and 20 diffuse parenchymal lung disease (DPLD) patients using a newly developed instrument and then filtered off the heart sounds using a novel technology. The collected sounds were thereafter analysed digitally on several characteristics as dynamical complexity, texture information and regularity index to find and define their unique digital signatures for differentiating normality and abnormality. For convenience of testing, these characteristic signatures of normal and DPLD lung sounds were transformed into coloured visual representations. The predictive power of these images has been validated by six independent observers that include three physicians. The proposed method gives a classification accuracy of 100% for composite features for both the normal as well as lung sound signals from DPLD patients. When tested by independent observers on the visually transformed images, the positive predictive value to diagnose the normality and DPLD remained 100%. The lung sounds from the normal and DPLD subjects could be differentiated and expressed according to their digital signatures. On visual transformation to coloured images, they retain 100% predictive power. This technique may assist physicians to diagnose DPLD from visual images bearing the digital signature of the condition. © 2015 Asian Pacific Society of Respirology.

Classification of diffuse lung diseases: why and how.

PubMed

Hansell, David M

2013-09-01

The understanding of complex lung diseases, notably the idiopathic interstitial pneumonias and small airways diseases, owes as much to repeated attempts over the years to classify them as to any single conceptual breakthrough. One of the many benefits of a successful classification scheme is that it allows workers, within and between disciplines, to be clear that they are discussing the same disease. This may be of particular importance in the recruitment of individuals for a clinical trial that requires a standardized and homogeneous study population. Different specialties require fundamentally different things from a classification: for epidemiologic studies, a classification that requires categorization of individuals according to histopathologic pattern is not usually practicable. Conversely, a scheme that simply divides diffuse parenchymal disease into inflammatory and noninflammatory categories is unlikely to further the understanding about the pathogenesis of disease. Thus, for some disease groupings, for example, pulmonary vasculopathies, there may be several appropriate classifications, each with its merits and demerits. There has been an interesting shift in the past few years, from the accepted primacy of histopathology as the sole basis on which the classification of parenchymal lung disease has rested, to new ways of considering how these entities relate to each other. Some inventive thinking has resulted in new classifications that undoubtedly benefit patients and clinicians in their endeavor to improve management and outcome. The challenge of understanding the logic behind current classifications and their shortcomings are explored in various examples of lung diseases.

Is the iron regulatory hormone hepcidin a risk factor for alcoholic liver disease?

PubMed Central

Harrison-Findik, Duygu Dee

2009-01-01

Despite heavy consumption over a long period of time, only a small number of alcoholics develop alcoholic liver disease. This alludes to the possibility that other factors, besides alcohol, may be involved in the progression of the disease. Over the years, many such factors have indeed been identified, including iron. Despite being crucial for various important biological processes, iron can also be harmful due to its ability to catalyze Fenton chemistry. Alcohol and iron have been shown to interact synergistically to cause liver injury. Iron-mediated cell signaling has been reported to be involved in the pathogenesis of experimental alcoholic liver disease. Hepcidin is an iron-regulatory hormone synthesized by the liver, which plays a pivotal role in iron homeostasis. Both acute and chronic alcohol exposure suppress hepcidin expression in the liver. The sera of patients with alcoholic liver disease, particularly those exhibiting higher serum iron indices, have also been reported to display reduced prohepcidin levels. Alcohol-mediated oxidative stress is involved in the inhibition of hepcidin promoter activity and transcription in the liver. This in turn leads to an increase in intestinal iron transport and liver iron storage. Hepcidin is expressed primarily in hepatocytes. It is noteworthy that both hepatocytes and Kupffer cells are involved in the progression of alcoholic liver disease. However, the activation of Kupffer cells and TNF-α signaling has been reported not to be involved in the down-regulation of hepcidin expression by alcohol in the liver. Alcohol acts within the parenchymal cells of the liver to suppress the synthesis of hepcidin. Due to its crucial role in the regulation of body iron stores, hepcidin may act as a secondary risk factor in the progression of alcoholic liver disease. The clarification of the mechanisms by which alcohol disrupts iron homeostasis will allow for further understanding of the pathogenesis of alcoholic liver disease. PMID:19291818

Non-operative management versus operative management in high-grade blunt hepatic injury.

PubMed

Cirocchi, Roberto; Trastulli, Stefano; Pressi, Eleonora; Farinella, Eriberto; Avenia, Stefano; Morales Uribe, Carlos Hernando; Botero, Ana Maria; Barrera, Luis M

2015-08-24

Surgery used to be the treatment of choice in cases of blunt hepatic injury, but this approach gradually changed over the last two decades as increasing non-operative management (NOM) of splenic injury led to its use for hepatic injury. The improvement in critical care monitoring and computed tomographic scanning, as well as the more frequent use of interventional radiology techniques, has helped to bring about this change to non-operative management. Liver trauma ranges from a small capsular tear, without parenchymal laceration, to massive parenchymal injury with major hepatic vein/retrohepatic vena cava lesions. In 1994, the Organ Injury Scaling Committee of the American Association for the Surgery of Trauma (AAST) revised the Hepatic Injury Scale to have a range from grade I to VI. Minor injuries (grade I or II) are the most frequent liver injuries (80% to 90% of all cases); severe injuries are grade III-V lesions; grade VI lesions are frequently incompatible with survival. In the medical literature, the majority of patients who have undergone NOM have low-grade liver injuries. The safety of NOM in high-grade liver lesions, AAST grade IV and V, remains a subject of debate as a high incidence of liver and collateral extra-abdominal complications are still described. To assess the effects of non-operative management compared to operative management in high-grade (grade III-V) blunt hepatic injury. The search for studies was run on 14 April 2014. We searched the Cochrane Injuries Group's Specialised Register, The Cochrane Library, Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic+Embase (Ovid), PubMed, ISI WOS (SCI-EXPANDED, SSCI, CPCI-S & CPSI-SSH), clinical trials registries, conference proceedings, and we screened reference lists. All randomised trials that compare non-operative management versus operative management in high-grade blunt hepatic injury. Two authors independently applied the selection criteria to relevant study reports. We used standard methodological procedures as defined by the Cochrane Collaboration. We were unable to find any randomised controlled trials of non-operative management versus operative management in high-grade blunt hepatic injury. In order to further explore the preliminary findings provided by animal models and observational clinical studies that suggests there may be a beneficial effect of non-operative management versus operative management in high-grade blunt hepatic injury, large, high quality randomised trials are needed.

Immune tolerance: what is unique about the liver.

PubMed

Tiegs, Gisa; Lohse, Ansgar W

2010-02-01

The 'liver tolerance effect' mediates local and systemic tolerance to self and foreign antigens and has been attributed to specialized resident cells expressing anti-inflammatory mediators and inhibitory cell surface ligands for T cell activation. Non-parenchymal liver cells responsible for the tolerogenic properties of the liver are the resident dendritic cells (DCs), which comprise myeloid as well as plasmacytoid DCs, liver sinusoidal endothelial cells (LSECs), Kupffer cells (KCs) as well as hepatic stellate cells (HSCs), also known as Ito cells. These cells mediate immunosuppression by production of anti-inflammatory cytokines such as IL-10 and TGFbeta as well as by expression of the negative co-stimulator for T cell activation programmed cell death ligand-1 (PD-L1). An interesting observation in this context is that knockout of IL-10 or PD-L1 (or the receptor PD-1) does not necessarily result in inflammatory liver damage whereas transgenic inhibition of TGFbeta signaling induces liver disease in mice resembling chronic cholangitis. However, depending on the mouse model and on the type of injury, e.g. autoimmune disease, allograft rejection or viral infection, IL-10 or TGFbeta and/or PD-1 as well as cytotoxic T lymphocyte antigen-4 (CTLA-4) contribute to the immunosuppressive mechanisms of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), which seem to be converted in the liver from infiltrating conventional naïve CD4(+) T cells and/or effector CD4(+) T cells to control the disease. Finally, hepatocytes also contribute to the 'liver tolerance effect' by expression of MHC class II molecules, probably low levels of co-stimulatory molecules and high levels of the co-inhibitory molecule PD-L1. Copyright 2009 Elsevier Ltd. All rights reserved.

Fuzzy logic algorithm for quantitative tissue characterization of diffuse liver diseases from ultrasound images.

PubMed

Badawi, A M; Derbala, A S; Youssef, A M

1999-08-01

Computerized ultrasound tissue characterization has become an objective means for diagnosis of liver diseases. It is difficult to differentiate diffuse liver diseases, namely cirrhotic and fatty liver by visual inspection from the ultrasound images. The visual criteria for differentiating diffused diseases are rather confusing and highly dependent upon the sonographer's experience. This often causes a bias effects in the diagnostic procedure and limits its objectivity and reproducibility. Computerized tissue characterization to assist quantitatively the sonographer for the accurate differentiation and to minimize the degree of risk is thus justified. Fuzzy logic has emerged as one of the most active area in classification. In this paper, we present an approach that employs Fuzzy reasoning techniques to automatically differentiate diffuse liver diseases using numerical quantitative features measured from the ultrasound images. Fuzzy rules were generated from over 140 cases consisting of normal, fatty, and cirrhotic livers. The input to the fuzzy system is an eight dimensional vector of feature values: the mean gray level (MGL), the percentile 10%, the contrast (CON), the angular second moment (ASM), the entropy (ENT), the correlation (COR), the attenuation (ATTEN) and the speckle separation. The output of the fuzzy system is one of the three categories: cirrhosis, fatty or normal. The steps done for differentiating the pathologies are data acquisition and feature extraction, dividing the input spaces of the measured quantitative data into fuzzy sets. Based on the expert knowledge, the fuzzy rules are generated and applied using the fuzzy inference procedures to determine the pathology. Different membership functions are developed for the input spaces. This approach has resulted in very good sensitivities and specificity for classifying diffused liver pathologies. This classification technique can be used in the diagnostic process, together with the history information, laboratory, clinical and pathological examinations.

Imaging-based quantification of hepatic fat: methods and clinical applications.

PubMed

Ma, Xiaozhou; Holalkere, Nagaraj-Setty; Kambadakone R, Avinash; Mino-Kenudson, Mari; Hahn, Peter F; Sahani, Dushyant V

2009-01-01

Fatty liver disease comprises a spectrum of conditions (simple hepatic steatosis, steatohepatitis with inflammatory changes, and end-stage liver disease with fibrosis and cirrhosis). Hepatic steatosis is often associated with diabetes and obesity and may be secondary to alcohol and drug use, toxins, viral infections, and metabolic diseases. Detection and quantification of liver fat have many clinical applications, and early recognition is crucial to institute appropriate management and prevent progression. Histopathologic analysis is the reference standard to detect and quantify fat in the liver, but results are vulnerable to sampling error. Moreover, it can cause morbidity and complications and cannot be repeated often enough to monitor treatment response. Imaging can be repeated regularly and allows assessment of the entire liver, thus avoiding sampling error. Selection of appropriate imaging methods demands understanding of their advantages and limitations and the suitable clinical setting. Ultrasonography is effective for detecting moderate or severe fatty infiltration but is limited by lack of interobserver reliability and intraobserver reproducibility. Computed tomography allows quantitative and qualitative evaluation and is generally highly accurate and reliable; however, the results may be confounded by hepatic parenchymal changes due to cirrhosis or depositional diseases. Magnetic resonance (MR) imaging with appropriate sequences (eg, chemical shift techniques) has similarly high sensitivity, and MR spectroscopy provides unique advantages for some applications. However, both are expensive and too complex to be used to monitor steatosis. (c) RSNA, 2009.

Real-time ultrasound imaging of irreversible electroporation in a porcine liver model adequately characterizes the zone of cellular necrosis.

PubMed

Schmidt, Carl R; Shires, Peter; Mootoo, Mary

2012-02-01

  Irreversible electroporation (IRE) is a largely non-thermal method for the ablation of solid tumours. The ability of ultrasound (US) to measure the size of the IRE ablation zone was studied in a porcine liver model.   Three normal pig livers were treated in vivo with a total of 22 ablations using IRE. Ultrasound was used within minutes after ablation and just prior to liver harvest at either 6 h or 24 h after the procedure. The area of cellular necrosis was measured after staining with nitroblue tetrazolium and the percentage of cell death determined by histomorphometry.   Visible changes in the hepatic parenchyma were apparent by US after all 22 ablations using IRE. The mean maximum diameter of the ablation zone measured by US during the procedure was 20.1 ± 2.7 mm. This compared with a mean cellular necrosis zone maximum diameter of 20.3 ± 2.9 mm as measured histologically. The mean percentage of dead cells within the ablation zone was 77% at 6 h and 98% at 24 h after ablation.   Ultrasound is a useful modality for measuring the ablation zone within minutes of applying IRE to normal liver tissue. The area of parenchymal change measured by US correlates with the area of cellular necrosis. © 2011 International Hepato-Pancreato-Biliary Association.

Preservation of Intestinal Structural Integrity by Zinc Is Independent of Metallothionein in Alcohol-Intoxicated Mice

PubMed Central

Lambert, Jason C.; Zhou, Zhanxiang; Wang, Lipeng; Song, Zhenyuan; McClain, Craig J.; Kang, Y. James

2004-01-01

Intestinal-derived endotoxins are importantly involved in alcohol-induced liver injury. Disruption of intestinal barrier function and endotoxemia are common features associated with liver inflammation and injury due to acute ethanol exposure. Zinc has been shown to inhibit acute alcohol-induced liver injury. This study was designed to determine the inhibitory effect of zinc on alcohol-induced endotoxemia and whether the inhibition is mediated by metallothionein (MT) or is independent of MT. MT knockout (MT-KO) mice were administered three oral doses of zinc sulfate (2.5 mg zinc ion/kg body weight) every 12 hours before being administered a single dose of ethanol (6 g/kg body weight) by gavage. Ethanol administration caused liver injury as determined by increased serum transaminases, parenchymal fat accumulation, necrotic foci, and an elevation of tumor necrosis factor (TNF-α). Increased plasma endotoxin levels were detected in ethanol-treated animals whose small intestinal structural integrity was compromised as determined by microscopic examination. Zinc supplementation significantly inhibited acute ethanol-induced liver injury and suppressed hepatic TNF-α production in association with decreased circulating endotoxin levels and a significant protection of small intestine structure. As expected, MT levels remained undetectable in the MT-KO mice under the zinc treatment. These results thus demonstrate that zinc preservation of intestinal structural integrity is associated with suppression of endotoxemia and liver injury induced by acute exposure to ethanol and the zinc protection is independent of MT. PMID:15161632

Pulmonary hypertensive vasculopathy in parenchymal lung diseases and/or hypoxia: Number 1 in the Series "Pathology for the clinician" Edited by Peter Dorfmüller and Alberto Cavazza.

PubMed

Ghigna, Maria Rosa; Mooi, Wolter J; Grünberg, Katrien

2017-06-30

Pulmonary hypertension (PH) with complicating chronic lung diseases and/or hypoxia falls into group 3 of the updated classification of PH. Patients with chronic obstructive lung disease (COPD), diffuse lung disease (such as idiopathic pulmonary fibrosis (IPF)) and with sleep disordered breathing are particularly exposed to the risk of developing PH. Although PH in such a context is usually mild, a minority of patients exhibit severe haemodynamic impairment, defined by a mean pulmonary arterial pressure (mPAP) of ≥35 mmHg or mPAP values ranging between 25 mmHg and 35 mmHg with a low cardiac index (<2 L·min -1 ·m -2 ). The overlap between lung parenchymal disease and PH heavily affects life expectancy in such a patient population and complicates their therapeutic management. In this review we illustrate the pathological features and the underlying pathophysiological mechanisms of pulmonary circulation in chronic lung diseases, with an emphasis on COPD, IPF and obstructive sleep apnoea syndrome. Copyright ©ERS 2017.

Inflammatory cells in minor salivary glands of patients with chronic hepatitis C: immunophenotype, pattern of distribution, and comparison with liver samples.

PubMed

Caldeira, Patrícia Carlos; Oliveira e Silva, Karla Rachel; Vidigal, Paula Vieira Teixeira; Grossmann, Soraya de Mattos Camargo; do Carmo, Maria Auxiliadora Vieira

2014-05-01

To characterize the immunophenotype and the distribution of the inflammatory infiltrate (INF) in salivary glands (SG) of patients with chronic hepatitis C, comparing with laboratorial data (genotype, viral load, METAVIR, and HCV RNA in SG), and liver. INF was classified as diffuse or focal. Immunohistochemistry for CD3, CD20, CD8, CD4, CD57, CD68, and S100 was performed in 61 SG and 59 livers. Diffuse INF was more common in SG than in liver. CD3(+), CD20(+), and CD8(+) were the most frequent cells in both tissues, with few CD57(+), CD68(+), and S100(+) cells. CD4(+) cells were common in liver, but rare in SG. Liver presented higher indexes for all markers, except S100(+) (p<0.05). Higher CD3(+), CD20(+), and CD8(+) (p<0.05) were observed in SG with focal infiltrate than with diffuse infiltrate. In liver, CD20(+) and CD3(+) were higher in focal infiltrate, and CD68(+) in diffuse infiltrate (p<0.05). Comparisons with laboratorial data did not show statistical significance. The INF in SG was mainly composed by T and B lymphocytes, mostly cytotoxic T cells. The glandular INF can present differences in composition according to its distribution. A more intense inflammation was observed in liver, but similar cell types were identified in SG, except for CD4(+). Copyright © 2014 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Traumatic common hepatic artery injury causing isolated right hepatic ischemia due to a left accessory artery. A case report.

PubMed

Fernandes, Eduardo; Pedrazzani, Corrado; Gerena, Marielia; Omi, Ellen

2017-01-01

Hepatic arterial liver flow is renowned for its redundancy. Previous studies have demonstrated that the common hepatic artery is not essential for liver survival. We present a case of a 31year-old involved in a high-speed motor vehicle accident whose liver survived thanks to the presence of an accessory hepatic artery. We present the case of a 31year-old male who sustained a traumatic injury of the proper hepatic artery following a motor vehicle accident. The patient suffered temporary right liver lobe ischemia due to the presence of an accessory left hepatic artery. This resulted in the selective formation of 'biliary lakes' distinctively within the territory of the right hepatic artery supply. Simultaneously the patient developed a pseudo-aneurysm of the proper hepatic artery which required radiology intervention. At the time of pseudo-aneurysm embolisation, a rich network of arterial collaterals had formed between the accessory left hepatic and the inferior phrenic artery. On follow up the biliary lakes to the right lobe had resolved, but a small area at the periphery of the right lobe had encountered atrophy. This case report is an 'in vivo' demonstration of liver resilience to arterial flow re-distribution and demonstrates the ability of the biliary epithelium to recover from and ischemic injury. Parenchymal liver survival is mostly independent from flow within the common hepatic artery. Acute and chronic liver parenchyma changes following interruption of hepatic artery flow can still occur. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

MR elastography in primary sclerosing cholangitis: correlating liver stiffness with bile duct strictures and parenchymal changes.

PubMed

Bookwalter, Candice A; Venkatesh, Sudhakar K; Eaton, John E; Smyrk, Thomas D; Ehman, Richard L

2018-04-07

To determine correlation of liver stiffness measured by MR Elastography (MRE) with biliary abnormalities on MR Cholangiopancreatography (MRCP) and MRI parenchymal features in patients with primary sclerosing cholangitis (PSC). Fifty-five patients with PSC who underwent MRI of the liver with MRCP and MRE were retrospectively evaluated. Two board-certified abdominal radiologists in agreement reviewed the MRI, MRCP, and MRE images. The biliary tree was evaluated for stricture, dilatation, wall enhancement, and thickening at segmental duct, right main duct, left main duct, and common bile duct levels. Liver parenchyma features including signal intensity on T2W and DWI, and hyperenhancement in arterial, portal venous, and delayed phase were evaluated in nine Couinaud liver segments. Atrophy or hypertrophy of segments, cirrhotic morphology, varices, and splenomegaly were scored as present or absent. Regions of interest were placed in each of the nine segments on stiffness maps wherever available and liver stiffness (LS) was recorded. Mean segmental LS, right lobar (V-VIII), left lobar (I-III, and IVA, IVB), and global LS (average of all segments) were calculated. Spearman rank correlation analysis was performed for significant correlation. Features with significant correlation were then analyzed for significant differences in mean LS. Multiple regression analysis of MRI and MRCP features was performed for significant correlation with elevated LS. A total of 439/495 segments were evaluated and 56 segments not included in MRE slices were excluded for correlation analysis. Mean segmental LS correlated with the presence of strictures (r = 0.18, p < 0.001), T2W hyperintensity (r = 0.38, p < 0.001), DWI hyperintensity (r = 0.30, p < 0.001), and hyperenhancement of segment in all three phases. Mean LS of atrophic and hypertrophic segments were significantly higher than normal segments (7.07 ± 3.6 and 6.67 ± 3.26 vs. 5.1 ± 3.6 kPa, p < 0.001). In multiple regression analysis, only the presence of segmental strictures (p < 0.001), T2W hyperintensity (p = 0.01), and segmental hypertrophy (p < 0.001) were significantly associated with elevated segmental LS. Only left ductal stricture correlated with left lobe LS (r = 0.41, p = 0.018). Global LS correlated significantly with CBD stricture (r = 0.31, p = 0.02), number of segmental strictures (r = 0.28, p = 0.04), splenomegaly (r = 0.56, p < 0.001), and varices (r = 0.58, p < 0.001). In PSC, there is low but positive correlation between segmental LS and segmental duct strictures. Segments with increased LS show T2 hyperintensity, DWI hyperintensity, and post-contrast hyperenhancement. Global liver stiffness shows a moderate correlation with number of segmental strictures and significantly correlates with spleen stiffness, splenomegaly, and varices.

Water-jet dissection for parenchymal division during hepatectomy1

PubMed Central

Dixon, Elijah; Sahajpal, Ajay; Cattral, Mark S.; Grant, David R.; Gallinger, Steven; Taylor, Bryce R.; Greig, Paul D.

2006-01-01

Background. High-pressure water-jet dissection was originally developed for industry where ultra-precise cutting and engraving were desirable. This technology has been adapted for medical applications with favorable results, but little is understood about its performance in hepatic resections. Blood loss may be limited by the thin laminar liquid-jet effect that provides precise, controllable, tissue-selective dissection with excellent visualization and minimal trauma to surrounding fibrous structures. Patients and methods. The efficacy of the Water-jet system for hepatic parenchymal dissection was examined in a consecutive case series of 101 hepatic resections (including 22 living donor transplantation resections) performed over 11 months. Perioperative outcomes, including blood loss, transfusion requirements, complications, and length of stay (LOS), were assessed. Results. Three-quarters of the cases were major hepatectomies and 22% were cirrhotic. Malignancy was the most common indication (77%). Median operative time was 289 min. Median estimated blood loss (EBL) was 900 ml for all cases, and only 14% of patients had >2000 ml EBL. Furthermore, EBL was 1000 ml for major resections, 775 ml for living donor resections, 600 ml in cirrhotic patients, and 1950 ml for steatotic livers. In all, 14% of patients received heterologous packed red blood cell (PRBC) transfusions for an average of 0.59 units per case. Median LOS was 7 days. EBL, transfusion requirements, and LOS were slightly increased in the major resection cohort. There was one mortality (1%) overall. These results are equivalent to, or better than, those from our contemporary series of resections performed with ultrasonic dissection. Conclusion. Water-jet dissection minimizes large blood volume loss, requirements for transfusion, and complications. This initial experience suggests that this precision tool is safe and effective for hepatic division, and compares favorably to other established methods for hepatic parenchymal transection. PMID:18333091

Comparison of T2, T1rho, and diffusion metrics in assessment of liver fibrosis in rats.

PubMed

Zhang, Hui; Yang, Qihua; Yu, Taihui; Chen, Xiaodong; Huang, Jingwen; Tan, Cui; Liang, Biling; Guo, Hua

2017-03-01

To evaluate the value of T 2 , T 1 rho, and diffusion metrics in assessment of liver fibrosis in rats. Liver fibrosis in a rat model (n = 72) was induced by injection of carbon tetrachloride (CCl 4 ) at 3T. T 2 , T 1 rho, and diffusion parameters (apparent diffusion coefficient (ADC), D true ) via spin echo (SE) diffusion-weighted imaging (DWI) and stimulated echo acquisition mode (STEAM) DWI with three diffusion times (DT: 80, 106, 186 msec) were obtained in surviving rats with hepatic fibrosis (n = 52) and controls (n = 8). Liver fibrosis stage (F0-F6) was identified based on pathological results using the traditional liver fibrosis staging method for rodents. Nonparametric statistical methods and receiver operating characteristic (ROC) curve analysis were employed to determine the diagnostic accuracy. Mean T 2 , T 1 rho, ADC, and D true with DT = 186 msec correlated with the severity of fibrosis with r = 0.73, 0.83, -0.83, and -0.85 (all P < 0.001), respectively. The average areas under the ROC curve at different stages for T 1 rho and diffusion parameters (DT = 186 msec) were larger than those of T 2 and SE DWI (0.92, 0.92, and 0.92 vs. 0.86, 0.82, and 0.83). The corresponding average sensitivity and specificity for T 1 rho and diffusion parameters with a long DT were larger (89.35 and 88.90, 88.36 and 89.97, 90.16 and 87.13) than T 2 and SE DWI (90.28 and 79.93, 85.30 and 77.64, 78.21 and 82.41). The performances of T 1 rho and D true (DT = 186 msec) were comparable (average AUC: 0.92 and 0.92). Among the evaluated sequences, T 1 rho and STEAM DWI with a long DT may serve as superior imaging biomarkers for assessing liver fibrosis and monitoring disease severity. 1 J. Magn. Reson. Imaging 2017;45:741-750. © 2016 International Society for Magnetic Resonance in Medicine.

ELECTRON MICROSCOPIC STUDY OF CHANGES IN LIVER CELLS AFTER COMBINED TREATMENT WITH CARBON TETRACHLORIDE AND X RAYS (in Italian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Longostrevi, G.P.; Lombardi, L.

Adult rats were treated with low doses of both CCl/sub 4/ and x rays, shown previously not to produce ultrastructural changes in liver parenchymal cells when given separately. The rats were exposed to a single, whole-body, 200- r dose of 160-kv x rays and then injected subcutaneously with 0.1 ml of a 30% solution of CCl/sub 4/ in peanut oil, corresponding to 0.15 ml CCl/sub 4/ per 100 g body wt. When the rats were sacrificed three days later, all showed pronounced changes in mitochondria and endoplasmic reticulum of liver cells, which were not seen following either individual treatment. Themore » mitochondria showed marked swelling, detachment of cristae, and accumulation of granular material in their interior. Endoplasmic reticulum underwent dilatation and detachment of normally adherent ribonucleoprotein granules. A different picture was observed following injection of toxic doses of CCl/sub 4/ (0.5 m1/100 g body wt). This produced marked disruption and ballooning of mitochondria and endoplasmic reticulum. The results indicate that subliminal doses of CCl/sub 4/ and x rays, presumably acting by different mechanisms, synergistically damage the liver cell, particularly its mitochondria. (BBB)« less

MDCT diagnosis of post-traumatic hepatic arterio-portal fistulas.

PubMed

Nguyen, Cuong T; Nguyen, Coung; Saksobhavivat, Nitima; Saksobahavivat, Nitima; Shanmuganathan, Kathirkamanathan; Steenburg, Scott D; Steenburg, Scott; Moeslein, Fred M; Moeslein, Fred; Mirvis, Stuart E; Chiu, William

2013-06-01

The purpose of this study is to evaluate the performance of multidetector computed tomography (MDCT) in diagnosing arterioportal fistulas (APF) in high-grade liver injury. A retrospective analysis of catheter-based hepatic angiograms performed for major penetrating and blunt liver injuries identified 11 patients with APFs. Using the trauma registry, two additional demographically matched groups with and without liver injury were formed. A randomized qualitative consensus review of 33 MDCTs was performed by three trauma radiologists for the following MDCT findings of APF: transient hepatic parenchymal attenuation differences (THPAD), early increased attenuation of a peripheral or central portal vein compared with the main portal vein, and the "double-barrel" or "rail tract" signs. THPAD was the most sensitive finding and also had a high specificity for diagnosing APF. Both the early increased attenuation of a peripheral or central portal vein compared with the main portal vein and the double-barrel or rail tract signs had a100% specificity and a sensitivity of 64% and 36%, respectively. Measurement of differences in attenuation values between the APF and the contralateral central portal vein was most sensitive and specific in diagnosing APF. Traumatic APF of the liver can be optimally diagnosed with arterial phase imaging of solid organ using MDCT.

Volume change and liver parenchymal signal intensity in Gd-EOB-DTPA-enhanced magnetic resonance imaging after portal vein embolization prior to hepatectomy.

PubMed

Akiba, Ayako; Murata, Satoru; Mine, Takahiko; Onozawa, Shiro; Sekine, Tetsuro; Amano, Yasuo; Kawano, Youichi; Uchida, Eiji; Kumita, Shin-ichiro

2014-01-01

To investigate the liver volume change and the potential of early evaluation by contrast-enhanced magnetic resonance imaging (MRI) using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) after portal vein embolization (PVE). Retrospective evaluations of computed tomography (CT) volumetry of total liver and nonembolized areas were performed before and 3 weeks after PVE in 37 cases. The percentage of future liver remnant (%FLR) and the change ratio of %FLR (%FLR ratio) were calculated. Prospective evaluation of signal intensities (SIs) was performed to estimate the role of Gd-EOB-DTPA-enhanced MRI as a predictor of hypertrophy in 16 cases. The SI contrast between embolized and nonembolized areas was calculated 1 week after PVE. The change in SI contrast before and after PVE (SI ratio) was also calculated in 11 cases. %FLR ratio significantly increased, and SI ratio significantly decreased (both P < 0.01). There were significant negative correlations between %FLR and SI contrast and between %FLR and SI ratio (both P < 0.01). Hypertrophy in the nonembolized area after PVE was indicated by CT volumetry, and measurement of SI contrast and SI ratio in Gd-EOB-DTPA-enhanced MRI early after PVE may be useful to predict the potential for hepatic hypertrophy.

Immunohistochemical study of retinol-binding protein in livers of polar bears (Thalarctos maritimus).

PubMed

Heier, A; Gröne, A; Völlm, J; Kübber-Heiss, A; Bacciarini, L N

2003-03-01

Liver tumors of unknown cause have frequently been described in polar bears. Concurrent decrease of vitamin A levels and chronic liver disease are associated with hepatic carcinogenesis in humans. More than 90% of the body's vitamin A is stored in the liver, where it is bound to an intracellular retinol-binding protein (RBP). Therefore, in this retrospective study, RBP was assessed by immunohistochemistry in liver sections of 11 polar bears. Two of these polar bears had hepatocellular carcinoma, four showed other chronic liver changes, and five had normal livers. In normal livers, the cytoplasm stained diffusely positive with intensely staining cytoplasmic granules. RBP staining was evaluated and the abundance of diffuse cytoplasmic staining and intracytoplasmic large granules was determined. All cases with pathologic liver changes had markedly decreased staining intensities for RBP compared with normal livers. The findings of this study suggest that in polar bears, as in humans, vitamin A metabolism may play a role in hepatic carcinogenesis.

Optical spectroscopy for differentiation of liver tissue under distinct stages of fibrosis: an ex vivo study

NASA Astrophysics Data System (ADS)

Fabila, D. A.; Hernández, L. F.; de la Rosa, J.; Stolik, S.; Arroyo-Camarena, U. D.; López-Vancell, M. D.; Escobedo, G.

2013-11-01

Liver fibrosis is the decisive step towards the development of cirrhosis; its early detection affects crucially the diagnosis of liver disease, its prognosis and therapeutic decision making. Nowadays, several techniques are employed to this task. However, they have the limitation in estimating different stages of the pathology. In this paper we present a preliminary study to evaluate if optical spectroscopy can be employed as an auxiliary tool of diagnosis of biopsies of human liver tissue to differentiate the fibrosis stages. Ex vivo fluorescence and diffuse reflectance spectra were acquired from biopsies using a portable fiber-optic system. Empirical discrimination algorithms based on fluorescence intensity ratio at 500 nm and 680 nm as well as diffuse reflectance intensity at 650 nm were developed. Sensitivity and specificity of around 80% and 85% were respectively achieved. The obtained results show that combined use of fluorescence and diffuse reflectance spectroscopy could represent a novel and useful tool in the early evaluation of liver fibrosis.

Spatially constrained incoherent motion method improves diffusion-weighted MRI signal decay analysis in the liver and spleen

PubMed Central

Taimouri, Vahid; Afacan, Onur; Perez-Rossello, Jeannette M.; Callahan, Michael J.; Mulkern, Robert V.; Warfield, Simon K.; Freiman, Moti

2015-01-01

Purpose: To evaluate the effect of the spatially constrained incoherent motion (SCIM) method on improving the precision and robustness of fast and slow diffusion parameter estimates from diffusion-weighted MRI in liver and spleen in comparison to the independent voxel-wise intravoxel incoherent motion (IVIM) model. Methods: We collected diffusion-weighted MRI (DW-MRI) data of 29 subjects (5 healthy subjects and 24 patients with Crohn’s disease in the ileum). We evaluated parameters estimates’ robustness against different combinations of b-values (i.e., 4 b-values and 7 b-values) by comparing the variance of the estimates obtained with the SCIM and the independent voxel-wise IVIM model. We also evaluated the improvement in the precision of parameter estimates by comparing the coefficient of variation (CV) of the SCIM parameter estimates to that of the IVIM. Results: The SCIM method was more robust compared to IVIM (up to 70% in liver and spleen) for different combinations of b-values. Also, the CV values of the parameter estimations using the SCIM method were significantly lower compared to repeated acquisition and signal averaging estimated using IVIM, especially for the fast diffusion parameter in liver (CVIV IM = 46.61 ± 11.22, CVSCIM = 16.85 ± 2.160, p < 0.001) and spleen (CVIV IM = 95.15 ± 19.82, CVSCIM = 52.55 ± 1.91, p < 0.001). Conclusions: The SCIM method characterizes fast and slow diffusion more precisely compared to the independent voxel-wise IVIM model fitting in the liver and spleen. PMID:25832079

Genetic disruption of NRF2 promotes the development of necroinflammation and liver fibrosis in a mouse model of HFE-hereditary hemochromatosis.

PubMed

Duarte, Tiago L; Caldas, Carolina; Santos, Ana G; Silva-Gomes, Sandro; Santos-Gonçalves, Andreia; Martins, Maria João; Porto, Graça; Lopes, José Manuel

2017-04-01

In hereditary hemochromatosis, iron deposition in the liver parenchyma may lead to fibrosis, cirrhosis and hepatocellular carcinoma. Most cases are ascribed to a common mutation in the HFE gene, but the extent of clinical expression is greatly influenced by the combined action of yet unidentified genetic and/or environmental modifying factors. In mice, transcription factor NRF2 is a critical determinant of hepatocyte viability during exposure to acute dietary iron overload. We evaluated if the genetic disruption of Nrf2 would prompt the development of liver damage in Hfe -/- mice (an established model of human HFE-hemochromatosis). Wild-type, Nrf2 -/- , Hfe -/- and double knockout (Hfe/Nrf2 -/- ) female mice on C57BL/6 genetic background were sacrificed at the age of 6 (young), 12-18 (middle-aged) or 24 months (old) for evaluation of liver pathology. Despite the parenchymal iron accumulation, Hfe -/- mice presented no liver injury. The combination of iron overload (Hfe -/- ) and defective antioxidant defences (Nrf2 -/- ) increased the number of iron-related necroinflammatory lesions (sideronecrosis), possibly due to the accumulation of toxic oxidation products such as 4-hydroxy-2-nonenal-protein adducts. The engulfment of dead hepatocytes led to a gradual accumulation of iron within macrophages, featuring large aggregates. Myofibroblasts recruited towards the injury areas produced substantial amounts of collagen fibers involving the liver parenchyma of double-knockout animals with increased hepatic fibrosis in an age-dependent manner. The genetic disruption of Nrf2 promotes the transition from iron accumulation (siderosis) to liver injury in Hfe -/- mice, representing the first demonstration of spontaneous hepatic fibrosis in the long term in a mouse model of hereditary hemochromatosis displaying mildly elevated liver iron. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Reactive oxygen species mediate human hepatocyte injury during hypoxia/reoxygenation.

PubMed

Bhogal, Ricky Harminder; Curbishley, Stuart M; Weston, Christopher J; Adams, David H; Afford, Simon C

2010-11-01

Increasing evidence shows that reactive oxygen species (ROS) may be critical mediators of liver damage during the relative hypoxia of ischemia/reperfusion injury (IRI) associated with transplant surgery or of the tissue microenvironment created as a result of chronic hepatic inflammation or infection. Much work has been focused on Kupffer cells or liver resident macrophages with respect to the generation of ROS during IRI. However, little is known about the contribution of endogenous hepatocyte ROS production or its potential impact on the parenchymal cell death associated with IRI and chronic hepatic inflammation. For the first time, we show that human hepatocytes isolated from nondiseased liver tissue and human hepatocytes isolated from diseased liver tissue exhibit marked differences in ROS production in response to hypoxia/reoxygenation (H-R). Furthermore, several different antioxidants are able to abrogate hepatocyte ROS-induced cell death during hypoxia and H-R. These data provide clear evidence that endogenous ROS production by mitochondria and nicotinamide adenine dinucleotide phosphate oxidase drives human hepatocyte apoptosis and necrosis during hypoxia and H-R and may therefore play an important role in any hepatic diseases characterized by a relatively hypoxic liver microenvironment. In conclusion, these data strongly suggest that hepatocytes and hepatocyte-derived ROS are active participants driving hepatic inflammation. These novel findings highlight important functional/metabolic differences between hepatocytes isolated from normal donor livers, hepatocytes isolated from normal resected tissue obtained during surgery for malignant neoplasms, and hepatocytes isolated from livers with end-stage disease. Furthermore, the targeting of hepatocyte ROS generation with antioxidants may offer therapeutic potential for the adjunctive treatment of IRI and chronic inflammatory liver diseases. © 2010 AASLD.

Hepatic sarcoidosis in patients presenting with liver dysfunction: imaging appearance, pathological correlation and disease evolution.

PubMed

Fetzer, David T; Rees, Mitchell A; Dasyam, Anil K; Tublin, Mitchell E

2016-09-01

We hypothesize that hepatic sarcoidosis is a dynamic process that can lead to cirrhosis and portal hypertension, independent of the course of thoracic disease. Therefore, we assess the imaging appearance and progression of hepatic sarcoidosis in subjects presenting with hepatic dysfunction. An IRB-approved, HIPAA-compliant, single-institution retrospective review identified 39 subjects with sarcoidosis-related liver dysfunction. Clinical information was collected. Two abdominal radiologists analyzed baseline and follow-up imaging studies, scoring features of cirrhosis. Chest CT was also analyzed. At presentation, 23 subjects (59.0 %) exhibited >3 cirrhotic features and 15 (38.5 %) >2 findings of portal hypertension. Of subjects with available follow-up, 57.9 % (19 subjects; mean interval 4.7 years) showed worsening of >3 cirrhotic features (Pearson rho = 0.58; p = 0.009). Parenchymal nodules were uncommon (25.6 %), and most regressed. Although 87.2 % of subjects were diagnosed with thoracic sarcoidosis, there was poor correlation between severity of hepatic and chest disease (Pearson rho = 0.30; p = 0.119). A mean of 7.2 years elapsed between diagnosis of pulmonary and liver involvement. Sarcoidosis may present as liver dysfunction, cirrhosis or portal hypertension. Sarcoid-related liver disease may progress and can manifest without, alongside or significantly after a diagnosis of pulmonary disease. • Patients often present with elevated liver function tests indicating cholestasis. • Patients may present with portal hypertension, and some progress to cirrhosis. • Though biopsy can be considered for focal liver lesions, most will regress. • Extent of intra-abdominal involvement may not correlate with severity of thoracic disease. • Liver disease may manifest alongside, prior to or significantly after initial diagnosis.

Bronchoscopic lung biopsy using noninvasive ventilatory support: case series and review of literature of NIV-assisted bronchoscopy.

PubMed

Agarwal, Ritesh; Khan, Ajmal; Aggarwal, Ashutosh N; Gupta, Dheeraj

2012-11-01

Fiberoptic bronchoscopy and lung biopsy are important diagnostic tools in patients with diffuse pulmonary infiltrates. However, these patients often have hypoxemic respiratory failure that makes this procedure hazardous. Noninvasive ventilation (NIV) has been shown to improve oxygenation in hypoxemic patients. To report the efficacy and safety of an innovative technique of NIV-assisted bronchoscopic lung biopsy in a small case-series of hypoxemic subjects with diffuse parenchymal infiltrates; also to systematically review the literature on NIV-assisted bronchoscopy. Subjects with bilateral diffuse parenchymal infiltrates and P(aO(2))/F(IO(2)) < 200 mm Hg underwent bronchoscopic lung biopsy under NIV support. NIV was initiated 10 min before the procedure and continued for 30 min after the procedure. The primary outcomes were performance of successful procedure and episodes of decline in S(pO(2)) < 90%. Secondary end points were the change in the respiratory and hemodynamic parameters during the procedure and occurrence of complications such as pneumothorax, hemorrhage, and endotracheal intubation. Six subjects, with a mean ± SD age of 44.5 ± 11.6 years, were included in the study. The median (interquartile range [IQR]) P(aO(2))/F(IO(2)) prior to lung biopsy was 164.5 mm Hg (146.3-176.3 mm Hg), and the median (IQR) inspiratory and expiratory positive airway pressures were 14 cm H(2)O (12-15 cm H(2)O) and 5 cm H(2)O. Fiberoptic bronchoscopy was well tolerated and all subjects maintained S(pO(2)) > 92% during the procedure. One subject required endotracheal intubation due to hemoptysis. A definite diagnosis was obtained in 5 of the 6 subjects. A repeat procedure was performed in one subject, which again yielded no diagnosis. No other periprocedural complications were encountered. NIV-assisted bronchoscopic lung biopsy is a novel method for obtaining diagnosis in hypoxemic patients with diffuse lung infiltrates. However, this approach should be reserved for centers with extensive experience in NIV. More studies are required to define the utility of this approach.

MRI findings in acute hyperammonemic encephalopathy resulting from decompensated chronic liver disease.

PubMed

Sureka, Jyoti; Jakkani, Ravi Kanth; Panwar, Sanuj

2012-06-01

Hyperammonemic encephalopathy is a type of metabolic encephalopathy with diversified etiology. Hyperammonemia is the end result of several metabolic disorders such as congenital deficiencies of urea cycle enzymes, hepatic encephalopathy, Reye's syndrome and other toxic encephalopathies. Non-specific clinical presentation poses a great challenge in early diagnosis of this entity. Irrespective of the underlying etiology, hyperammonemia causes a distinctive pattern of brain parenchymal injury. The cingulate gyrus and insular cortex are more vulnerable to this type of toxic insult. Characteristic magnetic resonance imaging findings in combination with laboratory parameters can help to differentiate this entity from other metabolic encephalopathy and thus aiding in early diagnosis and treatment.

Test of the 'glymphatic' hypothesis demonstrates diffusive and aquaporin-4-independent solute transport in rodent brain parenchyma.

PubMed

Smith, Alex J; Yao, Xiaoming; Dix, James A; Jin, Byung-Ju; Verkman, Alan S

2017-08-21

Transport of solutes through brain involves diffusion and convection. The importance of convective flow in the subarachnoid and paravascular spaces has long been recognized; a recently proposed 'glymphatic' clearance mechanism additionally suggests that aquaporin-4 (AQP4) water channels facilitate convective transport through brain parenchyma. Here, the major experimental underpinnings of the glymphatic mechanism were re-examined by measurements of solute movement in mouse brain following intracisternal or intraparenchymal solute injection. We found that: (i) transport of fluorescent dextrans in brain parenchyma depended on dextran size in a manner consistent with diffusive rather than convective transport; (ii) transport of dextrans in the parenchymal extracellular space, measured by 2-photon fluorescence recovery after photobleaching, was not affected just after cardiorespiratory arrest; and (iii) Aqp4 gene deletion did not impair transport of fluorescent solutes from sub-arachnoid space to brain in mice or rats. Our results do not support the proposed glymphatic mechanism of convective solute transport in brain parenchyma.

Test of the 'glymphatic' hypothesis demonstrates diffusive and aquaporin-4-independent solute transport in rodent brain parenchyma

PubMed Central

Yao, Xiaoming; Dix, James A; Jin, Byung-Ju

2017-01-01

Transport of solutes through brain involves diffusion and convection. The importance of convective flow in the subarachnoid and paravascular spaces has long been recognized; a recently proposed ‘glymphatic’ clearance mechanism additionally suggests that aquaporin-4 (AQP4) water channels facilitate convective transport through brain parenchyma. Here, the major experimental underpinnings of the glymphatic mechanism were re-examined by measurements of solute movement in mouse brain following intracisternal or intraparenchymal solute injection. We found that: (i) transport of fluorescent dextrans in brain parenchyma depended on dextran size in a manner consistent with diffusive rather than convective transport; (ii) transport of dextrans in the parenchymal extracellular space, measured by 2-photon fluorescence recovery after photobleaching, was not affected just after cardiorespiratory arrest; and (iii) Aqp4 gene deletion did not impair transport of fluorescent solutes from sub-arachnoid space to brain in mice or rats. Our results do not support the proposed glymphatic mechanism of convective solute transport in brain parenchyma. PMID:28826498

The Role of Diffusion-Weighted Magnetic Resonance Imaging in the Differential Diagnosis of Simple and Hydatid Cysts of the Liver.

PubMed

Aksoy, S; Erdil, I; Hocaoglu, E; Inci, E; Adas, G T; Kemik, O; Turkay, R

2018-02-01

The present study indicates that simple and hydatid cysts in liver are a common health problem in Turkey. The aim of the study is to differentiate different types of hydatid cysts from simple cysts by using diffusion-weighted images. In total, 37 hydatid cysts and 36 simple cysts in the liver were diagnosed. We retrospectively reviewed the medical records of the patients who had both ultrasonography and magnetic resonance imaging. We measured apparent diffusion coefficient (ADC) values of all the cysts and then compared the findings. There was no statistically meaningful difference between the ADC values of simple cysts and type 1 hydatid cysts. However, for the other types of hydatid cysts, it is possible to differentiate hydatid cysts from simple cysts using the ADC values. Although in our study we cannot differentiate between type I hydatid cysts and simple cysts in the liver, diffusion-weighted images are very useful to differentiate different types of hydatid cysts from simple cysts using the ADC values.

Improved differentiation between hepatic hemangioma and metastases on diffusion-weighted MRI by measurement of standard deviation of apparent diffusion coefficient.

PubMed

Hardie, Andrew D; Egbert, Robert E; Rissing, Michael S

2015-01-01

Diffusion-weighted magnetic resonance imaging (DW-MR) can be useful in the differentiation of hemangiomata from liver metastasis, but improved methods other than by mean apparent diffusion coefficient (mADC) are needed. A retrospective review identified 109 metastatic liver lesions and 86 hemangiomata in 128 patients who had undergone DW-MR. For each lesion, mADC and the standard deviation of the mean ADC (sdADC) were recorded and compared by receiver operating characteristic analysis. Mean mADC was higher in benign hemangiomata (1.52±0.12 mm(2)/s) than in liver metastases (1.33±0.18 mm(2)/s), but there was significant overlap in values. The mean sdADC was lower in hemangiomata (101±17 mm(2)/s) than metastases (245±25 mm(2)/s) and demonstrated no overlap in values, which was significantly different (P<.0001). Hemangiomata may be better able to be differentiated from liver metastases on the basis of sdADC than by mADC, although further studies are needed. Copyright © 2015 Elsevier Inc. All rights reserved.

Idiopathic Interstitial Pneumonia

PubMed Central

Flaherty, Kevin R.; Andrei, Adin-Cristian; King, Talmadge E.; Raghu, Ganesh; Colby, Thomas V.; Wells, Athol; Bassily, Nadir; Brown, Kevin; du Bois, Roland; Flint, Andrew; Gay, Steven E.; Gross, Barry H.; Kazerooni, Ella A.; Knapp, Robert; Louvar, Edmund; Lynch, David; Nicholson, Andrew G.; Quick, John; Thannickal, Victor J.; Travis, William D.; Vyskocil, James; Wadenstorer, Frazer A.; Wilt, Jeffrey; Toews, Galen B.; Murray, Susan; Martinez, Fernando J.

2007-01-01

Rationale: Treatment and prognoses of diffuse parenchymal lung diseases (DPLDs) varies by diagnosis. Obtaining a uniform diagnosis among observers is difficult. Objectives: Evaluate diagnostic agreement between academic and community-based physicians for patients with DPLDs, and determine if an interactive approach between clinicians, radiologists, and pathologists improved diagnostic agreement in community and academic centers. Methods: Retrospective review of 39 patients with DPLD. A total of 19 participants reviewed cases at 2 community locations and 1 academic location. Information from the history, physical examination, pulmonary function testing, high-resolution computed tomography, and surgical lung biopsy was collected. Data were presented in the same sequential fashion to three groups of physicians on separate days. Measurements and Main Results: Each observer's diagnosis was coded into one of eight categories. A κ statistic allowing for multiple raters was used to assess agreement in diagnosis. Interactions between clinicians, radiologists, and pathologists improved interobserver agreement at both community and academic sites; however, final agreement was better within academic centers (κ = 0.55–0.71) than within community centers (κ = 0.32–0.44). Clinically significant disagreement was present between academic and community-based physicians (κ = 0.11–0.56). Community physicians were more likely to assign a final diagnosis of idiopathic pulmonary fibrosis compared with academic physicians. Conclusions: Significant disagreement exists in the diagnosis of DPLD between physicians based in communities compared with those in academic centers. Wherever possible, patients should be referred to centers with expertise in diffuse parenchymal lung disorders to help clarify the diagnosis and provide suggestions regarding treatment options. PMID:17255566

Is there evidence for more than two diffusion components in abdominal organs? - A magnetic resonance imaging study in healthy volunteers.

PubMed

Wurnig, Moritz C; Germann, Manon; Boss, Andreas

2018-01-01

The most commonly applied model for the description of diffusion-weighted imaging (DWI) data in perfused organs is bicompartmental intravoxel incoherent motion (IVIM) analysis. In this study, we assessed the ground truth of underlying diffusion components in healthy abdominal organs using an extensive DWI protocol and subsequent computation of apparent diffusion coefficient 'spectra', similar to the computation of previously described T 2 relaxation spectra. Diffusion datasets of eight healthy subjects were acquired in a 3-T magnetic resonance scanner using 68 different b values during free breathing (equidistantly placed in the range 0-1005 s/mm 2 ). Signal intensity curves as a function of the b value were analyzed in liver, spleen and kidneys using non-negative least-squares fitting to a distribution of decaying exponential functions with minimum amplitude energy regularization. In all assessed organs, the typical slow- and fast-diffusing components of the IVIM model were detected [liver: true diffusion D = (1.26 ± 0.01) × 10 -3 mm 2 /s, pseudodiffusion D* = (270 ± 44) × 10 -3 mm 2 /s; kidney cortex: D = (2.26 ± 0.07) × 10 -3 mm 2 /s, D* = (264 ± 78) × 10 -3 mm 2 /s; kidney medulla: D = (1.57 ± 0.28) × 10 -3 mm 2 /s, D* = (168 ± 18) × 10 -3 mm 2 /s; spleen: D = (0.91 ± 0.01) × 10 -3 mm 2 /s, D* = (69.8 ± 0.50) × 10 -3 mm 2 /s]. However, in the liver and kidney, a third component between D and D* was found [liver: D' = (43.8 ± 5.9) × 10 -3 mm 2 /s; kidney cortex: D' = (23.8 ± 11.5) × 10 -3 mm 2 /s; kidney medulla: D' = (5.23 ± 0.93) × 10 -3 mm 2 /s], whereas no third component was detected in the spleen. Fitting with a diffusion kurtosis model did not lead to a better fit of the resulting curves to the acquired data compared with apparent diffusion coefficient spectrum analysis. For a most accurate description of diffusion properties in the liver and the kidneys, a more sophisticated model seems to be required including three diffusion components. Copyright © 2017 John Wiley & Sons, Ltd.

Can diffusion-weighted imaging distinguish between benign and malignant pediatric liver tumors?

PubMed

Caro-Domínguez, Pablo; Gupta, Abha A; Chavhan, Govind B

2018-01-01

There are limited data on utility of diffusion-weighted imaging (DWI) in the evaluation of pediatric liver lesions. To determine whether qualitative and quantitative DWI can be used to differentiate benign and malignant pediatric liver lesions. We retrospectively reviewed MRIs in children with focal liver lesions to qualitatively evaluate lesions noting diffusion restriction, T2 shine-through, increased diffusion, hypointensity on DWI and apparent diffusion coefficient (ADC) maps, and intermediate signal on both, and to measure ADC values. Pathology confirmation or a combination of clinical, laboratory and imaging features, and follow-up was used to determine final diagnosis. We included 112 focal hepatic lesions in 89 children (median age 11.5 years, 51 female), of which 92 lesions were benign and 20 malignant. Interobserver agreement was almost perfect for both qualitative (kappa 0.8735) and quantitative (intraclass correlation coefficient [ICC] 0.96) diffusion assessment. All malignant lesions showed diffusion restriction. Most benign lesions other than abscesses were not restricted. There was significant association of qualitative restriction with malignancy and non-restriction with benignancy (Fisher exact test P<0.0001). Mean normalized ADC values of malignant lesions (1.23x10 -3  mm 2 /s) were lower than benign lesions (1.62x10 -3  mm 2 /s; Student's t-test, P<0.015). However, there was significant overlap of ADC between benign and malignant lesions, with wide range for each diagnosis. Receiver operating characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.63 for predicting malignancy using an ADC cut-off value of ≤1.20x10 -3  mm 2 /s, yielding a sensitivity of 78% and a specificity of 54% for differentiating malignant from benign lesions. Qualitative diffusion restriction in pediatric liver lesions is a good predictor of malignancy and can help to differentiate between benign and malignant lesions, in conjunction with conventional MR sequences. Even though malignant lesions demonstrated significantly lower ADC values than benign lesions, the use of quantitative diffusion remains limited in its utility for distinguishing them because of the significant overlap and wide ranges of ADC values.

[Association between the use of blood components and the five-year mortality after liver transplant].

PubMed

de Morais, Bruno Salomé; Sanches, Marcelo Dias; Ribeiro, Daniel Dias; Lima, Agnaldo Soares; de Abreu Ferrari, Teresa Cristina; Duarte, Malvina Maria de Freitas; Cançado, Guilherme Henrique Gomes Moreira

2011-01-01

Liver transplant (LT) surgery is associated with significant bleeding in 20% of cases, and several authors have demonstrated the risks related to blood components. The objective of the present study was to evaluate the impact of using blood components during hospitalization in five-year survival of patients undergoing LT. One hundred and thirteen patients were evaluated retrospectively. Several variables, including the use of blood components intraoperatively and throughout hospitalization, were categorized and evaluated by univariate analysis using Fisher's test. A level of significance of 5% was adopted. Results with p < 0.2 underwent multivariate analysis using multinomial logistic regression. Parenchymal diseases, preoperative renal dysfunction, and longer stay in hospital and ICU are associated with greater five-year mortality after LT (p < 0.05). Unlike the intraoperative use of blood components, the accumulated transfusion of packed red blood cell, frozen fresh plasma, and platelets during the entire hospitalization was associated with greater five-year mortality after liver transplantation (p < 0.01). This study emphasizes the relationship between the use of blood components during hospitalization and increased mortality in five years after LT. 2011 Elsevier Editora Ltda. All rights reserved.

Pathology of idiopathic non-cirrhotic portal hypertension.

PubMed

Guido, Maria; Sarcognato, Samantha; Sacchi, Diana; Colloredo, Guido

2018-04-12

Idiopathic non-cirrhotic portal hypertension is an under-recognized vascular liver disease of unknown etiology, characterized by clinical signs of portal hypertension in the absence of cirrhosis. By definition, any disorder known to cause portal hypertension in the absence of cirrhosis and any cause of chronic liver disease must be excluded to make a diagnosis of idiopathic non-cirrhotic portal hypertension. However, the diagnosis is often difficult because the disease resembles cirrhosis and there is no gold standard test. Liver biopsy is an essential tool: it is able to exclude cirrhosis and other causes of portal hypertension and it allows the identification of the characteristic lesions. Nonetheless, the histological diagnosis of idiopathic non-cirrhotic portal hypertension is not always straightforward, in particular by needle biopsy samples, because there is no pathognomonic lesion, but rather a variety of vascular changes which are unevenly distributed, very subtle, and not all necessarily identified in a single specimen. Pathologists should be able to recognize several patterns of injury, involving portal/periportal areas as well as parenchymal structures.The histological features of idiopathic non-cirrhotic portal hypertension are described in this review, focusing on their interpretation in needle biopsy specimens.

The role of high-energy synchrotron radiation in biomedical trace element research

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pounds, J.G.; Long, G.J.; Kwiatek, W.M.

1987-01-01

This paper will present the results of an investigation of the distribution of essential elements in the normal hepatic lobule. the liver is the organ responsible for metabolism and storage of most trace elements. Although parenchymal hepatocytes are rather uniform histologically, morphometry, histochemistry, immunohistochemistry, and microdissection with microchemical investigations have revealed marked heterogeneity on a functional and biochemical level. Hepatocytes from the periportal and perivenous zones of the liver parrenchyma differ in oxidative energy metabolism, glucose uptake and output, unreagenesis, biotransformation, bile acid secretion, and palsma protein synthesis and secretion. Although trace elements are intimately involved in the regulation andmore » maintenance of these functions, little is known regarding the heterogeneity of trace element localization of the liver parenchyma. Histochemical techniques for trace elements generally give high spatial resolution, but lack specificity and stoichiometry. Microdissection has been of marginal usefulness for trace element analyses due to the very small size of the dissected parenchyma. The characteristics of the high-energy x-ray microscope provide an effective approach for elucidating the trace element content of these small biological structures or regions. 5 refs., 1 fig., 1 tab.« less

Simultaneous Multislice Accelerated Free-Breathing Diffusion-Weighted Imaging of the Liver at 3T.

PubMed

Obele, Chika C; Glielmi, Christopher; Ream, Justin; Doshi, Ankur; Campbell, Naomi; Zhang, Hoi Cheung; Babb, James; Bhat, Himanshu; Chandarana, Hersh

2015-10-01

To perform image quality comparison between accelerated multiband diffusion acquisition (mb2-DWI) and conventional diffusion acquisition (c-DWI) in patients undergoing clinically indicated liver MRI. In this prospective study 22 consecutive patients undergoing clinically indicated liver MRI on a 3-T scanner equipped to perform multiband diffusion-weighed imaging (mb-DWI) were included. DWI was performed with single-shot spin-echo echo-planar technique with fat-suppression in free breathing with matching parameters when possible using c-DWI, mb-DWI, and multiband DWI with a twofold acceleration (mb2-DWI). These diffusion sequences were compared with respect to various parameters of image quality, lesion detectability, and liver ADC measurements. Accelerated mb2-DWI was 40.9% faster than c-DWI (88 vs. 149 s). Various image quality parameter scores were similar or higher on mb2-DWI when compared to c-DWI. The overall image quality score (averaged over the three readers) was significantly higher for mb-2 compared to c-DWI for b = 0 s/mm(2) (3.48 ± 0.52 vs. 3.21 ± 0.54; p = 0.001) and for b = 800 s/mm(2) (3.24 ± 0.76 vs. 3.06 ± 0.86; p = 0.010). Total of 25 hepatic lesions were visible on mb2-DWI and c-DWI, with identical lesion detectability. There was no significant difference in liver ADC between mb2-DWI and c-DWI (p = 0.12). Bland-Altman plot demonstrates lower mean liver ADC with mb2-DWI compared to c-DWI (by 0.043 × 10(-3) mm(2)/s or 3.7% of the average ADC). Multiband technique can be used to increase acquisition speed nearly twofold for free-breathing DWI of the liver with similar or improved overall image quality and similar lesion detectability compared to conventional DWI.

Hepatic "BOLSA" a novel method of perihepatic wrapping for hepatic hemorrhage "BOLSA".

PubMed

Ng, Nathaniel; McLean, Susan F; Ghaleb, Melhem R; Tyroch, Alan H

2015-01-01

Severe traumatic liver hemorrhage quickly leads to exsanguination. Perihepatic packing is frequently used in damage control surgery. This method can be unsuccessful and accompanied by complications. Vicryl mesh wraps have been described in the treatment of liver hemorrhage. In this report, we describe an enhanced technique of hepatic wrapping in a case of hepatic bleeding after liver biopsy in a coagulopathic patient. The technique is called the hepatic "BOLSA" (Bag on Liver Supporting Anti-Hemorrhage). A 59 year old male presented in the recovery room after liver biopsy of a mass, followed by angio-embolization of the hepatic mass 9h earlier. The patient was acidotic, coagulopathic, and demonstrated intra-abdominal hypertension. Computed tomography demonstrated perihepatic fluid. The patient continued hemorrhaging despite attempts to correct coagulopathy by transfusion. Multiple operating room visits were required where a combination of packing and hemostatic agents could not stop hepatic venous parenchymal hemorrhage. Mesh wrap consisting of Vicryl and PDS suture were used to create the "BOLSA" to achieve hemostasis. Perihepatic packing compromises pulmonary excursion, elevates intra-abdominal pressure, is a risk factor for sepsis, and requires an additional trip to the operating room for removal. The use of Vicryl mesh wrap obviates these complications. Previously described mesh wraps require anchoring. The self-supporting structure of the BOLSA simplifies construction and application. The BOLSA is an effective tool in treatment of severe liver hemorrhage in coagulopathic patients. It is the modern simplification of hepatic wrapping and the solution to the side effects of perihepatic packing. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Liver Volumetry Plug and Play: Do It Yourself with ImageJ

PubMed Central

Dello, Simon A. W. G.; van Dam, Ronald M.; Slangen, Jules J. G.; van de Poll, Marcel C. G.; Bemelmans, Marc H. A.; Greve, Jan Willem W. M.; Beets-Tan, Regina G. H.; Wigmore, Stephen J.

2007-01-01

Background A small remnant liver volume is an important risk factor for posthepatectomy liver failure and can be predicted accurately by computed tomography (CT) volumetry using radiologic image analysis software. Unfortunately, this software is expensive and usually requires support by a radiologist. ImageJ is a freely downloadable image analysis software package developed by the National Institute of Health (NIH) and brings liver volumetry to the surgeon’s desktop. We aimed to assess the accuracy of ImageJ for hepatic CT volumetry. Methods ImageJ was downloaded from http://www.rsb.info.nih.gov/ij/. Preoperative CT scans of 15 patients who underwent liver resection for colorectal cancer liver metastases were retrospectively analyzed. Scans were opened in ImageJ; and the liver, all metastases, and the intended parenchymal transection line were manually outlined on each slice. The area of each selected region, metastasis, resection specimen, and remnant liver was multiplied by the slice thickness to calculate volume. Volumes of virtual liver resection specimens measured with ImageJ were compared with specimen weights and calculated volumes obtained during pathology examination after resection. Results There was an excellent correlation between the volumes calculated with ImageJ and the actual measured weights of the resection specimens (r² = 0.98, p < 0.0001). The weight/volume ratio amounted to 0.88 ± 0.04 (standard error) and was in agreement with our earlier findings using CT-linked radiologic software. Conclusion ImageJ can be used for accurate hepatic CT volumetry on a personal computer. This application brings CT volumetry to the surgeon’s desktop at no expense and is particularly useful in cases of tertiary referred patients, who already have a proper CT scan on CD-ROM from the referring institution. Most likely the discrepancy between volume and weight results from exsanguination of the liver after resection. PMID:17726630

Evaluation of Focal Liver Reaction after Proton Beam Therapy for Hepatocellular Carcinoma Examined Using Gd-EOB-DTPA Enhanced Hepatic Magnetic Resonance Imaging.

PubMed

Takamatsu, Shigeyuki; Yamamoto, Kazutaka; Maeda, Yoshikazu; Kawamura, Mariko; Shibata, Satoshi; Sato, Yoshitaka; Terashima, Kazuki; Shimizu, Yasuhiro; Tameshige, Yuji; Sasaki, Makoto; Asahi, Satoko; Kondou, Tamaki; Kobayashi, Satoshi; Matsui, Osamu; Gabata, Toshifumi

2016-01-01

Proton beam therapy (PBT) achieves good local control for hepatocellular carcinoma (HCC), and toxicity tends to be lower than for photon radiotherapy. Focal liver parenchymal damage in radiotherapy is described as the focal liver reaction (FLR); the threshold doses (TDs) for FLR in the background liver have been analyzed in stereotactic ablative body radiotherapy and brachytherapy. To develop a safer approach for PBT, both TD and liver volume changes are considered clinically important in predicting the extent of damage before treatment, and subsequently in reducing background liver damage. We investigated appearance time, TDs and volume changes regarding FLR after PBT for HCC. Patients who were treated using PBT and were followed up using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA MRI) after PBT were enrolled. Sixty-eight lesions in 58 patients were eligible for analysis. MRI was acquired at the end of treatment, and at 1, 2, 3 and 6 months after PBT. We defined the FLR as a clearly depicted hypointense area on the hepatobiliary phase of Gd-EOB-DTPA MRI, and we monitored TDs and volume changes in the FLR area and the residual liver outside of the FLR area. FLR was depicted in all lesions at 3 months after PBT. In FLR expressed as the 2-Gy equivalent dose (α/β = 3 Gy), TDs did not differ significantly (27.0±6.4 CGE [10 fractions [Fr] vs. 30.5±7.3 CGE [20 Fr]). There were also no correlations between the TDs and clinical factors, and no significant differences between Child-Pugh A and B scores. The volume of the FLR area decreased and the residual liver volume increased, particularly during the initial 3 months. This study established the FLR dose for liver with HCC, which might be useful in the prediction of remnant liver volume for PBT.

Clonal tracing of Sox9+ liver progenitors in oval cell injury

PubMed Central

Tarlow, Branden D.; Finegold, Milton J.; Grompe, Markus

2014-01-01

Proliferating ducts, termed “oval cells”, have long thought to be bipotential, i.e. produce both biliary ducts and hepatocytes during chronic liver injury. The precursor to oval cells is considered to be a facultative liver stem cell (LSC). Recent lineage tracing experiments indicated that the LSC is Sox9+ and can replace the bulk of hepatocyte mass in several settings. However, no clonal relationship between Sox9+ cells and the two epithelial liver lineages was established. We labeled Sox9+ mouse liver cells at low density with a multicolor fluorescent confetti reporter. Organoid formation validated the progenitor activity of the labeled population. Sox9+ cells were traced in multiple oval cell injury models using both histology and FACS. Surprisingly, only rare clones containing both hepatocytes and oval cells were found in any experiment. Quantitative analysis showed that Sox9+ cells contributed only minimally (<1%) to the hepatocyte pool, even in classic oval cell injury models. In contrast, clonally marked mature hepatocytes demonstrated the ability to self-renew in all classic mouse oval cell activation injuries. A hepatocyte chimera model to trace hepatocytes and non-parenchymal cells also demonstrated the prevalence of hepatocyte-driven regeneration in mouse oval cell injury models. Conclusion Sox9+ ductal progenitor cells give rise to clonal oval cell proliferation and bipotential organoids but rarely produce hepatocytes in vivo. Hepatocytes themselves are the predominant source of new parenchyma cells in prototypical mouse models of oval cell activation. PMID:24700457

Urinary L-FABP as a marker of vesicoureteral reflux in children: could it also have a protective effect on the kidney?

PubMed

Benzer, Meryem; Tekin Neijmann, Sebnem; Gültekin, Nazlı Dilay; Uluturk Tekin, Aslı

2017-01-01

Liver-type fatty acid-binding protein is a small cytoplasmic protein which is expressed in the human renal proximal tubular epithelium and synthesized in response to renal tubular injury. The aim of the present study was to investigate the importance of urinary liver-type fatty acid-binding protein levels in children who diagnosed with vesicoureteral reflux. Fifty-six patients with vesicoureteral reflux and 51 healthy controls were enrolled to the study. The cases were divided into three groups as follows: group A-the controls, group B-the patients who had renal parenchymal scarring and group C-the patients who had no scarring. Urinary liver-type fatty acid-binding protein was measured by enzyme-linked immunosorbent assay method. Creatinine was measured by modified Jaffe method, protein was measured by turbidimetric method, and urine density was determined by using the "falling drop" procedure. Urinary liver-type fatty acid-binding protein and urinary liver-type fatty acid-binding protein/creatinine levels were significantly higher in the whole patient group than in the controls (p = 0.016, 0.006). Significant differences were also determined by comparing the three groups (p = 0.015, 0.014), and those levels were found as significantly higher in group C. Urinary liver-type fatty acid-binding protein was considered to be helpful for the diagnosis of vesicoureteral reflux, and also it might contribute to understand the mechanisms causing scar tissue formation especially for the patients who had vesicoureteral reflux. Further clinical and experimental investigations are required to elucidate in detail the physiology of liver-type fatty acid-binding protein.

The fatty liver dystrophy (fld) mutation: Developmentally related alterations in hepatic triglyceride metabolism and protein expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reue, K.; Rehnmark, S.; Cohen, R.D.

1997-07-01

Fatty liver dystrophy (fld) is an autosomal recessive mutation in mice characterized by hypertriglyceridemia and development of a fatty liver in the early neonatal period. Also associated with the fld phenotype is a tissue-specific deficiency in the expression of lipoprotein lipase and hepatic lipase, as well as elevations in hepatic apolipoprotein A-IV and apolipoprotein C-II mRNA levels. Although these lipid abnormalities resolve at the age of weaning, adult mutant mice exhibit a peripheral neuropathy associated with abnormal myelin formation. The fatty liver in fld/fld neonates is characterized by the accumulation of large triglyceride droplets within the parenchymal cells, and thesemore » droplets persist within isolated hepatocytes maintained in culture for several days. To identify the metabolic defect that leads to lipid accumulation, the authors investigated several aspects of cellular triglyceride metabolism. The mutant mice exhibited normal activity of acid triacylglycerol lipase, an enzyme thought to be responsible for hydrolysis of dietary triglycerides in the liver. Metabolic labeling studies performed with oleic acid revealed that free fatty acids accumulate in the liver of 3 day old fld/fld mice, but not in adults. This accumulation in liver was mirrored by elevated free fatty acid levels in plasma of fld/fld neonates, with levels highest in very young mice and returning to normal by the age of one month. Quantitation of fatty acid oxidation in cells isolated from fld/fld neonates revealed that oxidation rate is reduced 60% in hepatocytes and 40% in fibroblasts; hepatocytes from adult fld/fld mice exhibited an oxidation rate similar to those from wild-type mice.« less

Critical Role for Very-Long Chain Sphingolipids in Invariant Natural Killer T Cell Development and Homeostasis.

PubMed

Saroha, Ashish; Pewzner-Jung, Yael; Ferreira, Natalia S; Sharma, Piyush; Jouan, Youenn; Kelly, Samuel L; Feldmesser, Ester; Merrill, Alfred H; Trottein, François; Paget, Christophe; Lang, Karl S; Futerman, Anthony H

2017-01-01

The role of sphingolipids (SLs) in the immune system has come under increasing scrutiny recently due to the emerging contributions that these important membrane components play in regulating a variety of immunological processes. The acyl chain length of SLs appears particularly critical in determining SL function. Here, we show a role for very-long acyl chain SLs (VLC-SLs) in invariant natural killer T ( i NKT) cell maturation in the thymus and homeostasis in the liver. Ceramide synthase 2-null mice, which lack VLC-SLs, were susceptible to a hepatotropic strain of lymphocytic choriomeningitis virus, which is due to a reduction in the number of i NKT cells. Bone marrow chimera experiments indicated that hematopoietic-derived VLC-SLs are essential for maturation of i NKT cells in the thymus, whereas parenchymal-derived VLC-SLs are crucial for i NKT cell survival and maintenance in the liver. Our findings suggest a critical role for VLC-SL in i NKT cell physiology.

Iron deposition in skin of patients with haemochromatosis

NASA Astrophysics Data System (ADS)

Pinheiro, T.; Silva, J. N.; Alves, L. C.; Filipe, P.

2003-09-01

Haemochromatosis is the most common inherited liver disease in Caucasians and the most common autosomal recessive genetic disorder. It is characterized by inappropriately high iron absorption resulting in progressive iron overload in parenchymal organs such as liver, heart, pancreas, pituitary, joints, and skin. Upon early detection, haemochromatosis can be a manageable chronic disease but, if undetected, is potentially fatal. Skin biopsies were obtained from patients and from healthy donors. Images of the elemental distributions in skin were obtained using nuclear microscopy techniques (nuclear microprobe, NMP). Elemental profiles along skin, and intra-, and extra-cellular iron concentrations, were determined. Results for patients with haemochromatosis were cross-examined with morphologic features and with data obtained for healthy skin. Skin iron content is much increased in patients with haemochromatosis when compared with healthy subjects. Extensive iron deposits are observed at dermis, at the dermo-epidermal interface, at upper epidermis layers and at stratum corneum. Iron deposition was observed preferentially at cell boundaries or at the interstitial matrix.

Transhepatic Hilar Approach for Perihilar Cholangiocarcinoma: Significance of Early Judgment of Resectability and Safe Vascular Reconstruction.

PubMed

Kuriyama, Naohisa; Isaji, Shuji; Tanemura, Akihiro; Iizawa, Yusuke; Kato, Hiroyuki; Murata, Yasuhiro; Azumi, Yoshinori; Kishiwada, Masashi; Mizuno, Shugo; Usui, Masanobu; Sakurai, Hiroyuki

2017-03-01

In the most common surgical procedure for perihilar cholangiocarcinoma, the margin status of the proximal bile duct is determined at the final step. Our procedure, the transhepatic hilar approach, confirms a cancer-negative margin status of the proximal bile duct first. We first performed a partial hepatic parenchymal transection to expose the hilar plate, and then transected the proximal bile duct to confirm margin status. Then, divisions of the hepatic artery and portal vein of the future resected liver are performed, followed by the residual hepatic parenchymal transection. The transhepatic hilar approach offers a wide surgical field for safe resection and reconstruction of the portal vein in the middle of the hepatectomy. We reviewed 23 patients with perihilar cholangiocarcinoma who underwent major hepatectomy using our procedure from 2011 to 2015. A combined vascular resection and reconstruction was carried out in 14 patients (60.9%). R0 resection was achieved in 17 patients (73.9%), and the overall 3-year survival rate was 52.9% (median survival time 52.4 months). The transhepatic hilar approach is useful and practicable regardless of local tumor extension, enabling us to determine tumor resectability and perform safe resection and reconstruction of the portal vein early in the operation.

Longitudinal brain white matter alterations in minimal hepatic encephalopathy before and after liver transplantation.

PubMed

Lin, Wei-Che; Chou, Kun-Hsien; Chen, Chao-Long; Chen, Hsiu-Ling; Lu, Cheng-Hsien; Li, Shau-Hsuan; Huang, Chu-Chung; Lin, Ching-Po; Cheng, Yu-Fan

2014-01-01

Cerebral edema is the common pathogenic mechanism for cognitive impairment in minimal hepatic encephalopathy. Whether complete reversibility of brain edema, cognitive deficits, and their associated imaging can be achieved after liver transplantation remains an open question. To characterize white matter integrity before and after liver transplantation in patients with minimal hepatic encephalopathy, multiple diffusivity indices acquired via diffusion tensor imaging was applied. Twenty-eight patients and thirty age- and sex-matched healthy volunteers were included. Multiple diffusivity indices were obtained from diffusion tensor images, including mean diffusivity, fractional anisotropy, axial diffusivity and radial diffusivity. The assessment was repeated 6-12 month after transplantation. Differences in white matter integrity between groups, as well as longitudinal changes, were evaluated using tract-based spatial statistical analysis. Correlation analyses were performed to identify first scan before transplantation and interval changes among the neuropsychiatric tests, clinical laboratory tests, and diffusion tensor imaging indices. After transplantation, decreased water diffusivity without fractional anisotropy change indicating reversible cerebral edema was found in the left anterior cingulate, claustrum, postcentral gyrus, and right corpus callosum. However, a progressive decrease in fractional anisotropy and an increase in radial diffusivity suggesting demyelination were noted in temporal lobe. Improved pre-transplantation albumin levels and interval changes were associated with better recoveries of diffusion tensor imaging indices. Improvements in interval diffusion tensor imaging indices in the right postcentral gyrus were correlated with visuospatial function score correction. In conclusion, longitudinal voxel-wise analysis of multiple diffusion tensor imaging indices demonstrated different white matter changes in minimal hepatic encephalopathy patients. Transplantation improved extracellular cerebral edema and the results of associated cognition tests. However, white matter demyelination may advance in temporal lobe.

Irreversible electroporation in the treatment of locally advanced pancreas and liver metastases of colorectal carcinoma.

PubMed

Wichtowski, Mateusz; Nowaczyk, Piotr; Kocur, Jacek; Murawa, Dawid

2016-01-01

Irreversible electroporation is a new, non-thermal ablation technique in the treatment of parenchymal organ tumors which uses short high voltage pulses of electricity in order to induce apoptosis of targeted cells. In this paper the application of this method of treatment in locally advanced pancreatic cancer (LAPC) and liver cancer is analyzed. Between 04.2014 and 09.2014 two patients with LAPC and one with colorectal liver metastasis (CRLM) were qualified for treatment with irreversible electroporation. Both patients remained under constant observation and control. PubMed/Medline, Embase and Google Scholar databases were searched and eight original reports on irreversible electroporation of pancreatic and liver tumors based on the biggest groups of patients were found. Two patients with LAPC and one with CRLM were qualified for ablation with irreversible electroporation. In all three patients a successful irreversible electroporation (IRE) procedure of the whole tumor was conducted. In the minimum seven-month follow-up 100% local control was achieved - without progression. In the literature review the local response to treatment ranged from 41% to 100%. The event-free survival rate in six-month observation was 94%. Ablation with irreversible electroporation is a new non-thermal ablation technique which has been demonstrated, both in the previously published studies and in the cases described in this paper, as a safe and efficient therapeutic method for patients with LAPC and CRLM.

Emergency liver resection for combined biliary and vascular injury following laparoscopic cholecystectomy: case report and review of the literature.

PubMed

Felekouras, Evangelos; Megas, Thomas; Michail, Othon P; Papaconstantinou, Ioannis; Nikiteas, Nikolaos; Dimitroulis, Dimitrios; Griniatsos, John; Tsechpenakis, Anastasios; Kouraklis, Gregorios

2007-03-01

A 75-year-old woman suffering from symptomatic cholelithiasis was admitted to our hospital for elective laparoscopic cholecystectomy (LC). Intraoperatively, because of severe inflammation and dense adhesions in the region of the Calot triangle and bleeding arising from the porta hepatis which obscured the operating field, the method was converted to a conventional open approach. Copious hemostasis was achieved using sutures, clips and diathermy, and no bile duct or vascular injuries were recognized intraoperatively. Because of severe right upper quadrant abdominal pain and significant deterioration of the liver function tests (LFTs) on the first postoperative day, the patient underwent a Doppler ultrasound scan which showed absence of blood flow at the level of porta hepatis. Urgent relaparotomy revealed an ischemic liver on the right, a transected common bile duct at the level of its confluence, a divided and ligated right hepatic artery and thrombosed portal vein down to its confluence. Thrombectomy and reconstruction of the portal vein were performed to salvage the left hemiliver, and after restoration of blood flow to the left hemiliver, a right hemihepatectomy and a Roux-en-Y hepaticojejunostomy on the left were performed. Liver resection serves an important role in the case of parenchymal necrosis due to combined biliary, hepatic artery and portal vein injury following laparoscopic cholecystectomy and moreover, the operation can be safely performed in the acute setting.

Evaluation of medicinal plant hepatotoxicity in co-cultures of hepatocytes and monocytes.

PubMed

Saad, Bashar; Dakwar, Suha; Said, Omar; Abu-Hijleh, Ghassan; Al Battah, Feras; Kmeel, Abedelsalam; Aziazeh, Hassan

2006-03-01

Non-parenchymal cells might play an important role in the modulation of xenobiotic metabolism in liver and its pharmacological and toxicological consequences. Therefore, the role of cell-to-cell interactions in herbal induced liver toxicity was investigated in monocultures of cells from the human hepatocyte cell line (HepG2) and in co-cultures of cells from the HepG2 cell line and cells from the human monocyte cell line (THP1). Cells were treated with various concentrations (1-500 microg ml(-1)) of extracts of Pistacia palaestina, Juglans regia and Quercus ithaburensis for 24 h. Extracts from Cleome droserifolia, a known toxic plant, were taken as positive control. In the co-culture system, toxic effects were observed after exposure to extracts of Pistacia palestina and C. droserifolia. These two extracts significantly reduced by cell viability as measured the MTT test and the LDH assay. Whereas in hepatocyte cultures, only extracts of C. droserifolia were found to affect the cell viability. The production levels of albumin from hepatocytes were not affected by treatment with plant extracts in both culture systems. It seems that the observed reduction in cell viability after exposure to extracts of P. palestina in co-cultures but not in monocultures is a result of monocyte-derived factors. The use of liver cell co-cultures is therefore a useful approach to investigate the influence of intercellular communication on xenobiotic metabolism in liver.

Postthrombolysis hemorrhage risk is affected by stroke assessment bias between hemispheres

PubMed Central

Singer, O.C.; Gotzler, B.; Vatankhah, B.; Boy, S.; Fiehler, J.; Lansberg, M.G.; Albers, G.W.; Kastrup, A.; Rovira, A.; Gass, A.; Rosso, C.; Derex, L.; Kim, J.S.; Heuschmann, P.

2011-01-01

Objective: Stroke symptoms in right hemispheric stroke tend to be underestimated in clinical assessment scales, resulting in greater infarct volumes in right as compared to left hemispheric strokes despite similar clinical stroke severity. We hypothesized that patients with right hemispheric nonlacunar stroke are at higher risk for secondary intracerebral hemorrhage after thrombolysis despite similar stroke severity. Methods: We analyzed data of 2 stroke cohorts with CT-based and MRI-based imaging before thrombolysis. Initial stroke severity was measured with the NIH Stroke Scale (NIHSS). Lacunar strokes were excluded through either the presence of cortical symptoms (CT cohort) or restriction to patients with prestroke diffusion-weighted imaging (DWI) lesion size >3.75 mL (MRI cohort). Probabilities of having a parenchymal hematoma were determined using multivariate logistic regression. Results: A total of 392 patients in the CT cohort and 400 patients in the MRI cohort were evaluated. Although NIHSS scores were similar in strokes of both hemispheres (median NIHSS: CT: 15 vs 13, MRI: 14 vs 16), the frequencies of parenchymal hematoma were higher in right hemispheric compared to left hemispheric strokes (CT: 12.4% vs 5.7%, MRI: 10.4% vs 6.8%). After adjustment for potential confounders (but not pretreatment lesion volume), the probability of parenchymal hematoma was higher in right hemispheric nonlacunar strokes (CT: odds ratio [OR] 2.3; 95% confidence interval [CI] 1.08–4.89; p = 0.032) and showed a borderline significant effect in the MRI cohort (OR 2.1; 95% CI 0.98–4.49; p = 0.057). Adjustment for pretreatment DWI lesion size eliminated hemispheric differences in hemorrhage risk. Conclusions: Higher hemorrhage rates in right hemispheric nonlacunar strokes despite similar stroke severity may be caused by clinical underestimation of the proportion of tissue at bleeding risk. PMID:21248275

Opportunities and challenges in the wider adoption of liver and interconnected microphysiological systems

PubMed Central

Kostrzewski, Tomasz; Sceats, Emma L

2017-01-01

Liver disease represents a growing global health burden. The development of in vitro liver models which allow the study of disease and the prediction of metabolism and drug-induced liver injury in humans remains a challenge. The maintenance of functional primary hepatocytes cultures, the parenchymal cell of the liver, has historically been difficult with dedifferentiation and the consequent loss of hepatic function limiting utility. The desire for longer term functional liver cultures sparked the development of numerous systems, including collagen sandwiches, spheroids, micropatterned co-cultures and liver microphysiological systems. This review will focus on liver microphysiological systems, often referred to as liver-on-a-chip, and broaden to include platforms with interconnected microphysiological systems or multi-organ-chips. The interconnection of microphysiological systems presents the opportunity to explore system level effects, investigate organ cross talk, and address questions which were previously the preserve of animal experimentation. As a field, microphysiological systems have reached a level of maturity suitable for commercialization and consequent evaluation by a wider community of users, in academia and the pharmaceutical industry. Here scientific, operational, and organizational considerations relevant to the wider adoption of microphysiological systems will be discussed. Applications in which microphysiological systems might offer unique scientific insights or enable studies currently feasible only with animal models are described, and challenges which might be addressed to enable wider adoption of the technologies are highlighted. A path forward which envisions the development of microphysiological systems in partnerships between academia, vendors and industry, is proposed. Impact statement Microphysiological systems are in vitro models of human tissues and organs. These systems have advanced rapidly in recent years and are now being commercialized. To achieve wide adoption in the biological and pharmaceutical research communities, microphysiological systems must provide unique insights which translate to humans. This will be achieved by identifying key applications and making microphysiological systems intuitive to use. PMID:28504617

Opportunities and challenges in the wider adoption of liver and interconnected microphysiological systems.

PubMed

Hughes, David J; Kostrzewski, Tomasz; Sceats, Emma L

2017-10-01

Liver disease represents a growing global health burden. The development of in vitro liver models which allow the study of disease and the prediction of metabolism and drug-induced liver injury in humans remains a challenge. The maintenance of functional primary hepatocytes cultures, the parenchymal cell of the liver, has historically been difficult with dedifferentiation and the consequent loss of hepatic function limiting utility. The desire for longer term functional liver cultures sparked the development of numerous systems, including collagen sandwiches, spheroids, micropatterned co-cultures and liver microphysiological systems. This review will focus on liver microphysiological systems, often referred to as liver-on-a-chip, and broaden to include platforms with interconnected microphysiological systems or multi-organ-chips. The interconnection of microphysiological systems presents the opportunity to explore system level effects, investigate organ cross talk, and address questions which were previously the preserve of animal experimentation. As a field, microphysiological systems have reached a level of maturity suitable for commercialization and consequent evaluation by a wider community of users, in academia and the pharmaceutical industry. Here scientific, operational, and organizational considerations relevant to the wider adoption of microphysiological systems will be discussed. Applications in which microphysiological systems might offer unique scientific insights or enable studies currently feasible only with animal models are described, and challenges which might be addressed to enable wider adoption of the technologies are highlighted. A path forward which envisions the development of microphysiological systems in partnerships between academia, vendors and industry, is proposed. Impact statement Microphysiological systems are in vitro models of human tissues and organs. These systems have advanced rapidly in recent years and are now being commercialized. To achieve wide adoption in the biological and pharmaceutical research communities, microphysiological systems must provide unique insights which translate to humans. This will be achieved by identifying key applications and making microphysiological systems intuitive to use.

Detection of antibodies to single-stranded DNA in naturally acquired and experimentally induced viral hepatitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gust, I.D.; Feinstone, S.M.; Purcell, R.H.

1980-01-01

A sensitive ''Farr'' assay, utilizing /sup 125/I-labelled DNA was developed for detecting antibody to single-stranded DNA (anti-ssDNA). The test was shown to be specific and as sensitive as assays using /sup 14/C-labelled DNA, for the detection of antibody in patients with connective tissue diseases. Groups of sera from patients with naturally acquired viral hepatitis and experimentally infected chimpanzees were tested for anti-ssDNA by the /sup 125/I assay and by counterimmunoelectrophoresis (CIEP). No consistent pattern was observed with either technique, indicating the elevated levels of this antibody are not as reliable markers of parenchymal liver damage as had been previously suggested.

Post-traumatic hepatic arterial pseudoaneurysm and arterioportal shunt.

PubMed

Maes, J; D'Archambeau, O; Snoeckx, A; Op de Beeck, B; Voormolen, M; Parizel, P M

2010-01-01

The authors report the case of a 21-year-old man who suffered from a blunt abdominal trauma. Initial imaging revealed a liver laceration at the right lobe, a perirenal hematoma of the right kidney and a hematoma of the right adrenal gland. Follow-up MDCT-scan on day 10 after admission showed at the arterial-phase contrast-enhanced study perfusion alterations and two hepatic pseudoaneurysms. The diagnosis of pseudoaneurysm was confirmed and treated angiographically with superselective coil embolization. A follow-up CT-scan on day 17 showed at a nontreated area an arterioportal shunt and a wedge-shaped transient hepatic parenchymal enhancement. This was confirmed angiographically and subsequently treated with coil embolization.

[Liver Atrophy and Failure Associated with Paclitaxel and Bevacizumab Combination Therapy for Metastatic Breast Cancer].

PubMed

Yamamoto, Mari; Ikeda, Masahiko; Kubo, Shinichiro; Tsukioki, Takahiro; Nakamoto, Shougo

2016-07-01

We managed 6 cases of severe liver atrophy and failure associated with paclitaxel and bevacizumab combination therapy (PB therapy)for HER2-negative metastatic breast cancer. In this case-controlstudy, we examined the records of these 6 patients to investigate past treatment, medication history, and degree of atrophy, and compared their data with that of 67 patients without liver atrophy. The degree of the liver atrophy used SYNAPSE VINCENT®of the image analysis software. The results showed that patients with liver atrophy had a longer pretreatment period than those without liver atrophy(33.5 months vs 15.5 months), and they also experienced a longer median time to treatment failure with PB therapy than other patients(11 months vs 6 months). The ratio of individuals presenting with diffuse liver metastasis among patients with liver metastasis was 80% with liver atrophy, compared to 8% without liver atrophy. The degree of liver atrophy was an average of 67%in terms of volume ratio before/after PB therapy(57-82%). The individualwith the greatest extent of liver atrophy died of liver failure, not as a result of breast cancer progression. The direct causal link between bevacizumab and liver atrophy and failure is unclear, but the individuals in this study had a long previous history of treatment, and diffuse liver metastases may develop in patients undergoing long periods of PB therapy, which may also cause liver atrophy; therefore, the possibility of liver failure should be considered in such cases.

General Anesthesia Inhibits the Activity of the “Glymphatic System”

PubMed Central

Gakuba, Clement; Gaberel, Thomas; Goursaud, Suzanne; Bourges, Jennifer; Di Palma, Camille; Quenault, Aurélien; Martinez de Lizarrondo, Sara; Vivien, Denis; Gauberti, Maxime

2018-01-01

INTRODUCTION: According to the “glymphatic system” hypothesis, brain waste clearance is mediated by a continuous replacement of the interstitial milieu by a bulk flow of cerebrospinal fluid (CSF). Previous reports suggested that this cerebral CSF circulation is only active during general anesthesia or sleep, an effect mediated by the dilatation of the extracellular space. Given the controversies regarding the plausibility of this phenomenon and the limitations of currently available methods to image the glymphatic system, we developed original whole-brain in vivo imaging methods to investigate the effects of general anesthesia on the brain CSF circulation. METHODS: We used magnetic resonance imaging (MRI) and near-infrared fluorescence imaging (NIRF) after injection of a paramagnetic contrast agent or a fluorescent dye in the cisterna magna, in order to investigate the impact of general anesthesia (isoflurane, ketamine or ketamine/xylazine) on the intracranial CSF circulation in mice. RESULTS: In vivo imaging allowed us to image CSF flow in awake and anesthetized mice and confirmed the existence of a brain-wide CSF circulation. Contrary to what was initially thought, we demonstrated that the parenchymal CSF circulation is mainly active during wakefulness and significantly impaired during general anesthesia. This effect was especially significant when high doses of anesthetic agent were used (3% isoflurane). These results were consistent across the different anesthesia regimens and imaging modalities. Moreover, we failed to detect a significant change in the brain extracellular water volume using diffusion weighted imaging in awake and anesthetized mice. CONCLUSION: The parenchymal diffusion of small molecular weight compounds from the CSF is active during wakefulness. General anesthesia has a negative impact on the intracranial CSF circulation, especially when using a high dose of anesthetic agent. PMID:29344300

General Anesthesia Inhibits the Activity of the "Glymphatic System".

PubMed

Gakuba, Clement; Gaberel, Thomas; Goursaud, Suzanne; Bourges, Jennifer; Di Palma, Camille; Quenault, Aurélien; de Lizarrondo, Sara Martinez; Vivien, Denis; Gauberti, Maxime

2018-01-01

INTRODUCTION: According to the "glymphatic system" hypothesis, brain waste clearance is mediated by a continuous replacement of the interstitial milieu by a bulk flow of cerebrospinal fluid (CSF). Previous reports suggested that this cerebral CSF circulation is only active during general anesthesia or sleep, an effect mediated by the dilatation of the extracellular space. Given the controversies regarding the plausibility of this phenomenon and the limitations of currently available methods to image the glymphatic system, we developed original whole-brain in vivo imaging methods to investigate the effects of general anesthesia on the brain CSF circulation. METHODS: We used magnetic resonance imaging (MRI) and near-infrared fluorescence imaging (NIRF) after injection of a paramagnetic contrast agent or a fluorescent dye in the cisterna magna, in order to investigate the impact of general anesthesia (isoflurane, ketamine or ketamine/xylazine) on the intracranial CSF circulation in mice. RESULTS: In vivo imaging allowed us to image CSF flow in awake and anesthetized mice and confirmed the existence of a brain-wide CSF circulation. Contrary to what was initially thought, we demonstrated that the parenchymal CSF circulation is mainly active during wakefulness and significantly impaired during general anesthesia. This effect was especially significant when high doses of anesthetic agent were used (3% isoflurane). These results were consistent across the different anesthesia regimens and imaging modalities. Moreover, we failed to detect a significant change in the brain extracellular water volume using diffusion weighted imaging in awake and anesthetized mice. CONCLUSION: The parenchymal diffusion of small molecular weight compounds from the CSF is active during wakefulness. General anesthesia has a negative impact on the intracranial CSF circulation, especially when using a high dose of anesthetic agent.

Experiment K-6-12. Morphometric studies of atrial or granules and hepatocytes. Part 1: Morphometric study of the liver; Part 2: The atrial granular accumulations

NASA Technical Reports Server (NTRS)

Kraft, L. M.; Keil, L. C.; Popova, I. A.

1990-01-01

The livers of flight, F, rats from the Cosmos 1887 mission were markedly paler and heavier than those of the synchronous, S, and vivarium, V, controls. In the F group, microscopic study revealed extensive hepatocytic intracytoplasmic vacuolization which was moderate in the S and minimal in the V groups. The vacuoles were not sudanophilic and therefore were regarded as glycogenic in origin. To obtain objective data concerning the extent of the vacuolization, livers were examined by computer assisted morphometry. Measurements of profile area and perimeter of the hepatocyte nuclei and vacuoles were evaluated according to stereological principles. Results indicated that the volume density of the nuclei was less in the F group than in the S(p equal less than 0.0002) and V(p equal less than 0.001) groups. Mean volume of individual nuclei did not differ. Volume density of the vacuoles was greater in the F than in the V group (p equal less than 0.02) while their mean diameter was less (p equal less than 0.05). To ascertain the relationship between increase in liver weight of the flight animals and the results of this study, an assumption was made that the specific gravity of the vacuolar contents was similar to the other extranuclear components of the hepatocyte. On that basis, calculations showed that the elevated vacuolar volume density in the flight group did not cause the increased liver weight in those animals, but that the non-nuclear, non-vacuolar parenchymal compartment did contribute significantly. Factors that may have played a causal role in liver weight and vacuolar compartment increases are discussed.

Systematic review and meta-analysis of feasibility, safety, and efficacy of a novel procedure: associating liver partition and portal vein ligation for staged hepatectomy.

PubMed

Schadde, Erik; Schnitzbauer, Andreas A; Tschuor, Christoph; Raptis, Dimitri A; Bechstein, Wolf O; Clavien, Pierre-Alain

2015-09-01

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a novel strategy to resect liver tumors despite the small size of the liver remnant. It is an hepatectomy in two stages, with PVL and parenchymal transection during the first stage, which induces rapid growth of the remnant liver exceeding any other technique. Despite high postoperative morbidity and mortality in most reports, the technique was adopted by a number of surgeons. This systematic review explores current data regarding the feasibility, safety, and oncologic efficacy of ALPPS; the search strategy has been published online. A meta-analysis of hypertrophy, feasibility (ALPPS stage 2 performed), mortality, complications, and R0 (complete) resection was performed. A literature search revealed a total of 13 publications that met the search criteria, reporting data from 295 patients. Evidence levels were low, with the highest Oxford evidence level being 2c. The most common indication was colorectal liver metastasis in 203 patients. Hypertrophy in the meta-analysis was 84 %, feasibility (ALPPS stage 2 performed) 97 % (CI 94-99 %), 90-day mortality 11 % (CI 8-16 %), and complications grade IIIa or higher occured in 44 % (CI 38-50 %) of patients. A standardized reporting format for complications is lacking despite the widespread use of the Clavien-Dindo classification. Oncological outcome is not well-documented. The most common topics in the selected studies published were technical feasibility and indications for the procedures. Publication bias due to case-series and single-center reports is common. A systematic exploration of this novel operation with a rigid methodology, such as registry analyses and a randomized controlled trial, is highly advised.

Chip-based human liver-intestine and liver-skin co-cultures--A first step toward systemic repeated dose substance testing in vitro.

PubMed

Maschmeyer, Ilka; Hasenberg, Tobias; Jaenicke, Annika; Lindner, Marcus; Lorenz, Alexandra Katharina; Zech, Julie; Garbe, Leif-Alexander; Sonntag, Frank; Hayden, Patrick; Ayehunie, Seyoum; Lauster, Roland; Marx, Uwe; Materne, Eva-Maria

2015-09-01

Systemic repeated dose safety assessment and systemic efficacy evaluation of substances are currently carried out on laboratory animals and in humans due to the lack of predictive alternatives. Relevant international regulations, such as OECD and ICH guidelines, demand long-term testing and oral, dermal, inhalation, and systemic exposure routes for such evaluations. So-called "human-on-a-chip" concepts are aiming to replace respective animals and humans in substance evaluation with miniaturized functional human organisms. The major technical hurdle toward success in this field is the life-like combination of human barrier organ models, such as intestine, lung or skin, with parenchymal organ equivalents, such as liver, at the smallest biologically acceptable scale. Here, we report on a reproducible homeostatic long-term co-culture of human liver equivalents with either a reconstructed human intestinal barrier model or a human skin biopsy applying a microphysiological system. We used a multi-organ chip (MOC) platform, which provides pulsatile fluid flow within physiological ranges at low media-to-tissue ratios. The MOC supports submerse cultivation of an intact intestinal barrier model and an air-liquid interface for the skin model during their co-culture with the liver equivalents respectively at (1)/100.000 the scale of their human counterparts in vivo. To increase the degree of organismal emulation, microfluidic channels of the liver-skin co-culture could be successfully covered with human endothelial cells, thus mimicking human vasculature, for the first time. Finally, exposure routes emulating oral and systemic administration in humans have been qualified by applying a repeated dose administration of a model substance - troglitazone - to the chip-based co-cultures. Copyright © 2015. Published by Elsevier B.V.

Intraoperative Hyperglycemia during Liver Resection: Predictors and Association with the Extent of Hepatocytes Injury

PubMed Central

Han, Sangbin; Ko, Justin Sangwook; Jin, Sang-Man; Park, Hyo-Won; Kim, Jong Man; Joh, Jae-Won; Kim, Gaabsoo; Choi, Soo Joo

2014-01-01

Background Patients undergoing liver resection are at risk for intraoperative hyperglycemia and acute hyperglycemia is known to induce hepatocytes injury. Thus, we aimed to evaluate whether intraoperative hyperglycemia during liver resection is associated with the extent of hepatic injury. Methods This 1 year retrospective observation consecutively enrolled 85 patients undergoing liver resection for hepatocellular carcinoma. Blood glucose concentrations were measured at predetermined time points including every start/end of intermittent hepatic inflow occlusion (IHIO) via arterial blood analysis. Postoperative transaminase concentrations were used as surrogate parameters indicating the extent of surgery-related acute hepatocytes injury. Results Thirty (35.5%) patients developed hyperglycemia (blood glucose > 180 mg/dl) during surgery. Prolonged (≥ 3 rounds) IHIO (odds ratio [OR] 7.34, P = 0.004) was determined as a risk factors for hyperglycemia as well as cirrhosis (OR 4.07, P = 0.022), lower prothrombin time (OR 0.01, P = 0.025), and greater total cholesterol level (OR 1.04, P = 0.003). Hyperglycemia was independently associated with perioperative increase in transaminase concentrations (aspartate transaminase, β 105.1, standard error 41.7, P = 0.014; alanine transaminase, β 81.6, standard error 38.1, P = 0.035). Of note, blood glucose > 160 or 140 mg/dl was not associated with postoperative transaminase concentrations. Conclusions Hyperglycemia during liver resection might be associated with the extent of hepatocytes injury. It would be rational to maintain blood glucose concentration < 180 mg/dl throughout the surgery in consideration of parenchymal disease, coagulation status, lipid profile, and the cumulative hepatic ischemia in patients undergoing liver resection for hepatocellular carcinoma. PMID:25295519

MRI-based staging of hepatic fibrosis: Comparison of intravoxel incoherent motion diffusion-weighted imaging with magnetic resonance elastography.

PubMed

Ichikawa, Shintaro; Motosugi, Utaroh; Morisaka, Hiroyuki; Sano, Katsuhiro; Ichikawa, Tomoaki; Enomoto, Nobuyuki; Matsuda, Masanori; Fujii, Hideki; Onishi, Hiroshi

2015-07-01

To evaluate the use of intravoxel incoherent motion (IVIM) imaging for staging hepatic fibrosis, and compare its staging ability with that of magnetic resonance elastography (MRE). This study included 129 patients with pathologically staged liver fibrosis, and 53 patients with healthy livers. All patients underwent both MRE and IVIM imaging. Four diffusivity indices were calculated with 11 b-values; slow diffusion coefficient related to molecular diffusion (D), fast diffusion coefficient related to perfusion in micro-vessels (D*), perfusion-related diffusion fraction (f), and apparent diffusion coefficient (ADC). Receiver operating characteristic curve analysis was performed to determine the accuracy of IVIM imaging and MRE for staging hepatic fibrosis. D*, f, and ADC values decreased significantly with fibrosis stage (P < 0.0124), and liver stiffness increased (P < 0.0001). The Az value of MRE was significantly higher than that of D* for all fibrosis stages (D* vs. MRE for ≥ F1, 0.851 vs. 0.992 [P < 0.0001]; ≥ F2, 0.898 vs. 0.998 [P = 0.0003]; ≥ F3, 0.904 vs. 0.995 [P = 0.0004]; F4, 0.885 vs. 0.996 [P < 0.0001]). IVIM imaging is a useful technique for evaluating hepatic fibrosis, but MRE is better able to discriminate fibrosis stages than IVIM imaging. © 2014 Wiley Periodicals, Inc.

Neural net classification of liver ultrasonogram for quantitative evaluation of diffuse liver disease

NASA Astrophysics Data System (ADS)

Lee, Dong Hyuk; Kim, JongHyo; Kim, Hee C.; Lee, Yong W.; Min, Byong Goo

1997-04-01

There have been a number of studies on the quantitative evaluation of diffuse liver disease by using texture analysis technique. However, the previous studies have been focused on the classification between only normal and abnormal pattern based on textural properties, resulting in lack of clinically useful information about the progressive status of liver disease. Considering our collaborative research experience with clinical experts, we judged that not only texture information but also several shape properties are necessary in order to successfully classify between various states of disease with liver ultrasonogram. Nine image parameters were selected experimentally. One of these was texture parameter and others were shape parameters measured as length, area and curvature. We have developed a neural-net algorithm that classifies liver ultrasonogram into 9 categories of liver disease: 3 main category and 3 sub-steps for each. Nine parameters were collected semi- automatically from the user by using graphical user interface tool, and then processed to give a grade for each parameter. Classifying algorithm consists of two steps. At the first step, each parameter was graded into pre-defined levels using neural network. in the next step, neural network classifier determined disease status using graded nine parameters. We implemented a PC based computer-assist diagnosis workstation and installed it in radiology department of Seoul National University Hospital. Using this workstation we collected 662 cases during 6 months. Some of these were used for training and others were used for evaluating accuracy of the developed algorithm. As a conclusion, a liver ultrasonogram classifying algorithm was developed using both texture and shape parameters and neural network classifier. Preliminary results indicate that the proposed algorithm is useful for evaluation of diffuse liver disease.

The Impact of Iron Overload in Patients with Acute Leukemia and Myelodysplastic Syndrome on Hepatic and Endocrine functions.

PubMed

Yassin, Mohamed A; Soliman, Ashraf; De Sanctis, Vincenzo; Hmissi, Saloua M; Abdulla, Mohammad Aj; Ekeibed, Yeslem; Ismail, Omer; Nashwan, Abdulqadir; Soliman, Dina; Almusharaf, Mohammed; Hussein, Redwa

2018-04-03

Patients with hematologic malignancies undergoing chemotherapy and requiring blood transfusion usually have an elevated serum ferritin. These findings have led to the suggestion that iron overload is common and may have deleterious effects in these patients. However, the relationship between serum ferritin and parenchymal iron overload in such patients is unknown. Therefore, we measured the liver iron content (LIC) by the FerriScan® method and investigated the liver function and some endocrine tests in 27 patients with acute leukemia (AL) or myelodysplastic syndromes (MDS). Using FerriScan® method, the normal mean LIC levels are: 4.3 ± 2.9 mg Fe/g dry weight (d.w.). In our patients, the mean serum ferritin level was 1965 ± 2428 ng/mL. In our patients, the mean total iron in the blood received by them was 7177 ± 5009 mg. In 6 out of 27 patients LIC was > 7 mg Fe/g d.w. and in 11/27 serum ferritin was > 1000 ng/ml. Measuring fasting blood glucose revealed 3/27 with diabetes mellitus and 4/27 with impaired fasting glucose (IFG). All patients had normal serum concentrations of calcium, parathormone (PTH), free thyroxine (FT4) and thyrotropin (TSH). Four patients had elevated serum alanine transferase (ALT). LIC was correlated significantly with ferritin level (r = 0.5666; P < 0.001) and the cumulative amount of iron in the transfused blood (r = 0.523; P <0.001). LIC was correlated significantly with ALT (r = 0.277; P = 0.04) and fasting blood glucose (FBG) was correlated significantly with the amount of iron transfused (r = 0.52, p < 0.01) and ALT level (r = 0.44; P< 0.01). The age of patients did not correlate with LIC, FBG or ALT. In conclusions, these results contribute to our understanding of the prevalence of dysglycemia and hepatic dysfunction in relation to parenchymal iron overload in patients with hematologic malignancies undergoing chemotherapy and requiring blood transfusions.

Synchronous development of HCC and CCC in the same subsegment of the liver in a patient with type C liver cirrhosis.

PubMed

Watanabe, Takuya; Sakata, Jun; Ishikawa, Takashi; Shirai, Yoshio; Suda, Takeyasu; Hirono, Haruka; Hasegawa, Katsuhiko; Soga, Kenji; Shibasaki, Koichi; Saito, Yukifumi; Umezu, Hajime

2009-10-31

As a result of having undergone computed tomography (CT), a 75-year-old woman with type-C liver cirrhosiswas shown to have two tumors on the ventral and dorsal sides of subsegment 3 (S3). The tumor on the ventral side was diagnosed as a classic hepatocellular carcinoma (HCC), while that on the dorsal side was considered atypical for a HCC. Although the indocyanine green (ICG) findings indicated poor hepatic reserve, the prothrombin time (PT) was relatively good. An operation was performed in February 2007; however, this resulted in exploratory laparotomy. Dynamic CT performed 12 mo after the operation revealed that the tumor on the dorsal side of S3 had apparently increased. The marginal portion of the tumor was shown to be in the early and parenchymal phases, while the internal portion was found to have grown only slightly in the delayed phase. We diagnosed this tumor as a cholangiocellular carcinoma (CCC). S3 subsegmentectomy was performed in April 2008. The tumor on the ventral side was pathologically diagnosed as a moderately differentiated HCC, and that on the dorsal side was diagnosed as a CCC. We can therefore report a rare case of synchronous development of HCC and CCC in the same subsegment of the liver in a patient with type-C liver cirrhosis. We also add a literature review for all the reported cases published in Japan and around the world, and summarize the features of double cancer exhibiting both HCC and CCC.

Radiologic-Pathologic Analysis of Contrast-enhanced and Diffusion-weighted MR Imaging in Patients with HCC after TACE: Diagnostic Accuracy of 3D Quantitative Image Analysis

PubMed Central

Chapiro, Julius; Wood, Laura D.; Lin, MingDe; Duran, Rafael; Cornish, Toby; Lesage, David; Charu, Vivek; Schernthaner, Rüdiger; Wang, Zhijun; Tacher, Vania; Savic, Lynn Jeanette; Kamel, Ihab R.

2014-01-01

Purpose To evaluate the diagnostic performance of three-dimensional (3Dthree-dimensional) quantitative enhancement-based and diffusion-weighted volumetric magnetic resonance (MR) imaging assessment of hepatocellular carcinoma (HCChepatocellular carcinoma) lesions in determining the extent of pathologic tumor necrosis after transarterial chemoembolization (TACEtransarterial chemoembolization). Materials and Methods This institutional review board–approved retrospective study included 17 patients with HCChepatocellular carcinoma who underwent TACEtransarterial chemoembolization before surgery. Semiautomatic 3Dthree-dimensional volumetric segmentation of target lesions was performed at the last MR examination before orthotopic liver transplantation or surgical resection. The amount of necrotic tumor tissue on contrast material–enhanced arterial phase MR images and the amount of diffusion-restricted tumor tissue on apparent diffusion coefficient (ADCapparent diffusion coefficient) maps were expressed as a percentage of the total tumor volume. Visual assessment of the extent of tumor necrosis and tumor response according to European Association for the Study of the Liver (EASLEuropean Association for the Study of the Liver) criteria was performed. Pathologic tumor necrosis was quantified by using slide-by-slide segmentation. Correlation analysis was performed to evaluate the predictive values of the radiologic techniques. Results At histopathologic examination, the mean percentage of tumor necrosis was 70% (range, 10%–100%). Both 3Dthree-dimensional quantitative techniques demonstrated a strong correlation with tumor necrosis at pathologic examination (R2 = 0.9657 and R2 = 0.9662 for quantitative EASLEuropean Association for the Study of the Liver and quantitative ADCapparent diffusion coefficient, respectively) and a strong intermethod agreement (R2 = 0.9585). Both methods showed a significantly lower discrepancy with pathologically measured necrosis (residual standard error [RSEresidual standard error] = 6.38 and 6.33 for quantitative EASLEuropean Association for the Study of the Liver and quantitative ADCapparent diffusion coefficient, respectively), when compared with non-3Dthree-dimensional techniques (RSEresidual standard error = 12.18 for visual assessment). Conclusion This radiologic-pathologic correlation study demonstrates the diagnostic accuracy of 3Dthree-dimensional quantitative MR imaging techniques in identifying pathologically measured tumor necrosis in HCChepatocellular carcinoma lesions treated with TACEtransarterial chemoembolization. © RSNA, 2014 Online supplemental material is available for this article. PMID:25028783

Does apparent diffusion coefficient predict the degree of liver regeneration of donor and recipient after living donor liver transplantation?

PubMed

Morita, Koichiro; Nishie, Akihiro; Asayama, Yoshiki; Ishigami, Kousei; Ushijima, Yasuhiro; Takayama, Yukihisa; Okamoto, Daisuke; Fujita, Nobuhiro; Ikegami, Toru; Yoshizumi, Tomoharu; Shirabe, Ken; Honda, Hiroshi

2017-05-01

To elucidate the relationship between the ADCs of the liver graft and the remnant liver and the degree of liver regeneration in LDLT. 15 recipients and 15 corresponding donors underwent magnetic resonance imaging and computed tomography 1-2 weeks after living donor liver transplantation (LDLT). For diffusion-weighted imaging (DWI), a single-shot echo-planar sequence with b-factors of 0, 500, and 1000s/mm 2 was scanned. ADCs of the liver parenchyma were calculated at b factors of 0 and 500 and 1000 (ADC 0-500-1000) or 0 and 500 (ADC 0-500) or 500 and 1000 (ADC 500-1000). The liver volume ratio at LDLT, the mean ADCs and the regeneration rate were compared between the graft and the remnant liver using paired-t tests. The mean liver volume ratio of the recipients (41.3±9.8%) tended to be smaller than that of the donors (51.8±13.8%). The mean ADC 0-500 of the remnant liver (1.72±0.33) was significantly higher than that of the graft (1.43±0.32). The regeneration rate of the graft (2.07±0.41) was significantly higher than that of the remnant liver (1.53±0.49). ADC 0-500 can describe differences in blood perfusion between liver grafts and the remnant liver according to the degree of liver regeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

Test-retest reliability of diffusion tensor imaging of the liver at 3.0 T.

PubMed

Girometti, Rossano; Maieron, Marta; Lissandrello, Giovanni; Bazzocchi, Massimo; Zuiani, Chiara

2015-06-01

This study was done to evaluate test-retest reliability of liver diffusion tensor imaging (LDTI). Ten healthy volunteers (median age 23 years) underwent two LDTI scans on a 3.0 T magnet during two imaging sessions separated by 2 weeks (session-1/-2, respectively). Fifteen gradient directions and b values of 0-1,000 s/mm(2) were used. Two radiologists in consensus assessed liver apparent diffusion coefficient (ADC) and fraction of anisotropy (FA) values on ADC and FA maps at four reference levels, namely: right upper level (RUL), right lower level (RLL), left upper level (LUL) and left lower level (LLL). We then assessed (a) whether ADC and FA values overlapped when measured on different levels within the same imaging session or between different imaging sessions; (b) the degree of variability on an intra-session and inter-session basis, respectively, using the coefficient of variation (CV). In sessions 1 and 2, the ADC/FA values were significantly larger in the left liver lobe (LUL/LLL) compared to right liver lobe (RUL/RLL) (p < 0.05/6). Intra-session CVs were 9.51 % (session 1) and 9.73 % (session 2) for ADC, and 12.93 % (session 1) and 11.82 % (session 2) for FA, respectively. When comparing RUL, RLL, LUL and LLL on an inter-session basis, CVs were 6.52, 8.20, 6.52 and 11.06 % for ADC, and 15.42, 15.80, 15.42 and 6.80 % for FA, respectively. LDTI provides consistent and repeatable measurements. However, since larger left lobe ADC/FA values can be attributed to artefacts, right lobe values should be considered the most reliable measurements of water diffusivity within the liver.

Pulmonary distribution of an inhaled radioaerosol in obstructive pulmonary disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, M.S.; Goodwin, D.A.

1976-03-01

Pulmonary distribution of an inhaled radioaerosol was analyzed in 20 cases of chronic obstructive pulmonary disease (COPD) and 8 of other OPD. Nonciliary/ciliary partition of the distribution correlated with the severity of airway obstruction and approximated 3 : 1 in mild and 1 : 3 in very severe obstruction. In nuclear images, the distribution featured contrast abnormalities of hyperdeposition and hypodeposition. Intense hyperdeposition most commonly occurred in hilar and perihilar large airways. In isolated instances, hyperdeposition almost certainly occurred focally at sites of partial bronchial obstruction and diffusely by expiratory trapping; hypodeposition occurred distally to bronchial obstruction and in areasmore » of parenchymal loss. (auth)« less

Update in Diffuse Parenchymal Lung Disease 2013

PubMed Central

Kaminski, Naftali

2015-01-01

The period covered by this update can be considered as the most exciting period in idiopathic pulmonary fibrosis (IPF) research. It started with the identification of genetic variants that are associated with IPF in the majority of patients and continued with discovery of molecular and genetic biomarkers that predict distinct clinical presentations of patients with IPF and potential new biological mechanisms. More importantly, the period ends with the publication of two groundbreaking studies that confirmed that two drugs, pirfenidone and nintedanib, slowed disease progression, leading to a historic approval by the FDA. In this update, we describe these key advances, their scientific and significant clinical implications, and future directions. PMID:25635490

Diagnosis of focal liver lesions suspected of metastases by diffusion-weighted imaging (DWI): systematic comparison favors free-breathing technique.

PubMed

Baltzer, Pascal A T; Schelhorn, Juliane; Benndorf, Matthias; Dietzel, Matthias; Kaiser, Werner A

2013-01-01

Two echo planar imaging diffusion-weighted imaging (DWI) techniques [one breath hold (DWI(bh)), repetition time/echo time (TR/TE) 2100/62 ms; one at free breathing (DWI(fb)), TR/TE 2000/65 ms] were compared regarding diagnosis of focal liver lesions (FLLs) in 45 patients with suspected liver metastasis without prior treatment. Apparent diffusion coefficient values of 46 benign and 67 malignant FLLs were analyzed by receiver operating characteristics (ROC) analysis. DWI(fb) detected more malignant lesions than DWI(bh) (P=.002). Lesion size ≤10 mm was associated with FLLs missed by DWI(bh) (P=.018). Area under the ROC curve of DWI(fb) (0.801) was higher compared to that of DWI(bh) (0.669, P<.0113), demonstrating the diagnostic superiority of DWI(fb). Copyright © 2013 Elsevier Inc. All rights reserved.

Optimization of the isolation and cultivation of Cyprinus carpio primary hepatocytes.

PubMed

Yanhong, Fan; Chenghua, He; Guofang, Liu; Haibin, Zhang

2008-10-01

The aquatic environment is affected by numerous chemical contaminants. There is an increasing need to identify these chemicals and to evaluate their potential toxicity towards aquatic life. In this research we optimized techniques for primary cell culture of Cyprinus carpio hepatocytes as one adjunct model for ecotoxicological evaluation of the potential hazards of xenobiotics in the aquatic environment. In this study, Cyprinus carpio hepatocytes were isolated by mechanical separation, two-step collagenase perfusion, and pancreatin digestion. The hepatocytes or parenchymal cells could be separated from cell debris and from non-parenchymal cells by low-speed centrifugation (Percoll gradient centrifugation). The harvested hepatocytes were suspended in DMEM, M199 (cultured in 5% CO(2)), or L-15 (cultured without 5% CO(2)) medium then cultured at 17, 27, or 37 degrees C. Cell yield was counted by use of a hemocytometer, and the viability of the cells was assessed by use of the Trypan blue exclusion test. Results from these studies showed that the best method of isolation was pancreatin digestion (the cell yield was 2.7 x 10(8) per g (liver weight) and the viability was 98.4%) and the best medium was M199 (cultured in 5% CO(2)) or L-15 (cultured without 5% CO(2)). The optimum culture temperature was 27 degrees C. The primary hepatocytes culture of Cyprimus carpio grew well and satisfied requirements for most toxicological experiments in this condition.

Irreversible electroporation in the treatment of locally advanced pancreas and liver metastases of colorectal carcinoma

PubMed Central

Wichtowski, Mateusz; Nowaczyk, Piotr; Kocur, Jacek

2016-01-01

Aim of the study Irreversible electroporation is a new, non-thermal ablation technique in the treatment of parenchymal organ tumors which uses short high voltage pulses of electricity in order to induce apoptosis of targeted cells. In this paper the application of this method of treatment in locally advanced pancreatic cancer (LAPC) and liver cancer is analyzed. Material and methods Between 04.2014 and 09.2014 two patients with LAPC and one with colorectal liver metastasis (CRLM) were qualified for treatment with irreversible electroporation. Both patients remained under constant observation and control. PubMed/Medline, Embase and Google Scholar databases were searched and eight original reports on irreversible electroporation of pancreatic and liver tumors based on the biggest groups of patients were found. Results Two patients with LAPC and one with CRLM were qualified for ablation with irreversible electroporation. In all three patients a successful irreversible electroporation (IRE) procedure of the whole tumor was conducted. In the minimum seven-month follow-up 100% local control was achieved – without progression. In the literature review the local response to treatment ranged from 41% to 100%. The event-free survival rate in six-month observation was 94%. Conclusions Ablation with irreversible electroporation is a new non-thermal ablation technique which has been demonstrated, both in the previously published studies and in the cases described in this paper, as a safe and efficient therapeutic method for patients with LAPC and CRLM. PMID:27095938

Mediated effect of endotoxin and lead upon hepatic metabolism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuttner, R.E.; Ebata, T.; Schumer, W.

A test was made of the possibility that gram-negative bacterial cell wall lipopolysaccharides acted directly on key glucoregulatory enzymes in rat liver cytosol to cause the characteristic hypoglycemia of severe endotoxemia. Fasted male rats were sensitized to endotoxin by the simultaneous intravenous injection of lead acetate. The minimum systemic dosage of endotoxin necessary to perturb the normal pattern of hepatic glycolytic intermediates was determined by serial testing with diminishing dosages of endotoxin. The hepatocyte concentration of endotoxin was then calculated from this minimum dosage by use of literature data on the fraction of endotoxin delivered to liver cells after amore » systemic intravenous injection of radiochromium labeled lipopolysaccharides. Accepting a molecular weight of 118,000 daltons for the smallest endotoxin monomer capable of evoking a physiologic response, the molar amount of endotoxin present in 1 gram of hepatocytes was readily calculated. The concentration of glucoregulatory enzymes in parenchymal cells was then estimated from other literature sources. It was found that the amount of endotoxin in the hepatocytes was insufficient to combine directly with even 1 per cent of the quantity of a single key glucoregulatory enzyme in liver parenchyma. Since a one to one stoichiometric reaction between endotoxin and enzyme could not occur in the liver cytosol, a direct interaction mechanism between agonist and biocatalyst can be ruled out. It is concluded that bacterial endotoxin must act on hepatic glucoregulation by an indirect mechanism presumably based upon the release and operation of mediators.« less

Evaluation of Medicinal Plant Hepatotoxicity in Co-cultures of Hepatocytes and Monocytes

PubMed Central

Saad, Bashar; Dakwar, Suha; Said, Omar; Abu-Hijleh, Ghassan; Battah, Feras Al; Kmeel, Abedelsalam; Aziazeh, Hassan

2006-01-01

Non-parenchymal cells might play an important role in the modulation of xenobiotic metabolism in liver and its pharmacological and toxicological consequences. Therefore, the role of cell-to-cell interactions in herbal induced liver toxicity was investigated in monocultures of cells from the human hepatocyte cell line (HepG2) and in co-cultures of cells from the HepG2 cell line and cells from the human monocyte cell line (THP1). Cells were treated with various concentrations (1–500 µg ml−1) of extracts of Pistacia palaestina, Juglans regia and Quercus ithaburensis for 24 h. Extracts from Cleome droserifolia, a known toxic plant, were taken as positive control. In the co-culture system, toxic effects were observed after exposure to extracts of Pistacia palestina and C. droserifolia. These two extracts significantly reduced by cell viability as measured the MTT test and the LDH assay. Whereas in hepatocyte cultures, only extracts of C. droserifolia were found to affect the cell viability. The production levels of albumin from hepatocytes were not affected by treatment with plant extracts in both culture systems. It seems that the observed reduction in cell viability after exposure to extracts of P. palestina in co-cultures but not in monocultures is a result of monocyte-derived factors. The use of liver cell co-cultures is therefore a useful approach to investigate the influence of intercellular communication on xenobiotic metabolism in liver. PMID:16550229

Comparison of renal ultrasonography and dimercaptosuccinic acid renal scintigraphy in febrile urinary tract infection.

PubMed

Ayazi, Parviz; Mahyar, Abolfazl; Noroozian, Elham; Esmailzadehha, Neda; Barikani, Ameneh

2015-12-01

Accurate and early diagnosis and appropriate treatment of patient with urinary tract infection (UTI) are essential for the prevention or restriction of permanent damage to the kidneys in children. The aim of this study was to compare renal ultrasonography (US) and dimercaptosuccinic acid (DMSA) renal scan in the diagnosis of patients with febrile urinary tract infection. This study involved the medical records of children with febrile urinary tract infection who were admitted to the children's hospital in Qazvin, Iran. Pyelonephritis was diagnosed on the basis of clinical symptoms, laboratory tests and abnormal DMSA renal scans. The criteria for abnormality of renal US were an increase or a decrease in diffuse or focal parenchymal echogenicity, loss of corticomedullary differentiation, kidney position irregularities, parenchymal reduction and increased kidney size. Of the 100 study patients, 23% had an abnormal US and 46% had an abnormal DMSA renal scan. Of the latter patients, 15 had concurrent abnormal US (P value ≤ 0.03, concordance rate: 18%). Renal US had a sensitivity of 32%, specificity of 85%, positive predictive value of 65% and negative predictive value of 60%. Of the 77 patients with normal US, 31 (40.2%) had an abnormal DMSA renal scan. Despite the benefits and accessibility of renal US, its value in the diagnosis of pyelonephritis is limited.

Craniofacial and brain abnormalities in Laron syndrome (primary growth hormone insensitivity).

PubMed

Kornreich, L; Horev, G; Schwarz, M; Karmazyn, B; Laron, Z

2002-04-01

To investigate abnormalities in the craniofacial structures and in the brain in patients with Laron syndrome. Eleven patients with classical Laron syndrome, nine untreated adults aged 36-68 years and two children aged 4 and 9 years (the latter treated by IGF-I), were studied. Magnetic resonance images of the brain were obtained in all the patients. One patient also underwent computed tomography. The maximal diameter of the maxillary and frontal sinuses was measured and compared with reference values, the size of the sphenoid sinus was evaluated in relation to the sella, and the mastoids were evaluated qualitatively (small or normal). The brain was evaluated for congenital anomalies and parenchymal lesions. In the adult untreated patients, the paranasal sinuses and mastoids were small; in six patients, the bone marrow in the base of the skull was not mature. The diploe of the calvaria was thin. On computed tomography in one adult patient, the sutures were still open. A minimal or mild degree of diffuse brain parenchymal loss was seen in ten patients. One patient demonstrated a lacunar infarct and another periventricular high signals on T2-weighted images. Two patients had cerebellar atrophy. The present study has demonstrated the important role IGF-I plays in the development of the brain and bony structures of the cranium.

Quantitative liver ADC measurements using diffusion-weighted MRI at 3 Tesla: evaluation of reproducibility and perfusion dependence using different techniques for respiratory compensation.

PubMed

Larsen, Nis Elbrønd; Haack, Søren; Larsen, Lars Peter Skovgaard; Pedersen, Erik Morre

2013-10-01

Diffusion weighted imaging (DWI) of the liver suffers from low signal to noise making 3 Tesla (3 T) an attractive option, but 3 T data is scarce. It was the aim to study the influence of different b values and respiratory compensation methods (RCM) on the apparent diffusion coefficient (ADC) level and on ADC reproducibility at 3 T. Ten healthy volunteers and 12 patients with malignant liver lesions underwent repeated (2-22 days) breathhold, free-breathing and respiratory triggered DWI at 3 T using b values between 0 and 1,000 s/mm(2). The ADCs changed up to 150% in healthy livers and up to 48% in malignant lesions depending on b value combinations. Best ADC reproducibility in healthy livers were obtained with respiratory triggering (95% limits of agreement: ±0.12) and free-breathing (±0.14). In malignant lesions equivalent reproducibility was obtained with less RCM dependence. The use of a lower maximum b value (b = 500) decreased reproducibility (±0.14 to ±0.32) in both normal liver and malignant lesions. Large differences in absolute ADC values and reproducibility caused by varying combinations of clinically realistic b values were demonstrated. Different RCMs caused smaller differences. Lowering maximum b value to 500 increased limits of agreement up to a factor of two. Serial ADC changes larger than approximately 15% can be detected confidently on an individual basis in both malignant lesions and normal liver parenchyma at 3 T using appropriate b values and respiratory compensation.

Regulation of CTL responses to MHC-restricted class I peptide of the gp70 tumour antigen by splenic parenchymal CD4+ T cells in mice failing immunotherapy with DISC-mGM-CSF.

PubMed

Ahmad, Murrium; Rees, Robert C; McArdle, Stephanie E; Li, Geng; Mian, Shahid; Entwisle, Claire; Loudon, Peter; Ali, Selman A

2005-07-20

Direct intratumour injection of the disabled infectious single-cycle-herpes simplex virus-encoding murine granulocyte/macrophage colony-stimulating factor (DISC-HSV-mGM-CSF) into established colon carcinoma CT26 tumours induced complete tumour rejection in up to 70% of treated animals (regressors), while the remaining mice developed progressive tumours (progressors). This murine Balb/c model was used to dissect the cellular mechanisms involved in tumour regression or progression following immunotherapy. CTLs were generated by coculturing lymphocytes and parenchymal cells from the same spleens of individual regressor or progressor animals in the presence of the relevant AH-1 peptide derived from the gp70 tumour-associated antigens expressed by CT26 tumours. Tumour regression was correlated with potent CTL responses, spleen weight and cytokine (IFN-gamma) production. Conversely, progressor splenocytes exhibited weak to no CTL activity and poor IFN-gamma production, concomitant with the presence of a suppressor cell population in the progressor splenic parenchymal cell fraction. Further fractionation of this parenchymal subpopulation demonstrated that cells inhibitory to the activation of AH-1-specific CTLs, restimulated in vitro with peptide, were present in the nonadherent parenchymal fraction. In vitro depletion of progressor parenchymal CD3+/CD4+ T cells restored the CTL response of the cocultured splenocytes (regressor lymphocytes and progressor parenchymal cells) and decreased the production of IL-10, suggesting that CD3+CD4+ T lymphocytes present in the parenchymal fraction regulated the CTL response to AH-1. We examined the cellular responses associated with tumour rejection and progression, identifying regulatory pathways associated with failure to respond to immunotherapy. Copyright 2005 Wiley-Liss, Inc.

Cross-sectional investigation of correlation between hepatic steatosis and IVIM perfusion on MR imaging.

PubMed

Lee, James T; Liau, Joy; Murphy, Paul; Schroeder, Michael E; Sirlin, Claude B; Bydder, Mark

2012-05-01

The purpose of this study was to investigate the relationship between liver fat fraction (FF) and diffusion parameters derived from the intravoxel incoherent motion (IVIM) model. Thirty-six subjects with suspected nonalcoholic fatty liver disease underwent diffusion-weighted magnetic resonance imaging with 10 b-values and spoiled gradient recalled echo imaging with six echoes for fat quantification. Correlations were measured between FF, transverse relaxivity (R2), diffusivity (D) and perfusion fraction (f). The primary finding was that no significant correlation was obtained for D vs. FF or f vs. FF. Significant correlations were obtained for D vs. R2 (r=-0.490, P=.002) and f vs. D (r=-0.458, P=.005). The conclusion is that hepatic steatosis does not affect measurement of perfusion or diffusion and therefore is unlikely to confound the use of apparent diffusivity to evaluate hepatic fibrosis. Copyright © 2012 Elsevier Inc. All rights reserved.

Altered expression and activation of signal transducers and activators of transcription (STATs) in hepatitis C virus infection: in vivo and in vitro studies.

PubMed

Larrea, E; Aldabe, R; Molano, E; Fernandez-Rodriguez, C M; Ametzazurra, A; Civeira, M P; Prieto, J

2006-08-01

Signal transducers and activators of transcription (STATs) play a critical role in antiviral defence. STAT3 is also important in cell protection against inflammatory damage. STAT proteins are activated by interferons and by hepatoprotective cytokines of the interleukin 6 superfamily, including cardiotrophin 1. We analysed the status of STATs in hepatitis C virus (HCV) infected livers and the relationship between expression and activation of STATs and HCV replication in Huh7 cells transfected with HCV genomic replicon. STAT3alpha expression was reduced in HCV infected livers showing an inverse correlation with serum alanine aminotransferase. In patients with HCV infection, nuclear staining for phosphorylated STAT3 was faint in parenchymal cells (although conspicuous in infiltrating leucocytes), in contrast with strong nuclear staining in hepatocytes from control livers. Expression and activation of STAT1 (a factor activated by both interferon (IFN)-alpha and IFN-gamma) were increased in HCV infected livers, particularly in those with high inflammatory activity. Conversely, phosphorylated STAT2 (a factor selectively activated by IFN-alpha) was undetectable in livers with HCV infection, a finding that was associated with marked downregulation of the two functional subunits of the IFN-alpha receptor. HCV replication in Huh7 cells caused STAT3alpha downregulation and blocked STAT3 phosphorylation by either IFN-alpha or cardiotrophin 1. HCV replication in Huh7 cells also inhibited STAT1 and STAT2 activation by IFN-alpha while there was no impairment of STAT1 phosphorylation by the proinflammatory cytokine IFN-gamma. STAT3 is downregulated in HCV infected livers and in Huh7 cells bearing the full length HCV replicon. HCV replication is associated with impaired Jak-STAT signalling by antiviral and cytoprotective cytokines. These effects may favour viral replication while facilitating the progression of liver disease.

Hybrid procedure in living donor liver transplantation.

PubMed

Soyama, A; Takatsuki, M; Hidaka, M; Adachi, T; Kitasato, A; Kinoshita, A; Natsuda, K; Baimakhanov, Z; Kuroki, T; Eguchi, S

2015-04-01

We have previously reported a hybrid procedure that uses a combination of laparoscopic mobilization of the liver and subsequent hepatectomy under direct vision in living donor liver transplantation (LDLT). We present the details of this hybrid procedure and the outcomes of the procedure. Between January 1997 and August 2014, 204 LDLTs were performed at Nagasaki University Hospital. Among them, 67 recent donors underwent hybrid donor hepatectomy. Forty-one donors underwent left hemihepatectomy, 25 underwent right hemihepatectomy, and 1 underwent posterior sectionectomy. First, an 8-cm subxiphoid midline incision was made; laparoscopic mobilization of the liver was then achieved with a hand-assist through the midline incision under the pneumoperitoneum. Thereafter, the incision was extended up to 12 cm for the right lobe and posterior sector graft and 10 cm left lobe graft procurement. Under direct vision, parenchymal transection was performed by means of the liver-hanging maneuver. The hybrid procedure for LDLT recipients was indicated only for selected cases with atrophic liver cirrhosis without a history of upper abdominal surgery, significant retroperitoneal collateral vessels, or hypertrophic change of the liver (n = 29). For total hepatectomy and splenectomy, the midline incision was sufficiently extended. All of the hybrid donor hepatectomies were completed without an extra subcostal incision. No significant differences were observed in the blood loss or length of the operation compared with conventional open procedures. All of the donors have returned to their preoperative activity level, with fewer wound-related complaints compared with those treated with the use of the conventional open procedure. In recipients treated with the hybrid procedure, no clinically relevant drawbacks were observed compared with the recipients treated with a regular Mercedes-Benz-type incision. Our hybrid procedure was safely conducted with the same quality as the conventional open procedure in both LDLT donors and recipients. Copyright © 2015 Elsevier Inc. All rights reserved.

Coexpression of CD14 and CD326 discriminate hepatic precursors in the human fetal liver.

PubMed

Fomin, Marina E; Tai, Lung-Kuo; Bárcena, Alicia; Muench, Marcus O

2011-07-01

The molecular and cellular profile of liver cells during early human development is incomplete, complicating the isolation and study of hepatocytes, cholangiocytes, and hepatic stem cells from the complex amalgam of hepatic and hematopoietic cells, that is, the fetal liver. Epithelial cell adhesion molecule, CD326, has emerged as a marker of hepatic stem cells, and lipopolysaccharide receptor CD14 is known to be expressed on adult hepatocytes. Using flow cytometry, we studied the breadth of CD326 and CD14 expression in midgestation liver. Both CD45(+) hematopoietic and CD45(-) nonhematopoietic cells expressed CD326. Moreover, diverse cell types expressing CD326 were revealed among CD45(-) cells by costaining for CD14. Fluorescence-activated cell sorting was used to isolate nonhematopoietic cells distinguished by expression of high levels of CD326 and low CD14 (CD326(++)CD14(lo)), which were characterized for gene expression associated with liver development. CD326(++)CD14(lo) cells expressed the genes albumin, α-fetoprotein, hepatic nuclear factor 3α, prospero-related homeobox 1, cytochrome P450 3A7, α(1)-antitrypsin, and transferrin. Proteins expressed included cell-surface CD24, CD26, CD29, CD34, CD49f, CD243, and CD324 and, in the cytoplasm, cytokeratins-7/8 (CAM 5.2 antigen) and some cytokeratin-19. Cultured CD326(++)CD14(lo) cells yielded albumin(+) hepatocytes, cytokeratin-19(+) cholangiocytes, and hepatoblasts expressing both markers. Using epifluorescence microscopy we observed CD326 and CD14 expression on fetal hepatocytes comprising the liver parenchyma, as well as on cells associated with ductal plates and surrounding large vessels. These findings indicate that expression of CD14 and CD326 can be used to identify functionally distinct subsets of fetal liver cells, including CD326(++)CD14(lo) cells, representing a mixture of parenchymal cells, cholangiocytes, and hepatoblasts.

Endoscopic management of biliary complications following liver transplantation after donation from cardiac death donors.

PubMed

Croome, Kris P; McAlister, Vivian; Adams, Paul; Marotta, Paul; Wall, William; Hernandez-Alejandro, Roberto

2012-09-01

Previous studies have shown a higher incidence of biliary complications following donation after cardiac death (DCD) liver transplantation compared with donation after brain death (DBD) liver transplantation. The endoscopic management of ischemic type biliary strictures in patients who have undergone DCD liver transplants needs to be characterized further. A retrospective institutional review of all patients who underwent DCD liver transplant from January 2006 to September 2011 was performed. These patients were compared with all patients who underwent DBD liver transplantation in the same time period. A descriptive analysis of all DCD patients who developed biliary complications and their subsequent endoscopic management was also performed. Of the 36 patients who received DCD liver transplants, 25% developed biliary complications compared with 13% of patients who received DBD liver transplants (P=0.062). All DCD allograft recipients who developed biliary complications became symptomatic within three months of transplantation. Ischemic type biliary strictures in DCD allograft recipients included disseminated biliary strictures in two patients, biliary strictures of the hepatic duct bifurcation in three patients and biliary strictures of the donor common hepatic duct in three patients. There was a trend toward increasing incidence of total biliary complications in recipients of DCD liver allografts compared with those receiving DBD livers, and the rate of diffuse ischemic cholangiopathy was significantly higher. Focal ischemic type biliary strictures can be treated effectively in DCD liver transplant recipients with favourable results. Diffuse ischemic type biliary strictures in DCD liver transplant recipients ultimately requires retransplantation.

Changes in Water Mobility Measured by Diffusion MRI Predict Response of Metastatic Breast Cancer to Chemotherapy

PubMed Central

Theilmann, Rebecca J; Borders, Rebecca; Trouard, Theodore P; Xia, Guowei; Outwater, Eric; Ranger-Moore, James; Gillies, Robert J; Stopeck, Alison

2004-01-01

Abstract A goal of oncology is the individualization of patient care to optimize therapeutic responses and minimize toxicities. Achieving this will require noninvasive, quantifiable, and early markers of tumor response. Preclinical data from xenografted tumors using a variety of antitumor therapies have shown that magnetic resonance imaging (MRI)-measured mobility of tissue water (apparent diffusion coefficient of water, or ADCw) is a biomarker presaging cell death in the tumor. This communication tests the hypothesis that changes in water mobility will quantitatively presage tumor responses in patients with metastatic liver lesions from breast cancer. A total of 13 patients with metastatic breast cancer and 60measurable liver lesionsweremonitored by diffusion MRI after initiation of new courses of chemotherapy. MR images were obtained prior to, and at 4, 11, and 39 days following the initiation of therapy for determination of volumes and ADCw values. The data indicate that diffusion MRI can predict response by 4 or 11 days after commencement of therapy, depending on the analytic method. The highest concordance was observed in tumor lesions that were less than 8 cm3 in volume at presentation. These results suggest that diffusion MRI can be useful to predict the response of liver metastases to effective chemotherapy. PMID:15720810

Near-infrared fluorescence cholangiography with indocyanine green for biliary atresia. Real-time imaging during the Kasai procedure: a pilot study.

PubMed

Hirayama, Yutaka; Iinuma, Yasushi; Yokoyama, Naoyuki; Otani, Tetsuya; Masui, Daisuke; Komatsuzaki, Naoko; Higashidate, Naruki; Tsuruhisa, Shiori; Iida, Hisataka; Nakaya, Kengo; Naito, Shinichi; Nitta, Koju; Yagi, Minoru

2015-12-01

Hepatoportoenterostomy (HPE) with the Kasai procedure is the treatment of choice for biliary atresia (BA) as the initial surgery. However, the appropriate level of dissection level of the fibrous cone (FC) of the porta hepatis (PH) is frequently unclear, and the procedure sometimes results in unsuccessful outcomes. Recently, indocyanine green near-infrared fluorescence imaging (ICG-FCG) has been developed as a form of real-time cholangiography. We applied this technique in five patients with BA to visualize the biliary flow at the PH intraoperatively. ICG was injected intravenously the day before surgery as the liver function test, and the liver was observed with a near-infrared camera system during the operation while the patient's feces was also observed. In all patients, the whole liver fluoresced diffusely with ICG-containing stagnant bile, whereas no extrahepatic structures fluoresced. The findings of the ICG fluorescence pattern of the PH after dissection of the FC were classified into three types: spotty fluorescence, one patient; diffuse weak fluorescence, three patients; and diffuse strong fluorescence, one patient. In all five patients, the feces evacuated after HPE showed distinct fluorescent spots, although that obtained before surgery showed no fluorescence. One patient with diffuse strong fluorescence who did not achieve JF underwent living related liver transplantation six months after the initial HPE procedure. Four patients, including three cases involving diffuse weak fluorescence and one case involving spotty fluorescence showed weak fluorescence compared to that of the surrounding liver surface. We were able to detect the presence of bile excretion at the time of HPE intraoperatively and successfully evaluated the extent of bile excretion using this new technique. Furthermore, the ICG-FCG findings may provide information leading to a new classification and potentially function as an indicator predicting the clinical outcomes after HPE.

Diffusion-weighted imaging of the liver with multiple b values: effect of diffusion gradient polarity and breathing acquisition on image quality and intravoxel incoherent motion parameters--a pilot study.

PubMed

Dyvorne, Hadrien A; Galea, Nicola; Nevers, Thomas; Fiel, M Isabel; Carpenter, David; Wong, Edmund; Orton, Matthew; de Oliveira, Andre; Feiweier, Thorsten; Vachon, Marie-Louise; Babb, James S; Taouli, Bachir

2013-03-01

To optimize intravoxel incoherent motion (IVIM) diffusion-weighted (DW) imaging by estimating the effects of diffusion gradient polarity and breathing acquisition scheme on image quality, signal-to-noise ratio (SNR), IVIM parameters, and parameter reproducibility, as well as to investigate the potential of IVIM in the detection of hepatic fibrosis. In this institutional review board-approved prospective study, 20 subjects (seven healthy volunteers, 13 patients with hepatitis C virus infection; 14 men, six women; mean age, 46 years) underwent IVIM DW imaging with four sequences: (a) respiratory-triggered (RT) bipolar (BP) sequence, (b) RT monopolar (MP) sequence, (c) free-breathing (FB) BP sequence, and (d) FB MP sequence. Image quality scores were assessed for all sequences. A biexponential analysis with the Bayesian method yielded true diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (PF) in liver parenchyma. Mixed-model analysis of variance was used to compare image quality, SNR, IVIM parameters, and interexamination variability between the four sequences, as well as the ability to differentiate areas of liver fibrosis from normal liver tissue. Image quality with RT sequences was superior to that with FB acquisitions (P = .02) and was not affected by gradient polarity. SNR did not vary significantly between sequences. IVIM parameter reproducibility was moderate to excellent for PF and D, while it was less reproducible for D*. PF and D were both significantly lower in patients with hepatitis C virus than in healthy volunteers with the RT BP sequence (PF = 13.5% ± 5.3 [standard deviation] vs 9.2% ± 2.5, P = .038; D = [1.16 ± 0.07] × 10(-3) mm(2)/sec vs [1.03 ± 0.1] × 10(-3) mm(2)/sec, P = .006). The RT BP DW imaging sequence had the best results in terms of image quality, reproducibility, and ability to discriminate between healthy and fibrotic liver with biexponential fitting.

Toxicity of Doxorubicin on Pig Liver After Chemoembolization with Doxorubicin-loaded Microspheres: A Pilot DNA-microarrays and Histology Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Verret, Valentin, E-mail: valentin.verret@archimmed.com; Namur, Julien; Ghegediban, Saieda Homayra

The potential mechanisms accounting for the hepatotoxicity of doxorubicin-loaded microspheres in chemoembolization were examined by combining histology and DNA-microarray techniques.The left hepatic arteries of two pigs were embolized with 1 mL of doxorubicin-loaded (25 mg; (DoxMS)) or non-loaded (BlandMS) microspheres. The histopathological effects of the embolization were analyzed at 1 week. RNAs extracted from both the embolized and control liver areas were hybridized onto Agilent porcine microarrays. Genes showing significantly different expression (p < 0.01; fold-change > 2) between two groups were classified by biological process. At 1 week after embolization, DoxMS caused arterial and parenchymal necrosis in 51 andmore » 38 % of embolized vessels, respectively. By contrast, BlandMS did not cause any tissue damage. Up-regulated genes following embolization with DoxMS (vs. BlandMS, n = 353) were mainly involved in cell death, apoptosis, and metabolism of doxorubicin. Down-regulated genes (n = 120) were mainly related to hepatic functions, including enzymes of lipid and carbohydrate metabolisms. Up-regulated genes included genes related to cell proliferation (growth factors and transcription factors), tissue remodeling (MMPs and several collagen types), inflammatory reaction (interleukins and chemokines), and angiogenesis (angiogenic factors and HIF1a pathway), all of which play an important role in liver healing and regeneration. DoxMS caused lesions to the liver, provoked cell death, and disturbed liver metabolism. An inflammatory repair process with cell proliferation, tissue remodeling, and angiogenesis was rapidly initiated during the first week after chemoembolization. This pilot study provides a comprehensive method to compare different types of DoxMS in healthy animals or tumor models.« less

Comparison of breathhold, navigator-triggered, and free-breathing diffusion-weighted MRI for focal hepatic lesions.

PubMed

Choi, Ji Soo; Kim, Myeong-Jin; Chung, Yong Eun; Kim, Kyung Ah; Choi, Jin-Young; Lim, Joon Seok; Park, Mi-Suk; Kim, Ki Whang

2013-07-01

To compare the breathhold, navigator-triggered, and free-breathing techniques in diffusion-weighted magnetic resonance imaging (MRI) for the evaluation of focal liver lesions on a 3.0T system. Fifty-two patients (36 men, 16 women; mean age, 56.4 years) with focal liver lesions underwent breathhold, navigator-triggered, and free-breathing diffusion-weighted imaging (DWI) of the liver on a 3.0 Tesla (T) system. All sequences were performed with b values of 50 and 800 s/mm(2) and identical parameters except for signal averages (two for navigator-triggered, one for breathhold, and four for free-breathing) and repetition time (3389 ms for navigator-triggered, 1500 ms for breathhold, and 4400 ms for free-breathing). A total of 74 lesions (50 malignant, 24 benign) were evaluated. The signal-to-noise ratios (SNR) of the liver and lesions, contrast-to-noise ratios (CNR) of each lesion, and ADC values of the liver and lesions were compared for each DWI sequence. The detection sensitivity and characterization accuracy were also compared. The SNRs of the liver and lesions were significantly lower for breathhold DWI than for non-breathhold DWI (navigator-triggered and free-breathing DWI) for all b values. The CNRs of the lesions were also significantly lower for breathhold DWI than for non-breathhold DWI. The ADC values of the liver and focal lesions measured using the three DWI techniques were not significantly different and showed good correlation. For lesion detection and characterization, there were no significant differences between breathhold and non-breathhold DWI. Both breathhold and non-breathhold DWI are comparable for the detection or characterization of focal liver lesions at 3.0T; however, non-breathhold DWI provides higher SNR and CNR than breathhold DWI. In addition, although free-breathing and navigator-triggered DWI sequences show similar performance for 3.0T liver imaging, free-breathing DWI is more time efficient than navigator-triggered DWI. Copyright © 2013 Wiley Periodicals, Inc.

Nonthermal Ablation by Using Intravascular Oxygen Radical Generation with WST11: Dynamic Tissue Effects and Implications for Focal Therapy

PubMed Central

Kimm, Simon Y.; Tarin, Tatum V.; Monette, Sébastien; Srimathveeravalli, Govindarajan; Gerber, Daniel; Durack, Jeremy C.; Solomon, Stephen B.; Scardino, Peter T.; Scherz, Avigdor

2016-01-01

Purpose To examine the hypothesis that vascular-targeted photodynamic therapy (VTP) with WST11 and clinically relevant parameters can be used to ablate target tissues in a non–tumor-bearing large-animal model while selectively sparing blood vessels and collagen. Materials and Methods By using an institutional animal care and use committee–approved protocol, 68 ablations were performed in the kidneys (cortex and medulla) and livers of 27 adult pigs. Posttreatment evaluation was conducted with contrast material–enhanced computed tomography in the live animals at 24 hours. Immunohistochemistry was evaluated and histologic examination with hematoxylin-eosin staining was performed at 4 hours, 24 hours, and 7 days. Intravenous infusion of WST11 (4 mg per kilogram of body weight) was followed by using near-infrared illumination (753 nm for 20 minutes) through optical fibers prepositioned in target tissues by using a fixed template. Treated areas were scanned, measured, and statistically analyzed by using the Student t test and two-way analysis of variance. Results Focal WST11 VTP treatment in the liver and kidney by using a single optical fiber resulted in well-demarcated cylindrical zones of nonthermal necrosis concentrically oriented around the light-emitting diffuser, with no intervening viable parenchymal cells. The radius of ablated tissue increased from approximately 5 mm at 150 mW to approximately 7 mm at 415 mW (P < .01). Illumination through fiber triads at 1-cm separation resulted in confluent homogeneous necrosis. Patterns of acute injury within 24 hours were consistent with microcirculatory flow arrest and collagen preservation (demonstrated with trichrome staining). In the peripheral ablation zone, blood vessels at least 40 μm in diameter were selectively preserved and remained functional at 7 days. Ablated tissues exhibited progressive fibrosis and chronic inflammatory cell infiltrates. No histologic changes consistent with thermal injury were observed in blood vessels or collagen. The renal hilum and collecting system did not show treatment effect, despite treatment proximity. Conclusion WST11 VTP induces nonthermal tissue ablation in target tissue while preserving critical organ structures and bystander blood vessels within solid organs. © RSNA, 2016 Online supplemental material is available for this article. PMID:26986047

Magnetic Resonance Imaging of Liver Metastasis.

PubMed

Karaosmanoglu, Ali Devrim; Onur, Mehmet Ruhi; Ozmen, Mustafa Nasuh; Akata, Deniz; Karcaaltincaba, Musturay

2016-12-01

Liver magnetic resonance imaging (MRI) is becoming the gold standard in liver metastasis detection and treatment response assessment. The most sensitive magnetic resonance sequences are diffusion-weighted images and hepatobiliary phase images after Gd-EOB-DTPA. Peripheral ring enhancement, diffusion restriction, and hypointensity on hepatobiliary phase images are hallmarks of liver metastases. In patients with normal ultrasonography, computed tomography (CT), and positron emission tomography (PET)-CT findings and high clinical suspicion of metastasis, MRI should be performed for diagnosis of unseen metastasis. In melanoma, colon cancer, and neuroendocrine tumor metastases, MRI allows confident diagnosis of treatment-related changes in liver and enables differential diagnosis from primary liver tumors. Focal nodular hyperplasia-like nodules in patients who received platinum-based chemotherapy, hypersteatosis, and focal fat can mimic metastasis. In cancer patients with fatty liver, MRI should be preferred to CT. Although the first-line imaging for metastases is CT, MRI can be used as a problem-solving method. MRI may be used as the first-line method in patients who would undergo curative surgery or metastatectomy. Current limitation of MRI is low sensitivity for metastasis smaller than 3mm. MRI fingerprinting, glucoCEST MRI, and PET-MRI may allow simpler and more sensitive diagnosis of liver metastasis. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantification of Liver Fat with Magnetic Resonance Imaging

PubMed Central

Reeder, Scott B.; Sirlin, Claude

2010-01-01

Intracellular fat accumulation is common feature of liver disease. Intracellular fat (steatosis) is the histological hallmark of non-alcoholic fatty liver disease (NAFLD) but also may occur with alcohol abuse, viral hepatitis, HIV and genetic lipodystrophies, and chemotherapy. This article reviews emerging magnetic resonance imaging techniques that attempt to quantify liver fat. The content provides an overview of fatty liver disease and diseases where fat is an important disease feature. Also discussed is the current use and limitation of non-targeted biopsy in diffuse liver disease, and why quantitative non-invasive biomarkers of liver fat would be beneficial. PMID:21094444

Alcoholic liver disease.

PubMed

Penny, Steven M

2013-01-01

In the United States, approximately 100,000 deaths are attributed to alcohol abuse each year. In 2009, the World Health Organization listed alcohol use as one of the leading causes of the global burden of disease and injury. Alcoholic liver disease, a direct result of chronic alcohol abuse, insidiously destroys the normal functions of the liver. The end result of the disease, cirrhosis, culminates in a dysfunctional and diffusely scarred liver. This article discusses the clinical manifestations, imaging considerations, and treatment of alcoholic liver disease and cirrhosis. Normal liver function, liver hemodynamics, the disease of alcoholism, and the deleterious effects of alcohol also are reviewed.

High-resolution diffusion and relaxation-edited magic angle spinning 1H NMR spectroscopy of intact liver tissue.

PubMed

Rooney, O M; Troke, J; Nicholson, J K; Griffin, J L

2003-11-01

High-resolution magic angle spinning (HRMAS) (1)H NMR spectroscopy is ideal for monitoring the metabolic environment within tissues, particularly when spectra are weighted by physical properties such as T(1) and T(2) relaxation times and apparent diffusion coefficients (ADCs). In this study, spectral-editing using T(1) and T(2) relaxation times and ADCs at variable diffusion times was used in conjunction with HRMAS (1)H NMR spectroscopy at 14.1 T in liver tissue. To enhance the sensitivity of ADC measurements to low molecular weight metabolites a T(2) spin echo was included in a standard stimulated gradient spin-echo sequence. Fatty liver induced in rats by chronic orotic acid feeding was investigated using this modified sequence. An increase in the combined ADC for the co-resonant peaks glucose, betaine, and TMAO during fatty liver disease was detected (ADCs = 0.60 +/- 0.11 and 0.35 +/- 0.1 * 10(-9) m(2)s(-1) (n = 3) for rats fed with and without orotic acid), indicative of a reduction in glucose and betaine and an increase in TMAO. Copyright 2003 Wiley-Liss, Inc.

NonHodgkin's Lymphoma with Peritoneal Localization

PubMed Central

Curakova, E.; Genadieva-Dimitrova, M.; Misevski, J.; Caloska-Ivanova, V.; Andreevski, V.; Todorovska, B.; Isahi, U.; Trajkovska, M.; Misevska, P.; Joksimovic, N.; Genadieva-Stavric, S.; Antovic, S.; Jankulovski, N.

2014-01-01

The gastrointestinal tract is the most common extranodal site involved with lymphoma accounting for 5–20% of all cases. Lymphoma can occur at any site of the body, but diffuse and extensive involvement of the peritoneal cavity is unusual and rare. We report a case of diffuse large B-cell lymphoma in a 57-year-old female infiltrating the peritoneum and omentum and presenting with ascites and pleural effusion. The performed examinations did not discover any pathological findings affecting the digestive tract or parenchymal organs, except for diffuse thickening of the peritoneum and omentum. Peripheral, mediastinal, or retroperitoneal lymphadenopathy was not registered. The blood count revealed only elevated leukocytes and on examination there were no immature blood cells in the peripheral blood. The cytology from the ascites and pleural effusion did not detect any malignant cells. Due to the rapid disease progression the patient died after twenty-two days of admission. The diagnosis was discovered postmortem with the histological examination and immunohistochemical study of the material taken during the surgical laparoscopy performed four days before the lethal outcome. Although cytology is diagnostic in most cases, laparoscopy with peritoneal biopsy is the only procedure which can establish the definitive diagnosis of peritoneal lymphomatosis. PMID:24711934

Diffusion kurtosis imaging of the liver at 3 Tesla: in vivo comparison to standard diffusion-weighted imaging.

PubMed

Budjan, Johannes; Sauter, Elke A; Zoellner, Frank G; Lemke, Andreas; Wambsganss, Jens; Schoenberg, Stefan O; Attenberger, Ulrike I

2018-01-01

Background Functional techniques like diffusion-weighted imaging (DWI) are gaining more and more importance in liver magnetic resonance imaging (MRI). Diffusion kurtosis imaging (DKI) is an advanced technique that might help to overcome current limitations of DWI. Purpose To evaluate DKI for the differentiation of hepatic lesions in comparison to conventional DWI at 3 Tesla. Material and Methods Fifty-six consecutive patients were examined using a routine abdominal MR protocol at 3 Tesla which included DWI with b-values of 50, 400, 800, and 1000 s/mm 2 . Apparent diffusion coefficient maps were calculated applying a standard mono-exponential fit, while a non-Gaussian kurtosis fit was used to obtain DKI maps. ADC as well as Kurtosis-corrected diffusion ( D) values were quantified by region of interest analysis and compared between lesions. Results Sixty-eight hepatic lesions (hepatocellular carcinoma [HCC] [n = 25]; hepatic adenoma [n = 4], cysts [n = 18]; hepatic hemangioma [HH] [n = 18]; and focal nodular hyperplasia [n = 3]) were identified. Differentiation of malignant and benign lesions was possible based on both DWI ADC as well as DKI D-values ( P values were in the range of 0.04 to < 0.0001). Conclusion In vivo abdominal DKI calculated using standard b-values is feasible and enables quantitative differentiation between malignant and benign liver lesions. Assessment of conventional ADC values leads to similar results when using b-values below 1000 s/mm 2 for DKI calculation.

Pulmonary asbestosis: radiologic-pathologic brief report.

PubMed

Ahn, C S; Kim, S J; Oh, S J; Park, K J; Kim, H J; Ahn, C M; Kim, H K; Shin, D H; Cho, S H; Yang, K M

1997-10-01

Pulmonary asbestosis is defined as bilateral diffuse interstitial fibrosis of the lungs caused by exposure to asbestos. Many occupations are at risk for asbestos exposure, particularly in the mining, milling, manufacturing, construction, shipbuilding, and automotive industries. Therefore, the prevalence of asbestosis should be fairly widespread. The diagnosis of asbestosis can be made on either clinical or pathological grounds. We recently encountered one case of asbestosis which was confirmed histologically. On HRCT, there was ground-glass opacity with irregular linear shadows, subpleural curvilinear lines and parenchymal bands. Neither plaque nor calcification were noted. The histologic findings observed on open-lung biopsy specimen were well in accord with those in HRCT. Many asbestos-coated bodies were present along with black dust.

Expression of hydroxyindole-O-methyltransferase enzyme in the human central nervous system and in pineal parenchymal cell tumors.

PubMed

Fukuda, Takahiro; Akiyama, Nobutake; Ikegami, Masahiro; Takahashi, Hitoshi; Sasaki, Atsushi; Oka, Hidehiro; Komori, Takashi; Tanaka, Yuko; Nakazato, Youichi; Akimoto, Jiro; Tanaka, Masahiko; Okada, Yoshikazu; Saito, Saburo

2010-05-01

Pineal parenchymal tumor (PPT) cells usually show immunoreactivity for synaptophysin, neuron-specific enolase, neurofilament protein, class III beta-tubulin, tau protein, PGP9.5, chromogranin, serotonin, retinal S-antigen, and rhodopsin, but these markers are not specific for PPTs. Melatonin is produced and secreted mainly bypineal parenchymal cells; hydroxyindole-O-methyltransferase (HIOMT) catalyzes the final reaction in melatonin biosynthesis. We hypothesized that HIOMT could serve as a tumor marker of PPTs, and we investigated HIOMT localization and HIOMT expression in samples of normal human tissue and in PPTs, primitive neuroectodermal tumors, and medulloblastomas. In normal tissue, HIOMT was expressed in retinal cells, pineal parenchymal cells, neurons of the Edinger-Westphal nucleus, microglia, macrophages, thyroid follicular epithelium, principal and oxyphil cells of parathyroid gland, adrenal cortical cells, hepatic parenchymal cells, renal tubule epithelium, and enteroendocrine cells of stomach and duodenum. The HIOMT was also expressed in all 46 PPTs studied. The proportions of HIOMT-immunoreactive cells successively decreased in the following tumors: pineocytoma, pineal parenchymal tumor of intermediate differentiation, and pineoblastoma. A few HIOMT-immunoreactive cells were observed in one of 6 primitive neuroectodermal tumors and 23 of 42 medulloblastomas. These results indicate that HIOMT immunohistochemistry may be useful for the diagnosis of PPTs and be a prognostic factor in PPTs.

Experimental induction of hepatic lipidosis in cats.

PubMed

Biourge, V C; Groff, J M; Munn, R J; Kirk, C A; Nyland, T G; Madeiros, V A; Morris, J G; Rogers, Q R

1994-09-01

The effect of long-term voluntary fasting on hematologic variables, biochemical profiles, and liver histologic findings was assessed in 15 obese cats (> 40% overweight). Clinical signs and laboratory results consistent with hepatic lipidosis were observed in 12 of 15 cats after 5 to 7 weeks of fasting, and were associated with 30 to 35% reduction of initial body weight. Histologic examination of successive liver biopsy specimens revealed that obesity was not associated with liver parenchymal lipid accumulation, but that fasting resulted in lipidosis in all 15 cats. The long-term fast was associated with an early (after 2 to 4 weeks of fasting) and significant (P < 0.05) reduction in serum urea, glucose, and albumin concentrations, and RBC mass. Fasting for 5 to 7 weeks was associated with a significant (P < 0.05) increase in hepatic-associated enzyme activities and in total and direct serum bilirubin concentrations. Significant (P < 0.05) changes in serum alkaline phosphatase developed as early as 3 weeks before the onset of hyperbilirubinemia. Except for development of hepatic lipidosis, cats appeared to tolerate the fast without other adverse effect. This study confirmed that long-term fasting may induce clinical hepatic lipidosis in obese cats. Fasting appears to induce a syndrome of hepatic lipidosis that is indistinguishable from feline idiopathic hepatic lipidosis and may be an appropriate model to study the pathophysiologic features and treatment of hepatic lipidosis.

Localization of peroxisome proliferator-activated receptor in mouse and rat-tissues and demonstration of its nuclear translocation in transfected cv-1 cells.

PubMed

Huang, Q; Yeldandi, A; Alvares, K; Ide, H; Reddy, J; Rao, M

1995-02-01

Hepatocarcinogenesis in rodents induced by nongenotoxic peroxisome proliferators is postulated to be a receptor-mediated process. The peroxisome proliferator-activated receptors (PPAR) are members of the steroid hormone receptor superfamily, which participate in ligand-dependent transcriptional activation of peroxisomal fatty acid beta oxidation enzyme system genes in liver parenchymal cells of rats and mice. In order to study the tissue distribution and cellular localization of PPAR, we raised polyclonal antibodies against PPAR using a recombinant rat PPAR (rPPAR) expressed as a glutathione-S-transferase-rPPAR fusion protein. On immunoblot analysis the antibodies specifically recognized a 55 kDa PPAR protein in rat, mouse and human liver homogenates. Immunoblotting also showed that in the mouse and rat, PPAR is expressed in liver, kidney and heart, and only weakly in brain and testis. Immunohistochemical localization in the rat and mouse revealed that PPAR is highly expressed in perivenular (i.e., those surrounding hepatic vein) hepatocytes and very weakly in the cytoplasm of remaining hepatocytes. In the kidney, PPAR was visualized predominantly in the p(3) segments of proximal convoluted tubular epithelium. CV-1 cells transiently transfected with rPPAR cDNA construct showed predominant cytoplasmic fluorescence; treatment of these cells with ciprofibrate, a peroxisome proliferator, resulted in the nuclear translocation of PPAR signal.

Percutaneous ablation of malignant liver tumor in rabbits using low radio frequency energy.

PubMed

Nativ, O; Moskovitz, B; Sabo, E; Shalhav, A; Kaftori, J; Barbara, Y; Mordohovich, D; Goldwasser, B

1996-09-01

Radio frequency (RF) current has been used successfully to ablate normal human tissue. To further investigate the clinical application of this modality in tumors we studied the potential of using RF percutaneously to destroy experimental liver tumors. Thirty five outbred albino rabbits underwent liver VX2 tumor direct-implantation during open surgery. After 21 days ultrasonography was performed revealing tumor presence and size. A shielded RF needle was designed so that it could be inserted percutaneously through an introducing needle, and an electrical insulation shield covering the RF needle could be retracted to control the length of the exposed RF needle inside the tissue. Twenty two days after tumor implantation RF was applied via the aforementioned needle using a ZoMed International RF generator. In one group of rabbits the procedure was performed under direct vision during open surgery and on the other group treatment was applied percutaneously, guiding the needle by tumor palpation. Rabbits were killed 3 days later and pathology revealed 4 to 25 mm intratumoral RF induced lesions. A direct relation was found between lesion size, power and duration of RF application (At 7.5 W, r = 0.48, p = 0.032). Based on our preliminary results we may conclude that RF may have clinical application in the near future for percutaneous local tumor control in parenchymal organs.

Computerized breast parenchymal analysis on DCE-MRI

NASA Astrophysics Data System (ADS)

Li, Hui; Giger, Maryellen L.; Yuan, Yading; Jansen, Sanaz A.; Lan, Li; Bhooshan, Neha; Newstead, Gillian M.

2009-02-01

Breast density has been shown to be associated with the risk of developing breast cancer, and MRI has been recommended for high-risk women screening, however, it is still unknown how the breast parenchymal enhancement on DCE-MRI is associated with breast density and breast cancer risk. Ninety-two DCE-MRI exams of asymptomatic women with normal MR findings were included in this study. The 3D breast volume was automatically segmented using a volume-growing based algorithm. The extracted breast volume was classified into fibroglandular and fatty regions based on the discriminant analysis method. The parenchymal kinetic curves within the breast fibroglandular region were extracted and categorized by use of fuzzy c-means clustering, and various parenchymal kinetic characteristics were extracted from the most enhancing voxels. Correlation analysis between the computer-extracted percent dense measures and radiologist-noted BIRADS density ratings yielded a correlation coefficient of 0.76 (p<0.0001). From kinetic analyses, 70% (64/92) of most enhancing curves showed persistent curve type and reached peak parenchymal intensity at the last postcontrast time point; with 89% (82/92) of most enhancing curves reaching peak intensity at either 4th or 5th post-contrast time points. Women with dense breast (BIRADS 3 and 4) were found to have more parenchymal enhancement at their peak time point (Ep) with an average Ep of 116.5% while those women with fatty breasts (BIRADS 1 and 2) demonstrated an average Ep of 62.0%. In conclusion, breast parenchymal enhancement may be associated with breast density and may be potential useful as an additional characteristic for assessing breast cancer risk.

Renal Parenchymal Area Growth Curves for Children 0 to 10 Months Old.

PubMed

Fischer, Katherine; Li, Chunming; Wang, Huixuan; Song, Yihua; Furth, Susan; Tasian, Gregory E

2016-04-01

Low renal parenchymal area, which is the gross area of the kidney in maximal longitudinal length minus the area of the collecting system, has been associated with increased risk of end stage renal disease during childhood in boys with posterior urethral valves. To our knowledge normal values do not exist. We aimed to increase the clinical usefulness of this measure by defining normal renal parenchymal area during infancy. In a cross-sectional study of children with prenatally detected mild unilateral hydronephrosis who were evaluated between 2000 and 2012 we measured the renal parenchymal area of normal kidney(s) opposite the kidney with mild hydronephrosis. Measurement was done with ultrasound from birth to post-gestational age 10 months. We used the LMS method to construct unilateral, bilateral, side and gender stratified normalized centile curves. We determined the z-score and the centile of a total renal parenchymal area of 12.4 cm(2) at post-gestational age 1 to 2 weeks, which has been associated with an increased risk of kidney failure before age 18 years in boys with posterior urethral valves. A total of 975 normal kidneys of children 0 to 10 months old were used to create renal parenchymal area centile curves. At the 97th centile for unilateral and single stratified curves the estimated margin of error was 4.4% to 8.8%. For bilateral and double stratified curves the estimated margin of error at the 97th centile was 6.6% to 13.2%. Total renal parenchymal area less than 12.4 cm(2) at post-gestational age 1 to 2 weeks had a z-score of -1.96 and fell at the 3rd percentile. These normal renal parenchymal area curves may be used to track kidney growth in infants and identify those at risk for chronic kidney disease progression. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Value of 3 Tesla diffusion-weighted magnetic resonance imaging for assessing liver fibrosis

PubMed Central

Papalavrentios, Lavrentios; Sinakos, Emmanouil; Chourmouzi, Danai; Hytiroglou, Prodromos; Drevelegas, Konstantinos; Constantinides, Manos; Drevelegas, Antonios; Talwalkar, Jayant; Akriviadis, Evangelos

2015-01-01

Background Limited data are available regarding the role of magnetic resonance imaging (MRI), particularly the new generation 3 Tesla technology, and especially diffusion-weighted imaging (DWI) in predicting liver fibrosis. The aim of our pilot study was to assess the clinical performance of the apparent diffusion coefficient (ADC) of liver parenchyma for the assessment of liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Methods 18 patients with biopsy-proven NAFLD underwent DWI with 3 Tesla MRI. DWI was performed with single-shot echo-planar technique at b values of 0-500 and 0-1000 s/mm2. ADC was measured in four locations in the liver and the mean ADC value was used for analysis. Staging of fibrosis was performed according to the METAVIR system. Results The median age of patients was 52 years (range 23-73). The distribution of patients in different fibrosis stages was: 0 (n=1), 1 (n=7), 2 (n=1), 3 (n=5), 4 (n=4). Fibrosis stage was poorly associated with ADC at b value of 0-500 s/mm2 (r= -0.30, P=0.27). However it was significantly associated with ADC at b value of 0-1000 s/mm2 (r= -0.57, P=0.01). For this b value (0-1000 s/mm2) the area under receiver-operating characteristic curve was 0.93 for fibrosis stage ≥3 and the optimal ADC cut-off value was 1.16 ×10-3 mm2/s. Conclusion 3 Tesla DWI can possibly predict the presence of advanced fibrosis in patients with NAFLD. PMID:25608776

Value of 3 Tesla diffusion-weighted magnetic resonance imaging for assessing liver fibrosis.

PubMed

Papalavrentios, Lavrentios; Sinakos, Emmanouil; Chourmouzi, Danai; Hytiroglou, Prodromos; Drevelegas, Konstantinos; Constantinides, Manos; Drevelegas, Antonios; Talwalkar, Jayant; Akriviadis, Evangelos

2015-01-01

Limited data are available regarding the role of magnetic resonance imaging (MRI), particularly the new generation 3 Tesla technology, and especially diffusion-weighted imaging (DWI) in predicting liver fibrosis. The aim of our pilot study was to assess the clinical performance of the apparent diffusion coefficient (ADC) of liver parenchyma for the assessment of liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). 18 patients with biopsy-proven NAFLD underwent DWI with 3 Tesla MRI. DWI was performed with single-shot echo-planar technique at b values of 0-500 and 0-1000 s/mm 2 . ADC was measured in four locations in the liver and the mean ADC value was used for analysis. Staging of fibrosis was performed according to the METAVIR system. The median age of patients was 52 years (range 23-73). The distribution of patients in different fibrosis stages was: 0 (n=1), 1 (n=7), 2 (n=1), 3 (n=5), 4 (n=4). Fibrosis stage was poorly associated with ADC at b value of 0-500 s/mm 2 (r= -0.30, P=0.27). However it was significantly associated with ADC at b value of 0-1000 s/mm 2 (r= -0.57, P=0.01). For this b value (0-1000 s/mm 2 ) the area under receiver-operating characteristic curve was 0.93 for fibrosis stage ≥3 and the optimal ADC cut-off value was 1.16 ×10 -3 mm 2 /s. 3 Tesla DWI can possibly predict the presence of advanced fibrosis in patients with NAFLD.

Hereditary haemochromatosis: a case of iron accumulation in the basal ganglia associated with a parkinsonian syndrome.

PubMed Central

Nielsen, J E; Jensen, L N; Krabbe, K

1995-01-01

Hereditary haemochromatosis is characterised by excessive parenchymal iron deposition, particularly in the liver. Usually hereditary haemochromatosis is not associated with neurological symptoms and iron deposition in the brain has not previously been described as a pathological phenomenon. A patient is reported with hereditary haemochromatosis and a syndrome of dementia, dysarthria, a slowly progressive gait disturbance, imbalance, muscle weakness, rigidity, bradykinesia, tremor, ataxia, and dyssynergia. The findings on MRI of a large signal decrease in the basal ganglia, consistent with excessive iron accumulation, indicate a causal relation to the symptoms. Although the neurological symptoms did not improve in our patient, hereditary haemochromatosis should be considered in the differential diagnosis of parkinsonian syndromes, because complications of iron induced organ injury may be prevented by phlebotomy. Images PMID:7673967

Hepatic FcRn regulates albumin homeostasis and susceptibility to liver injury

PubMed Central

Pyzik, Michal; Rath, Timo; Kuo, Timothy T.; Win, Sanda; Baker, Kristi; Hubbard, Jonathan J.; Grenha, Rosa; Gandhi, Amit; Krämer, Thomas D.; Mezo, Adam R.; McDonnell, Kevin; Nienaber, Vicki; Andersen, Jan Terje; Mizoguchi, Atsushi; Blumberg, Laurence; Purohit, Shalaka; Jones, Susan D.; Christianson, Greg; Lencer, Wayne I.; Sandlie, Inger; Kaplowitz, Neil; Roopenian, Derry C.; Blumberg, Richard S.

2017-01-01

The neonatal crystallizable fragment receptor (FcRn) is responsible for maintaining the long half-life and high levels of the two most abundant circulating proteins, albumin and IgG. In the latter case, the protective mechanism derives from FcRn binding to IgG in the weakly acidic environment contained within endosomes of hematopoietic and parenchymal cells, whereupon IgG is diverted from degradation in lysosomes and is recycled. The cellular location and mechanism by which FcRn protects albumin are partially understood. Here we demonstrate that mice with global or liver-specific FcRn deletion exhibit hypoalbuminemia, albumin loss into the bile, and increased albumin levels in the hepatocyte. In vitro models with polarized cells illustrate that FcRn mediates basal recycling and bidirectional transcytosis of albumin and uniquely determines the physiologic release of newly synthesized albumin into the basal milieu. These properties allow hepatic FcRn to mediate albumin delivery and maintenance in the circulation, but they also enhance sensitivity to the albumin-bound hepatotoxin, acetaminophen (APAP). As such, global or liver-specific deletion of FcRn results in resistance to APAP-induced liver injury through increased albumin loss into the bile and increased intracellular albumin scavenging of reactive oxygen species. Further, protection from injury is achieved by pharmacologic blockade of FcRn–albumin interactions with monoclonal antibodies or peptide mimetics, which cause hypoalbuminemia, biliary loss of albumin, and increased intracellular accumulation of albumin in the hepatocyte. Together, these studies demonstrate that the main function of hepatic FcRn is to direct albumin into the circulation, thereby also increasing hepatocyte sensitivity to toxicity. PMID:28330995

First ALPPS procedure using a total robotic approach.

PubMed

Vicente, E; Quijano, Y; Ielpo, B; Fabra, I

2016-12-01

ALPPS procedure is gaining interest. Indications and technical aspects of this technique are still under debate [1]. Only 4 totally laparoscopic ALPPS procedures have been described in the literature and none by robotic approach [2-4]. This video demonstrates the technical aspects of totally robotic ALPPS. A 58 year old man with sigmoid adenocarcinoma with multiple right liver metastases extended to segment IV and I underwent Xelox and 5 Fluoro-uracil neoadjuvancy. Preoperative CT volumetric scan showed a FLR/TLV (Future Liver Remnant/Total Liver Volume) of 28%. ALPPS totally robotic procedure was planned using the DaVinci Si. Tumor resection from the FLR (including segment I) is followed by parenchymal transection between the FLR and the diseased part of the liver with concomitant right portal vein ligation. Small branches to segment IV from left portal vein have been resected along the round ligament, at this step. The right biliary tract was resected as it was partially debilitated after its dissection as partially encircled by a metastasis at segment IV. Second stage was performed totally robotic on 13th postoperative days with a FLR/TLV of 40%. No strong adherences are found, making this stage much easer than open approach. During this step, right hepatic artery and right supra hepatic vein are resected. Finally, the specimen was retrieved inside a plastic bag through a Pfannenstiel incision. Postoperative pathology showed margins free from disease. ALPPS procedure performed by robotic approach could be a safe and feasible technique in experienced centers with advanced robotic skills. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hepatic dendritic cell subsets in the mouse.

PubMed

Jomantaite, Ieva; Dikopoulos, Nektarios; Kröger, Andrea; Leithäuser, Frank; Hauser, Hansjörg; Schirmbeck, Reinhold; Reimann, Jörg

2004-02-01

The CD11c(+) cell population in the non-parenchymal cell population of the mouse liver contains dendritic cells (DC), NK cells, B cells and T cells. In the hepatic CD11c(+) DC population from immunocompetent or immunodeficient [recombinase-activating gene-1 (RAG1)(-/-)] C57BL/6 mice (rigorously depleted of T cells, B cells and NK cells), we identified a B220(+) CD11c(int) subset of 'plasmacytoid' DC, and a B220(-) CD11c(+) DC subset. The latter DC population could be subdivided into a major, immature (CD40(lo) CD80(lo) CD86(lo) MHC class II(lo)) CD11c(int) subset, and a minor, mature (CD40(hi) CD80(hi) CD86(hi) MHC class II(hi)) CD11c(hi) subset. Stimulated B220(+) but not B220(-) DC produced type I interferon. NKT cell activation in vivo increased the number of liver B220(-) DC three- to fourfold within 18 h post-injection, and up-regulated their surface expression of activation marker, while it contracted the B220(+) DC population. Early in virus infection, the hepatic B220(+) DC subset expanded, and both, the B220(+) as well as B220(-) DC populations in the liver matured. In vitro, B220(-) but not B220(+) DC primed CD4(+) or CD8(+)T cells. Expression of distinct marker profiles and functions, and distinct early reaction to activation signals hence identify two distinct B220(+) and B220(-) subsets in CD11c(+) DC populations freshly isolated from the mouse liver.

Targeted delivery of antisense oligonucleotides to hepatocytes using triantennary N-acetyl galactosamine improves potency 10-fold in mice.

PubMed

Prakash, Thazha P; Graham, Mark J; Yu, Jinghua; Carty, Rick; Low, Audrey; Chappell, Alfred; Schmidt, Karsten; Zhao, Chenguang; Aghajan, Mariam; Murray, Heather F; Riney, Stan; Booten, Sheri L; Murray, Susan F; Gaus, Hans; Crosby, Jeff; Lima, Walt F; Guo, Shuling; Monia, Brett P; Swayze, Eric E; Seth, Punit P

2014-07-01

Triantennary N-acetyl galactosamine (GalNAc, GN3: ), a high-affinity ligand for the hepatocyte-specific asialoglycoprotein receptor (ASGPR), enhances the potency of second-generation gapmer antisense oligonucleotides (ASOs) 6-10-fold in mouse liver. When combined with next-generation ASO designs comprised of short S-cEt (S-2'-O-Et-2',4'-bridged nucleic acid) gapmer ASOs, ∼ 60-fold enhancement in potency relative to the parent MOE (2'-O-methoxyethyl RNA) ASO was observed. GN3: -conjugated ASOs showed high affinity for mouse ASGPR, which results in enhanced ASO delivery to hepatocytes versus non-parenchymal cells. After internalization into cells, the GN3: -ASO conjugate is metabolized to liberate the parent ASO in the liver. No metabolism of the GN3: -ASO conjugate was detected in plasma suggesting that GN3: acts as a hepatocyte targeting prodrug that is detached from the ASO by metabolism after internalization into the liver. GalNAc conjugation also enhanced potency and duration of the effect of two ASOs targeting human apolipoprotein C-III and human transthyretin (TTR) in transgenic mice. The unconjugated ASOs are currently in late stage clinical trials for the treatment of familial chylomicronemia and TTR-mediated polyneuropathy. The ability to translate these observations in humans offers the potential to improve therapeutic index, reduce cost of therapy and support a monthly dosing schedule for therapeutic suppression of gene expression in the liver using ASOs. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Diagnostic value of diffusion weighted MRI and ADC in differential diagnosis of cavernous hemangioma of the liver.

PubMed

Tokgoz, Ozlem; Unlu, Ebru; Unal, Ilker; Serifoglu, Ismail; Oz, Ilker; Aktas, Elif; Caglar, Emrah

2016-03-01

To investigate the use of diffusion weighted magnetic resonance imaging (DWI) and the apparent diffusion coefficient (ADC) values in the diagnosis of hemangioma. The study population consisted of 72 patients with liver masses larger than 1 cm (72 focal lesions). DWI examination with a b value of 600 s/mm2 was carried out for all patients. After DWI examination, an ADC map was created and ADC values were measured for 72 liver masses and normal liver tissue (control group). The average ADC values of normal liver tissue and focal liver lesions, the "cut-off" ADC values, and the diagnostic sensitivity and specificity of the ADC map in diagnosing hemangioma, benign and malignant lesions were researched. Of the 72 liver masses, 51 were benign and 21 were malignant. Benign lesions comprised 38 hemangiomas and 13 simple cysts. Malignant lesions comprised 9 hepatocellular carcinomas, and 12 metastases. The highest ADC values were measured for cysts (3.782±0.53×10(-3) mm(2)/s) and hemangiomas (2.705±0.63×10(-3) mm(2)/s). The average ADC value of hemangiomas was significantly higher than malignant lesions and the normal control group (p<0.001). The average ADC value of cysts were significantly higher when compared to hemangiomas and normal control group (p<0.001). To distinguish hemangiomas from malignant liver lesions, the "cut-off" ADC value of 1.800×10(-3) mm(2)/s had a sensitivity of 97.4% and a specificity of 90.9%. To distinguish hemangioma from normal liver parenchyma the "cut-off" value of 1.858×10(-3) mm(2)/s had a sensitivity of 97.4% and a specificity of 95.7%. To distinguish benign liver lesions from malignant liver lesions the "cut-off" value of 1.800×10(-3) mm(2)/s had a sensitivity of 96.1% and a specificity of 90.0%. DWI and quantitative measurement of ADC values can be used in differential diagnosis of benign and malignant liver lesions and also in the diagnosis and differentiation of hemangiomas. When dynamic examination cannot distinguish cases with vascular metastasis and lesions from hemangioma, DWI and ADC values can be useful in the primary diagnosis and differential diagnosis. The technique does not require contrast material, so it can safely be used in patients with renal failure.

Optimization of the isolation and cultivation of Cyprinus carpio primary hepatocytes

PubMed Central

Yanhong, Fan; Chenghua, He; Guofang, Liu

2008-01-01

The aquatic environment is affected by numerous chemical contaminants. There is an increasing need to identify these chemicals and to evaluate their potential toxicity towards aquatic life. In this research we optimized techniques for primary cell culture of Cyprinus carpio hepatocytes as one adjunct model for ecotoxicological evaluation of the potential hazards of xenobiotics in the aquatic environment. In this study, Cyprinus carpio hepatocytes were isolated by mechanical separation, two-step collagenase perfusion, and pancreatin digestion. The hepatocytes or parenchymal cells could be separated from cell debris and from non-parenchymal cells by low-speed centrifugation (Percoll gradient centrifugation). The harvested hepatocytes were suspended in DMEM, M199 (cultured in 5% CO2), or L-15 (cultured without 5% CO2) medium then cultured at 17, 27, or 37 °C. Cell yield was counted by use of a hemocytometer, and the viability of the cells was assessed by use of the Trypan blue exclusion test. Results from these studies showed that the best method of isolation was pancreatin digestion (the cell yield was 2.7 × 108 per g (liver weight) and the viability was 98.4%) and the best medium was M199 (cultured in 5% CO2) or L-15 (cultured without 5% CO2). The optimum culture temperature was 27 °C. The primary hepatocytes culture of Cyprimus carpio grew well and satisfied requirements for most toxicological experiments in this condition. PMID:19002769

Hepatocyte growth factor incorporated chitosan nanoparticles augment the differentiation of stem cell into hepatocytes for the recovery of liver cirrhosis in mice

PubMed Central

2011-01-01

Background Short half-life and low levels of growth factors in the niche of injured microenvironment necessitates the exogenous and sustainable delivery of growth factors along with stem cells to augment the regeneration of injured tissues. Methods Here, recombinant human hepatocyte growth factor (HGF) was incorporated into chitosan nanoparticles (CNP) by ionic gelation method and studied for its morphological and physiological characteristics. Cirrhotic mice received either hematopoietic stem cells (HSC) or mesenchymal stemcells (MSC) with or without HGF incorporated chitosan nanoparticles (HGF-CNP) and saline as control. Biochemical, histological, immunostaining and gene expression assays were carried out using serum and liver tissue samples. One way analysis of variance was used for statics application Results Serum levels of selected liver protein and enzymes were significantly increased in the combination of MSC and HGF-CNP (MSC+HGF-CNP) treated group. Immunopositive staining for albumin (Alb) and cytokeratin 18 (CK18), and reverse transcription-polymerase chain reaction (RT-PCR) for Alb, alpha fetoprotein (AFP), CK18, cytokeratin 19 (CK19) ascertained that MSC-HGF-CNP treatment could be an effective combination to repopulate liver parenchymal cells in the liver cirrhosis. Zymogram and western blotting for matrix metalloproteinases 2 and 9 (MMP2 and MMP9) revealed that MMP2 actively involved in the fibrolysis of cirrhotic tissue. Immunostaining for alpha smooth muscle actin (αSMA) and type I collagen showed decreased expression in the MSC+HGF-CNP treatment. These results indicated that HGF-CNP enhanced the differentiation of stem cells into hepatocytes and supported the reversal of fibrolysis of extracellular matrix (ECM). Conclusion Bone marrow stem cells were isolated, characterized and transplanted in mice model. Biodegradable biopolymeric nanoparticles were prepared with the pleotrophic protein molecule and it worked well for the differentiation of stem cells, especially mesenchymal phenotypic cells. Transplantation of bone marrow MSC in combination with HGF-CNP could be an ideal approach for the treatment of liver cirrhosis. PMID:21526984

Random-Walk Model of Diffusion in Three Dimensions in Brain Extracellular Space: Comparison with Microfiberoptic Photobleaching Measurements

PubMed Central

Jin, Songwan; Zador, Zsolt; Verkman, A. S.

2008-01-01

Diffusion through the extracellular space (ECS) in brain is important in drug delivery, intercellular communication, and extracellular ionic buffering. The ECS comprises ∼20% of brain parenchymal volume and contains cell-cell gaps ∼50 nm. We developed a random-walk model to simulate macromolecule diffusion in brain ECS in three dimensions using realistic ECS dimensions. Model inputs included ECS volume fraction (α), cell size, cell-cell gap geometry, intercellular lake (expanded regions of brain ECS) dimensions, and molecular size of the diffusing solute. Model output was relative solute diffusion in water versus brain ECS (Do/D). Experimental Do/D for comparison with model predictions was measured using a microfiberoptic fluorescence photobleaching method involving stereotaxic insertion of a micron-size optical fiber into mouse brain. Do/D for the small solute calcein in different regions of brain was in the range 3.0–4.1, and increased with brain cell swelling after water intoxication. Do/D also increased with increasing size of the diffusing solute, particularly in deep brain nuclei. Simulations of measured Do/D using realistic α, cell size and cell-cell gap required the presence of intercellular lakes at multicell contact points, and the contact length of cell-cell gaps to be least 50-fold smaller than cell size. The model accurately predicted Do/D for different solute sizes. Also, the modeling showed unanticipated effects on Do/D of changing ECS and cell dimensions that implicated solute trapping by lakes. Our model establishes the geometric constraints to account quantitatively for the relatively modest slowing of solute and macromolecule diffusion in brain ECS. PMID:18469079

Random-walk model of diffusion in three dimensions in brain extracellular space: comparison with microfiberoptic photobleaching measurements.

PubMed

Jin, Songwan; Zador, Zsolt; Verkman, A S

2008-08-01

Diffusion through the extracellular space (ECS) in brain is important in drug delivery, intercellular communication, and extracellular ionic buffering. The ECS comprises approximately 20% of brain parenchymal volume and contains cell-cell gaps approximately 50 nm. We developed a random-walk model to simulate macromolecule diffusion in brain ECS in three dimensions using realistic ECS dimensions. Model inputs included ECS volume fraction (alpha), cell size, cell-cell gap geometry, intercellular lake (expanded regions of brain ECS) dimensions, and molecular size of the diffusing solute. Model output was relative solute diffusion in water versus brain ECS (D(o)/D). Experimental D(o)/D for comparison with model predictions was measured using a microfiberoptic fluorescence photobleaching method involving stereotaxic insertion of a micron-size optical fiber into mouse brain. D(o)/D for the small solute calcein in different regions of brain was in the range 3.0-4.1, and increased with brain cell swelling after water intoxication. D(o)/D also increased with increasing size of the diffusing solute, particularly in deep brain nuclei. Simulations of measured D(o)/D using realistic alpha, cell size and cell-cell gap required the presence of intercellular lakes at multicell contact points, and the contact length of cell-cell gaps to be least 50-fold smaller than cell size. The model accurately predicted D(o)/D for different solute sizes. Also, the modeling showed unanticipated effects on D(o)/D of changing ECS and cell dimensions that implicated solute trapping by lakes. Our model establishes the geometric constraints to account quantitatively for the relatively modest slowing of solute and macromolecule diffusion in brain ECS.

Can a Six-Minute Walk Distance Predict Right Ventricular Dysfunction in Patients with Diffuse Parenchymal Lung Disease and Pulmonary Hypertension?

PubMed

Ussavarungsi, Kamonpun; Lee, Augustine S; Burger, Charles D

2016-09-01

Pulmonary hypertension (PH) is commonly observed in patients with diffuse parenchymal lung disease (DPLD). The purpose of this study was to explore the influence of the 6-minute walk test (6MWT) as a simple, non-invasive tool to assess right ventricular (RV) function in patients with DPLD and to identify the need for an echocardiogram (ECHO) to screen for PH. We retrospectively reviewed 48 patients with PH secondary to DPLD, who were evaluated in the PH clinic at the Mayo Clinic in Jacksonville, Florida, from January 1999 to December 2014. Fifty-two percent of patients had RV dysfunction. They had a significantly greater right heart pressure by ECHO and mean pulmonary arterial pressure (MPAP) from right heart catheterization (RHC) than those with normal RV function. A reduced 6-minute walk distance (6MWD) did not predict RV dysfunction (OR 0.995; 95% CI 0.980-1.001, p = 0.138). In addition, worsening restrictive physiology, heart rate at one-minute recovery and desaturation were not different between patients with and without RV dysfunction. However, there were inverse correlations between 6MWD and MPAP from RHC (r = -0.41, 
p = 0.010), 6MWD and RV systolic pressure (r = -0.51, p < 0.001), and 6MWD and MPAP measured by ECHO (r = -0.46, p =0.013). We also found no significant correlation between 6MWD and pulmonary function test parameters. Our single-center cohort of patients with PH secondary to DPLD, PH was found to have an impact on 6MWD. In contrast to our expectations, 6MWD was not useful to predict RV dysfunction. Interestingly, a severe reduction in the 6MWD was related to PH and not to pulmonary function; therefore, it may be used to justify an ECHO to identify patients with a worse prognosis.

Evaluation of radiation necrosis and malignant glioma in rat models using diffusion tensor MR imaging

PubMed Central

Wang, Silun; Chen, Yifei; Lal, Bachchu; Ford, Eric; Tryggestad, Erik; Armour, Michael; Yan, Kun; Laterra, John; Zhou, Jinyuan

2011-01-01

Standard MRI cannot distinguish between radiation necrosis and tumor progression; however, this distinction is critical in the assessment of tumor response to therapy. In this study, one delayed radiation necrosis model (dose, 40 Gy; radiation field, 10 × 10 mm2; n = 13) and two orthotopic glioma models in rats (9L gliosarcoma, n = 8; human glioma xenografts, n = 5) were compared using multiple DTI indices. A visible isotropic apparent diffusion coefficient (ADC) pattern was observed in the lesion due to radiation necrosis, which consisted of a hypointense central zone and a hyperintense peripheral zone. There were significantly lower ADC, parallel diffusivity, and perpendicular diffusivity in the necrotic central zone than in the peripheral zone (all p < 0.001). When radiation-induced necrosis was compared with viable tumor, radiation necrosis had significantly lower ADC than 9L gliosarcoma and human glioma xenografts (both p < 0.01) in the central zone, and significantly lower FA than 9L gliosarcoma (p = 0.005) and human glioma xenografts (p = 0.012) in the peripheral zone. Histological analysis revealed parenchymal coagulative necrosis in the central zone, and damaged vessels and reactive astrogliosis in the peripheral zone. These data suggest that qualitative and quantitative analysis of the DTI maps can provide useful information by which to distinguish between radiation necrosis and viable glioma. PMID:21948114

Accuracy of ultrasound in the detection of liver fibrosis in chronic viral hepatitis.

PubMed

D'Onofrio, Mirko; Martone, Enrico; Brunelli, Silvia; Faccioli, Niccolò; Zamboni, Giulia; Zagni, Irene; Fattovich, Giovanna; Pozzi Mucelli, Roberto

2005-10-01

To assess the accuracy of ultrasonography (US) in the identification and grading of hepatic fibrosis in patients afflicted with chronic viral liver disease, compared to histological examination as a gold standard. We prospectively studied 105 patients (32 F, 73 M) affected by chronic viral liver disease in 36 months. Patients were studied with B-mode US and then underwent US-guided liver biopsy. All the patients were studied with conventional US with a Sequoia 512, 6.0 (Acuson, Mountain View CA, USA). We evaluated the following US parameters: liver margins, parenchymal echotexture, portal vein caliber and spleen diameter. The four B-mode US parameters were used for the US grading (from 0 to 4). Scheuer's grading (from 0 to 4) was used for the histological score. Grades 3 and 4 were considered as positive for fibrosis. Sensitivity, specificity, positive and negative predictive values and accuracy were calculated in the case of absence, positivity of one or all the US parameters. The correlation between US and histological scores was evaluated with Spearman's test. At histology seventy-seven patients (73%) had absent grade 0 (1 patient; 1%), low-moderate grade 1 (35 patients; 33%) or grade 2 (41 patients; 39%) liver fibrosis. Twenty-eight patients (27%) had severe grade 3 (16 patients; 15%) or grade 4 (12 patients; 11%) fibrosis. In the case of absence of US parameters sensitivity was 32%, specificity 32%, positive predictive value 15%, negative predictive value 57% and accuracy 32%. In the case of positivity of at least one of the US parameters the values were 68%, 68%, 43%, 84% and 69%. In the case of presence of all the US signs the results were 25%, 100%, 100%, 79% and 80%. None of the 77 patients with a healthy liver or with low-grade fibrosis was positive for all the US parameters. All the patients positive for all of the ultrasonographic parameters had high-grade fibrosis or cirrhosis at liver biopsy. Correlation between B-mode and histological scores was not statistically significant (Rs=0.45; p=0.0001). US identification of liver fibrosis in chronic liver disease is possible with 25% sensitivity, 100% specificity, 100% positive predictive value and 79% negative predictive value, with an 80% diagnostic accuracy.

Induction, immunochemical identity and immunofluorescence localization of an 80 000-molecular-weight peroxisome-proliferation-associated polypeptide (polypeptide PPA-80) and peroxisomal enoyl-CoA hydratase of mouse liver and renal cortex.

PubMed

Lalwani, N D; Reddy, M K; Mangkornkanok-Mark, M; Reddy, J K

1981-07-15

The hypolipidaemic drugs methyl clofenapate, BR-931, Wy-14643 and procetofen induced a marked proliferation of peroxisomes in the parenchymal cells of liver and the proximal-convoluted-tubular epithelium of mouse kidney. The proliferation of peroxisomes was associated with 6-12-fold increase in the peroxisomal palmitoyl-CoA oxidizing capacity of the mouse liver. Enhanced activity of the peroxisomal palmitoyl-CoA oxidation system was also found in the renal-cortical homogenates of hypolipidaemic-drug-treated mice. The activity of enoyl-CoA hydratase in the mouse liver increased 30-50-fold and in the kidney cortex 3-5-fold with hypolipidaemic-drug-induced peroxisome proliferation in these tissues, and over 95% of this induced activity was found to be heat-labile peroxisomal enzyme in both organs. Sodium dodecyl sulphate/polyacrylamide-gel-electrophoretic analysis of large-particle and microsomal fractions obtained from the liver and kidney cortex of mice treated with hypolipidaemic peroxisome proliferators demonstrated a substantial increase in the quantity of an 80000-mol.wt. peroxisome-proliferation-associated polypeptide (polypeptide PPA-80). The heat-labile peroxisomal enoyl-CoA hydratase was purified from the livers of mice treated with the hypolipidaemic drug methyl clofenapate; the antibodies raised against this electrophoretically homogeneous protein yielded a single immunoprecipitin band with purified mouse liver enoyl-CoA hydratase and with liver and kidney cortical extracts of normal and hypolipidaemic-drug-treated mice. These anti-(mouse liver enoyl-CoA hydratase) antibodies also cross-reacted with purified rat liver enoyl-CoA hydratase and with the polypeptide PPA-80 obtained from rat and mouse liver. Immunofluorescence studies with anti-(polypeptide PPA-80) and anti-(peroxisomal enoyl-CoA hydratase) provided visual evidence for the localization and induction of polypeptide PPA-80 and peroxisomal enoyl-CoA hydratase in the liver and kidney respectively of normal and hypolipidaemic-drug-treated mice. In the kidney, the distribution of these two proteins is identical and limited exclusively to the cytoplasm of proximal-convoluted-tubular epithelium. The immunofluorescence studies clearly complement the biochemical and ultrastructural observations of peroxisome induction in the liver and kidney cortex of mice fed on hypolipidaemic drugs. In addition, preliminary ultrastructural studies with the protein-A-gold-complex technique demonstrate that the heat-labile hepatic enoyl-CoA hydratase is localized in the peroxisome matrix.

Results of a questionnaire on the treatment of patients with Behçet's syndrome: a trend for more intensive treatment.

PubMed

Turkstra, F; van Vugt, R M; Dijkmans, B A C; Yazici, Y; Yazici, H

2012-01-01

To determine the preferred treatment for patients with Behçet's syndrome. A questionnaire was given to all participants of the 2010 meeting of the International Society for Behçet's Disease. Forty-one respondents from 6 different subspecialties. In the case of a patient with (severe) posterior uveitis or parenchymal central nervous system (CNS) disease no consensus was seen. A diffuse spectrum of different schedules were given. In both uveitis and CNS disease the majority of respondents preferred treatment options consisting of combination systemic therapy and systemic corticosteroids. TNF was preferred as first line drug in uveitis in 7.5% and in severe uveitis in 32.5% of respondents. In parenchymal CNS disease TNF blockage was given by 17% of the respondents. EULAR guidelines regarding uveitis were followed by 12/40 physicians. In patients with a new deep vein thrombosis, 90% of respondents would intensify immunosuppression. More than half would also anticoagulate. Although consensus about how to treat patients with Behçet syndrome in different clinical situations is far from present, treatment has become more intensive when compared to 10-20 years ago. More uniformity should be sought for in the decision process in individual patients with Behçet's syndrome, regarding their treatment, as well as adhering to evidence, as presented in the EULAR guidelines, when present.

Systemic Venous Inflow to the Liver Allograft to Overcome Diffuse Splanchnic Venous Thrombosis

PubMed Central

Darius, Tom; Goffette, Pierre; Lerut, Jan

2015-01-01

Diffuse splanchnic venous thrombosis (DSVT), formerly defined as contraindication for liver transplantation (LT), is a serious challenge to the liver transplant surgeon. Portal vein arterialisation, cavoportal hemitransposition and renoportal anastomosis, and finally combined liver and small bowel transplantation are all possible alternatives to deal with this condition. Five patients with preoperatively confirmed extensive splanchnic venous thrombosis were transplanted using cavoportal hemitransposition (4x) and renoportal anastomosis (1x). Median follow-up was 58 months (range: 0,5 to 130 months). Two patients with previous radiation-induced peritoneal injury died, respectively, 18 days and 2 months after transplantation. The three other patients had excellent long-term survival, despite the fact that two of them needed a surgical reintervention for severe gastrointestinal bleeding. Extensive splanchnic venous thrombosis is no longer an absolute contraindication to liver transplantation. Although cavoportal hemitransposition and renoportal anastomosis undoubtedly are life-saving procedures allowing for ensuring adequate allograft portal flow, careful follow-up of these patients remains necessary as both methods are unable to completely eliminate the complications of (segmental) portal hypertension. PMID:26539214

Bronchial Artery Embolization in the Management of Pulmonary Parenchymal Endometriosis with Hemoptysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kervancioglu, Selim, E-mail: skervancioglu@yahoo.com; Andic, Cagatay; Bayram, Nazan

Pulmonary parenchymal endometriosis is extremely rare and usually manifests itself with a recurrent hemoptysis associated with the menstrual cycle. The therapies proposed for women with endometriosis consist of medical treatments and surgery. Bronchial artery embolization has become a well-established and minimally invasive treatment modality for hemoptysis, and to the best of our knowledge, it has not been reported in pulmonary endometriosis. We report a case of pulmonary parenchymal endometriosis treated with embolotheraphy for hemoptysis.

Calcified parenchymal central nervous system cysticercosis and clinical outcomes in epilepsy.

PubMed

Leon, Amanda; Saito, Erin K; Mehta, Bijal; McMurtray, Aaron M

2015-02-01

This study aimed to compare clinical outcomes including seizure frequency and psychiatric symptoms between patients with epilepsy with neuroimaging evidence of past brain parenchymal neurocysticercosis infection, patients with other structural brain lesions, and patients without structural neuroimaging abnormalities. The study included retrospective cross-sectional analysis of all patients treated for epilepsy in a community-based adult neurology clinic during a three-month period. A total of 160 patients were included in the analysis, including 63 with neuroimaging findings consistent with past parenchymal neurocysticercosis infection, 55 with structurally normal brain neuroimaging studies, and 42 with other structural brain lesions. No significant differences were detected between groups for either seizure freedom (46.03%, 50.91%, and 47.62%, respectively; p=0.944) or mean seizure frequency per month (mean=2.50, S.D.=8.1; mean=4.83, S.D.=17.64; mean=8.55, S.D.=27.31, respectively; p=0.267). Self-reported depressive symptoms were more prevalent in those with parenchymal neurocysticercosis than in the other groups (p=0.003). No significant differences were detected for prevalence of self-reported anxiety or psychotic symptoms. Calcified parenchymal neurocysticercosis results in refractory epilepsy about as often as other structural brain lesions. Depressive symptoms may be more common among those with epilepsy and calcified parenchymal neurocysticercosis; consequently, screening for depression may be indicated in this population. Published by Elsevier Inc.

Comparison and reproducibility of ADC measurements in breathhold, respiratory triggered, and free-breathing diffusion-weighted MR imaging of the liver.

PubMed

Kwee, Thomas C; Takahara, Taro; Koh, Dow-Mu; Nievelstein, Rutger A J; Luijten, Peter R

2008-11-01

To compare and determine the reproducibility of apparent diffusion coefficient (ADC) measurements of the normal liver parenchyma in breathhold, respiratory triggered, and free-breathing diffusion-weighted magnetic resonance imaging (DWI). Eleven healthy volunteers underwent three series of DWI. Each DWI series consisted of one breathhold, one respiratory triggered, and two free-breathing (thick and thin slice acquisition) scans of the liver, at b-values of 0 and 500 s/mm2. ADCs of the liver parenchyma were compared by using nonparametric tests. Reproducibility was assessed by the Bland-Altman method. Mean ADCs (in 10(-3) mm2/sec) in respiratory triggered DWI (2.07-2.27) were significantly higher than mean ADCs in breathhold DWI (1.57-1.62), thick slice free-breathing DWI (1.62-1.65), and thin slice free-breathing DWI (1.57-1.66) (P<0.005). Ranges of mean difference in ADC measurement+/-limits of agreement between two scans were -0.02-0.05+/-0.16-0.24 in breathhold DWI, -0.14-0.20+/-0.59-0.60 in respiratory triggered DWI, -0.03-0.03+/-0.20-0.29 in thick slice free-breathing DWI, and -0.01-0.09+/-0.21-0.29 in thin slice free-breathing DWI. ADC measurements of the normal liver parenchyma in respiratory triggered DWI are significantly higher and less reproducible than in breathhold and free-breathing DWI. Copyright (c) 2008 Wiley-Liss, Inc.

Robotic partial nephrectomy with selective parenchymal compression (Simon clamp).

PubMed

Castillo, O A; Rodriguez-Carlin, A; Lopez-Fontana, G; Aleman, E

2013-01-01

To present our initial experience using selective renal parenchymal ischemia, without hilar clamping, in robotic-assisted partial nephrectomy. In four patients with T1a renal tumor we performed robotic-assisted partial nephrectomy, using the Simon's clamp (Aesculap). It provides selective parenchymal compression without the need of vascular clamping. All patients had exofitic renal tumors in polar location. Renal parenchymal reconstruction was done as the standard technique. The median age was 49.6 years (42-59), 3 male and 1 female patient. Median operative time was 71,6 minutes (40-120). Mean stimated bleeding was 250 ml (50-400). Average tumor size was 3,25 cm (1,5-5,3). There were no complications and the average hospital stay was 3,5 days (1-7). The pathology was informed as renal cell carcinoma in three patients and one hemorrhagic cyst. The surgical margins were negative. Our preliminary results shows that selective renal parenchymal compression, with the Simon's clamp, provides an alternative to vascular control in selected patients with polar renal tumors. Copyright © 2012 AEU. Published by Elsevier Espana. All rights reserved.

[Delayed diagnosis of neurocysticercosis: two case reports].

PubMed

Vandenbos, F; Boscagli-Melaine, A; Roth, S; Mondain-Miton, V; Paquis, P; Gari-Toussaint, M; Saint-Paul, M C; Montagne, N

2002-04-01

Neurocysticercosis is the most frequently encountered cerebral parasitic infection worldwide. It is due to infection of the central nervous system by Taenia solium larval form. According to the location of the cysts, parenchymal and extra-parenchymal forms may be identified, with different clinical expressions. We report two cases of neurocysticercosis, one with typical parenchymal involvement and the second with extra-parenchymal involvement revealed by increased intra-cranial pressure. In both cases, the diagnosis was established over 10 years after the onset of symptoms. Neurocysticercosis is very frequent in non-Islamic developing countries, and its incidence is increasing in industrialized nations in relation to tourism and immigration from highly endemic areas. Symptoms usually appear several years after infection and this accounts for the frequent delays before the diagnosis is established.

Diffusion-weighted Imaging of the Liver with Multiple b Values: Effect of Diffusion Gradient Polarity and Breathing Acquisition on Image Quality and Intravoxel Incoherent Motion Parameters—A Pilot Study

PubMed Central

Dyvorne, Hadrien A.; Galea, Nicola; Nevers, Thomas; Fiel, M. Isabel; Carpenter, David; Wong, Edmund; Orton, Matthew; de Oliveira, Andre; Feiweier, Thorsten; Vachon, Marie-Louise; Babb, James S.

2013-01-01

Purpose: To optimize intravoxel incoherent motion (IVIM) diffusion-weighted (DW) imaging by estimating the effects of diffusion gradient polarity and breathing acquisition scheme on image quality, signal-to-noise ratio (SNR), IVIM parameters, and parameter reproducibility, as well as to investigate the potential of IVIM in the detection of hepatic fibrosis. Materials and Methods: In this institutional review board–approved prospective study, 20 subjects (seven healthy volunteers, 13 patients with hepatitis C virus infection; 14 men, six women; mean age, 46 years) underwent IVIM DW imaging with four sequences: (a) respiratory-triggered (RT) bipolar (BP) sequence, (b) RT monopolar (MP) sequence, (c) free-breathing (FB) BP sequence, and (d) FB MP sequence. Image quality scores were assessed for all sequences. A biexponential analysis with the Bayesian method yielded true diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (PF) in liver parenchyma. Mixed-model analysis of variance was used to compare image quality, SNR, IVIM parameters, and interexamination variability between the four sequences, as well as the ability to differentiate areas of liver fibrosis from normal liver tissue. Results: Image quality with RT sequences was superior to that with FB acquisitions (P = .02) and was not affected by gradient polarity. SNR did not vary significantly between sequences. IVIM parameter reproducibility was moderate to excellent for PF and D, while it was less reproducible for D*. PF and D were both significantly lower in patients with hepatitis C virus than in healthy volunteers with the RT BP sequence (PF = 13.5% ± 5.3 [standard deviation] vs 9.2% ± 2.5, P = .038; D = [1.16 ± 0.07] × 10−3 mm2/sec vs [1.03 ± 0.1] × 10−3 mm2/sec, P = .006). Conclusion: The RT BP DW imaging sequence had the best results in terms of image quality, reproducibility, and ability to discriminate between healthy and fibrotic liver with biexponential fitting. © RSNA, 2012 PMID:23220895

Advanced MRI Methods for Assessment of Chronic Liver Disease

PubMed Central

Taouli, Bachir; Ehman, Richard L.; Reeder, Scott B.

2010-01-01

MRI plays an increasingly important role for assessment of patients with chronic liver disease. MRI has numerous advantages, including lack of ionizing radiation and the possibility of performing multiparametric imaging. With recent advances in technology, advanced MRI methods such as diffusion-, perfusion-weighted MRI, MR elastography, chemical shift based fat-water separation and MR spectroscopy can now be applied to liver imaging. We will review the respective roles of these techniques for assessment of chronic liver disease. PMID:19542391

Diffusion-weighted and T2-weighted MR imaging for colorectal liver metastases detection in a rat model at 7 T: a comparative study using histological examination as reference.

PubMed

Wagner, Mathilde; Maggiori, Léon; Ronot, Maxime; Paradis, Valérie; Vilgrain, Valérie; Panis, Yves; Van Beers, Bernard E

2013-08-01

To compare diffusion-weighted (DW) and T2-weighted MR imaging in detecting colorectal liver metastases in a rat model, using histological examination as a reference method. Eighteen rats had four liver injections of colon cancer cells. MR examinations at 7 T included FSE-T2-weighted imaging and SE-DW MR imaging (b = 0, 20 and 150 s/mm(2)) and were analysed by two independent readers. Histological examination was performed on 0.4-mm slices. McNemar's test was used to compare the sensitivities and the Wilcoxon matched pairs test to compare the average number of false-positives per rat. One hundred and sixty-six liver metastases were identified on histological examination. The sensitivity in detecting liver metastases was significantly higher on DW MR than on T2-weighted images (99/166 (60 %) (reader 1) and 92/166 (55 %) (reader 2) versus 77/166 (46 %), P ≤ 0.001), without an increase in false-positives per rat (P = 0.773/P = 0.850). After stratification according to metastasis diameter, DW MR imaging had a significantly higher sensitivity than T2-weighted imaging only for metastases with a diameter (0.6-1.2 mm) similar to that of the spatial resolution of MR imaging in the current study. This MR study with histological correlations shows the higher sensitivity of DW relative to T2-weighted imaging at 7 T for detecting liver metastases, especially small ones. • Diffusion weighted (DW) sequences are increasingly used in magnetic resonance imaging (MRI). • DW has higher sensitivity for liver metastases than T2-weighted imaging at 7 T. • This increase in sensitivity is especially marked for small liver metastasis detection. • This higher sensitivity is confirmed in an animal model with histological correlation. • DW imaging has the potential for earlier diagnosis of small liver metastases.

The Use of Convection-Enhanced Delivery with Liposomal Toxins in Neurooncology

PubMed Central

Fiandaca, Massimo S.; Berger, Mitchel S.; Bankiewicz, Krystof S.

2011-01-01

Liposomes have long been effective delivery vehicles for transport of toxins to peripheral cancers. The combination of convection-enhanced delivery (CED) with liposomal toxins was originally proposed to circumvent the limited delivery of intravascular liposomes to the central nervous system (CNS) due to the blood-brain-barrier (BBB). CED offers markedly improved distribution of infused therapeutics within the CNS compared to direct injection or via drug eluting polymers, both of which depend on diffusion for parenchymal distribution. This review examines the basis for improved delivery of liposomal toxins via CED within the CNS, and discusses preclinical and clinical experience with these therapeutic techniques. How CED and liposomal technologies may influence future neurooncologic treatments are also considered. PMID:22069714

Pulmonary hemorrhage in acute heroin overdose: a report of two cases.

PubMed

Riccardello, Gerald J; Maldjian, Pierre D

2017-12-01

Diffuse alveolar hemorrhage (DAH) is a clinical syndrome characterized by pulmonary hemorrhage, respiratory failure, and high early mortality rates. DAH typically appears on chest radiographs as bilateral parenchymal consolidations. To our knowledge, pulmonary hemorrhage associated with heroin overdose has not been reported. We report the clinical and radiographic findings in two cases of acute DAH following heroin overdose. We speculate that an adulterating agent may be the underlying etiology in these cases. While pulmonary edema as a consequence of heroin overdose is well-documented and usually first suspected when consolidations are present on a chest radiograph in a patient with a history of recent heroin use, we believe that DAH should also be considered in the proper clinical context.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fullerton, Aaron M., E-mail: fuller22@msu.edu; Roth, Robert A., E-mail: rothr@msu.edu; Ganey, Patricia E., E-mail: ganey@msu.edu

Inflammation plays a major role in immune-mediated liver injury, and exposure to environmental pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been reported to alter the inflammatory response as well as affect immune cell activity. In this study, we tested the hypothesis that TCDD pretreatment exacerbates hepatotoxicity in a murine model of immune-mediated liver injury induced by concanavalin A (Con A) administration. Mice were pretreated with 30 μg/kg TCDD or vehicle control on day zero and then given either Con A or saline intravenously on day four. Mice treated with TCDD did not develop liver injury; however, TCDD pretreatment increased liver injurymore » resulting from moderate doses of Con A (4–10 mg/kg). TCDD-pretreated mice had altered plasma concentrations of inflammatory cytokines, including interferon gamma (IFNγ), and TCDD/Con A-induced hepatotoxicity was attenuated in IFNγ knockout mice. At various times after treatment, intrahepatic immune cells were isolated, and expression of cell activation markers as well as cytolytic proteins was determined. TCDD pretreatment increased the proportion of activated natural killer T (NKT) cells and the percent of cells expressing Fas ligand (FasL) after Con A administration. In addition FasL knockout mice and mice treated with CD18 antiserum were both protected from TCDD/Con A-induced hepatotoxicity, suggesting a requirement for direct cell–cell interaction between effector immune cells and parenchymal cell targets in the development of liver injury from TCDD/Con A treatment. In summary, exposure to TCDD increased NKT cell activation and exacerbated immune-mediated liver injury induced by Con A through a mechanism involving IFNγ and FasL expression. -- Highlights: ► TCDD pretreatment sensitizes mice to Con A-induced hepatotoxicity. ► TCDD pretreatment increased concentration of IFNγ in plasma after Con A. ► Con A-induced activation of NKT cells was increased by TCDD pretreatment. ► FasL-positive NKT cells increased with TCDD pretreatment versus Con A alone. ► IFNγ and FasL are critical to the development of liver injury from TCDD/Con A.« less

Role of glycerol 3-phosphate and glycerophosphate acyltransferase in the nutritional control of hepatic triacylglycerol synthesis

PubMed Central

Declercq, Peter E.; Debeer, Luc J.; Mannaerts, Guy P.

1982-01-01

1. Glycerol 3-phosphate content of isolated hepatocytes from starved rats and of glycogen-depleted hepatocytes from fed rats was low and severely limited triacylglycerol synthesis. 2. Raising the glycerol 3-phosphate content by addition of precursors to the cells resulted in a hyperbolic-like relationship between triacylglycerol synthesis and cellular glycerol 3-phosphate content. Statistical analysis of the curves showed no significant differences between the nutritional states either at saturating or at subsaturating glycerol 3-phosphate content. 3. Vmax. of glycerophosphate acyltransferase measured in homogenized hepatocytes was decreased by 30–40% in starvation. There was no change in apparent Km for glycerol 3-phosphate. Since at saturating glycerol 3-phosphate content esterification rates in hepatocytes of both nutritional states were identical, the enzyme is not limiting esterification under this condition. 4. At subsaturating glycerol 3-phosphate content the flux through glycerophosphate acyltransferase necessarily limits esterification. Therefore one would expect a decrease in esterification in starvation under this condition. This was the case when triacylglycerol synthesis was plotted against intracellular glycerol 3-phosphate concentration, calculated from the cellular glycerol 3-phosphate content and the intracellular water space, which was smaller in hepatocytes from starved rats. 5. The data obtained in hepatocytes were extrapolated to the intact liver by using the number of parenchymal cells per g of liver as determined from marker-enzyme analysis and the liver weight per 100g body weight. The extrapolation suggested that glycerol 3-phosphate is limiting esterification in vivo for contents below 0.3–0.4 and 0.5–0.65μmol/g for livers from fed and starved animals respectively. Also for a given fatty acid load and a glycerol 3-phosphate content below 0.3μmol/g the liver may esterify less in the starved state. However, at the glycerol 3-phosphate contents measured in freeze-clamped livers (0.30 and 0.44μmol/g for the fed and starved state respectively), livers in both nutritional states seemed capable of esterifying similar amounts of fatty acids. PMID:7115324

Diffusion-weighted imaging of the liver at 3 T using section-selection gradient reversal: emphasis on chemical shift artefacts and lesion conspicuity.

PubMed

Lee, J S; Kim, Y K; Jeong, W K; Choi, D; Lee, W J

2015-04-01

To assess the value of section-selection gradient reversal (SSGR) in liver diffusion-weighted imaging (DWI) by comparing it to conventional DWI with an emphasis on chemical shift artefacts and lesion conspicuity. Forty-eight patients (29 men and 19 women; age range 33-80 years) with 48 liver lesions underwent two DWI examinations using spectral presaturation with inversion recovery fat suppression with and without SSGR at 3 T. Two reviewers evaluated each DWI (b = 100 and b = 800 image) with respect to chemical shift artefacts and liver lesion conspicuity using five-point scales and performed pairwise comparisons between the two DWIs. The signal-to-noise ratio (SNR) of the liver and the lesion and the lesion-liver contrast-to-noise ratio (CNR) were also calculated. SSGR-DWI was significantly better than conventional DWI with respect to chemical shift artefacts and lesion conspicuity in both separate reviews and pairwise comparisons (p < 0.05). There were significant differences in the SNR of the liver (b = 100 and b = 800 images) and lesion (b = 800) between SSGR-DWI and conventional DWI (p < 0.05). Applying the SSGR method to DWI using SPIR fat suppression at 3 T could significantly reduce chemical shift artefacts without incurring additional acquisition time or SNR penalties, which leads to increased conspicuity of focal liver lesions. Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Abridged republication of FIGO's staging classification for cancer of the ovary, fallopian tube, and peritoneum.

PubMed

Prat, Jaime

2015-10-01

Ovarian, fallopian tube, and peritoneal cancers have a similar clinical presentation and are treated similarly, and current evidence supports staging all 3 cancers in a single system. The primary site (i.e. ovary, fallopian tube, or peritoneum) should be designated where possible. The histologic type should be recorded. Intraoperative rupture ("surgical spill") is IC1; capsule ruptured before surgery or tumor on ovarian or fallopian tube surface is IC2; and positive peritoneal cytology with or without rupture is IC3. The new staging includes a revision of stage III patients; assignment to stage IIIA1 is based on spread to the retroperitoneal lymph nodes without intraperitoneal dissemination. Extension of tumor from omentum to spleen or liver (stage IIIC) should be differentiated from isolated parenchymal metastases (stage IVB). © 2015 American Cancer Society.

Hepatic alveolar echinococcosis: correlative US and CT study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Didier, D.; Weiler, S.; Rohmer, P.

1985-01-01

A total of 24 cases of hepatic alveolar echinococcosis (HAE) due to Echinococcus multilocularis was assessed by US and CT. The diagnosis was confirmed in all cases by immunologic and histologic study. Both US and CT patterns of HAE showed changes of liver morphology in both contour and size. Abnormal areas of parenchyma were nodular or in fields, irregular, heterogeneous, and basically echogenic. Clustered microcalcifications were encountered within the abnormal parenchymal fields in 50% of cases, and necrotized zones occurred in 40% of cases. Dilatation of intrahepatic bile ducts was commonly seen, especially on US; hilar involvement was frequent. Follow-upmore » by both techniques can display increases of primary lesions, occurrence of new foci, and local or regional extensions. Precise evaluations of the lesions arising from correlative use of US and CT permits adequate therapeutic management.« less

Experimentally induced lead poisoning in goats: clinical observations and pathologic changes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Davis, J.W.; Libke, K.G.; Watson, D.F.

1976-10-01

The effects of orally administered lead acetate were investigated in 9 adult and 3 kid goats by clinical and necropsy studies. One kid and 6 adults died after having received from 100 to 1392.5 Gm each, given over periods of from 10 to 52 days. Anorexia, diarrhea and body weight loss occurred in all lead treated goats in the study. Basophilic stippling of red blood cells was found in 6 of 8 animals on which weekly hemograms were performed. The pathological changes were essentially the same as those that have been recorded for other ruminant species with lead poisoning. Intranuclearmore » acid-fast inclusions in the cells of the proximal convoluted tubules of the kidney were demonstrated in 9 of 12 lead treated goats and in the liver parenchymal cells of 2 of these animals.« less

Whole-body MRI including diffusion-weighted MRI compared with 5-HTP PET/CT in the detection of neuroendocrine tumors

PubMed Central

Carlbom, Lina; Caballero-Corbalán, José; Granberg, Dan; Sörensen, Jens; Eriksson, Barbro; Ahlström, Håkan

2017-01-01

Aim We wanted to explore if whole-body magnetic resonance imaging (MRI) including diffusion-weighted (DW) and liver-specific contrast agent-enhanced imaging could be valuable in lesion detection of neuroendocrine tumors (NET). [11C]-5-Hydroxytryptophan positron emission tomography/computed tomography (5-HTP PET/CT) was used for comparison. Materials and methods Twenty-one patients with NET were investigated with whole-body MRI, including DW imaging (DWI) and contrast-enhanced imaging of the liver, and whole-body 5-HTP PET/CT. Seven additional patients underwent upper abdomen MRI including DWI, liver-specific contrast agent-enhanced imaging, and 5-HTP PET/CT. Results There was a patient-based concordance of 61% and a lesion-based concordance of 53% between the modalities. MRI showed good concordance with PET in detecting bone metastases but was less sensitive in detecting metastases in mediastinal lymph nodes. MRI detected more liver metastases than 5-HTP PET/CT. Conclusion Whole-body MRI with DWI did not detect all NET lesions found with whole-body 5-HTP PET/CT. Our findings indicate that MRI of the liver including liver-specific contrast agent-enhanced imaging and DWI could be a useful complement to whole-body 5-HTP PET/CT. PMID:27894208

Gas embolization of the liver in a rat model of rapid decompression.

PubMed

L'Abbate, Antonio; Kusmic, Claudia; Matteucci, Marco; Pelosi, Gualtiero; Navari, Alessandro; Pagliazzo, Antonino; Longobardi, Pasquale; Bedini, Remo

2010-08-01

Occurrence of liver gas embolism after rapid decompression was assessed in 31 female rats that were decompressed in 12 min after 42 min of compression at 7 ATA (protocol A). Sixteen rats died after decompression (group I). Of the surviving rats, seven were killed at 3 h (group II), and eight at 24 h (group III). In group I, bubbles were visible in the right heart, aortic arch, liver, and mesenteric veins and on the intestinal surface. Histology showed perilobular microcavities in sinusoids, interstitial spaces, and hepatocytes. In group II, liver gas was visible in two rats. Perilobular vacuolization and significant plasma aminotransferase increase were present. In group III, liver edema was evident at gross examination in all cases. Histology showed perilobular cell swelling, vacuolization, or hydropic degeneration. Compared with basal, enzymatic markers of liver damage increased significantly. An additional 14 rats were decompressed twice (protocol B). Overall mortality was 93%. In addition to diffuse hydropic degeneration, centrilobular necrosis was frequently observed after the second decompression. Additionally, 10 rats were exposed to three decompression sessions (protocol C) with doubled decompression time. Their mortality rate decreased to 20%, but enzymatic markers still increased in surviving rats compared with predecompression, and perilobular cell swelling and vacuolization were present in five rats. Study challenges were 1) liver is not part of the pathophysiology of decompression in the existing paradigm, and 2) although significant cellular necrosis was observed in few animals, zonal or diffuse hepatocellular damage associated with liver dysfunction was frequently demonstrated. Liver participation in human decompression sickness should be looked for and clinically evaluated.

Hepatocellular carcinoma: short-term reproducibility of apparent diffusion coefficient and intravoxel incoherent motion parameters at 3.0T.

PubMed

Kakite, Suguru; Dyvorne, Hadrien; Besa, Cecilia; Cooper, Nancy; Facciuto, Marcelo; Donnerhack, Claudia; Taouli, Bachir

2015-01-01

To evaluate short-term test-retest and interobserver reproducibility of IVIM (intravoxel incoherent motion) diffusion parameters and ADC (apparent diffusion coefficient) of hepatocellular carcinoma (HCC) and liver parenchyma at 3.0T. In this prospective Institutional Review Board (IRB)-approved study, 11 patients were scanned twice using a free-breathing single-shot echo-planar-imaging, diffusion-weighted imaging (DWI) sequence using 4 b values (b = 0, 50, 500, 1000 s/mm(2)) and IVIM DWI using 16 b values (0-800 s/mm(2)) at 3.0T. IVIM parameters (D: true diffusion coefficient, D*: pseudodiffusion coefficient, PF: perfusion fraction) and ADC (using 4 b and 16 b) were calculated. Short-term test-retest and interobserver reproducibility of IVIM parameters and ADC were assessed by measuring correlation coefficient, coefficient of variation (CV), and Bland-Altman limits of agreements (BA-LA). Fifteen HCCs were assessed in 10 patients. Reproducibility of IVIM metrics in HCC was poor for D* and PF (mean CV 60.6% and 37.3%, BA-LA: -161.6% to 135.3% and -66.2% to 101.0%, for D* and PF, respectively), good for D and ADC (CV 19.7% and <16%, BA-LA -57.4% to 36.3% and -38.2 to 34.1%, for D and ADC, respectively). Interobserver reproducibility was on the same order of test-retest reproducibility except for PF in HCC. Reproducibility of diffusion parameters was better in liver parenchyma compared to HCC. Poor reproducibility of D*/PF and good reproducibility for D/ADC were observed in HCC and liver parenchyma. These findings may have implications for trials using DWI in HCC. © 2014 Wiley Periodicals, Inc.

Exercise-Induced Release of Pharmacologically Active Substances and Their Relevance for Therapy of Hepatic Injury

PubMed Central

Schon, Hans-Theo; Weiskirchen, Ralf

2016-01-01

Chronic liver disease (CLD) features constant parenchymal injury and repair together with an increasing hepatic impairment, finally leading to fibrosis and cirrhosis and a heightened risk of hepatocellular carcinoma (HCC). Closely related to the rise in obesity, the worldwide prevalence of nonalcoholic fatty liver disease, the most common form of CLD, has reached an epidemic dimension and is estimated to afflict up to 46% of the general population, including more than one out of three U.S. citizens. Up to now there is no effective drug treatment available, which is why recommendations encompass both exercise programs and changes in dietary habits. Exercise is well-known for unleashing potent anti-inflammatory effects, which can principally counteract liver inflammation and chronic low-grade inflammation. This review article summarizes the underlying mechanisms responsible for the exercise-mediated anti-inflammatory effects, illustrates the application in animal models as well as in humans, and highlights the therapeutic value when possible. Based on the available results there is no doubt that exercise can even be beneficial in an advanced stage of liver disease and it is the goal of this review article to provide evidence for the therapeutic impact on fibrosis, cirrhosis, and HCC and to assess whether exercise might be of value as adjuvant therapy in the treatment of CLD. In principle, all exercise programs carried out in these high-risk patients should be guided and observed by qualified healthcare professionals to guarantee the patients’ safety. Nevertheless, it is also necessary to additionally determine the optimal amount and intensity of exercise to maximize its value, which is why further studies are essential. PMID:27625607

Nesfatin-1 alleviates extrahepatic cholestatic damage of liver in rats

PubMed Central

Solmaz, Ali; Gülçiçek, Osman Bilgin; Erçetin, Candaş; Yiğitbaş, Hakan; Yavuz, Erkan; Arıcı, Sinan; Erzik, Can; Zengi, Oğuzhan; Demirtürk, Pelin; Çelik, Atilla; Çelebi, Fatih

2016-01-01

Obstructive jaundice (OJ) can be defined as cessation of bile flow into the small intestine due to benign or malignant changes. Nesfatin-1, recently discovered anorexigenic peptide derived from nucleobindin-2 in hypothalamic nuclei, was shown to have anti-inflammatory and antiapoptotic effects. This study is aimed to investigate the therapeutic effects of nesfatin-1 on OJ in rats. Twenty-four adult male Wistar-Hannover rats were randomly assigned to three groups: sham (n = 8), control (n = 8), and nesfatin (n = 8). After bile duct ligation, the study groups were treated with saline or nesfatin-1, for 10 days. Afterward, blood and liver tissue samples were obtained for biochemical analyses, measurement of cytokines, determination of the oxidative DNA damage, DNA fragmentation, and histopathologic analyses. Alanine aminotransferase and gamma-glutamyl transferase levels were decreased after the nesfatin treatment; however, these drops were statistically non-significant compared to control group (p = 0.345, p = 0.114). Malondialdehyde levels decreased significantly in nesfatin group compared to control group (p = 0.032). Decreases in interleukin-6 and tumor necrosis factor-α levels from the liver tissue samples were not statistically significant in nesfatin group compared to control group. The level of oxidative DNA damage was lower in nesfatin group, however this result was not statistically significant (p = 0.75). DNA fragmentation results of all groups were similar. Histopathological examination revealed that there was less neutrophil infiltration, edema, bile duct proliferation, hepatocyte necrosis, basement membrane damage, and parenchymal necrosis in nesfatin compared to control group. The nesfatin-1 treatment could alleviate cholestatic liver damage caused by OJ due to its anti-inflammatory and antioxidant effects. PMID:27524109

No-Touch Radiofrequency Ablation: A Comparison of Switching Bipolar and Switching Monopolar Ablation in Ex Vivo Bovine Liver

PubMed Central

Chang, Won; Lee, Sang Min; Han, Joon Koo

2017-01-01

Objective To evaluate the feasibility, efficiency, and safety of no-touch switching bipolar (SB) and switching monopolar (SM) radiofrequency ablation (RFA) using ex vivo bovine livers. Materials and Methods A pork loin cube was inserted as a tumor mimicker in the bovine liver block; RFA was performed using the no-touch technique in the SM (group A1; 10 minutes, n = 10, group A2; 15 minutes, n = 10) and SB (group B; 10 minutes, n = 10) modes. The groups were compared based on the creation of confluent necrosis with sufficient safety margins, the dimensions, and distance between the electrode and ablation zone margin (DEM). To evaluate safety, small bowel loops were placed above the liver surface and 30 additional ablations were performed in the same groups. Results Confluent necroses with sufficient safety margins were created in all specimens. SM RFA created significantly larger volumes of ablation compared to SB RFA (all p < 0.001). The DEM of group B was significantly lower than those of groups A1 and A2 (all p < 0.001). Although thermal injury to the small bowel was noted in 90%, 100%, and 30% of the cases in groups A1, A2, and B, respectively, full depth injury was noted only in 60% of group A2 cases. Conclusion The no-touch RFA technique is feasible in both the SB and SM modes; however, SB RFA appears to be more advantageous compared to SM RFA in the creation of an ablation zone while avoiding the unnecessary creation of an adjacent parenchymal ablation zone or adjacent small bowel injuries. PMID:28246508

Steatosis influences the clinical profiles and long-term outcomes of interferon-treated chronic hepatitis C and liver cirrhosis patients.

PubMed

Nirei, Kazushige; Matsumura, Hiroshi; Kumakawa, Mariko; Matsumoto, Naoki; Nakamura, Hitomi; Yamagami, Hiroaki; Matsuoka, Shunichi; Moriyama, Mitsuhiko

2017-01-01

Objective: This study aimed to assess the relationship between steatosis and long-term outcomes of patients with chronic hepatitis C (CH) and liver cirrhosis (LC). Patients and methods: The study population included 282 subjects with CH or LC who underwent liver biopsy at our institute. All patients achieved a sustained virological response (SVR) to interferon (IFN). Clinical characteristics, including age, gender and body mass index (BMI), were compared. The liver biopsy specimens of all patients were examined and scores were assigned to indicate the severity of each of the following features: inflammatory cell infiltration in the periportal, parenchymal and portal areas; F (fibrosis) stage; portal sclerotic change; perivenular fibrosis; pericellular fibrosis; bile duct damage; hepatic steatosis. Results: Of the 282 patients, 112 (39.7%) were free of steatosis. The other 170 patients (60.3%) had steatosis. The blood biochemical parameters of the patients with hepatic steatosis were significantly poorer than those of patients free of steatosis. Inflammatory cell infiltration and F stage were both significantly more severe in patients with than in those without steatosis. The incidences of hepatocellular carcinoma differed significantly between the two groups. However, the incidences of hepatocellular carcinoma did not differ significantly between the groups with BMI above and below 25. Conclusion: We consider hepatic steatosis to potentially affect the blood biochemical parameters and clinical profiles of Japanese patients with CH due to hepatitis virus type C. Patients with this form of CH showed favorable clinical responses to IFN. Furthermore, fibrosis and steatosis appear to affect the long-term outcomes of these patients. However, BMI alone cannot be used to predict HCC development.

Flow cytometric DNA analysis of cirrhotic liver cells in patients with hepatocellular carcinoma can provide a new prognostic factor.

PubMed

Ruà, S; Comino, A; Fruttero, A; Torchio, P; Bouzari, H; Taraglio, S; Torchio, B; Capussotti, L

1996-09-15

DNA flow cytometry of hepatocellular carcinoma (HCC) cells has been investigated in many studies, but, to the best of our knowledge, there are no data on DNA analysis of cirrhotic parenchyma around the HCC. In this study, cell kinetics and ploidy of parenchymal cells around HCC were performed to ascertain if this would predict the possibility of recurrence in the cirrhotic areas. The DNA content of 93 cases of HCC and of cirrhotic liver around the tumor nodules was analyzed by flow cytometry. Ploidy and proliferative index of HCC and cirrhotic liver were compared with macroscopic, histologic, and clinical features of each case and linked with the behavior of these tumors. Survival curves were assessed according to the Kaplan-Meier method. A multivariate analysis based on Cox proportional hazards regression model was performed on cases of diploid cirrhosis cells in which the S-phase fraction was evaluable. The univariate analysis of survival suggested significant roles for age, number of intrahepatic nodules, Edmondson-Steiner's classification, portal invasion, vascular invasion, presence of necrosis, hepatitis B surface antigen, alpha-feto-protein, Child's score, ploidy, and S-phase fraction of HCC cells. The DNA analysis of the cirrhotic cells showed that polyploidy was dramatically reduced in patients with HCC, compared with normal hepatocytes, and aneuploid clones were present among diploid cells. High S-phase fraction of cirrhotic cells and Child-Pugh classification were the strongest independent parameters affecting the tumor behavior in this study. The results of this study suggest that S-phase fraction of cirrhotic liver parenchyma may be employed as a new parameter in the prognostic evaluation of HCC patients.

Trichloroethylene Exposure Reduces Liver Injury in a Mouse Model of Primary Biliary Cholangitis

PubMed Central

Ray, Jessica L.; Kopec, Anna K.; Joshi, Nikita; Cline-Fedewa, Holly; Lash, Lawrence H.; Williams, Kurt J.; Leung, Patrick S.; Gershwin, M. Eric

2017-01-01

Abstract Trichloroethylene (TCE) is a persistent environmental contaminant proposed to contribute to autoimmune disease. Experimental studies in lupus-prone MRL+/+ mice have suggested that TCE exposure can trigger autoimmune hepatitis. The vast majority of studies examining the connection between TCE and autoimmunity utilize this model, and the impact of TCE exposure in other established models of autoimmune liver disease is not known. We tested the hypothesis that TCE exposure exacerbates experimental hepatic autoimmunity in dominant negative transforming growth factor beta receptor type II (dnTGFBRII) mice, which develop serological and histological features resembling human primary biliary cholangitis. Female 8-week-old wild-type and dnTGFBRII mice were exposed to TCE (0.5 mg/ml) or vehicle (1% ethoxylated castor oil) in the drinking water for 12 or 22 weeks. Liver histopathology in 20- and 30-week-old wild-type mice was unremarkable irrespective of treatment. Mild portal inflammation was observed in vehicle-exposed 20-week-old dnTGFBRII mice and was not exacerbated by TCE exposure. Vehicle-exposed 30-week-old dnTGFBRII mice developed anti-mitochondrial antibodies, marked hepatic inflammation with necrosis, and hepatic accumulation of both B and T lymphocytes. To our surprise, TCE exposure dramatically reduced hepatic parenchymal inflammation and injury in 30-week-old dnTGFBRII mice, reflected by changes in hepatic proinflammatory gene expression, serum chemistry, and histopathology. Interestingly, TCE did not affect hepatic B cell accumulation or induction of the anti-inflammatory cytokine IL10. These data indicate that TCE exposure reduces autoimmune liver injury in female dnTGFBRII mice and suggests that the precise effect of environmental chemicals in autoimmunity depends on the experimental model. PMID:28115651

Cost-Effective Surgical Management of Liver Disease Amidst a Financial Crisis.

PubMed

Arkadopoulos, Nikolaos; Gemenetzis, Georgios; Danias, Nikolaos; Kokoropoulos, Panagiotis; Koukopoulou, Ioanna; Bartsokas, Christos; Kostopanagiotou, Georgia; Smyrniotis, Vassilios

2016-07-01

Intraoperative use of specialized equipment and disposables contributes to the increasing cost of modern liver surgery. As a response to the recent severe financial crisis in our country we have employed a highly standardized protocol of liver resection that minimizes intraoperative and postoperative costs. Our goal is to evaluate cost-effectiveness of this protocol. We evaluated retrospectively all patients who underwent open hepatic resections for 4 years. All resections were performed by the same surgical team under selective hepatic vascular exclusion, i.e., occlusion of the hepatoduodenal ligament and the major hepatic veins, occasionally combined with extrahepatic ligation of the ipsilateral portal vein. Sharp parenchymal transection was performed with a scalpel and hemostasis was achieved with sutures without the use of energy devices. In each case we performed a detailed analysis of costs and surgical outcomes. Our cohort included 146 patients (median age 63 years). 113 patients were operated for primary or metastatic malignancies and 33 for benign lesions. Operating time was 121 ± 21 min (mean ± SD), estimated blood loss was 310 ± 159 ml (mean ± SD), and hospital stay was 7 ± 5 days (mean ± SD). Six patients required admission in the ICU postoperatively. 90-day mortality was 2.74 %, and 8.9 % of patients developed grade III/IV postoperative complications (Clavien-Dindo classification). Total in-hospital cost excluding physician fees was 6987.63 ± 3838.51 USD (mean ± SD). Our analysis suggests that, under pressing economic conditions, the proposed surgical protocol can significantly lessen the financial burden of liver surgery without compromising patient outcomes.

Selection of a right posterior sector graft for living donor liver transplantation.

PubMed

Yoshizumi, Tomoharu; Ikegami, Toru; Kimura, Koichi; Uchiyama, Hideaki; Ikeda, Tetsuo; Shirabe, Ken; Maehara, Yoshihiko

2014-09-01

Right posterior sector (RPS) grafts have been used to overcome graft size discrepancies, the major concern of living donor liver transplantation. Previous studies have reported the volumetry-based selection of RPS grafts without anatomical exclusion. We reviewed our data and established selection criteria for RPS grafts. The procurement of RPS grafts [conventional (n = 3) and extended (n = 5)] was performed for 8 of 429 recipients at our center. Extended RPS grafts contained the drainage area of the right hepatic vein. The mean graft weight (GW) according to 3-dimensional computed tomography volumetry was 488 g, and the GW/standard liver weight (SLW) ratio was 42.6%. The mean actual GW was 437 g, and the GW/SLW ratio was 38.4%. One donor exhibited standard bifurcation of the right portal vein (PV) and the left PV, and 2 donors exhibited trifurcation of the left PV, the right anterior portal vein (APV), and the posterior PV. The remaining 5 donors exhibited APV branching from the left PV, which is the most suitable anatomy for RPS grafts. Two recipients died of sepsis or small-for-size graft syndrome. One underwent retransplantation because of an intractable bile leak and fibrosing cholestatic hepatitis. Intractable bile duct (BD) stenosis developed in 4 of the 6 survivors. In conclusion, with the significant complications and potential concerns associated with RPS grafts, these grafts should be used very rarely and with extreme caution. Donors with the standard bifurcation of the PV and the posterior BD running through the dorsal side of the posterior PV are not suitable candidates for RPS grafts. Extended RPS graft procurement is recommended for easier parenchymal transection. © 2014 American Association for the Study of Liver Diseases.

Acetaminophen-induced hepatotoxicity is associated with early changes in NF-kB and NF-IL6 DNA binding activity.

PubMed

Blazka, M E; Germolec, D R; Simeonova, P; Bruccoleri, A; Pennypacker, K R; Luster, M I

Nuclear transcription factors, such as NF-kB and NF-IL6, are believed to play an important role in regulating the expression of genes that encode for products involved in tissue damage and inflammation and, thus, may represent early biomarkers for chemical toxicities. In the present study changes in DNA binding activity of these factors were examined in livers of mice administered hepatotoxic doses of acetaminophen (APAP). NF-kB and NF-IL6 DNA binding occurred constitutively in control mouse liver. However, within 4 hr following administration of hepatotoxic doses of APAP, their binding activities were transiently lost and is in contrast to AP-1 transcription factor where activation occurs under similar conditions. These changes corresponded with increased release of inflammatory mediators (IL-6, serum amyloid A) and increased levels of enzymatic markers of hepatocyte damage. Similarly, treatment of mice with gadolinium chloride, an inhibitor of Kupffer cell activation and known to protect against APAP-induced hepatotoxicity, reduced the observed pathophysiological response in the liver while altering the APAP-associated changes in NF-kB DNA binding activity. NF-kB was found predominantly in parenchymal and endothelial cells and was composed primarily of relatively inactive p50 homodimer subunits in control liver. Taken together, these studies suggest that hepatotoxicity is associated with early and complex changes in DNA binding activities of specific transcription factors. In particular, NF-kB and NF-IL6 may serve as negative regulators of hepatocyte-derived inflammatory mediators and is analogous to that previously observed in certain other cell systems such as B lymphocytes.

[Current practice in MR imaging of the liver].

PubMed

Kanematsu, M; Kondo, H; Matsuo, M; Hoshi, H

2001-12-01

MR imaging, which is able to evaluate T1- and T2-relaxation time, fat, hemorrhage, metal deposition, blood flow, perfusion, diffusion, and so on, has offered more information for the diagnosis of diffuse and focal hepatic diseases than CT. The spoiled-GRE sequence with high contrast resolution and ease of the aimed contrast capture derived from the k-space property, with the use of a phased-array multicoil, have remarkably increased the value of gadolinium-enhanced dynamic MR diagnosis of the liver. In recent years, the clinical use of ferumoxide has begun, and issues concerning the superiority or inferiority and combination of contrast media are being debated. This paper describes the value, role, and clinical practice of unenhanced, gadolinium-enhanced, and ferumoxide-enhanced MR imaging of the liver based on knowledge obtained in our institution, with some reference to the literature.

Pulmonary changes in liver transplant candidates with hepatitis C cirrhosis.

PubMed

Al-Moamary, M S; Gorka, T; Al-Traif, I H; Al-Jahdali, H H; Al-Shimemeri, A A; Al-Kanway, B; Abdulkareeem, A A; Abdulkareeem, A A

2001-12-01

Several studies have shown that pulmonary abnormalities are common in patients with end-stage liver disease. However, most of these studies were conducted on patients with heterogeneous etiologies. Therefore, we studied these changes in a homogenous group of hepatitis C cirrhotic patients who were potential candidates for liver transplantation. The charts of 81 patients from King Fahad National Guard Hospital, Riyadh, Kingdom of Saudi Arabia with hepatitis C cirrhosis who were evaluated for liver transplantation were reviewed. The following data was retrieved: echocardiography with micro-bubble study, arterial blood gases, and pulmonary function tests of 81 candidates and reviewed over 3 years from 1994 to 1997. The mean age was 53 (+/-9) years with male to female ratio of 1.4:1. Echocardiographic micro-bubble study, revealed 4 of 62 (7%) had an intrapulmonary shunt. Arterial blood gases results were pH of 7.44 (+/-0.4), partial arterial tension of carbon dioxide of 33 mm Hg (+/-4), partial arterial tension of oxygen of 84 mm Hg (+/-12), and alveolar-arterial gradient of 30 mm Hg (+/-10). Eleven percent had obstructive airway disease, 17% had restrictive lung impairment, and 43% had reduced diffusion capacity. Seventy five percent of patients with reduced diffusion capacity had normal lung volumes. Various pulmonary function test abnormalities did not lead to significant differences in arterial blood gases. Pulmonary changes were frequent in liver transplant candidates with hepatitis C virus cirrhosis with reduced diffusion capacity being the most. Apart from the effect of hepatopulmonary syndrome on arterial oxygenation, other pulmonary abnormalities were not significantly different.

Autoimmune hepatitis in children: what is different from adult AIH?

PubMed

Mieli-Vergani, Giorgina; Vergani, Diego

2009-08-01

Autoimmune hepatitis (AIH) is characterized by inflammatory liver histology, circulating non-organ-specific autoantibodies, and increased levels of immunoglobulin (Ig) G in the absence of a known etiology. Two types of childhood AIH are recognized according to seropositivity: smooth muscle antibody (SMA) and/or antinuclear antibody (ANA), which is AIH type 1; and antibodies to liver-kidney microsome type 1 (anti-LKM1), which is AIH type 2. There is a female predominance in both. Autoimmune hepatitis type 2 presents more acutely, at a younger age, and commonly with IgA deficiency; however, duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in the two groups. Immunosuppressive treatment with steroids and azathioprine, which should be instituted promptly to avoid progression to cirrhosis, induces remission in 80% of cases. Relapses are common, often due to nonadherence. Drugs effective in refractory cases include cyclosporine and mycophenolate mofetil. Long-term treatment is usually required, with only some 20% of AIH type 1 patients able to discontinue therapy successfully. In childhood, sclerosing cholangitis with strong autoimmune features, including interface hepatitis and serological features identical to AIH type 1, is as prevalent as AIH, but it affects boys and girls equally. The differential diagnosis relies on cholangiographic studies. In autoimmune sclerosing cholangitis, liver parenchymal damage responds satisfactorily to immunosuppressive treatment, whereas bile duct disease tends to progress. Copyright Thieme Medical Publishers.

Hepatic expression and cellular distribution of the glucose transporter family

PubMed Central

Karim, Sumera; Adams, David H; Lalor, Patricia F

2012-01-01

Glucose and other carbohydrates are transported into cells using members of a family of integral membrane glucose transporter (GLUT) molecules. To date 14 members of this family, also called the solute carrier 2A proteins have been identified which are divided on the basis of transport characteristics and sequence similarities into several families (Classes 1 to 3). The expression of these different receptor subtypes varies between different species, tissues and cellular subtypes and each has differential sensitivities to stimuli such as insulin. The liver is a contributor to metabolic carbohydrate homeostasis and is a major site for synthesis, storage and redistribution of carbohydrates. Situations in which the balance of glucose homeostasis is upset such as diabetes or the metabolic syndrome can lead metabolic disturbances that drive chronic organ damage and failure, confirming the importance of understanding the molecular regulation of hepatic glucose homeostasis. There is a considerable literature describing the expression and function of receptors that regulate glucose uptake and release by hepatocytes, the most import cells in glucose regulation and glycogen storage. However there is less appreciation of the roles of GLUTs expressed by non parenchymal cell types within the liver, all of which require carbohydrate to function. A better understanding of the detailed cellular distribution of GLUTs in human liver tissue may shed light on mechanisms underlying disease pathogenesis. This review summarises the available literature on hepatocellular expression of GLUTs in health and disease and highlights areas where further investigation is required. PMID:23239915

Assessing liver fibrosis: comparison of arterial enhancement fraction and diffusion-weighted imaging.

PubMed

Bonekamp, David; Bonekamp, Susanne; Ou, Hsin-You; Torbenson, Michael S; Corona-Villalobos, Celia Pamela; Mezey, Esteban; Kamel, Ihab R

2014-11-01

Noninvasive markers have been developed to reduce the need for liver biopsy. The aim of this study was to compare the strength of association of the arterial enhancement fraction (AEF), apparent diffusion coefficient (ADC), and serum biomarkers for staging hepatic fibrosis. Eighty-five patients with chronic liver disease underwent triple-phase contrast-enhanced MRI, used to calculate AEF, and diffusion-weighted MRI (b = 0,750 s/mm(2) ), used to calculate ADC. Hepatic fibrosis was staged according METAVIR criteria. The overall association of the four biomarkers (AEF, ADC, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, and aspartate aminotransferase to platelet ratio index [APRI]) was compared using nonparametric tests and receiver operating characteristic (ROC) curve, using histopathologic analysis as the reference standard. AEF and ADC values differed significantly between histopathologic fibrosis stages. AEF values correlated with fibrosis stage, ADC values correlated negatively with fibrosis stage. Compared with ADC, AEF showed a trend toward an improved capability of discriminating fibrosis stages. A weighted composite score of AEF and ADC had significantly better diagnostic accuracy than ADC alone (P ≤ 0.023). Imaging parameters had a significantly better diagnostic accuracy than AST/ALT ratio or APRI. AEF may be able to detect the presence of mild, moderate, and advanced liver fibrosis, and its value is increased with concomitant use of ADC. © 2013 Wiley Periodicals, Inc.

Eliminating the blood-flow confounding effect in intravoxel incoherent motion (IVIM) using the non-negative least square analysis in liver.

PubMed

Gambarota, Giulio; Hitti, Eric; Leporq, Benjamin; Saint-Jalmes, Hervé; Beuf, Olivier

2017-01-01

Tissue perfusion measurements using intravoxel incoherent motion (IVIM) diffusion-MRI are of interest for investigations of liver pathologies. A confounding factor in the perfusion quantification is the partial volume between liver tissue and large blood vessels. The aim of this study was to assess and correct for this partial volume effect in the estimation of the perfusion fraction. MRI experiments were performed at 3 Tesla with a diffusion-MRI sequence at 12 b-values. Diffusion signal decays in liver were analyzed using the non-negative least square (NNLS) method and the biexponential fitting approach. In some voxels, the NNLS analysis yielded a very fast-decaying component that was assigned to partial volume with the blood flowing in large vessels. Partial volume correction was performed by biexponential curve fitting, where the first data point (b = 0 s/mm 2 ) was eliminated in voxels with a very fast-decaying component. Biexponential fitting with partial volume correction yielded parametric maps with perfusion fraction values smaller than biexponential fitting without partial volume correction. The results of the current study indicate that the NNLS analysis in combination with biexponential curve fitting allows to correct for partial volume effects originating from blood flow in IVIM perfusion fraction measurements. Magn Reson Med 77:310-317, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Intrahepatic portal hypertension secondary to metastatic carcinoma of the prostate.

PubMed

Attila, Tan; Datta, Milton W; Sudakoff, Gary; Abu-Hajir, Majed; Massey, Benson T

2007-02-01

While the liver is a common site of metastasis, tumor metastases are not a common cause of portal hypertension. We report a case of a patient with symptomatic portal hypertension due to diffuse metastatic prostate carcinoma infiltration of liver parenchyma that was not appreciated with routine imaging.

Imaging of brain metastases.

PubMed

Fink, Kathleen R; Fink, James R

2013-01-01

Imaging plays a key role in the diagnosis of central nervous system (CNS) metastasis. Imaging is used to detect metastases in patients with known malignancies and new neurological signs or symptoms, as well as to screen for CNS involvement in patients with known cancer. Computed tomography (CT) and magnetic resonance imaging (MRI) are the key imaging modalities used in the diagnosis of brain metastases. In difficult cases, such as newly diagnosed solitary enhancing brain lesions in patients without known malignancy, advanced imaging techniques including proton magnetic resonance spectroscopy (MRS), contrast enhanced magnetic resonance perfusion (MRP), diffusion weighted imaging (DWI), and diffusion tensor imaging (DTI) may aid in arriving at the correct diagnosis. This image-rich review discusses the imaging evaluation of patients with suspected intracranial involvement and malignancy, describes typical imaging findings of parenchymal brain metastasis on CT and MRI, and provides clues to specific histological diagnoses such as the presence of hemorrhage. Additionally, the role of advanced imaging techniques is reviewed, specifically in the context of differentiating metastasis from high-grade glioma and other solitary enhancing brain lesions. Extra-axial CNS involvement by metastases, including pachymeningeal and leptomeningeal metastases is also briefly reviewed.

Contrast-enhanced ultrasound (CEUS) in blunt abdominal trauma

PubMed Central

Piccolo, Claudia Lucia; Galluzzo, Michele; Ianniello, Stefania; Sessa, Barbara; Trinci, Margherita

2016-01-01

Baseline ultrasound is essential in the early assessment of patients with a huge haemoperitoneum undergoing an immediate abdominal surgery; nevertheless, even with a highly experienced operator, it is not sufficient to exclude parenchymal injuries. More recently, a new ultrasound technique using second generation contrast agents, named contrast-enhanced ultrasound (CEUS) has been developed. This technique allows all the vascular phase to be performed in real time, increasing ultrasound capability to detect parenchymal injuries, enhancing some qualitative findings, such as lesion extension, margins and its relationship with capsule and vessels. CEUS has been demonstrated to be almost as sensitive as contrast-enhanced CT in the detection of traumatic injuries in patients with low-energy isolated abdominal trauma, with levels of sensitivity and specificity up to 95%. Several studies demonstrated its ability to detect lesions occurring in the liver, spleen, pancreas and kidneys and also to recognize active bleeding as hyperechoic bands appearing as round or oval spots of variable size. Its role seems to be really relevant in paediatric patients, thus avoiding a routine exposure to ionizing radiation. Nevertheless, CEUS is strongly operator dependent, and it has some limitations, such as the cost of contrast media, lack of panoramicity, the difficulty to explore some deep regions and the poor ability to detect injuries to the urinary tract. On the other hand, it is timesaving, and it has several advantages, such as its portability, the safety of contrast agent, the lack to ionizing radiation exposure and therefore its repeatability, which allows follow-up of those traumas managed conservatively, especially in cases of fertile females and paediatric patients. PMID:26607647

Parenchymal Texture Analysis in Digital Breast Tomosynthesis for Breast Cancer Risk Estimation: A Preliminary Study

PubMed Central

Kontos, Despina; Bakic, Predrag R.; Carton, Ann-Katherine; Troxel, Andrea B.; Conant, Emily F.; Maidment, Andrew D.A.

2009-01-01

Rationale and Objectives Studies have demonstrated a relationship between mammographic parenchymal texture and breast cancer risk. Although promising, texture analysis in mammograms is limited by tissue superimposition. Digital breast tomosynthesis (DBT) is a novel tomographic x-ray breast imaging modality that alleviates the effect of tissue superimposition, offering superior parenchymal texture visualization compared to mammography. Our study investigates the potential advantages of DBT parenchymal texture analysis for breast cancer risk estimation. Materials and Methods DBT and digital mammography (DM) images of 39 women were analyzed. Texture features, shown in studies with mammograms to correlate with cancer risk, were computed from the retroareolar breast region. We compared the relative performance of DBT and DM texture features in correlating with two measures of breast cancer risk: (i) the Gail and Claus risk estimates, and (ii) mammographic breast density. Linear regression was performed to model the association between texture features and increasing levels of risk. Results No significant correlation was detected between parenchymal texture and the Gail and Claus risk estimates. Significant correlations were observed between texture features and breast density. Overall, the DBT texture features demonstrated stronger correlations with breast percent density (PD) than DM (p ≤0.05). When dividing our study population in groups of increasing breast PD, the DBT texture features appeared to be more discriminative, having regression lines with overall lower p-values, steeper slopes, and higher R2 estimates. Conclusion Although preliminary, our results suggest that DBT parenchymal texture analysis could provide more accurate characterization of breast density patterns, which could ultimately improve breast cancer risk estimation. PMID:19201357

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marquez, Herman P., E-mail: hermanpaulo.marquezmasquiaran@usz.ch; Puippe, Gilbert; Mathew, Rishi Philip

PurposeTo investigate the value of perfusion CT (P-CT) for early assessment of treatment response in patients undergoing radiofrequency ablation (RFA) of focal liver lesions.Methods and Materials20 consecutive patients (14 men; mean age 64 ± 14) undergoing P-CT within 24 h after RFA of liver metastases (n = 10) or HCC (n = 10) were retrospectively included. Two readers determined arterial liver perfusion (ALP, mL/min/100 mL), portal liver perfusion (PLP, mL/min/100 mL), and hepatic perfusion index (HPI, %) in all post-RFA lesions by placing a volume of interest in the necrotic central (CZ), the transition (TZ), and the surrounding parenchymal (PZ) zone. Patients were classified into complete responders (no residual tumor)more » and incomplete responders (residual/progressive tumor) using imaging follow-up with contrast-enhanced CT or MRI after a mean of 57 ± 30 days. Prediction of treatment response was evaluated using the area under the curve (AUC) from receiver operating characteristic analysis.ResultsMean ALP/PLP/HPI of both readers were 4.8/15.4/61.2 for the CZ, 9.9/16.8/66.3 for the TZ and 20.7/29.0/61.8 for the PZ. Interreader agreement of HPI was fair for the CZ (intraclass coefficient 0.713), good for the TZ (0.813), and excellent for the PZ (0.920). For both readers, there were significant differences in HPI of the CZ and TZ between responders and nonresponders (both, P < 0.05). HPI of the TZ showed the highest AUC (0.911) for prediction of residual tumor, suggesting a cut-off value of 76 %.ConclusionIncreased HPI of the transition zone assessed with P-CT after RFA might serve as an early quantitative biomarker for residual tumor in patients with focal liver lesions.« less

IκB kinaseα/β control biliary homeostasis and hepatocarcinogenesis in mice by phosphorylating the cell-death mediator receptor-interacting protein kinase 1.

PubMed

Koppe, Christiane; Verheugd, Patricia; Gautheron, Jérémie; Reisinger, Florian; Kreggenwinkel, Karina; Roderburg, Christoph; Quagliata, Luca; Terracciano, Luigi; Gassler, Nikolaus; Tolba, René H; Boege, Yannick; Weber, Achim; Karin, Michael; Luedde, Mark; Neumann, Ulf P; Weiskirchen, Ralf; Tacke, Frank; Vucur, Mihael; Trautwein, Christian; Lüscher, Bernhard; Preisinger, Christian; Heikenwalder, Mathias; Luedde, Tom

2016-10-01

The IκB-Kinase (IKK) complex-consisting of the catalytic subunits, IKKα and IKKβ, as well as the regulatory subunit, NEMO-mediates activation of the nuclear factor κB (NF-κB) pathway, but previous studies suggested the existence of NF-κB-independent functions of IKK subunits with potential impact on liver physiology and disease. Programmed cell death is a crucial factor in the progression of liver diseases, and receptor-interacting kinases (RIPKs) exerts strategic control over multiple pathways involved in regulating novel programmed cell-death pathways and inflammation. We hypothesized that RIPKs might be unrecognized targets of the catalytic IKK-complex subunits, thereby regulating hepatocarcinogenesis and cholestasis. In this present study, mice with specific genetic inhibition of catalytic IKK activity in liver parenchymal cells (LPCs; IKKα/β(LPC-KO) ) were intercrossed with RIPK1(LPC-KO) or RIPK3(-/-) mice to examine whether RIPK1 or RIPK3 might be downstream targets of IKKs. Moreover, we performed in vivo phospho-proteome analyses and in vitro kinase assays, mass spectrometry, and mutagenesis experiments. These analyses revealed that IKKα and IKKβ-in addition to their known function in NF-κB activation-directly phosphorylate RIPK1 at distinct regions of the protein, thereby regulating cell viability. Loss of this IKKα/β-dependent RIPK1 phosphorylation in LPCs inhibits compensatory proliferation of hepatocytes and intrahepatic biliary cells, thus impeding HCC development, but promoting biliary cell paucity and lethal cholestasis. IKK-complex subunits transmit a previously unrecognized signal through RIPK1, which is fundamental for the long-term consequences of chronic hepatic inflammation and might have potential implications for future pharmacological strategies against cholestatic liver disease and cancer. (Hepatology 2016;64:1217-1231). © 2016 by the American Association for the Study of Liver Diseases.

Nitric oxide mediates the lipopolysaccharide dependent upregulation of the heme oxygenase-1 gene expression in cultured rat Kupffer cells.

PubMed

Immenschuh, S; Tan, M; Ramadori, G

1999-01-01

Heme oxygenase catalyzes the rate-limiting enzymatic step of heme degradation. The inducible isoform of heme oxygenase, heme oxygenase-1, is expressed at a low level in most tissues and is upregulated by its substrate heme and various stress stimuli. Kupffer cells which represent the largest population of the body's tissue macrophages serve physiological functions in the defense against various pathogens such as lipopolysaccharide. The goal of the present study was to investigate the heme oxygenase-1 gene expression in Kupffer cells of rat liver and in isolated Kupffer cell cultures during treatment with lipopolysaccharide. Cryostat sections of normal rat liver were investigated by immunofluorescence double-staining using specific antibodies for rat heme oxygenase-1 and ED2. Isolation and cell culture of Kupffer cells and primary hepatocytes from rat liver, as well as Northern and Western blot analysis, were performed with standard protocols. Heme oxygenase-1 protein was highly expressed in large sinusoidal cells of normal rat liver, which were identified as Kupffer cells by staining with the macrophage surface marker ED2. By contrast, no expression of heme oxygenase-1 was detected in liver parenchymal cells. High expression of heme oxygenase-1 was also found in isolated Kupffer cells in culture by immunocytochemical staining as well as by Western and Northern blot analysis. After treatment of Kupffer cells cultures with lipopolysaccharide, heme oxygenase-1 was upregulated on the protein and mRNA level in a time- and dose-dependent manner. This increase in heme oxygenase-1 expression by lipopolysaccharide was prevented by the nitric oxide inhibitor N(G)-monomethyl-L-arginine which was reversed by an excess of L-arginine. Various nitric oxide donors up-regulated heme oxygenase-1 mRNA expression in Kupffer cells. The lipopolysaccharide-dependent upregulation of the heme oxygenase-1 gene which is highly expressed in Kupffer cells is mediated by a nitric oxide-dependent mechanism.

Spatial model of convective solute transport in brain extracellular space does not support a “glymphatic” mechanism

PubMed Central

Jin, Byung-Ju; Smith, Alex J.

2016-01-01

A “glymphatic system,” which involves convective fluid transport from para-arterial to paravenous cerebrospinal fluid through brain extracellular space (ECS), has been proposed to account for solute clearance in brain, and aquaporin-4 water channels in astrocyte endfeet may have a role in this process. Here, we investigate the major predictions of the glymphatic mechanism by modeling diffusive and convective transport in brain ECS and by solving the Navier–Stokes and convection–diffusion equations, using realistic ECS geometry for short-range transport between para-arterial and paravenous spaces. Major model parameters include para-arterial and paravenous pressures, ECS volume fraction, solute diffusion coefficient, and astrocyte foot-process water permeability. The model predicts solute accumulation and clearance from the ECS after a step change in solute concentration in para-arterial fluid. The principal and robust conclusions of the model are as follows: (a) significant convective transport requires a sustained pressure difference of several mmHg between the para-arterial and paravenous fluid and is not affected by pulsatile pressure fluctuations; (b) astrocyte endfoot water permeability does not substantially alter the rate of convective transport in ECS as the resistance to flow across endfeet is far greater than in the gaps surrounding them; and (c) diffusion (without convection) in the ECS is adequate to account for experimental transport studies in brain parenchyma. Therefore, our modeling results do not support a physiologically important role for local parenchymal convective flow in solute transport through brain ECS. PMID:27836940

Spatial model of convective solute transport in brain extracellular space does not support a "glymphatic" mechanism.

PubMed

Jin, Byung-Ju; Smith, Alex J; Verkman, Alan S

2016-12-01

A "glymphatic system," which involves convective fluid transport from para-arterial to paravenous cerebrospinal fluid through brain extracellular space (ECS), has been proposed to account for solute clearance in brain, and aquaporin-4 water channels in astrocyte endfeet may have a role in this process. Here, we investigate the major predictions of the glymphatic mechanism by modeling diffusive and convective transport in brain ECS and by solving the Navier-Stokes and convection-diffusion equations, using realistic ECS geometry for short-range transport between para-arterial and paravenous spaces. Major model parameters include para-arterial and paravenous pressures, ECS volume fraction, solute diffusion coefficient, and astrocyte foot-process water permeability. The model predicts solute accumulation and clearance from the ECS after a step change in solute concentration in para-arterial fluid. The principal and robust conclusions of the model are as follows: (a) significant convective transport requires a sustained pressure difference of several mmHg between the para-arterial and paravenous fluid and is not affected by pulsatile pressure fluctuations; (b) astrocyte endfoot water permeability does not substantially alter the rate of convective transport in ECS as the resistance to flow across endfeet is far greater than in the gaps surrounding them; and (c) diffusion (without convection) in the ECS is adequate to account for experimental transport studies in brain parenchyma. Therefore, our modeling results do not support a physiologically important role for local parenchymal convective flow in solute transport through brain ECS. © 2016 Jin et al.

Evaluation of Free Breathing Versus Breath Hold Diffusion Weighted Imaging in Terms Apparent Diffusion Coefficient (ADC) and Signal-to-Noise Ratio (SNR) Values for Solid Abdominal Organs.

PubMed

Herek, Duygu; Karabulut, Nevzat; Kocyıgıt, Ali; Yagcı, Ahmet Baki

2016-01-01

Our aim was to compare the apparent diffusion coefficient (ADC) values of normal abdominal parenchymal organs and signal-to-noise ratio (SNR) measurements in the same patients with breath hold (BH) and free breathing (FB) diffusion weighted imaging (DWI). Forty-eight patients underwent both BH and FB DWI. Spherical region of interest (ROI) was placed on the right hepatic lobe, spleen, pancreas, and renal cortices. ADC values were calculated for each organ on each sequence using an automated software. Image noise, defined as the standard deviation (SD) of the signal intensities in the most artifact-free area of the image background was measured by placing the largest possible ROI on either the left or the right side of the body outside the object in the recorded field of view. SNR was calculated using the formula: SNR=signal intensity (SI) (organ) /standard deviation (SD) (noise) . There were no statistically significant differences in ADC values of the abdominal organs between BH and FB DWI sequences ( p >0.05). There were statistically significant differences between SNR values of organs on BH and FB DWIs. SNRs were found to be better on FB DWI than BH DWI ( p <0.001). Free breathing DWI technique reduces image noise and increases SNR for abdominal examinations. Free breathing technique is therefore preferable to BH DWI in the evaluation of abdominal organs by DWI.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swaminath, Anand; Knox, Jennifer J.; Brierley, James D.

Purpose: The purpose of this study was to quantify unexpected liver volume reductions in patients treated with sorafenib prior to and during liver radiation therapy (RT). Methods and Materials: Fifteen patients were treated in a phase 1 study of sorafenib for 1 week, followed by concurrent sorafenib-RT (in 6 fractions). Patients had either focal cancer (treated with stereotactic body RT [SBRT]) or diffuse disease (treated with whole-liver RT). Liver volumes were contoured and recorded at planning (day 0) from the exhale CT. After 1 week of sorafenib (day 8), RT image guidance at each fraction was performed using cone beam CT (CBCT).more » Planning liver contours were propagated and modified on the reconstructed exhale CBCT. This was repeated in 12 patients treated with SBRT alone without sorafenib. Three subsequent patients (2 sorafenib-RT and 1 non-sorafenib) were also assessed with multiphasic helical breath-hold CTs. Results: Liver volume reductions on CBCT were observed in the 15 sorafenib-RT patients (median decrease of 68 cc, P=.02) between day 0 and 8; greater in the focal (P=.025) versus diffuse (P=.52) cancer stratum. Seven patients (47%) had reductions larger than the 95% intraobserver contouring error. Liver reductions were also observed from multiphasic CTs in the 2 additional sorafenib-RT patients between days 0 and 8 (decreases of 232.5 cc and 331.7 cc, respectively) and not in the non-sorafenib patient (increase of 92 cc). There were no significant changes in liver volume between planning and first RT in 12 patients with focal cancer treated with SBRT alone (median increase, 4.8 cc, P=.86). Conclusions: Liver volume reductions were observed after 7 days of sorafenib, prior to RT, most marked in patients with focal liver tumors, suggesting an effect of sorafenib on normal liver. Careful assessment of potential liver volume changes immediately prior to SBRT may be necessary in patients in sorafenib or other targeted therapies.« less

Diffusion weighted magnetic resonance imaging and its recent trend—a survey

PubMed Central

Chilla, Geetha Soujanya; Tan, Cher Heng

2015-01-01

Since its inception in 1985, diffusion weighted magnetic resonance imaging has been evolving and is becoming instrumental in diagnosis and investigation of tissue functions in various organs including brain, cartilage, and liver. Even though brain related pathology and/or investigation remains as the main application, diffusion weighted magnetic resonance imaging (DWI) is becoming a standard in oncology and in several other applications. This review article provides a brief introduction of diffusion weighted magnetic resonance imaging, challenges involved and recent advancements. PMID:26029644

Volume transmission-mediated encephalopathies: a possible new concept?

PubMed

Hartung, Hans-Peter; Dihné, Marcel

2012-03-01

There is strong evidence that the composition of cerebrospinal fluid (CSF) influences brain development, neurogenesis, and behavior. The bidirectional exchange of CSF and interstitial fluid (ISF) across the ependymal and pia-glial membranes is required for these phenomena to occur. Because ISF surrounds the parenchymal compartment, neuroactive substances in the CSF and ISF can influence neuronal activity. Functionally important neuroactive substances are distributed to distant sites of the central nervous system by the convection and diffusion of CSF and ISF, a process known as volume transmission. It has recently been shown that pathologically altered CSF from patients with acute traumatic brain injury suppresses in vitro neuronal network activity (ivNNA) recorded by multielectrode arrays measuring synchronously bursting neural populations. Functionally relevant substances in pathologically altered CSF have been biochemically identified, and ivNNA has been partially recovered by pharmacologic intervention. It remains unclear whether the in vivo parenchymal compartment remains unaffected by pathologically altered CSF that significantly impairs ivNNA. We hypothesize that pathologic CSF alterations are not just passive indicators of brain diseases but that they actively and directly evoke functional disturbances in global brain activity through the distribution of neuroactive substances, for instance, secondary to focal neurologic disease. For this mechanism, we propose the new term volume transmission-mediated encephalopathies (VTE). Recording ivNNA in the presence of pure human CSF could help to identify and monitor functionally relevant CSF alterations that directly result in VTEs, and the collected data might point to therapeutic ways to antagonize these alterations.

Hepatic progenitor populations in embryonic, neonatal, and adult liver.

PubMed

Brill, S; Holst, P; Sigal, S; Zvibel, I; Fiorino, A; Ochs, A; Somasundaran, U; Reid, L M

1993-12-01

Oval cells, small cells with oval-shaped nuclei, are induced to proliferate in the livers of animals treated with carcinogens and are thought to be related to liver stem cells and/or committed liver progenitor cell populations. We have developed protocols for identifying and isolating antigenically related cell populations present in normal tissues using monoclonal antibodies to oval cell antigens and fluorescence-activated cell sorting. We have isolated oval cell-antigen-positive (OCAP) cells from embryonic, neonatal, and adult rat livers and have identified culture conditions permitting their growth in culture. The requirements for growth of the OCAP cells included substrata of type IV collagen mixed with laminin, basal medium with complex lipids and low calcium, specific growth factors (most potently, insulin-like growth factor II and granulocyte-macrophage colony-stimulating factor), and co-cultures of embryonic, liver-specific stroma, strongly suggesting paracrine signaling between hepatic and hemopoietic precursor cells. The growing OCAP cultures proved to be uniformly expressing oval cell markers but were nevertheless a mixture of hepatic and hemopoietic precursor cells. To separate the hepatic and hemopoietic subpopulations of OCAP cells, we surveyed known antibodies and found ones that uniquely identify either hepatic or hemopoietic cells. Several of these antibodies were used in panning procedures and fluorescence-activated cell sorting to eliminate contaminant cell populations, particularly hemopoietic and endothelial cells. Using specific flow cytometric parameters, three cellular subpopulations could be isolated separately that were identified by immunochemistry and molecular hybridization assays as probable: (i) committed progenitors to hepatocytes; (ii) committed progenitors to bile ducts; or (iii) a mixed population of hemopoietic cells that contained a small percentage of hepatic blasts that are possibly pluripotent. The hepatic precursor cells have been characterized using immunochemistry, flow cytometry, and molecular hybridization assays. The hepatic blasts are small (7-10 microns) cells with high nuclear to cytoplasmic ratios and with minimal complexity of the cytoplasm. Cultures of the committed progenitors were found to differentiate into cells with recognizable parenchymal cell fates. We discuss our studies in the context of our model of the liver as stem cell and lineage system and suggest that a slow, unidirectional, terminal differentiation process, paralleling more rapid ones in the skin or gut, occurs at all times in the liver and is thought to vary primarily in kinetics during quiescent versus regenerative states.(ABSTRACT TRUNCATED AT 400 WORDS)

Computer-aided diagnostic system for diffuse liver diseases with ultrasonography by neural networks

NASA Astrophysics Data System (ADS)

Ogawa, K.; Fukushima, M.; Kubota, K.; Hisa, N.

1998-12-01

The aim of the study is to establish a computer-aided diagnostic system for diffuse liver diseases such as chronic active hepatitis (CAH) and liver cirrhosis (LC). The authors introduced an artificial neural network in the classification of these diseases. In this system the neural network was trained by feature parameters extracted from B-mode ultrasonic images of normal liver (NL), CAH and LC. For input data the authors used six parameters calculated by a region of interest (ROI) and a parameter calculated by five ROIs in each image. They were variance of pixel values, coefficient of variation, annular Fourier power spectrum, longitudinal Fourier power spectrum which were calculated for the ROI, and variation of the means of the five ROIs. In addition, the authors used two more parameters calculated from a co-occurrence matrix of pixel values in the ROI. The results showed that the neural network classifier was 83.8% in sensitivity for LC, 90.0% in sensitivity for CAH and 93.6% in specificity, and the system was considered to be helpful for clinical and educational use.

A successful case of deceased donor liver transplantation for a patient with intrahepatic arterioportal fistula.

PubMed

Takagi, Kosei; Yagi, Takahito; Yoshida, Ryuichi; Shinoura, Susumu; Umeda, Yuzo; Nobuoka, Daisuke; Watanabe, Nobuyuki; Kuise, Takashi; Sui, Kenta; Hirose, Akira; Tsuboi, Makiko; Ogasawara, Mitsunari; Iwasaki, Shinji; Saibara, Toshiji; Fujiwara, Toshiyoshi

2016-12-01

Intrahepatic arterioportal fistula (IAPF) is a rare cause of portal hypertension that is often difficult to treat with interventional radiology or surgery. Liver transplantation for IAPF is extremely rare. We report a case of bilateral diffuse IAPF with severe portal hypertension requiring deceased donor liver transplantation (DDLT). A 51-year-old woman with no past medical history was admitted to another hospital complaining of abdominal distension and marasmus. A computed tomography scan and digital subtraction angiography indicated a massive pleural effusion, ascites, and a very large IAPF. Several attempts of interventional embolization of the feeding artery failed to ameliorate arterioportal shunt flow. As ruptures of the esophageal varices became more frequent, hepatic encephalopathy worsened. After repeated, uncontrollable attacks of hepatic coma, the patient was referred to our facility for further treatment. Surgical approaches to IAPF other than liver transplantation were challenging because of diffuse collateralization; therefore, we placed the patient on the national waiting list for DDLT. Although her Model for End-Stage Liver Disease score was relatively low, she received a DDLT 2 months after the waiting period. The postoperative course was uneventful, and the patient was discharged 44 days after her transplant. Liver transplantation may be a valid treatment option for uncontrollable IAPF with severe portal hypertension. © 2016 The Authors Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.

Neonatal Meningoventriculitis Due to Proteus Mirabilis – A Case Report

PubMed Central

Juyal, Deepak; Rathaur, Vyas Kumar; Sharma, Neelam

2013-01-01

A five day old full term born baby was admitted to our Neonatal Intensive Care Unit with seizures, opisthotonous posture and was icteric upto thigh. Baby had a three day history of poor feeding, lethargy and abnormal body movements. Mother was a 29 years old primigravida and had a normal vaginal delivery at home. Sepsis profile of the patient was requested, lumbar puncture and ventricular tap was performed. Patient was put on third generation cephalosporins, aminoglycosides and phenobarbitone. Culture and sensitivity report of blood, Cerebro spinal fluid and ventricular fluid showed Proteus mirabilis. Computerized Tomography scan showed a large parenchymal lesion in the right frontal lobe and diffuse ependymal enhancement along both the lateral ventricles suggestive of meningoventriculitis. We hereby present a fatal case of neonatal meningoventriculitis due to Proteus mirabilis. PMID:23543669

On trans-parenchymal transport after blood brain barrier opening: pump-diffuse-pump hypothesis

NASA Astrophysics Data System (ADS)

Postnov, D. E.; Postnikov, E. B.; Karavaev, A. S.; Glushkovskaya-Semyachkina, O. V.

2018-04-01

Transparenchymal transport attracted the attention of many research groups after the discovery of glymphatic mechanism for the brain drainage in 2012. While the main facts of rapid transport of substances across the parenchyma are well established experimentally, specific mechanisms that drive this drainage are just hypothezised but not proved yed. Moreover, the number of modeling studies show that the pulse wave powered mechanism is unlikely able to perform pumping as suggested. Thus, the problem is still open. In addition, new data obtained under the conditions of intensionally opened blood brain barrier shows the presence of equally fast transport in opposite durection. In our study we investigate the possible physical mechanisms for rapid transport of substances after the opening of blood-brain barrier under the conditions of zero net flow.

Rapid Diffusion of Green Fluorescent Protein in the Mitochondrial Matrix

PubMed Central

Partikian, Arthur; Ölveczky, Bence; Swaminathan, R.; Li, Yuxin; Verkman, A.S.

1998-01-01

Abstract. It is thought that the high protein density in the mitochondrial matrix results in severely restricted solute diffusion and metabolite channeling from one enzyme to another without free aqueous-phase diffusion. To test this hypothesis, we measured the diffusion of green fluorescent protein (GFP) expressed in the mitochondrial matrix of fibroblast, liver, skeletal muscle, and epithelial cell lines. Spot photobleaching of GFP with a 100× objective (0.8-μm spot diam) gave half-times for fluorescence recovery of 15–19 ms with >90% of the GFP mobile. As predicted for aqueous-phase diffusion in a confined compartment, fluorescence recovery was slowed or abolished by increased laser spot size or bleach time, and by paraformaldehyde fixation. Quantitative analysis of bleach data using a mathematical model of matrix diffusion gave GFP diffusion coefficients of 2–3 × 10−7 cm2/s, only three to fourfold less than that for GFP diffusion in water. In contrast, little recovery was found for bleaching of GFP in fusion with subunits of the fatty acid β-oxidation multienzyme complex that are normally present in the matrix. Measurement of the rotation of unconjugated GFP by time-resolved anisotropy gave a rotational correlation time of 23.3 ± 1 ns, similar to that of 20 ns for GFP rotation in water. A rapid rotational correlation time of 325 ps was also found for a small fluorescent probe (BCECF, ∼0.5 kD) in the matrix of isolated liver mitochondria. The rapid and unrestricted diffusion of solutes in the mitochondrial matrix suggests that metabolite channeling may not be required to overcome diffusive barriers. We propose that the clustering of matrix enzymes in membrane-associated complexes might serve to establish a relatively uncrowded aqueous space in which solutes can freely diffuse. PMID:9472034

Prediction of high-stage liver fibrosis using ADC value on diffusion-weighted imaging and quantitative enhancement ratio at the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI at 1.5 T.

PubMed

Harada, Taiyo L; Saito, Kazuhiro; Araki, Yoichi; Matsubayashi, Jun; Nagao, Toshitaka; Sugimoto, Katsutoshi; Tokuuye, Koichi

2018-05-01

Background Recently, diffusion-weighted imaging (DWI) and quantitative enhancement ratio measured at the hepatobiliary phase (HBP) of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) has been established as an effective method for evaluating liver fibrosis. Purpose To evaluate which is a more favorable surrogate marker in predicting high-stage liver fibrosis, apparently diffusion coefficient (ADC) value or quantitative enhancement ratio measured on HBP. Material and Methods Eighty-three patients with 99 surgically resected hepatic lesions were enrolled in this study. DWI was performed with b-values of 100 and 800 s/mm 2 . Regions of interest were set on ADC map, and the HBP of Gd-EOB-DTPA-enhanced MRI, to calculate ADC value, liver-to-muscle ratio (LMR), liver-to-spleen ratio (LSR), and contrast enhancement index (CEI) of liver. We compared these parameters between low-stage fibrosis (F0, F1, and F2) and high-stage fibrosis (F3 and F4). Receiver operating characteristic analysis was performed to compare the diagnostic performance when distinguishing low-stage fibrosis from high-stage fibrosis. Results LMR and CEI were significantly lower at high-stage fibrosis than at the low stage ( P < 0.01 and P = 0.04, respectively), whereas LSR did not show a significant difference ( P = 0.053). No significant difference was observed in diagnostic performance between LMR and CEI ( P = 0.185). The best sensitivity and specificity, when an LMR of 2.80 or higher was considered to be low-stage fibrosis, were 82.4% and 75.6%, respectively. ADC value showed no significant differences among fibrosis grades ( P = 0.320). Conclusion LMR and CEI were both adequate surrogate parameters to distinguish high-stage fibrosis from low-stage fibrosis.

Dependence of intravoxel incoherent motion diffusion MR threshold b-value selection for separating perfusion and diffusion compartments and liver fibrosis diagnostic performance.

PubMed

Wáng, Yì Xiáng J; Li, Yáo T; Chevallier, Olivier; Huang, Hua; Leung, Jason Chi Shun; Chen, Weitian; Lu, Pu-Xuan

2018-01-01

Background Intravoxel incoherent motion (IVIM) tissue parameters depend on the threshold b-value. Purpose To explore how threshold b-value impacts PF ( f), D slow ( D), and D fast ( D*) values and their performance for liver fibrosis detection. Material and Methods Fifteen healthy volunteers and 33 hepatitis B patients were included. With a 1.5-T magnetic resonance (MR) scanner and respiration gating, IVIM data were acquired with ten b-values of 10, 20, 40, 60, 80, 100, 150, 200, 400, and 800 s/mm 2 . Signal measurement was performed on the right liver. Segmented-unconstrained analysis was used to compute IVIM parameters and six threshold b-values in the range of 40-200 s/mm 2 were compared. PF, D slow , and D fast values were placed along the x-axis, y-axis, and z-axis, and a plane was defined to separate volunteers from patients. Results Higher threshold b-values were associated with higher PF measurement; while lower threshold b-values led to higher D slow and D fast measurements. The dependence of PF, D slow , and D fast on threshold b-value differed between healthy livers and fibrotic livers; with the healthy livers showing a higher dependence. Threshold b-value = 60 s/mm 2 showed the largest mean distance between healthy liver datapoints vs. fibrotic liver datapoints, and a classification and regression tree showed that a combination of PF (PF < 9.5%), D slow (D slow  < 1.239 × 10 -3 mm 2 /s), and D fast (D fast  < 20.85 × 10 -3 mm 2 /s) differentiated healthy individuals and all individual fibrotic livers with an area under the curve of logistic regression (AUC) of 1. Conclusion For segmented-unconstrained analysis, the selection of threshold b-value = 60 s/mm 2 improves IVIM differentiation between healthy livers and fibrotic livers.

Evaluation of Jaundice in Adults.

PubMed

Fargo, Matthew V; Grogan, Scott P; Saguil, Aaron

2017-02-01

Jaundice in adults can be an indicator of significant underlying disease. It is caused by elevated serum bilirubin levels in the unconjugated or conjugated form. The evaluation of jaundice relies on the history and physical examination. The initial laboratory evaluation should include fractionated bilirubin, a complete blood count, alanine transaminase, aspartate transaminase, alkaline phosphatase, ?-glutamyltransferase, prothrombin time and/or international normalized ratio, albumin, and protein. Imaging with ultrasonography or computed tomography can differentiate between extrahepatic obstructive and intrahepatic parenchymal disorders. Ultrasonography is the least invasive and least expensive imaging method. A more extensive evaluation may include additional cancer screening, biliary imaging, autoimmune antibody assays, and liver biopsy. Unconjugated hyperbilirubinemia occurs with increased bilirubin production caused by red blood cell destruction, such as hemolytic disorders, and disorders of impaired bilirubin conjugation, such as Gilbert syndrome. Conjugated hyperbilirubinemia occurs in disorders of hepatocellular damage, such as viral and alcoholic hepatitis, and cholestatic disorders, such as choledocholithiasis and neoplastic obstruction of the biliary tree.

Sudden multiple fractures in a patient with sarcoidosis in multiple organs.

PubMed

Sada, Mitsuru; Saraya, Takeshi; Ishii, Haruyuki; Goto, Hajime

2014-04-07

A 30-year-old man who incidentally fractured his right olecranon and other multiple phalanges was admitted to our hospital. He had a 2-year history of uveitis and bilateral hilar lymphadenopathy (BHL), and pulmonary sarcoidosis was diagnosed from transbronchial lung biopsy. Right elbow arthrodesis was performed, and biopsied specimens showed non-caseating epithelioid cell granuloma, suggesting osseous sarcoidosis. He was discharged uneventfully without further treatment, but BHL had progressed with the appearance of lung parenchymal lesions 3 months later. At that time, involvement of other organs was also noted on Gallium-67 scintigraphy, showing accumulations in BHL, axillary and inguinal lymph nodes, enlarged liver and spleen and subcutaneous areas. After initiation of steroid therapy, multiple organ involvement improved, and no further bone involvement has been recognised to date. Osseous sarcoidosis complicated by bone fracture is an extremely rare presentation, but should be considered in patients with sarcoidosis, especially when multiple organs are involved.

A novel “humanized mouse” model for autoimmune hepatitis and the association of gut microbiota with liver inflammation

PubMed Central

Yuksel, Muhammed; Wang, Yipeng; Tai, Ningwen; Peng, Jian; Guo, Junhua; Beland, Kathie; Lapierre, Pascal; David, Chella; Alvarez, Fernando; Colle, Isabelle; Yan, Huiping; Mieli-Vergani, Giorgina; Vergani, Diego; Ma, Yun; Wen, Li

2016-01-01

Background Autoimmune hepatitis (AIH) in humans is a severe inflammatory liver disease, characterized by interface hepatitis, the presence of circulating autoantibodies and hyper-gammaglobulinemia. There are two types of AIH, type-1 (AIH-1) and type-2 (AIH-2) characterized by distinct autoimmune serology. Patients with AIH-1 are positive for anti-smooth muscle and/or anti-nuclear (SMA/ANA) autoantibodies whereas patients with AIH-2 have anti-liver kidney microsomal type 1 (anti-LKM1) and/or anti-liver cytosol type 1 (anti-LC1) autoantibodies. Cytochrome P4502D6 (CYP2D6) is the antigenic target of anti-LKM1 and formiminotransferase cyclodeaminase (FTCD) is the antigenic target of anti-LC1. It is known that AIH, both type-1 and type-2, is strongly linked to the Human Leukocyte Antigen (HLA) alleles -DR3, -DR4 and -DR7. However, the direct evidence of the association of HLA with AIH is lacking. Methods We developed a novel mouse model of AIH using the HLA-DR3 transgenic mouse on the non-obese diabetic (NOD) background (HLA-DR3 NOD) by immunization of HLA-DR3− and HLA-DR3+ NOD mice with a DNA plasmid, coding for human CYP2D6/FTCD fusion protein. Results Immunization with CYP2D6/FTCD leads to a sustained elevation of alanine aminotransferase (ALT), development of ANA and anti-LKM1/anti-LC1 autoantibodies, chronic immune cell infiltration and parenchymal fibrosis on liver histology in HLA-DR3+ mice. Immunized mice also showed an enhanced Th1 immune response and paucity of the frequency of regulatory T-cell (Treg) in the liver. Moreover, HLA-DR3+ mice with exacerbated AIH showed reduced diversity and total load of gut bacteria. Conclusion Our humanized animal model has provided a novel experimental tool to further elucidate the pathogenesis of AIH and to evaluate the efficacy and safety of immunoregulatory therapeutic interventions in vivo. PMID:26185095

Protective effect of gastrodin on bile duct ligation-induced hepatic fibrosis in rats.

PubMed

Zhao, Shuangshuang; Li, Naren; Zhen, Yongzhan; Ge, Maoxu; Li, Yi; Yu, Bin; He, Hongwei; Shao, Rong-Guang

2015-12-01

Gastrodin has been showed to possess many beneficial physiological functions, including protection against inflammation and oxidation and apoptosis. Studies showed inflammation and oxidation play important roles in producing liver damage and initiating hepatic fibrogenesis. However, it has not been reported whether gastrodin has a protective effect against hepatic fibrosis or not. This is first ever made attempts to test gastrodin against liver fibrosis in bile duct ligation (BDL) rats. The aim of the present study is to evaluate the effect of gastrodin on BDL-induced hepatic fibrosis in rats. BDL rats were divided into two groups, BDL alone group, and BDL-gastrodin group treated with gastrodin (5 mg/ml in drinking water). The effects of gastrodin on BDL-induced hepatic injury and fibrosis in rats were estimated by assessing serum, urine, bile and liver tissue biochemistry followed by liver histopathology (using hematoxylin & eosin and sirius red stain) and hydroxyproline content measurement. The results showed that gastrodin treatment significantly reduced collagen content, bile duct proliferation and parenchymal necrosis after BDL. The serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) decreased with gastrodin treatment by 15.1 and 23.6 percent respectively in comparison to BDL group did not receive gastrodin. Gastrodin also significantly increased the level of serum high density lipoprotein (HDL) by 62.5 percent and down-regulated the elevated urine total bilirubin (TBIL) by 56.5 percent, but had no effect on total bile acid (TBA) in serum, bile and liver tissues. The immunohistochemical assay showed gastrodin remarkably reduced the expressions of CD68 and NF-κB in BDL rats. Hepatic SOD levels, depressed by BDL, were also increased by gastrodin by 8.4 percent. In addition, the increases of hepatic MDA and NO levels in BDL rats were attenuated by gastrodin by 31.3 and 38.7 percent separately. Our results indicate that gastrodin significantly attenuated the severity of BDL-induced hepatic injury and fibrosis by attenuating oxidative stress and inflammation. Taken together, these findings suggest that gastrodin might be an effective antifibrotic drug in cholestatic liver disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Multifaceted Therapeutic Benefits of Factors Derived From Dental Pulp Stem Cells for Mouse Liver Fibrosis.

PubMed

Hirata, Marina; Ishigami, Masatoshi; Matsushita, Yoshihiro; Ito, Takanori; Hattori, Hisashi; Hibi, Hideharu; Goto, Hidemi; Ueda, Minoru; Yamamoto, Akihito

2016-10-01

: Chronic liver injury from various causes often results in liver fibrosis (LF). Although the liver possesses endogenous tissue-repairing activities, these can be overcome by sustained inflammation and excessive fibrotic scar formation. Advanced LF leads to irreversible cirrhosis and subsequent liver failure and/or hepatic cancer. Here, using the mouse carbon tetrachloride (CCl 4 )-induced LF model, we showed that a single intravenous administration of stem cells derived from human exfoliated deciduous teeth (SHEDs) or of SHED-derived serum-free conditioned medium (SHED-CM) resulted in fibrotic scar resolution. SHED-CM suppressed the gene expression of proinflammatory mediators, such as TNF-α, IL-1β, and iNOS, and eliminated activated hepatic stellate cells by inducing their apoptosis, but protected parenchymal hepatocytes from undergoing apoptosis. In addition, SHED-CM induced tissue-repairing macrophages that expressed high levels of the profibrinolytic factor, matrix metalloproteinase 13. Furthermore, SHED-CM suppressed the CCl 4 -induced apoptosis of primary cultured hepatocytes. SHED-CM contained a high level of hepatocyte growth factor (HGF). Notably, HGF-depleted SHED-CM (dHGF-CM) did not suppress the proinflammatory response or resolve fibrotic scarring. Furthermore, SHED-CM, but not dHGF-CM, inhibited CCl 4 -induced hepatocyte apoptosis. These results suggest that HGF plays a central role in the SHED-CM-mediated resolution of LF. Taken together, our findings suggest that SHED-CM provides multifaceted therapeutic benefits for the treatment of LF. This study demonstrated that a single intravenous administration of stem cells from human exfoliated deciduous teeth (SHEDs) or of the serum-free conditioned medium (CM) derived from SHEDs markedly improved mouse liver fibrosis (LF). SHED-CM suppressed chronic inflammation, eliminated activated hepatic stellate cells by inducing their apoptosis, protected hepatocytes from undergoing apoptosis, and induced differentiation of tissue-repairing macrophages expressing high levels of the profibrinolytic factor matrix metalloproteinase 13. Furthermore, hepatocyte growth factor played a central role in the SHED-CM-mediated resolution of LF. This is the first report demonstrating the multifaceted therapeutic benefits of secreted factors derived from SHEDs for LF. ©AlphaMed Press.

Parenchymal texture measures weighted by breast anatomy: preliminary optimization in a case-control study

NASA Astrophysics Data System (ADS)

Gastounioti, Aimilia; Keller, Brad M.; Hsieh, Meng-Kang; Conant, Emily F.; Kontos, Despina

2016-03-01

Growing evidence suggests that quantitative descriptors of the parenchymal texture patterns hold a valuable role in assessing an individual woman's risk for breast cancer. In this work, we assess the hypothesis that breast cancer risk factors are not uniformly expressed in the breast parenchymal tissue and, therefore, breast-anatomy-weighted parenchymal texture descriptors, where different breasts ROIs have non uniform contributions, may enhance breast cancer risk assessment. To this end, we introduce an automated breast-anatomy-driven methodology which generates a breast atlas, which is then used to produce a weight map that reinforces the contributions of the central and upper-outer breast areas. We incorporate this methodology to our previously validated lattice-based strategy for parenchymal texture analysis. In the framework of a pilot case-control study, including digital mammograms from 424 women, our proposed breast-anatomy-weighted texture descriptors are optimized and evaluated against non weighted texture features, using regression analysis with leave-one-out cross validation. The classification performance is assessed in terms of the area under the curve (AUC) of the receiver operating characteristic. The collective discriminatory capacity of the weighted texture features was maximized (AUC=0.87) when the central breast area was considered more important than the upperouter area, with significant performance improvement (DeLong's test, p-value<0.05) against the non-weighted texture features (AUC=0.82). Our results suggest that breast-anatomy-driven methodologies have the potential to further upgrade the promising role of parenchymal texture analysis in breast cancer risk assessment and may serve as a reference in the design of future studies towards image-driven personalized recommendations regarding women's cancer risk evaluation.

Patterns of liver iron accumulation in patients with sickle cell disease and thalassemia with iron overload.

PubMed

Hankins, Jane S; Smeltzer, Matthew P; McCarville, M Beth; Aygun, Banu; Hillenbrand, Claudia M; Ware, Russell E; Onciu, Mihaela

2010-07-01

The rate and pattern of iron deposition and accumulation are important determinants of liver damage in chronically transfused patients. To investigate iron distribution patterns at various tissue iron concentrations, effects of chelation on hepatic iron compartmentalization, and differences between patients with sickle cell disease (SCD) and thalassemia major (TM), we prospectively investigated hepatic histologic and biochemical findings in 44 patients with iron overload (35 SCD and 9 TM). The median hepatic iron content (HIC) in patients with TM and SCD was similar at 12.9 and 10.3 mg Fe/g dry weight, respectively (P = 0.73), but patients with SCD had significantly less hepatic fibrosis and inflammation (P < 0.05), less hepatic injury, and significantly less blood exposure. Patients with SCD had predominantly sinusoidal iron deposition, but hepatocyte iron deposition was observed even at low HIC. Chelated patients had more hepatocyte and portal tract iron than non-chelated ones, but similar sinusoidal iron deposition. These data suggest that iron deposition in patients with SCD generally follows the traditional pattern of transfusional iron overload; however, parenchymal hepatocyte deposition also occurs early and chelation removes iron preferentially from the reticuloendothelium. Pathophysiological and genetic differences affecting iron deposition and accumulation in SCD and TM warrants further investigation.

Pathogenesis of venous hypertrophy associated with schistosomiasis in whooper swans (Cygnus cygnus) in Japan.

PubMed

Akagami, Masataka; Nakamura, Kikuyasu; Nishino, Hiroto; Seki, Satoko; Shimizu, Hiromi; Yamamoto, Yu

2010-03-01

Thirteen whooper swans (Cygnus cygnus) affected with schistosomiasis were examined pathologically. Venous hypertrophy, characterized by marked nodular proliferation of medial smooth muscle fibers with frequent obliteration of the vascular lumen, was observed in eight of the 13 whooper swans. Venous hypertrophy was located in the medium-sized veins of the mesentery, the serosa, and the muscular layer of the duodenum, jejunum, ileum, and cecum. In addition, vascular lesions were seen in the capsule and parenchymal interstitia of the liver, spleen, kidney, heart, aorta, air sac, and pleura. In mild lesions, segmental proliferation of medial smooth muscles was observed in the venous medium of the mesentery and serosa. Moderate lesions had a proliferation of smooth muscles in the veins with obliteration of venous lumens. In marked lesions, more severe proliferation of veins extended into the intestinal muscular layers and depressed them. Schistosome parasites were found in the venous lumens of each of the eight whooper swans with vascular lesions. Bile pigments and hemosiderin were observed in the livers of whooper swans. In addition, adult nematodes (Sarconema sp.) were localized in the myocardium of four of the eight whooper swans. The venous hypertrophy may be caused by the proliferation of medial smooth muscle fibers induced by schistosomiasis.

Hepatic lipidosis associated with cobalt deficiency in Omani goats.

PubMed

Johnson, E H; Muirhead, D E; Annamalai, K; King, G J; Al-Busaidy, R; Hameed, M S

1999-06-01

Livers from 36 of 684 (5.3%) apparently healthy goats examined at an abattoir in the greater Muscat area of Oman exhibited gross pathological findings characterized by extremely pale, friable, fatty livers encompassing the entire organ. Histopathologically, diffuse hepatic lipidosis and occasional bile duct proliferation were observed. Periodic acid Schiff-positive, diastase-resistant pigment was observed in the macrophages lining the sinusoids. These histopathological lesions were consistent with those characteristic of ovine white liver disease. Cobalt analysis revealed that normal livers had six times more cobalt and a 3-fold less fat content than those measured in the fatty livers. This is the first report of an association between cobalt deficiency and hepatic lipidosis in Omani goats.

Free-breathing echo-planar imaging based diffusion-weighted magnetic resonance imaging of the liver with prospective acquisition correction.

PubMed

Asbach, Patrick; Hein, Patrick A; Stemmer, Alto; Wagner, Moritz; Huppertz, Alexander; Hamm, Bernd; Taupitz, Matthias; Klessen, Christian

2008-01-01

To evaluate soft tissue contrast and image quality of a respiratory-triggered echo-planar imaging based diffusion-weighted sequence (EPI-DWI) with different b values for magnetic resonance imaging (MRI) of the liver. Forty patients were examined. Quantitative and qualitative evaluation of contrast was performed. Severity of artifacts and overall image quality in comparison with a T2w turbo spin-echo (T2-TSE) sequence were scored. The liver-spleen contrast was significantly higher (P < 0.05) for the EPI-DWI compared with the T2-TSE sequence (0.47 +/- 0.11 (b50); 0.48 +/- 0.13 (b300); 0.47 +/- 0.13 (b600) vs 0.38 +/- 0.11). Liver-lesion contrast strongly depends on the b value of the DWI sequence and decreased with higher b values (b50, 0.47 +/- 0.19; b300, 0.40 +/- 0.20; b600, 0.28 +/- 0.23). Severity of artifacts and overall image quality were comparable to the T2-TSE sequence when using a low b value (P > 0.05), artifacts increased and image quality decreased with higher b values (P < 0.05). Respiratory-triggered EPI-DWI of the liver is feasible because good image quality and favorable soft tissue contrast can be achieved.

IVIM diffusion-weighted imaging of the liver at 3.0 T: Comparison with 1.5 T

PubMed Central

Cui, Yong; Dyvorne, Hadrien; Besa, Cecilia; Cooper, Nancy; Taouli, Bachir

2015-01-01

Purpose To compare intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) of the liver between 1.5 T and 3.0 T in terms of parameter quantification and inter-platform reproducibility. Materials and methods In this IRB approved prospective study, 19 subjects (17 patients with chronic liver disease and 2 healthy volunteers) underwent two repeat scans at 1.5 T and 3.0 T. Each scan included IVIM DWI using 16 b values from 0 to 800 s/mm2. A single observer measured IVIM parameters for each platform and estimated signal to noise ratio (eSNR) at b0, 200, 400 and 800 s/mm2. Wilcoxon paired tests were used to compare liver eSNR and IVIM parameters. Inter-platform reproducibility was assessed by calculating within-subject coefficient of variation (CV) and Bland–Altman limits of agreement. An ice water phantom was used to test ADC variability between the two MRI systems. Results The mean invitro difference in ADC between the two platforms was 6.8%. eSNR was significantly higher at 3.0T for all selected b values (p = 0.006–0.020), except for b0 (p = 0.239). Liver IVIM parameters were significantly different between 1.5 T and 3.0 T (p = 0.005–0.044), except for ADC (p = 0.748). The inter-platform reproducibility of true diffusion coefficient (D) and ADC were good, with mean CV of 10.9% and 11.1%, respectively. Perfusion fraction (PF) and pseudodiffusion coefficient (D*) showed more limited inter-platform reproducibility (mean CV of 22.6% for PF and 46.9% for D*). Conclusion Liver D and ADC values showed good reproducibility between 1.5 T and 3.0 T platforms; while there was more variability in PF, and large variability in D* parameters between the two platforms. These findings may have implications for drug trials assessing the role of IVIM DWI in tumor response and liver fibrosis. PMID:26393236

Toxin-Induced Autoimmune Hepatitis Caused by Raw Cashew Nuts.

PubMed

Crismale, James F; Stueck, Ashley; Bansal, Meena

2016-08-01

A 64-year-old man with no past medical history presented with abnormally elevated liver enzymes 1 year after developing a diffuse rash thought to be related to eating large quantities of raw cashew nuts. Liver biopsy was performed, which revealed features concerning for drug- or toxin-induced autoimmune hepatitis. The patient began treatment with azathioprine and prednisone, and liver enzymes normalized. We describe a unique case of a toxin-induced autoimmune hepatitis precipitated not by a drug or dietary supplement but by a food product.

Vasculo-Neuronal Coupling: Retrograde Vascular Communication to Brain Neurons.

PubMed

Kim, Ki Jung; Ramiro Diaz, Juan; Iddings, Jennifer A; Filosa, Jessica A

2016-12-14

Continuous cerebral blood flow is essential for neuronal survival, but whether vascular tone influences resting neuronal function is not known. Using a multidisciplinary approach in both rat and mice brain slices, we determined whether flow/pressure-evoked increases or decreases in parenchymal arteriole vascular tone, which result in arteriole constriction and dilation, respectively, altered resting cortical pyramidal neuron activity. We present evidence for intercellular communication in the brain involving a flow of information from vessel to astrocyte to neuron, a direction opposite to that of classic neurovascular coupling and referred to here as vasculo-neuronal coupling (VNC). Flow/pressure increases within parenchymal arterioles increased vascular tone and simultaneously decreased resting pyramidal neuron firing activity. On the other hand, flow/pressure decreases evoke parenchymal arteriole dilation and increased resting pyramidal neuron firing activity. In GLAST-CreERT2; R26-lsl-GCaMP3 mice, we demonstrate that increased parenchymal arteriole tone significantly increased intracellular calcium in perivascular astrocyte processes, the onset of astrocyte calcium changes preceded the inhibition of cortical pyramidal neuronal firing activity. During increases in parenchymal arteriole tone, the pyramidal neuron response was unaffected by blockers of nitric oxide, GABA A , glutamate, or ecto-ATPase. However, VNC was abrogated by TRPV4 channel, GABA B , as well as an adenosine A 1 receptor blocker. Differently to pyramidal neuron responses, increases in flow/pressure within parenchymal arterioles increased the firing activity of a subtype of interneuron. Together, these data suggest that VNC is a complex constitutive active process that enables neurons to efficiently adjust their resting activity according to brain perfusion levels, thus safeguarding cellular homeostasis by preventing mismatches between energy supply and demand. We present evidence for vessel-to-neuron communication in the brain slice defined here as vasculo-neuronal coupling. We showed that, in response to increases in parenchymal arteriole tone, astrocyte intracellular Ca 2+ increased and cortical neuronal activity decreased. On the other hand, decreasing parenchymal arteriole tone increased resting cortical pyramidal neuron activity. Vasculo-neuronal coupling was partly mediated by TRPV4 channels as genetic ablation, or pharmacological blockade impaired increased flow/pressure-evoked neuronal inhibition. Increased flow/pressure-evoked neuronal inhibition was blocked in the presence of adenosine A1 receptor and GABA B receptor blockade. Results provide evidence for the concept of vasculo-neuronal coupling and highlight the importance of understanding the interplay between basal CBF and resting neuronal activity. Copyright © 2016 the authors 0270-6474/16/3612624-16$15.00/0.

Familial Danish dementia: a novel form of cerebral amyloidosis associated with deposition of both amyloid-Dan and amyloid-beta.

PubMed

Holton, Janice L; Lashley, Tammaryn; Ghiso, Jorge; Braendgaard, Hans; Vidal, Ruben; Guerin, Christopher J; Gibb, Graham; Hanger, Diane P; Rostagno, Agueda; Anderton, Brian H; Strand, Catherine; Ayling, Hilary; Plant, Gordon; Frangione, Blas; Bojsen-Møller, Marie; Revesz, Tamas

2002-03-01

Familial Danish dementia (FDD) is pathologically characterized by widespread cerebral amyloid angiopathy (CAA), parenchymal protein deposits, and neurofibrillary degeneration. FDD is associated with a mutation of the BRI2 gene located on chromosome 13. In FDD there is a decamer duplication, which abolishes the normal stop codon, resulting in an extended precursor protein and the release of an amyloidogenic fragment, ADan. The aim of this study was to describe the major neuropathological changes in FDD and to assess the distribution of ADan lesions, neurofibrillary pathology, glial, and microglial response using conventional techniques, immunohistochemistry, confocal microscopy, and immunoelectron microscopy. We showed that ADan is widely distributed in the central nervous system (CNS) in the leptomeninges, blood vessels, and parenchyma. A predominance of parenchymal pre-amyloid (non-fibrillary) lesions was found. Abeta was also present in a proportion of both vascular and parenchymal lesions. There was severe neurofibrillary pathology, and tau immunoblotting revealed a triplet electrophoretic migration pattern comparable with PHF-tau. FDD is a novel form of CNS amyloidosis with extensive neurofibrillary degeneration occurring with parenchymal, predominantly pre-amyloid rather than amyloid, deposition. These findings support the notion that parenchymal amyloid fibril formation is not a prerequisite for the development of neurofibrillary tangles. The significance of concurrent ADan and Abeta deposition in FDD is under further investigation.

Whole brain C-arm computed tomography parenchymal blood volume measurements

PubMed Central

Byrne, James V

2016-01-01

Introduction C-arm flat detector computed tomography (FDCT) parenchymal blood volume (PBV) imaging in the neuro-interventional suite is a new technique for which detailed whole brain measurements have not been previously reported. This study aims to create a catalogue of PBV measurements for various anatomical regions encompassing the whole brain, using a three-dimensional volume-of-interest (3D-VOI) analysis. Methods We acquired and analysed 30 C-arm FDCT datasets from 26 patients with aneurysmal subarachnoid haemorrhage (SAH), as part of a prospective study comparing C-arm computed tomography (CT) PBV with magnetic resonance perfusion-weighted imaging (MR-PWI). We calculated the PBV values for various brain regions with an automated analysis, using 58 pre-defined atlas-based 3D-VOIs encompassing the whole brain. VOIs partially or completely overlapping regions of magnetic resonance diffusion weighted imaging (MR-DWI) abnormality or magnetic resonance cerebral blood flow (MR-CBF) asymmetry were excluded from the analysis. Results Of the 30 C-arm CT PBV datasets, 14 (54%; 12 patients) had areas of restricted diffusion, the majority of which were focal. The PBV values for the cerebral cortex and cerebral white matter were 4.01 ± 0.47 (mean ± SD) and 3.01 ± 0.39 ml per 100 ml. Lobar PBV values were: frontal lobe 4.2 ± 0.8, temporal lobe 4.2 ± 0.9, parietal lobe 3.9 ± 0.7 and occipital lobe 4.3 ± 0.8 ml/100 ml. The basal ganglia and brainstem PBV values were 3.4 ± 0.7 and 4.6 ± 0.6 ml/100 ml, respectively. Conclusions Compared with the typical reference cerebral blood volume (CBV) values reported in the literature for Positron Emission Tomography (PET), the PBV values were relatively high for the white matter and relatively low for the cortical grey matter. The reported catalogue of PBV values for various brain regions would be useful to inform future studies and could be used in clinical practice, when interpreting PBV maps. PMID:26769737

Whole brain C-arm computed tomography parenchymal blood volume measurements.

PubMed

Kamran, Mudassar; Byrne, James V

2016-04-01

C-arm flat detector computed tomography (FDCT) parenchymal blood volume (PBV) imaging in the neuro-interventional suite is a new technique for which detailed whole brain measurements have not been previously reported. This study aims to create a catalogue of PBV measurements for various anatomical regions encompassing the whole brain, using a three-dimensional volume-of-interest (3D-VOI) analysis. We acquired and analysed 30 C-arm FDCT datasets from 26 patients with aneurysmal subarachnoid haemorrhage (SAH), as part of a prospective study comparing C-arm computed tomography (CT) PBV with magnetic resonance perfusion-weighted imaging (MR-PWI). We calculated the PBV values for various brain regions with an automated analysis, using 58 pre-defined atlas-based 3D-VOIs encompassing the whole brain. VOIs partially or completely overlapping regions of magnetic resonance diffusion weighted imaging (MR-DWI) abnormality or magnetic resonance cerebral blood flow (MR-CBF) asymmetry were excluded from the analysis. Of the 30 C-arm CT PBV datasets, 14 (54%; 12 patients) had areas of restricted diffusion, the majority of which were focal. The PBV values for the cerebral cortex and cerebral white matter were 4.01 ± 0.47 (mean ± SD) and 3.01 ± 0.39 ml per 100 ml. Lobar PBV values were: frontal lobe 4.2 ± 0.8, temporal lobe 4.2 ± 0.9, parietal lobe 3.9 ± 0.7 and occipital lobe 4.3 ± 0.8 ml/100 ml. The basal ganglia and brainstem PBV values were 3.4 ± 0.7 and 4.6 ± 0.6 ml/100 ml, respectively. Compared with the typical reference cerebral blood volume (CBV) values reported in the literature for Positron Emission Tomography (PET), the PBV values were relatively high for the white matter and relatively low for the cortical grey matter. The reported catalogue of PBV values for various brain regions would be useful to inform future studies and could be used in clinical practice, when interpreting PBV maps. © The Author(s) 2016.

Cerebral hypoxia during cardiopulmonary bypass: a magnetic resonance imaging study.

PubMed

Mutch, W A; Ryner, L N; Kozlowski, P; Scarth, G; Warrian, R K; Lefevre, G R; Wong, T G; Thiessen, D B; Girling, L G; Doiron, L; McCudden, C; Saunders, J K

1997-09-01

Neurocognitive deficits after open heart operations have been correlated to jugular venous oxygen desaturation on rewarming from hypothermic cardiopulmonary bypass (CPB). Using a porcine model, we looked for evidence of cerebral hypoxia by magnetic resonance imaging during CPB. Brain oxygenation was assessed by T2*-weighted imaging, based on the blood oxygenation level-dependent effect (decreased T2*-weighted signal intensity with increased tissue concentrations of deoxyhemoglobin). Pigs were placed on normothermic CPB, then cooled to 28 degrees C for 2 hours of hypothermic CPB, then rewarmed to baseline temperature. T2*-weighted, imaging was undertaken before CPB, during normothermic CPB, at 30-minute intervals during hypothermic CPB, after rewarming, and then 15 minutes after death. Imaging was with a Bruker 7.0 Tesla, 40-cm bore magnetic resonance scanner with actively shielded gradient coils. Regions of interest from the magnetic resonance images were analyzed to identify parenchymal hypoxia and correlated with jugular venous oxygen saturation. Post-hoc fuzzy clustering analysis was used to examine spatially distributed regions of interest whose pixels followed similar time courses. Attention was paid to pixels showing decreased T2* signal intensity over time. T2* signal intensity decreased with rewarming and in five of seven experiments correlated with the decrease in jugular venous oxygen saturation. T2* imaging with fuzzy clustering analysis revealed two diffusely distributed pixel groups during CPB. One large group of pixels (50% +/- 13% of total pixel count) showed increased T2* signal intensity (well-oxygenated tissue) during hypothermia, with decreased intensity on rewarming. Changes in a second group of pixels (34% +/- 8% of total pixel count) showed a progressive decrease in T2* signal intensity, independent of temperature, suggestive of increased brain hypoxia during CPB. Decreased T2* signal intensity in a diffuse spatial distribution indicates that a large proportion of cerebral parenchyma is hypoxic (evidenced by an increased proportion of tissue deoxyhemoglobin) during CPB in this porcine model. Neuronal damage secondary to parenchymal hypoxia may explain the postoperative neuropsychological dysfunction after cardiac operations.

Liver diffusivity in healthy volunteers and patients with chronic liver disease: Comparison of breath-hold and free-breathing techniques

PubMed Central

Eatesam, Mamak; Noworolski, Susan M; Tien, Phyllis C; Nystrom, Michelle; Dodge, Jennifer L.; Merriman, Raphael B.; Qayyum, Aliya

2011-01-01

Purpose To compare liver ADC obtained with breath-hold and free-breathing diffusion weighted imaging (DWI) in healthy volunteers and patients with liver disease. Materials and Methods Twenty-eight subjects, 12 healthy volunteers and 16 patients (9 NAFLD, 7 chronic active HCV), underwent breath-hold (BH) and free-breathing (FB) DWI MRI at 1.5T. Pearson’s correlation coefficient was used to determine correlation while paired t-tests assessed differences between BH and FB ADC. Estimated bias was calculated using the Bland-Altman method. Results Liver ADC (×10−3 mm2/sec) was lower on BH for all groups (mean difference 0.36±0.20; p<0.01). ADC was higher in healthy volunteers (BH 1.80±0.18; FB 2.24±0.20) compared to NAFLD patients (BH 1.43±0.27; FB 1.78±0.28) (p<0.001) and HCV patients (BH 1.63±0.191; FB 1.88±0.12). Overall correlation between BH and FB ADC was (r =0.75), greatest in NAFLD (r =0.90) compared to the correlation in HCV (r =0.24) and healthy subjects (r =0.34). Bland-Altman plots did not show agreement in mean absolute difference and estimated bias between subjects. Conclusion Correlation between BH and FB liver ADC is moderate indicating that BH and FB should not be used interchangeably. Additionally, the lower ADC values in BH versus FB should be accounted for when comparing different liver DWI studies. PMID:22034200

Liver diffusivity in healthy volunteers and patients with chronic liver disease: comparison of breathhold and free-breathing techniques.

PubMed

Eatesam, Mamak; Noworolski, Susan M; Tien, Phyllis C; Nystrom, Michelle; Dodge, Jennifer L; Merriman, Raphael B; Qayyum, Aliya

2012-01-01

To compare liver ADC obtained with breathhold and free-breathing diffusion weighted imaging (DWI) in healthy volunteers and patients with liver disease. Twenty-eight subjects, 12 healthy volunteers and 16 patients (9 NAFLD, 7 chronic active HCV), underwent breathhold (BH) and free-breathing (FB) DWI MRI at 1.5 Tesla. Pearson's correlation coefficient was used to determine correlation while paired t-tests assessed differences between BH and FB ADC. Estimated bias was calculated using the Bland-Altman method. Liver ADC (×10(-3) mm(2) /s) was lower on BH for all groups (mean difference 0.36 ± 0.20; P < 0.01). ADC was higher in healthy volunteers (BH 1.80 ± 0.18; FB 2.24 ± 0.20) compared with NAFLD patients (BH 1.43 ± 0.27; FB 1.78 ± 0.28) (P < 0.001) and HCV patients (BH 1.63 ± 0.191; FB 1.88 ± 0.12). Overall correlation between BH and FB ADC was (r = 0.75), greatest in NAFLD (r = 0.90) compared with the correlation in HCV (r = 0.24) and healthy subjects (r = 0.34). Bland-Altman plots did not show agreement in mean absolute difference and estimated bias between subjects. Correlation between BH and FB liver ADC is moderate indicating that BH and FB should not be used interchangeably. Additionally, the lower ADC values in BH versus FB should be accounted for when comparing different liver DWI studies. Copyright © 2011 Wiley-Liss, Inc.

Is ketogenic diet treatment hepatotoxic for children with intractable epilepsy?

PubMed

Arslan, Nur; Guzel, Orkide; Kose, Engin; Yılmaz, Unsal; Kuyum, Pınar; Aksoy, Betül; Çalık, Tansel

2016-12-01

Long-term ketogenic diet (KD) treatment has been shown to induce liver steatosis and gallstone formation in some in vivo and clinical studies. The aim of this retrospective study was to evaluate the hepatic side effects of KD in epileptic children. A total of 141 patients (mean age: 7.1±4.1years [2-18 years], 45.4% girls), receiving KD at least one year for intractable epilepsy due to different diagnoses (congenital brain defects, GLUT-1 deficiency, West syndrome, tuberous sclerosis, hypoxic brain injury, etc.) were included in the study. Serum triglyceride, cholesterol, aminotransferase, bilirubin, protein and albumin levels and abdominal ultrasonography were recorded before and at 1, 3, 6, and 12 months following after diet initiation. The mean duration of KD was 15.9±4.3months. At one month of therapy, three patients had elevated alanine and aspartate aminotransferase levels. These patients were receiving ketogenic diet for Doose syndrome, idiopathic epilepsy and GLUT-1 deficiency. Hepatosteatosis was detected in three patients at 6 months of treatment. Two of these patients were treated with KD for the primary diagnosis of tuberous sclerosis and one for Landau Kleffner syndrome. Cholelithiasis was detected in two patients at 12 months of treatment. They were receiving treatment for West syndrome and hypoxic brain injury sequelae. Long-term ketogenic diet treatment stimulates liver parenchymal injury, hepatic steatosis and gallstone formation. Patients should be monitored by screening liver enzymes and abdominal ultrasonography in order to detect these side effects. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Zonal differences in DNA synthesis activity and cytochrome P450 gene expression in livers of male F344 rats treated with five nongenotoxic carcinogens

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Zhi-Ying; White, C.C.; He, Cheng-Yi

1995-12-31

Both increased cell proliferation and {open_quotes}altered{close_quotes}CYP gene expression are prominent phenomena associated with liver tumor promotion by nongenotoxic carcinogen treatment. BRDU-labeled parenchymal nuclei were observed primarily in the periportal area of groups of rats, independent of nongenotoxic carcinogen treatment. Treatment with each of the 5 nongenotoxic carcinogens resulted in profound alterations in CPY gene expression at both the transcriptional and translational levels. Expression of CYP1A1, 1A1/2, 3A1, 2B1/2, and 4A immunoproteins demonstrated nongenotoxic carcinogen-specific patterns in both magnitude and zonal distribution. In agreement with the CYP immunoprotein data, treatment with each of the five nongenotoxic carcinogens resulted in a uniquemore » composition of mRNAs of CYP2B1, 2B2, 2C6, 2C11, 3A1, 3A2, and 4A1, which were variably increased or decreased relative to the untreated control livers, depending on the treatment. Similarly, the rate and pattern of CYP enzyme-mediated hydroxylation toward testosterone, 17{beta}-estradiol, corticosterone, and lauric acid were greatly altered by nongenotoxic carcinogen treatment. Because many endogenous substrates are modulators of DNA and RNA synthesis, intracellular kinetics of endogenous substrates of CYP enzymes in the corresponding hepatocytes could contribute, at least in part, to the differences in gene expression, differentiation, and cell proliferation among the hepatocytes in the cell plate. 64 refs., 11 figs., 2 tabs.« less

Ameliorative Effect of Curcumin-Encapsulated Hyaluronic Acid-PLA Nanoparticles on Thioacetamide-Induced Murine Hepatic Fibrosis.

PubMed

Chen, Yu-Nong; Hsu, Shih-Lan; Liao, Ming-Yuan; Liu, Yi-Ting; Lai, Chien-Hung; Chen, Ji-Feng; Nguyen, Mai-Huong Thi; Su, Yung-Hsiang; Chen, Shang-Ting; Wu, Li-Chen

2016-12-24

In this study, we developed curcumin-encapsulated hyaluronic acid-polylactide nanoparticles (CEHPNPs) to be used for liver fibrosis amelioration. CD44, the hyaluronic acid (HA) receptor, is upregulated on the surface of cancer cells and on activated hepatic stellate cells (aHSCs) rather than normal cells. CEHPNPs could bind to CD44 and be internalized effectively through endocytosis to release curcumin, a poor water-soluble liver protective agent. Thus, CEHPNPs were potentially not only improving drug efficiency, but also targeting aHSCs. HA and polylactide (PLA) were crosslinked by adipic acid dihydrazide (ADH). The synthesis of HA-PLA was monitored by Fourier-transform infrared (FTIR) and Nuclear Magnetic Resonance (NMR). The average particle size was approximately 60-70 nm as determined by dynamic light scattering (DLS) and scanning electron microscope (SEM). Zeta potential was around -30 mV, which suggested a good stability of the particles. This drug delivery system induced significant aHSC cell death without affecting quiescent HSCs, hepatic epithelial, and parenchymal cells. This system reduced drug dosage without sacrificing therapeutic efficacy. The cytotoxicity IC 50 (inhibitory concentration at 50%) value of CEHPNPs was approximately 1/30 to that of the free drug treated group in vitro. Additionally, the therapeutic effects of CEHPNPs were as effective as the group treated with the same curcumin dose intensity in vivo. CEHPNPs significantly reduced serum aspartate transaminase/alanine transaminase (ALT/AST) significantly, and attenuated tissue collagen production and cell proliferation as revealed by liver biopsy. Conclusively, the advantages of superior biosafety and satisfactory therapeutic effect mean that CEHPNPs hold great potential for treating hepatic fibrosis.

The Association Between Liver and Tumor [18F]FDG Uptake in Patients with Diffuse Large B Cell Lymphoma During Chemotherapy.

PubMed

Wu, Xingchen; Bhattarai, Abhisek; Korkola, Pasi; Pertovaara, Hannu; Eskola, Hannu; Kellokumpu-Lehtinen, Pirkko-Liisa

2017-10-01

The aim of this study was to explore the association between liver, mediastinum and tumor 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) uptake during chemotherapy in diffuse large B cell lymphoma (DLBCL). Nineteen patients with proven DLBCL underwent positron emission tomography (PET)/X-ray computed tomography scan at baseline, 1 week and 2 cycles after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy, and again after chemotherapy completion. The mean and maximal standardized uptake value (SUVmean and SUVmax) of the liver and mediastinum were measured and correlated with the tumor SUVmax, SUVsum, whole-body metabolic tumor volume (MTVwb), and total lesion glycolysis (TLG). At baseline, both the liver and mediastinum SUVmean and SUVmax correlated inversely with the tumor MTVwb or TLG (p < 0.01 or 0.001). The liver SUVmean and SUVmax increased significantly after 1 week of R-CHOP therapy and remained at the high level until chemotherapy completion. The mediastinum SUVmean and SUVmax remained stable during chemotherapy. The tumor SUVmax, SUVsum, MTVwb, and TLG decreased significantly after 1 week of R-CHOP therapy. The change of the liver SUVmean correlated inversely with the change of tumor MTVwb and TLG after 1 week of chemotherapy (p < 0.05, respectively). The intersubject variability of liver and mediastinum [ 18 F]FDG uptake ranged from 11 to 26 %. The liver [ 18 F]FDG uptake increased significantly after R-CHOP therapy. One of the possible reasons is the distribution of a greater fraction of the tracer to healthy tissues rather than tumor after effective chemotherapy. The variability of the liver [ 18 F]FDG uptake during chemotherapy might affect the visual analysis of the interim PET scan and this needs to be confirmed in future studies with a large patient cohort. In addition, the intersubject variability of the liver and mediastinum [ 18 F]FDG uptake should be considered.

Effect of ultrasound frequency on the Nakagami statistics of human liver tissues.

PubMed

Tsui, Po-Hsiang; Zhou, Zhuhuang; Lin, Ying-Hsiu; Hung, Chieh-Ming; Chung, Shih-Jou; Wan, Yung-Liang

2017-01-01

The analysis of the backscattered statistics using the Nakagami parameter is an emerging ultrasound technique for assessing hepatic steatosis and fibrosis. Previous studies indicated that the echo amplitude distribution of a normal liver follows the Rayleigh distribution (the Nakagami parameter m is close to 1). However, using different frequencies may change the backscattered statistics of normal livers. This study explored the frequency dependence of the backscattered statistics in human livers and then discussed the sources of ultrasound scattering in the liver. A total of 30 healthy participants were enrolled to undergo a standard care ultrasound examination on the liver, which is a natural model containing diffuse and coherent scatterers. The liver of each volunteer was scanned from the right intercostal view to obtain image raw data at different central frequencies ranging from 2 to 3.5 MHz. Phantoms with diffuse scatterers only were also made to perform ultrasound scanning using the same protocol for comparisons with clinical data. The Nakagami parameter-frequency correlation was evaluated using Pearson correlation analysis. The median and interquartile range of the Nakagami parameter obtained from livers was 1.00 (0.98-1.05) for 2 MHz, 0.93 (0.89-0.98) for 2.3 MHz, 0.87 (0.84-0.92) for 2.5 MHz, 0.82 (0.77-0.88) for 3.3 MHz, and 0.81 (0.76-0.88) for 3.5 MHz. The Nakagami parameter decreased with the increasing central frequency (r = -0.67, p < 0.0001). However, the effect of ultrasound frequency on the statistical distribution of the backscattered envelopes was not found in the phantom results (r = -0.147, p = 0.0727). The current results demonstrated that the backscattered statistics of normal livers is frequency-dependent. Moreover, the coherent scatterers may be the primary factor to dominate the frequency dependence of the backscattered statistics in a liver.

Effect of increasing energy and protein intake on mammary development in heifer calves.

PubMed

Brown, E G; Vandehaar, M J; Daniels, K M; Liesman, J S; Chapin, L T; Forrest, J W; Akers, R M; Pearson, R E; Nielsen, M S Weber

2005-02-01

The objective of this study was to determine if increased energy and protein intake from 2 to 14 wk of age would affect mammary development in heifer calves. At 2 wk of age, Holstein heifer calves were assigned to 1 of 4 treatments in a 2 x 2 factorial arrangement with 2 levels of protein and energy intake (moderate, M; high, H) in period 1 (2 to 8 wk of age) and 2 levels of protein and energy intake (low, L; high, H) in period 2 (8 to 14 wk of age), so that mean initial body weights were approximately equal for all 4 treatments (ML, MH, HL, and HH). The M diet in period 1 consisted of a standard milk replacer (21.3% CP, 21.3% fat) fed at 1.1% of BW on a DM basis and a 16.5% CP grain mix fed at restricted intake to promote 400 g of daily gain, whereas the L diet in period 2 consisted only of the grain mix. The H diet in period 1 consisted of a high-protein milk replacer (30.3% CP, 15.9% fat) fed at 2.0% of body weight on a DM basis and a 21.3% CP grain mix available ad libitum. In period 2, the H diet consisted of just the 21.3% grain mix. Calves were gradually weaned from milk replacer by 7 wk and slaughtered at 8 (n = 11) or 14 wk of age (n = 41). Parenchyma from the distal region, midgland, and proximal region relative to the teat from one half of the udder was collected, fixed, and embedded in paraffin. The other half of the gland was used to determine parenchymal mass, protein, fat, DNA, RNA, and extraparenchymal mass. Total parenchymal tissue, parenchymal DNA, parenchymal RNA, and concentrations of DNA and RNA were higher for calves on the H diet during period 1, but were not affected by diet during period 2. Parenchymal fat percentage was increased by the H diet during period 2. The H diet increased extraparenchymal fat during both periods. The area of parenchyma occupied by epithelium was not affected by treatment, but at the end of period 2, the percentage of proliferating epithelial cells as indicated by Ki67, an marker of cell proliferation, expression was greater for calves on the M diet in period 1 compared with calves on the H diet in period 1. Diets did not influence parenchymal protein percentage or the ratio of RNA to DNA. Higher energy and protein intake from 2 to 8 wk of age increased parenchymal mass and parenchymal DNA and RNA in mammary glands of heifer calves without increasing deposition of parenchymal fat. Diet also influenced histological development of mammary parenchyma and subsequent proliferation of ductal epithelial cells. Implications of these effects for future milk production potential are unknown.

MRI diffusion tensor reconstruction with PROPELLER data acquisition.

PubMed

Cheryauka, Arvidas B; Lee, James N; Samsonov, Alexei A; Defrise, Michel; Gullberg, Grant T

2004-02-01

MRI diffusion imaging is effective in measuring the diffusion tensor in brain, cardiac, liver, and spinal tissue. Diffusion tensor tomography MRI (DTT MRI) method is based on reconstructing the diffusion tensor field from measurements of projections of the tensor field. Projections are obtained by appropriate application of rotated diffusion gradients. In the present paper, the potential of a novel data acquisition scheme, PROPELLER (Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction), is examined in combination with DTT MRI for its capability and sufficiency for diffusion imaging. An iterative reconstruction algorithm is used to reconstruct the diffusion tensor field from rotated diffusion weighted blades by appropriate rotated diffusion gradients. DTT MRI with PROPELLER data acquisition shows significant potential to reduce the number of weighted measurements, avoid ambiguity in reconstructing diffusion tensor parameters, increase signal-to-noise ratio, and decrease the influence of signal distortion.

Effect of Contrast Media on Single Shot EPI: Implications for Abdominal Diffusion Imaging

PubMed Central

Gulani, Vikas; Willatt, Jonathan M.; Blaimer, Martin; Hussain, Hero K.; Duerk, Jeffrey L.; Griswold, Mark A.

2010-01-01

Purpose The goal of this study was to determine the effect of contrast media on the signal behavior of single shot echo planar imaging (ssEPI) used for abdominal diffusion imaging. Materials and Methods The signal of a ssEPI spin echo sequence in a water phantom with varying concentrations of gadolinium was modeled with Bloch equations and the predicted behavior validated on a phantom at 1.5 T. Six volunteers were given gadolinium contrast, and signal intensity (SI) time courses for regions of interest (ROIs) in the liver, pancreas, spleen, renal cortex and medulla were analyzed. The Student's t-test was used to compare pre-contrast SI to 0, 1, 4, 5, 10, and 13 minutes following contrast. Results The results show that following contrast, ssEPI SI goes through a nadir, recovering differently for each organ. Maximal contrast related signal losses relative to pre-contrast signal are 20%, 20%, 53%, and 67%, for the liver, pancreas, renal cortex and medulla respectively. The SIs remain statistically below the pre-contrast values for 5, 4, and 1 minutes for the pancreas, liver, and spleen, and for all times measured for the renal cortex and medulla. Conclusion Abdominal diffusion imaging should be performed prior to contrast due to adverse effects on the signal in ssEPI. PMID:19856456

Fetal diffusion tensor quantification of brainstem pathology in Chiari II malformation.

PubMed

Woitek, Ramona; Prayer, Daniela; Weber, Michael; Amann, Gabriele; Seidl, Rainer; Bettelheim, Dieter; Schöpf, Veronika; Brugger, Peter C; Furtner, Julia; Asenbaum, Ulrika; Kasprian, Gregor

2016-05-01

This prenatal MRI study evaluated the potential of diffusion tensor imaging (DTI) metrics to identify changes in the midbrain of fetuses with Chiari II malformations compared to fetuses with mild ventriculomegaly, hydrocephalus and normal CNS development. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were calculated from a region of interest (ROI) in the midbrain of 46 fetuses with normal CNS, 15 with Chiari II malformations, eight with hydrocephalus and 12 with mild ventriculomegaly. Fetuses with different diagnoses were compared group-wise after age-matching. Axial T2W-FSE sequences and single-shot echo planar DTI sequences (16 non-collinear diffusion gradient-encoding directions, b-values of 0 and 700 s/mm(2), 1.5 Tesla) were evaluated retrospectively. In Chiari II malformations, FA was significantly higher than in age-matched fetuses with a normal CNS (p = .003), while ADC was not significantly different. No differences in DTI metrics between normal controls and fetuses with hydrocephalus or vetriculomegaly were detected. DTI can detect and quantify parenchymal alterations of the fetal midbrain in Chiari II malformations. Therefore, in cases of enlarged fetal ventricles, FA of the fetal midbrain may contribute to the differentiation between Chiari II malformation and other entities. • FA in the fetal midbrain is elevated in Chiari II malformations. • FA is not elevated in hydrocephalus and mild ventriculomegaly without Chiari II. • Measuring FA may help distinguish different causes for enlarged ventricles prenatally. • Elevated FA may aid in the diagnosis of open neural tube defects. • Elevated FA might contribute to stratification for prenatal surgery in Chiari II.

[Antioxidant activity of hepatotropic preparations in the treatment of chronic diseases of the liver].

PubMed

Loginov, A S; Matiushin, B N; Sukhareva, G V; Tkachev, V D

1988-01-01

Hepatotropic drugs were shown to decrease blood lipid peroxidation activity (LPO) in patients with chronic diffuse liver diseases. A positive time course of LPO indices was noted in the treatment of chronic active hepatitis and liver cirrhosis of moderate activity. Comparison of antioxidant features of the drugs were suggestive of a noticeable effect of trophopar and essential in patients with chronic active hepatitis, trophopar in patients with liver lipodystrophy, and drugs of a silimarina series in patients with liver cirrhosis. Under clinical conditions the effect of the drugs on LPO processes was less noticeable than in experiments in vitro. It is assumed that the pharmacological effect of the hepatotropic drugs is associated with their antioxidant activity.

Diffusion-Weighted PROPELLER MRI for Quantitative Assessment of Liver Tumor Necrotic Fraction and Viable Tumor Volume in VX2 Rabbits

PubMed Central

Deng, Jie; Virmani, Sumeet; Young, Joseph; Harris, Kathleen; Yang, Guang-Yu; Rademaker, Alfred; Woloschak, Gayle; Omary, Reed A.; Larson, Andrew C.

2010-01-01

Purpose To test the hypothesis that diffusion-weighted (DW)-PROPELLER (periodically rotated overlapping parallel lines with enhanced reconstruction) MRI provides more accurate liver tumor necrotic fraction (NF) and viable tumor volume (VTV) measurements than conventional DW-SE-EPI (spin echo echo-planar imaging) methods. Materials and Methods Our institutional Animal Care and Use Committee approved all experiments. In six rabbits implanted with 10 VX2 liver tumors, DW-PROPELLER and DW-SE-EPI scans were performed at contiguous axial slice positions covering each tumor volume. Apparent diffusion coefficient maps of each tumor were used to generate spatially resolved tumor viability maps for NF and VTV measurements. We compared NF, whole tumor volume (WTV), and VTV measurements to corresponding reference standard histological measurements based on correlation and concordance coefficients and the Bland–Altman analysis. Results DW-PROPELLER generally improved image quality with less distortion compared to DW-SE-EPI. DW-PROPELLER NF, WTV, and VTV measurements were strongly correlated and satisfactorily concordant with histological measurements. DW-SE-EPI NF measurements were weakly correlated and poorly concordant with histological measurements. Bland–Altman analysis demonstrated that DWPROPELLER WTV and VTV measurements were less biased from histological measurements than the corresponding DW-SE-EPI measurements. Conclusion DW-PROPELLER MRI can provide spatially resolved liver tumor viability maps for accurate NF and VTV measurements, superior to DW-SE-EPI approaches. DWPROPELLER measurements may serve as a noninvasive surrogate for pathology, offering the potential for more accurate assessments of therapy response than conventional anatomic size measurements. PMID:18407540

Evaluation of background parenchymal enhancement on breast MRI: a systematic review

PubMed Central

Signori, Alessio; Valdora, Francesca; Rossi, Federica; Calabrese, Massimo; Durando, Manuela; Mariscotto, Giovanna; Tagliafico, Alberto

2017-01-01

Objective: To perform a systematic review of the methods used for background parenchymal enhancement (BPE) evaluation on breast MRI. Methods: Studies dealing with BPE assessment on breast MRI were retrieved from major medical libraries independently by four reviewers up to 6 October 2015. The keywords used for database searching are “background parenchymal enhancement”, “parenchymal enhancement”, “MRI” and “breast”. The studies were included if qualitative and/or quantitative methods for BPE assessment were described. Results: Of the 420 studies identified, a total of 52 articles were included in the systematic review. 28 studies performed only a qualitative assessment of BPE, 13 studies performed only a quantitative assessment and 11 studies performed both qualitative and quantitative assessments. A wide heterogeneity was found in the MRI sequences and in the quantitative methods used for BPE assessment. Conclusion: A wide variability exists in the quantitative evaluation of BPE on breast MRI. More studies focused on a reliable and comparable method for quantitative BPE assessment are needed. Advances in knowledge: More studies focused on a quantitative BPE assessment are needed. PMID:27925480

Volumetric Optical Frequency Domain Imaging of Pulmonary Pathology With Precise Correlation to Histopathology

PubMed Central

Hariri, Lida P.; Applegate, Matthew B.; Mino-Kenudson, Mari; Mark, Eugene J.; Medoff, Benjamin D.; Luster, Andrew D.; Bouma, Brett E.; Tearney, Guillermo J.

2013-01-01

Background: Lung cancer is the leading cause of cancer-related mortality. Radiology and bronchoscopy techniques do not have the necessary resolution to evaluate lung lesions on the microscopic scale, which is critical for diagnosis. Bronchial biopsy specimens can be limited by sampling error and small size. Optical frequency domain imaging (OFDI) provides volumetric views of tissue microstructure at near-histologic resolution and may be useful for evaluating pulmonary lesions to increase diagnostic accuracy. Bronchoscopic OFDI has been evaluated in vivo, but a lack of correlated histopathology has limited the ability to develop accurate image interpretation criteria. Methods: We performed OFDI through two approaches (airway-centered and parenchymal imaging) in 22 ex vivo lung specimens, using tissue dye to precisely correlate imaging and histology. Results: OFDI of normal airway allowed visualization of epithelium, lamina propria, cartilage, and alveolar attachments. Carcinomas exhibited architectural disarray, loss of normal airway and alveolar structure, and rapid light attenuation. Squamous cell carcinomas showed nested architecture. Atypical glandular formation was appreciated in adenocarcinomas, and uniform trabecular gland formation was seen in salivary gland carcinomas. Mucinous adenocarcinomas showed alveolar wall thickening with intraalveolar mucin. Interstitial fibrosis was visualized as signal-dense tissue, with an interstitial distribution in mild interstitial fibrotic disease and a diffuse subpleural pattern with cystic space formation in usual interstitial pneumonitis. Conclusions: To our knowledge, this study is the first demonstration of volumetric OFDI with precise correlation to histopathology in lung pathology. We anticipate that OFDI may play a role in assessing airway and parenchymal pathology, providing fresh insights into the volumetric features of pulmonary disease. PMID:22459781

Increased Lymphatic Vessel Length Is Associated With the Fibroblast Reticulum and Disease Severity in Usual Interstitial Pneumonia and Nonspecific Interstitial Pneumonia

PubMed Central

Cosgrove, Gregory P.; Janssen, William J.; Huie, Tristan J.; Burnham, Ellen L.; Heinz, David E.; Curran-Everett, Douglas; Sahin, Hakan; Schwarz, Marvin I.; Cool, Carlyne D.; Groshong, Steve D.; Geraci, Mark W.; Tuder, Rubin M.; Hyde, Dallas M.; Henson, Peter M.

2012-01-01

Background: Lymphangiogenesis responds to tissue injury as a key component of normal wound healing. The development of fibrosis in the idiopathic interstitial pneumonias may result from abnormal wound healing in response to injury. We hypothesize that increased lymphatic vessel (LV) length, a marker of lymphangiogenesis, is associated with parenchymal components of the fibroblast reticulum (organizing collagen, fibrotic collagen, and fibroblast foci), and its extent correlates with disease severity. Methods: We assessed stereologically the parenchymal structure of fibrotic lungs and its associated lymphatic network, which was highlighted immunohistochemically in age-matched samples of usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP) with FVC < 80%, COPD with a Global Initiative for Obstructive Lung Disease stage 0, and normal control lungs. Results: LV length density, as opposed to vessel volume density, was found to be associated with organizing and fibrotic collagen density (P < .0001). Length density of LVs and the volume density of organizing and fibrotic collagen were significantly associated with severity of both % FVC (P < .001) and diffusing capacity of the lung for carbon monoxide (P < .001). Conclusions: Severity of disease in UIP and NSIP is associated with increased LV length and is strongly associated with components of the fibroblast reticulum, namely organizing and fibrotic collagen, which supports a pathogenic role of LVs in these two diseases. Furthermore, the absence of definable differences between UIP and NSIP suggests that LVs are a unifying mechanism for the development of fibrosis in these fibrotic lung diseases. PMID:22797508

PATTERN OF INTERSTITIAL LUNG DISEASE AS SEEN BY HIGH RESOLUTION COMPUTERISED TOMOGRAPHY.

PubMed

Onyambu, C K; Waigwa, M N

2012-09-01

Diffuse lung diseases constitute a major cause of morbidity and mortality worldwide. High Resolution Computed Tomography (HRCT) is the recommended imaging technique in the diagnosis, assessment and followup of these diseases. To describe the pattern of HRCT findings in patients with suspected interstitial lung disease. Kenyatta National Hospital (KNH), Nairobi Hospital and MP Shah Hospital; all situated in Nairobi, during the period February to August 2010. One hundred and one patients sent for HRCT in the six month study period. A total of 101 patients were recruited with age range 18 to 100 years, with a mean age of 53.6 (SD 19.7) years and a median age of 54 years. The male-female ratio was 1.2:1. Cough [80.2% (n = 81)] was the most common presenting complaint followed by dyspnoea (53.5%, n = 53) and chest pain [24.8% (n = 25)]. Overall, the predominant pattern of involvement on chest HRCT was reticular pattern seen in 56.1% (n = 82) of patients, followed by honey-comb pattern (37.8%, n = 82). The study demonstrated marked lung parenchymal destruction in most cases; a poor prognostic indicator which could have been due to delayed referral. HRCT has a high pick up rate of subtle parenchymal lung lesions as well as defining the lesions and their distribution compared to plain chest radiography. This is important in narrowing the differential diagnosis as well as for pre-biopsy planning. The diagnosis of ILD requires a multidisciplinary approach including a detailed clinical history, physical findings, and laboratory investigations, radiological and histological assessment.

Magnetic Resonance Spectroscopy for Evaluating Portal-Systemic Encephalopathy in Patients with Chronic Hepatic Schistosomiasis Japonicum.

PubMed

Li, Ying; Mei, Lihong; Qiang, Jinwei; Ju, Shuai; Zhao, Shuhui

2016-12-01

Portal-systemic encephalopathy (PSE) is classified as type B hepatic encephalopathy. Portal-systemic shunting rather than liver dysfunction is the main cause of PSE in chronic hepatic schistosomiasis japonicum (HSJ) patients. Owing to lack of detectable evidence of intrinsic liver disease, chronic HSJ patients with PSE are frequently clinically undetected or misdiagnosed, especially chronic HSJ patients with covert PSE (subclinical encephalopathy). In this study, we investigated whether magnetic resonance spectroscopy (MRS) could be a useful tool for diagnosing PSE in chronic HSJ patients. Magnetic resonance (MR) T1-weighted imaging, diffusion-weighted imaging, and MRS were performed in 41 chronic HSJ patients with suspected PSE and in 21 age-matched controls. The T1 signal intensity index (T1SI) and apparent diffusion coefficient (ADC) value were obtained in the Globus pallidus. Liver function was also investigated via serum ammonia and liver function tests. Higher T1SI and ADC values, increased lactate and glutamine levels, and decreased myo-inositol were found in the bilateral Globus pallidus in chronic HSJ patients with PSE. No significantly abnormal serum ammonia or liver function tests were observed in chronic HSJ patients with PSE. On the basis of these findings, we propose a diagnostic procedure for PSE in chronic HSJ patients. This study reveals that MRS can be useful for diagnosing PSE in chronic HSJ patients.

Detection of liver metastasis: is diffusion-weighted imaging needed in Gd-EOB-DTPA-enhanced MR imaging for evaluation of colorectal liver metastases?

PubMed

Tajima, Taku; Akahane, Masaaki; Takao, Hidemasa; Akai, Hiroyuki; Kiryu, Shigeru; Imamura, Hiroshi; Watanabe, Yasushi; Kokudo, Norihiro; Ohtomo, Kuni

2012-10-01

We compared diagnostic ability for detecting hepatic metastases between gadolinium ethoxy benzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) on a 1.5-T system, and determined whether DWI is necessary in Gd-EOB-DTPA-enhanced MRI for diagnosing colorectal liver metastases. We assessed 29 consecutive prospectively enrolled patients with suspected metachronous colorectal liver metastases; all patients underwent surgery and had preoperative Gd-EOB-DTPA-enhanced MRI. Overall detection rate, sensitivity for detecting metastases and benign lesions, positive predictive value, and diagnostic accuracy (Az value) were compared among three image sets [unenhanced MRI (DWI set), Gd-EOB-DTPA-enhanced MRI excluding DWI (EOB set), and combined set]. Gd-EOB-DTPA-enhanced MRI yielded better overall detection rate (77.8-79.0 %) and sensitivity (87.1-89.4 %) for detecting metastases than the DWI set (55.9 % and 64.7 %, respectively) for one observer (P < 0.001). No statistically significant difference was seen between the EOB and combined sets, although several metastases were newly detected on additional DWI. Gd-EOB-DTPA-enhanced MRI yielded a better overall detection rate and higher sensitivity for detecting metastases compared with unenhanced MRI. Additional DWI may be able to reduce oversight of lesions in Gd-EOB-DTPA-enhanced 1.5-T MRI for detecting colorectal liver metastases.

An immunohistochemical study of retinol-binding protein (RBP) in livers of free-living polar bears (Ursus maritimus) from east Greenland.

PubMed

Heier, Annabelle; Sonne, Christian; Gröne, Andrea; Leifsson, Pall S; Dietz, Rune; Born, Erik W; Bacciarini, Luca N

2005-09-01

From 1999 to 2002 samples from 114 free-ranging polar bears (Ursus maritimus) were collected in the municipality of Scoresby Sound, East Greenland, to detect levels of organochlorines and potential histopathologic changes. Livers of 16 female polar bears from this group were evaluated histologically and analyzed for hepatic retinol-binding protein by immunohistochemistry. Retinol-binding protein is the main transport protein for retinol, an important vitamin A metabolite in the polar bear. Only mild pathologic changes were noted on histologic evaluation of the livers. Small lymphocytic or lymphohistiocytic infiltrates were present in all the livers. Small lipid granulomas, mild periportal fibrosis, and bile duct proliferation were found in several cases. Immunohistochemistry for retinol-binding protein of hepatic tissue from free-ranging polar bears showed no distinct difference in staining intensity by a number of criteria: age, season (fasting and nonfasting), or lactation status. The staining was diffuse to finely stippled in the cytoplasm and showed very little variation among the animals. Because of the lack of macroscopic changes and the absence of severe histologic liver lesions, these polar bears were assumed to be healthy. The diffuse cytoplasmic retinol-binding protein staining in hepatocytes of free-ranging polar bears varies markedly from the prominent granular, less intense staining of captive polar bears investigated previously.

Diagnostic Yield and Safety of Cerebellar and Brainstem Parenchymal Biopsy.

PubMed

Tobin, W Oliver; Meyer, Fredric B; Keegan, B Mark

2015-12-01

We aimed to determine the diagnostic yield and safety of posterior fossa parenchymal biopsy. One-hundred-thirty-six patients who underwent 137 posterior fossa (brainstem or cerebellar) parenchymal biopsies at Mayo Clinic (Rochester, Minnesota, USA) between 1996 and 2009 were identified by chart review. Case histories; radiologic, surgical, and pathologic reports; and safety outcomes were assessed. Posterior fossa parenchymal biopsies were performed on 78 male and 58 female patients of median age 47 years (interquartile range 28-61). Preoperative clinical diagnosis in the majority of cases was of a malignant neoplasm. Glial neoplasm (51%) was the most common finding followed by lymphoma (7%) and neurosarcoidosis (7%). Normal tissue or nonspecific changes were observed in 28 cases (20%). Three deaths occurred: 2 at the time of biopsy (1%) and 1 due to underlying disease. All deaths occurred in patients who had a cerebellar biopsy. Transient neurologic deficits occurred in 15 patients (11%): worsening of presenting symptoms (4), cardiac arrhythmia (3), vertigo (2), diplopia (2), ataxia (3), seizure (1), decreased consciousness (1), and limb numbness (3). Sustained neurologic deficits occurred in 3 patients: fourth nerve palsy (1), hemiparesis (1), and facial numbness (1). The diagnostic yield of posterior fossa parenchymal biopsy in Mayo Clinic patients with diverse pathologies was 80%. The complication rate was 11% with the majority being transient, but 2 deaths were attributed to biopsy. Evaluation of the diagnostic yield and complication rate at individual neurosurgical centers is needed to determine generalizability of these results. Copyright © 2015 Elsevier Inc. All rights reserved.

In vivo measurement of astrocytic endfoot Ca2+ and parenchymal vessel responses during 4-AP induced epilepsy using two-photon fluorescence lifetime microscopy

NASA Astrophysics Data System (ADS)

Zhang, Cong; Tabatabaei, Maryam; Bélanger, Samuel; Girouard, Hélène; Moeini, Mohammad; Lu, Xuecong; Lesage, Frédéric

2018-02-01

Neurovascular coupling (NVC) is defined as a local increase in cerebral blood flow in response to neuronal activity, it forms the basis of functional brain imaging and is altered during epilepsy. Because astrocytic calcium signaling (Ca2+) has been involved in the response of parenchymal vessels, this study investigates the role of this pathway during epilepsy. We exploit 4-Aminopyridine (4-AP) induced epileptic seizures to show that absolute Ca2+ concentration in astrocytic endfeet correlates with the changes in diameter of parenchymal vessels during neural activity in vivo. A two-photon laser scanning fluorescence lifetime microscopy was developed to simultaneously monitor free Ca2+ concentration in astrocytic endfeet with the calcium-sensitive indicator Oregon Green 488 BAPTA-1 (OGB-1) and the diameter of parenchymal vessels in the somatosensory cortex of mice following 4-AP injection. Our results reveal that the resting Ca2+ concentration in glial cells was spatially heterogeneous and that resting Ca2+ concentration in somatic regions was significantly higher than in endfoot regions. Moreover, following 4-AP injection in the somatosensory cortex of mice, we observed increases of Ca2+ in astrocytic endfeet associated with vasodilation of parenchymal vessels for each individual ictal event in the epileptic focus. However, vasodilation was seen to be inhibited by increase in absolute resting Ca2+ concentration. Our results suggest a role for baseline astrocytic Ca2+ concentration in vasodilation.

Volumetric MRI study of brain in children with intrauterine exposure to cocaine, alcohol, tobacco, and marijuana.

PubMed

Rivkin, Michael J; Davis, Peter E; Lemaster, Jennifer L; Cabral, Howard J; Warfield, Simon K; Mulkern, Robert V; Robson, Caroline D; Rose-Jacobs, Ruth; Frank, Deborah A

2008-04-01

The objective of this study was to use volumetric MRI to study brain volumes in 10- to 14-year-old children with and without intrauterine exposure to cocaine, alcohol, cigarettes, or marijuana. Volumetric MRI was performed on 35 children (mean age: 12.3 years; 14 with intrauterine exposure to cocaine, 21 with no intrauterine exposure to cocaine) to determine the effect of prenatal drug exposure on volumes of cortical gray matter; white matter; subcortical gray matter; cerebrospinal fluid; and total parenchymal volume. Head circumference was also obtained. Analyses of each individual substance were adjusted for demographic characteristics and the remaining 3 prenatal substance exposures. Regression analyses adjusted for demographic characteristics showed that children with intrauterine exposure to cocaine had lower mean cortical gray matter and total parenchymal volumes and smaller mean head circumference than comparison children. After adjustment for other prenatal exposures, these volumes remained smaller but lost statistical significance. Similar analyses conducted for prenatal ethanol exposure adjusted for demographics showed significant reduction in mean cortical gray matter; total parenchymal volumes; and head circumference, which remained smaller but lost statistical significance after adjustment for the remaining 3 exposures. Notably, prenatal cigarette exposure was associated with significant reductions in cortical gray matter and total parenchymal volumes and head circumference after adjustment for demographics that retained marginal significance after adjustment for the other 3 exposures. Finally, as the number of exposures to prenatal substances grew, cortical gray matter and total parenchymal volumes and head circumference declined significantly with smallest measures found among children exposed to all 4. CONCLUSIONS; These data suggest that intrauterine exposures to cocaine, alcohol, and cigarettes are individually related to reduced head circumference; cortical gray matter; and total parenchymal volumes as measured by MRI at school age. Adjustment for other substance exposures precludes determination of statistically significant individual substance effect on brain volume in this small sample; however, these substances may act cumulatively during gestation to exert lasting effects on brain size and volume.

Spleen magnetic resonance diffusion-weighted imaging for quantitative staging hepatic fibrosis in miniature pigs: An initial study.

PubMed

Chen, Xiao-Li; Chen, Tian-Wu; Zhang, Xiao-Ming; Li, Zhen-Lin; Li, Hang; Zeng, Nan-Lin; Tang, Hong-Jie; Pu, Yu; Chen, Nan; Yang, Qi; Li, Li; Xie, Xian-Yong; Hu, Jiani

2013-11-01

To determine whether spleen diffusion-weighted imaging (DWI) parameters might classify liver fibrosis stage. Sixteen miniature pigs were prospectively used to model liver fibrosis, and underwent spleen DWI by using b = 300, 500 and 800 s/mm(2) on 0, 5th, 9th, 16th and 21st weekend after the beginning of modeling. Signal intensity ratio of spleen to paraspinous muscles (S/M), spleen exponential apparent diffusion coefficient (eADC) and apparent diffusion coefficient (ADC) for each b-value were statistically analyzed. With increasing stages of fibrosis, S/M for all b-values showed a downward trend; and spleen eADC and ADC for b = 300 s/mm(2) showed downward and upward trends, respectively (all P < 0.05). The area under the receiver-operator curve (AUC) of spleen DWI parameters was 0.777 or more by S/M for classifying each fibrosis stage, and 0.65 or more by eADC and 0.648 or more by ADC for classifying stage ≥3 or cirrhosis. Among the spleen DWI parameters, S/M for b = 300 s/mm(2) was the best parameter in classifying stage 1 or more, 2 or more and 3 or more with AUC of 0.875, 0.851 and 0.843, respectively; and spleen eADC for b = 300 s/mm(2) was best in classifying stage 4 with an AUC of 0.988. Spleen DWI may be used to stage liver fibrosis. © 2013 The Japan Society of Hepatology.

Characterization of the anatomical structures involved in the contractile response of the rat lung periphery.

PubMed

Salerno, F G; Kurosawa, H; Eidelman, D H; Ludwig, M S

1996-06-01

1. When lung parenchymal strips are challenged with different smooth muscle agonists, the tensile and viscoelastic properties change. It is not clear, however, which of the different anatomical elements present in the parenchymal strip, i.e., small vessel, small airway or alveolar wall, contribute to the response. 2. Parenchymal lung strips from Sprague Dawley rats were suspended in an organ bath filled with Krebs solution (37 degrees C, pH = 7.4) bubbled with 95%O2/5%CO2. Resting tension (T) was set at 1.1 g and sinusoidal oscillations of 2.5% resting length (L0) at a frequency of 1 Hz were applied. Following 1 h of stress adaptation, measurements of length (L) and T were recorded under baseline conditions and after challenge with a variety of pharmacological agents, i.e., acetylcholine (ACh), noradrenaline (NA) and angiotensin II (AII). Elastance (E) and resistance (R) were calculated by fitting changes in T, L and delta L/ delta t to the equation of motion. Hysteresivity (eta, the ratio of the energy dissipated to that conserved) was obtained from the equation eta = (R/E)2 pi f. 3. In order to determine whether small airways or small vessels accounted for the responses to the different pharmacologic agents, further studies were carried out in lung explants. Excised lungs from Sprague Dawley rats were inflated with agarose. Transverse slices of lung (0.5-1.0 mm thick) were cultured overnight. By use of an inverted microscope and video camera, airway and vascular lumen area were measured with an image analysis system. 4. NA, ACh and AII constricted the parenchymal strips. Airways constricted after all agonists, vessels constricted only after All. Atropine (Atr) pre-incubation decreased the explanted airway and vessel response to AII, but no difference was found in the parenchymal strip response. 5. Preincubation with the arginine analogue N omega-nitro-L-arginine (L-NOARG) did not modify the response to ACh but mildly increased the oscillatory response to NA after co-preincubation with propranolol (Prop). 6. These results suggest that during ACh and NA challenge, small vessels do not contribute substantially to the parenchymal strip response. The discrepancy between results in airways, vessels and strips when Atr was administered prior to AII implicates a direct contractile response in the parenchymal strip.

Minimally invasive cone beam CT-guided evacuation of parenchymal and ventricular hemorrhage using the Apollo system: proof of concept in a cadaver model.

PubMed

Fiorella, David; Arthur, Adam; Schafer, Sebastian

2015-08-01

The Apollo system (Penumbra Inc, Alameda, California, USA) is a low profile irrigation-aspiration system designed for the evacuation of intracranial hemorrhage. To demonstrate the feasibility of using Apollo in combination with cone beam CT guidance. Parenchymal (n=1) and mixed parenchymal-intraventricular hematomas (n=1) were created in cadaver heads using a transvascular (n=1) or transcranial (n=1) approach. Hematomas were then imaged with cone beam CT (CB-CT), and the long axis of the hematoma defined. The CB-CT data were then used to guide transcranial access to the hematoma-defining the location of the burr hole and the path to the leading edge of the hematoma. An 8F vascular sheath was then placed under live fluoroscopic guidance into the hematoma. A second CB-CT was performed to confirm localization of the sheath. The hematoma was then demarcated on the CB-CT and the Apollo wand was introduced through the 8F sheath and irrigation-aspiration was performed under (periodic) live fluoroscopic guidance. The operators manipulated the wand within the visible boundaries of the hematoma. After irrigation-aspiration, a control CB-CT was performed to document reduction in hematoma volume. Transvascular and transcranial techniques were both successful in creating intracranial hematomas. Hematomas could be defined with conspicuity sufficient for localization and volumetric measurement using CB-CT. Live fluoroscopic guidance was effective in navigating a sheath into the leading aspect of a parenchymal hematoma and guiding irrigation-aspiration with the Apollo system. Irrigation-aspiration reduced the parenchymal hemorrhage volume from 14.8 to 1.7 cc in 189 s in the first case (parenchymal hemorrhage) and from 26.4 to 4.1 cc in 300 s in the second case (parenchymal and intraventricular hemorrhage). The cadaver model described is a useful means of studying interventional techniques for intracranial hemorrhage. It seems feasible to use CB-CT to guide the evacuation of intraparenchymal and intraventricular hemorrhage using the Apollo system through a minimally invasive transcranial access. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Changes of renal sinus fat and renal parenchymal fat during an 18-month randomized weight loss trial.

PubMed

Zelicha, Hila; Schwarzfuchs, Dan; Shelef, Ilan; Gepner, Yftach; Tsaban, Gal; Tene, Lilac; Yaskolka Meir, Anat; Bilitzky, Avital; Komy, Oded; Cohen, Noa; Bril, Nitzan; Rein, Michal; Serfaty, Dana; Kenigsbuch, Shira; Chassidim, Yoash; Sarusi, Benjamin; Thiery, Joachim; Ceglarek, Uta; Stumvoll, Michael; Blüher, Matthias; Haviv, Yosef S; Stampfer, Meir J; Rudich, Assaf; Shai, Iris

2018-08-01

Data regarding the role of kidney adiposity, its clinical implications, and its dynamics during weight-loss are sparse. We investigated the effect of long-term weight-loss induced intervention diets on dynamics of renal-sinus-fat, an ectopic fat depot, and %renal-parenchymal-fat, lipid accumulation within the renal parenchyma. We randomized 278 participants with abdominal obesity/dyslipidemia to low-fat or Mediterranean/low-carbohydrate diets, with or without exercise. We quantified renal-sinus-fat and %renal-parenchymal-fat by whole body magnetic-resonance-imaging. Participants (age = 48 years; 89% men; body-mass-index = 31 kg/m 2 ) had 86% retention to the trial after 18 months. Both increased renal-sinus-fat and %renal-parenchymal-fat were directly associated with hypertension, and with higher abdominal deep-subcutaneous-adipose-tissue and visceral-adipose-tissue (p of trend < 0.05 for all) after adjustment for body weight. Higher renal-sinus-fat was associated with lower estimated-glomerular-filtration-rate and with higher microalbuminuria and %HbA1C beyond body weight. After 18 months of intervention, overall renal-sinus-fat (-9%; p < 0.05 vs. baseline) but not %renal-parenchymal-fat (-1.7%; p = 0.13 vs. baseline) significantly decreased, and similarly across the intervention groups. Renal-sinus-fat and %renal-parenchymal-fat changes were correlated with weight-loss per-se (p < 0.05). In a model adjusted for age, sex, and visceral-adipose-tissue changes, 18 months reduction in renal-sinus-fat associated with decreased pancreatic, hepatic and cardiac fats (p < 0.05 for all) and with decreased cholesterol/high-density lipoprotein-cholesterol (HDL-c) (β = 0.13; p = 0.05), triglycerides/HDL-c (β = 0.13; p = 0.05), insulin (β = 0.12; p = 0.05) and gamma glutamyl transpeptidase (β = 0.24; p = 0.001), but not with improved renal function parameters or blood pressure. Decreased intake of sodium was associated with a reduction in %renal-parenchymal-fat, after adjustment for 18 months weight-loss (β = 0.15; p = 0.026) and hypertension (β = 0.14; p = 0.04). Renal-sinus-fat and renal-parenchymal-fat are fairly related to weight-loss. Decreased renal-sinus-fat is associated with improved hepatic parameters, independent of changes in weight or hepatic fat, rather than with improved renal function or blood pressure parameters. CLINICALTRIALS. NCT01530724. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

[Correlation between the mRNA expression of tissue inhibitor of metalloproteinase-1 and apparent diffusion coefficient on diffusion-weighted imaging in rats' liver fibrosis].

PubMed

Zhan, Yuefu; Liang, Xianwen; Han, Xiangjun; Chen, Jianqiang; Zhang, Shufang; Tan, Shun; Li, Qun; Wang, Xiong; Liu, Fan

2017-02-28

To explore the correlation between the apparent diffusion coefficient (ADC) and mRNA expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) in different stages of liver fibrosis in rats.
 Methods: A model of liver fibrosis in rats was established by intraperitoneal injection of high-fat diet combined with porcine serum. After drug administration for 4 weeks, 48 rats served as a model group and 12 rats served as a control group, then they underwent diffusion weighted imaging (DWI) scanning. The value of ADC was calculated at b value=800 s/mm2. The rats were sacrificed and carried out pathologic examination after DWI scanning immediately. The mRNA expression of TIMP-1 was detected by real time-polymerase chain reaction (RT-PCR). The rats of hepatic fibrosis were also divided into a S0 group (n=4), a S1 group (n=11), a S2 group (n=12), a S3 group (n=10), and a S4 group (n=9) according to their pathological stage. The value of ADC and the expression of TIMP-1 mRNA among the different stage groups of liver fibrosis were compared, and the correlation between ADC and the TIMP-1 mRNA were analyzed.
 Results: The ADC value and the TIMP-1 mRNA expression were significantly different between the control group and the liver fibrosis group (F=46.54 and 53.87, P<0.05). There were significant differences in the value of ADC between every two groups (all P<0.05), except the control group vs the S1 group, the S1 group vs the S2 group, and the S2 group vs the S3 group (all P>0.05). For the comparison of TIMP-1 mRNA, there was no significant difference between the S1 group and the S2 group, the S3 group and the S4 group (both P>0.05). There were significant differences among the rest of the groups (all P<0.05). Rank correlation analysis showed that there was a negative correlation between the ADC value and the TIMP-1 mRNA expression (r=-0.76, P<0.01).
 Conclusion: When the value of ADC decreases in the progress of rats' liver fibrosis, the mRNA expression of TIMP-1 increases gradually, and there is a negative correlation between them.

Joint groupwise registration and ADC estimation in the liver using a B-value weighted metric.

PubMed

Sanz-Estébanez, Santiago; Rabanillo-Viloria, Iñaki; Royuela-Del-Val, Javier; Aja-Fernández, Santiago; Alberola-López, Carlos

2018-02-01

The purpose of this work is to develop a groupwise elastic multimodal registration algorithm for robust ADC estimation in the liver on multiple breath hold diffusion weighted images. We introduce a joint formulation to simultaneously solve both the registration and the estimation problems. In order to avoid non-reliable transformations and undesirable noise amplification, we have included appropriate smoothness constraints for both problems. Our metric incorporates the ADC estimation residuals, which are inversely weighted according to the signal content in each diffusion weighted image. Results show that the joint formulation provides a statistically significant improvement in the accuracy of the ADC estimates. Reproducibility has also been measured on real data in terms of the distribution of ADC differences obtained from different b-values subsets. The proposed algorithm is able to effectively deal with both the presence of motion and the geometric distortions, increasing accuracy and reproducibility in diffusion parameters estimation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Application of ultrasound processed images in space: Quanitative assessment of diffuse affectations

NASA Astrophysics Data System (ADS)

Pérez-Poch, A.; Bru, C.; Nicolau, C.

The purpose of this study was to evaluate diffuse affectations in the liver using texture image processing techniques. Ultrasound diagnose equipments are the election of choice to be used in space environments as they are free from hazardous effects on health. However, due to the need for highly trained radiologists to assess the images, this imaging method is mainly applied on focal lesions rather than on non-focal ones. We have conducted a clinical study on 72 patients with different degrees of chronic hepatopaties and a group of control of 18 individuals. All subjects' clinical reports and results of biopsies were compared to the degree of affectation calculated by our computer system , thus validating the method. Full statistical results are given in the present paper showing a good correlation (r=0.61) between pathologist's report and analysis of the heterogenicity of the processed images from the liver. This computer system to analyze diffuse affectations may be used in-situ or via telemedicine to the ground.

Application of ultrasound processed images in space: assessing diffuse affectations

NASA Astrophysics Data System (ADS)

Pérez-Poch, A.; Bru, C.; Nicolau, C.

The purpose of this study was to evaluate diffuse affectations in the liver using texture image processing techniques. Ultrasound diagnose equipments are the election of choice to be used in space environments as they are free from hazardous effects on health. However, due to the need for highly trained radiologists to assess the images, this imaging method is mainly applied on focal lesions rather than on non-focal ones. We have conducted a clinical study on 72 patients with different degrees of chronic hepatopaties and a group of control of 18 individuals. All subjects' clinical reports and results of biopsies were compared to the degree of affectation calculated by our computer system , thus validating the method. Full statistical results are given in the present paper showing a good correlation (r=0.61) between pathologist's report and analysis of the heterogenicity of the processed images from the liver. This computer system to analyze diffuse affectations may be used in-situ or via telemedicine to the ground.

Automatic segmentation of the liver using multi-planar anatomy and deformable surface model in abdominal contrast-enhanced CT images

NASA Astrophysics Data System (ADS)

Jang, Yujin; Hong, Helen; Chung, Jin Wook; Yoon, Young Ho

2012-02-01

We propose an effective technique for the extraction of liver boundary based on multi-planar anatomy and deformable surface model in abdominal contrast-enhanced CT images. Our method is composed of four main steps. First, for extracting an optimal volume circumscribing a liver, lower and side boundaries are defined by positional information of pelvis and rib. An upper boundary is defined by separating the lungs and heart from CT images. Second, for extracting an initial liver volume, optimal liver volume is smoothed by anisotropic diffusion filtering and is segmented using adaptively selected threshold value. Third, for removing neighbor organs from initial liver volume, morphological opening and connected component labeling are applied to multiple planes. Finally, for refining the liver boundaries, deformable surface model is applied to a posterior liver surface and missing left robe in previous step. Then, probability summation map is generated by calculating regional information of the segmented liver in coronal plane, which is used for restoring the inaccurate liver boundaries. Experimental results show that our segmentation method can accurately extract liver boundaries without leakage to neighbor organs in spite of various liver shape and ambiguous boundary.

Liver imaging at 3.0 T: diffusion-induced black-blood echo-planar imaging with large anatomic volumetric coverage as an alternative for specific absorption rate-intensive echo-train spin-echo sequences: feasibility study.

PubMed

van den Bos, Indra C; Hussain, Shahid M; Krestin, Gabriel P; Wielopolski, Piotr A

2008-07-01

Institutional Review Board approval and signed informed consent were obtained by all participants for an ongoing sequence optimization project at 3.0 T. The purpose of this study was to evaluate breath-hold diffusion-induced black-blood echo-planar imaging (BBEPI) as a potential alternative for specific absorption rate (SAR)-intensive spin-echo sequences, in particular, the fast spin-echo (FSE) sequences, at 3.0 T. Fourteen healthy volunteers (seven men, seven women; mean age +/- standard deviation, 32.7 years +/- 6.8) were imaged for this purpose. Liver coverage (20 cm, z-axis) was always performed in one 25-second breath hold. Imaging parameters were varied interactively with regard to echo time, diffusion b value, and voxel size. Images were evaluated and compared with fat-suppressed T2-weighted FSE images for image quality, liver delineation, geometric distortions, fat suppression, suppression of the blood signal, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR). An optimized short- (25 msec) and long-echo (80 msec) BBEPI provided full anatomic, single breath-hold liver coverage (100 and 50 sections, respectively), with resulting voxel sizes of 3.3 x 2.7 x 2.0 mm and 3.3 x 2.7 x 4.0 mm, respectively. Repetition time was 6300 msec, matrix size was 160 x 192, and an acceleration factor of 2.00 was used. b Values of more than 20 sec/mm(2) showed better suppression of the blood signal but b values of 10 sec/mm(2) provided improved volume coverage and signal consistency. Compared with fat-suppressed T2-weighted FSE, the optimized BBEPI sequence provided (a) comparable image quality and liver delineation, (b) acceptable geometric distortions, (c) improved suppression of fat and blood signals, and (d) high CNR and SNR. BBEPI is feasible for fast, low-SAR, thin-section morphologic imaging of the entire liver in a single breath hold at 3.0 T. (c) RSNA, 2008.

Reactive Oxygen Species-Induced TXNIP Drives Fructose-Mediated Hepatic Inflammation and Lipid Accumulation Through NLRP3 Inflammasome Activation

PubMed Central

Zhang, Xian; Zhang, Jian-Hua; Chen, Xu-Yang; Hu, Qing-Hua; Wang, Ming-Xing; Jin, Rui; Zhang, Qing-Yu; Wang, Wei; Wang, Rong; Kang, Lin-Lin; Li, Jin-Sheng; Li, Meng

2015-01-01

Abstract Aims: Increased fructose consumption predisposes the liver to nonalcoholic fatty liver disease (NAFLD), but the mechanisms are elusive. Thioredoxin-interacting protein (TXNIP) links oxidative stress to NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation and this signaling axis may be involved in fructose-induced NAFLD. Here, we explore the role of reactive oxygen species (ROS)-induced TXNIP overexpression in fructose-mediated hepatic NLRP3 inflammasome activation, inflammation, and lipid accumulation. Results: Rats were fed a 10% fructose diet for 8 weeks and treated with allopurinol and quercetin during the last 4 weeks. Five millimolars of fructose-exposed hepatocytes (primary rat hepatocytes, rat hepatic parenchymal cells [RHPCs], HLO2, HepG2) were co-incubated with antioxidants or caspase-1 inhibitor or subjected to TXNIP or NLRP3 siRNA interference. Fructose induced NLRP3 inflammasome activation and pro-inflammatory cytokine secretion, janus-activated kinase 2/signal transducers and activators of transcription 3-mediated inflammatory signaling, and expression alteration of lipid metabolism-related genes in cultured hepatocytes and rat livers. NLRP3 silencing and caspase-1 suppression blocked these effects in primary rat hepatocytes and RHPCs, confirming that inflammasome activation alters hepatocyte lipid metabolism. Hepatocellular ROS and TXNIP were increased in animal and cell models. TXNIP silencing blocked NLRP3 inflammasome activation, inflammation, and lipid metabolism perturbations but not ROS induction in fructose-exposed hepatocytes, whereas antioxidants addition abrogated TXNIP induction and diminished the detrimental effects in fructose-exposed hepatocytes and rat livers. Innovation and Conclusions: This study provides a novel mechanism for fructose-induced NAFLD pathogenesis by which the ROS-TXNIP pathway mediates hepatocellular NLRP3 inflammasome activation, inflammation and lipid accumulation. Antioxidant-based interventions can inhibit the ROS-TXNIP pathway. Antioxid. Redox Signal. 22, 848–870. PMID:25602171

Mechanical ventilation drives pneumococcal pneumonia into lung injury and sepsis in mice: protection by adrenomedullin.

PubMed

Müller-Redetzky, Holger C; Will, Daniel; Hellwig, Katharina; Kummer, Wolfgang; Tschernig, Thomas; Pfeil, Uwe; Paddenberg, Renate; Menger, Michael D; Kershaw, Olivia; Gruber, Achim D; Weissmann, Norbert; Hippenstiel, Stefan; Suttorp, Norbert; Witzenrath, Martin

2014-04-14

Ventilator-induced lung injury (VILI) contributes to morbidity and mortality in acute respiratory distress syndrome (ARDS). Particularly pre-injured lungs are susceptible to VILI despite protective ventilation. In a previous study, the endogenous peptide adrenomedullin (AM) protected murine lungs from VILI. We hypothesized that mechanical ventilation (MV) contributes to lung injury and sepsis in pneumonia, and that AM may reduce lung injury and multiple organ failure in ventilated mice with pneumococcal pneumonia. We analyzed in mice the impact of MV in established pneumonia on lung injury, inflammation, bacterial burden, hemodynamics and extrapulmonary organ injury, and assessed the therapeutic potential of AM by starting treatment at intubation. In pneumococcal pneumonia, MV increased lung permeability, and worsened lung mechanics and oxygenation failure. MV dramatically increased lung and blood cytokines but not lung leukocyte counts in pneumonia. MV induced systemic leukocytopenia and liver, gut and kidney injury in mice with pneumonia. Lung and blood bacterial burden was not affected by MV pneumonia and MV increased lung AM expression, whereas receptor activity modifying protein (RAMP) 1-3 expression was increased in pneumonia and reduced by MV. Infusion of AM protected against MV-induced lung injury (66% reduction of pulmonary permeability p < 0.01; prevention of pulmonary restriction) and against VILI-induced liver and gut injury in pneumonia (91% reduction of AST levels p < 0.05, 96% reduction of alanine aminotransaminase (ALT) levels p < 0.05, abrogation of histopathological changes and parenchymal apoptosis in liver and gut). MV paved the way for the progression of pneumonia towards ARDS and sepsis by aggravating lung injury and systemic hyperinflammation leading to liver, kidney and gut injury. AM may be a promising therapeutic option to protect against development of lung injury, sepsis and extrapulmonary organ injury in mechanically ventilated individuals with severe pneumonia.

Trichloroethylene Exposure Reduces Liver Injury in a Mouse Model of Primary Biliary Cholangitis.

PubMed

Ray, Jessica L; Kopec, Anna K; Joshi, Nikita; Cline-Fedewa, Holly; Lash, Lawrence H; Williams, Kurt J; Leung, Patrick S; Gershwin, M Eric; Luyendyk, James P

2017-04-01

Trichloroethylene (TCE) is a persistent environmental contaminant proposed to contribute to autoimmune disease. Experimental studies in lupus-prone MRL+/+ mice have suggested that TCE exposure can trigger autoimmune hepatitis. The vast majority of studies examining the connection between TCE and autoimmunity utilize this model, and the impact of TCE exposure in other established models of autoimmune liver disease is not known. We tested the hypothesis that TCE exposure exacerbates experimental hepatic autoimmunity in dominant negative transforming growth factor beta receptor type II (dnTGFBRII) mice, which develop serological and histological features resembling human primary biliary cholangitis. Female 8-week-old wild-type and dnTGFBRII mice were exposed to TCE (0.5 mg/ml) or vehicle (1% ethoxylated castor oil) in the drinking water for 12 or 22 weeks. Liver histopathology in 20- and 30-week-old wild-type mice was unremarkable irrespective of treatment. Mild portal inflammation was observed in vehicle-exposed 20-week-old dnTGFBRII mice and was not exacerbated by TCE exposure. Vehicle-exposed 30-week-old dnTGFBRII mice developed anti-mitochondrial antibodies, marked hepatic inflammation with necrosis, and hepatic accumulation of both B and T lymphocytes. To our surprise, TCE exposure dramatically reduced hepatic parenchymal inflammation and injury in 30-week-old dnTGFBRII mice, reflected by changes in hepatic proinflammatory gene expression, serum chemistry, and histopathology. Interestingly, TCE did not affect hepatic B cell accumulation or induction of the anti-inflammatory cytokine IL10. These data indicate that TCE exposure reduces autoimmune liver injury in female dnTGFBRII mice and suggests that the precise effect of environmental chemicals in autoimmunity depends on the experimental model. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Analysis of soluble factors in conditioned media derived from primary cultures of cirrhotic liver of biliary atresia.

PubMed

Yamazaki, Taisuke; Wakai, Mariko; Enosawa, Shin; Tokiwa, Takayoshi

2017-06-01

Biliary atresia (BA) is a rare and serious liver disease in newborn infants. Previously, we reported that non-parenchymal cell (NPC) fractions from cirrhotic liver of BA may contain hepatic stem/progenitor cells in primary culture of NPC fractions. In this study, NPC fractions were subjected to primary or passage culture and found that clusters of hepatocyte-like cells appear even without adding hepatocyte growth factor (HGF) to the culture medium, but not in their passage culture used as a control. Based on these findings, conditioned media (CMs) were collected and soluble factors in the CMs were analyzed in order to elucidate the mechanism of the appearance of hepatocyte-like cells or their clusters. A large amount of active HGF consisting of α and β chains was detected in CMs derived from primary culture, but not in CMs from passage culture, as determined by western blot analysis, bone morphogenetic protein (BMP)-4, oncostatin M (OSM), and transforming growth factor (TGF)-β1 were not detected in any of the CMs. The number of hepatocyte-like cells in primary culture tended to decrease following treatment with the HGF receptor c-Met inhibitor, SU11274 in a dose-dependent manner. Furthermore, the clusters of hepatocyte-like cells tended to increase in size and number when freshly isolated NPC fractions were cultured in the presence of 10% of CMs collected after 3-4 wk of primary culture. In conclusion, these findings indicate that CMs derived from primary culture of NPC fractions of BA liver contain a large amount of active HGF, which may activate hepatic stem/progenitor cells and promote the appearance of hepatocyte-like cells or their clusters through HGF/c-Met signaling. The present study would lead to cell therapy using the patient's own cells for the treatment of BA.

Histopathology Image Analysis in Two Long-Term Animal Experiments with Helical Flow Total Artificial Heart.

PubMed

Wotke, Jiri; Homolka, Pavel; Vasku, Jaromír; Dobsak, Petr; Palanova, Petra; Mrkvicova, Veronika; Konecny, Petr; Soska, Vladimir; Pohanka, Michal; Novakova, Marie; Yurimoto, Terumi; Saito, Itsuro; Inoue, Yusuke; Isoyama, Takashi; Abe, Yusuke

2016-12-01

Histopathological analysis can provide important information in long-term experiments with total artificial heart (TAH). Recently, a new type of blood pump, the helical flow total artificial heart (HF-TAH) was developed. This study aimed to investigate the changes in selected vital organs in animal experiments with implanted HF-TAH. Samples from lung, liver, and kidneys from two female goats (No. 1301 and No. 1304) with implanted HF-TAH were analyzed. Tissue samples were fixed in 10% formaldehyde and 4 µm thick transverse sections were stained with hematoxylin-eosin (HE). Additional staining was done for detection of connective tissue (Masson-Goldner stain) and for detection of iron (hemosiderin) deposits (Perls stain). Sections were scanned at 100× and 500× magnification with a light microscope. Experiment no. 1301 survived 100 days (cause of termination was heavy damage of the right pump); experimental goat no.1304 survived 68 days and was sacrificed due to severe right hydrodynamic bearing malfunction. Histopathological analysis of liver samples proved signs of chronic venostasis with limited focal necrotic zones. Dilated tubules, proteinaceous material in tubular lumen, and hemosiderin deposits were detected in kidney samples. Contamination of the organs by embolized micro-particles was suspected at the autopsy after discovery of visible damage (scratches) of the pump impeller surface (made from titanium alloy) in both experiments. Sporadic deposits of foreign micro-particles (presumably titanium) were observed in most of the analyzed parenchymal organs. However, the described deposits were not in direct connection with inflammatory reactions in the analyzed tissues. Histopathological analysis showed the presence of minimal contamination of the lung, kidney, and liver tissue samples by foreign material (titanium very likely). The analysis showed only limited pathological changes, especially in liver and kidneys, which might be attributed to the influence of artificial perfusion often observed in chronic TAH experiments. © 2016 Wiley Periodicals, Inc. and International Center for Artificial Organs and Transplantation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meyer, Jeremy, E-mail: jeremy.meyer@hcuge.ch; Unit of Surgical Research, University of Geneva, Rue Michel-Servet 1, 1206 Genève; Lacotte, Stéphanie, E-mail: stephanie.lacotte@unige.ch

The objective of the present study was to develop an accurate and reproducible method for liver sinusoidal endothelial cell (LSEC) isolation in mice. Non-parenchymal cells were isolated using a modified two-step collagenase digestion combined with Optiprep density gradient centrifugation. LSEC were further purified using two prevalent methods, short-term selective adherence and CD146+ magnetic-activated cell sorting (MACS), and compared in terms of cell yield, viability and purity to our purification technique using CD11b cell depletion combined with long-term selective adherence. LSEC purification using our technique allowed to obtain 7.07±3.80 million LSEC per liver, while CD146+ MACS and short-term selective adherence yieldedmore » 2.94±1.28 and 0.99±0.66 million LSEC, respectively. Purity of the final cell preparation reached 95.10±2.58% when using our method. In contrast, CD146+ MACS and short-term selective adherence gave purities of 86.75±3.26% and 47.95±9.82%, respectively. Similarly, contamination by non-LSEC was the lowest when purification was performed using our technique, with a proportion of contaminating macrophages of only 1.87±0.77%. Further, isolated cells analysed by scanning electron microscopy presented typical LSEC fenestrations organized in sieve plates, demonstrating that the technique allowed to isolate bona fide LSEC. In conclusion, we described a reliable and reproducible technique for the isolation of high yields of pure LSEC in mice. This protocol provides an efficient method to prepare LSEC for studying their biological functions. - Highlights: • This protocol provides an efficient method to prepare primary mouse LSEC for studying their biological functions. • The liver cell dispersion step was improved by performing a retrograde cannulation of the liver. • The cell yield and the purity obtained were higher than comparative techniques in mice. • Contaminating macrophages were removed by introducing a CD11b- magnetic –activated cell sorting step.« less

Blueberry Husks and Probiotics Attenuate Colorectal Inflammation and Oncogenesis, and Liver Injuries in Rats Exposed to Cycling DSS-Treatment

PubMed Central

Håkansson, Åsa; Bränning, Camilla; Molin, Göran; Adawi, Diya; Hagslätt, Marie-Louise; Jeppsson, Bengt; Nyman, Margareta; Ahrné, Siv

2012-01-01

Long-term colonic inflammation promotes carcinogenesis and histological abnormalities of the liver, and colorectal tumours frequently arise in a background of dysplasia, a precursor of adenomas. Altered colonic microbiota with an increased proportion of bacteria with pro-inflammatory characteristics, have been implicated in neoplastic progression. The composition of the microbiota can be modified by dietary components such as probiotics, polyphenols and dietary fibres. In the present study, the influence of probiotics in combination with blueberry husks on colorectal carcinogenesis and subsequent liver damage was evaluated. Colorectal tumours were induced in rats by cyclic treatment with dextran sulphate sodium (DSS). Blueberry husks and a mixture of three probiotic strains (Bifidobacterium infantis DSM 15159, Lactobacillus gasseri, DSM 16737 and Lactobacillus plantarum DSM 15313) supplemented a basic diet fortified with oats. The condition of the rats was monitored using a disease activity index (DAI). A qualitative and quantitative histological judgement was performed on segments of distal colon and rectum and the caudate lobe of the liver. The formation of short-chain fatty acids, bacterial translocation, the inflammatory reaction and viable count of lactobacilli and Enterobaceriaceae were addressed. Blueberry husks with or without probiotics significantly decreased DAI, and significantly reduced the number of colonic ulcers and dysplastic lesions. With a decreased proportion of blueberry husk in the diet, the probiotic supplement was needed to achieve a significant decrease in numbers of dysplastic lesions. Probiotics decreased faecal viable count of Enterobacteriaceae and increased that of lactobacilli. Blueberry husks with or without probiotics lowered the proportion of butyric acid in distal colon, and decreased the haptoglobin levels. Probiotics mitigated hepatic injuries by decreasing parenchymal infiltration and the incidence of stasis and translocation. The results demonstrate a dietary option for use of blueberry husks and probiotics to delay colonic carcinogenesis and hepatic injuries in the rat model. PMID:22457771

In vivo tumor identification of colorectal liver metastases with diffuse reflectance and fluorescence spectroscopy.

PubMed

Tanis, Erik; Evers, Danny J; Spliethoff, Jarich W; Pully, Vishnu V; Kuhlmann, Koert; van Coevorden, Frits; Hendriks, Benno H W; Sanders, Joyce; Prevoo, Warner; Ruers, Theo J M

2016-11-01

Over the last decade, an increasing effort has been put towards the implementation of optical guidance techniques to aid surgeons during cancer surgery. Diffuse reflectance spectroscopy (DRS) and fluorescence spectroscopy (FS) are two of these new techniques. The objective of this study is to investigate whether in vivo optical spectroscopy is able to accurately discriminate colorectal liver metastases (CRLM) from normal liver tissue in vivo. DRS and FS were incorporated at the tip of a needle and were used for in vivo tissue differentiation during resection of CRLM. Measurements were taken in and around the tumor lesions and measurement sites were marked and correlated to histology (i.e., normal liver tissue or tumor tissue). Patients with and without neoadjuvant systemic chemotherapy were included into the study. Four hundred and eighty-four measurements were taken in and near 19 liver lesions prior to resection. Overall sensitivity and specificity for DRS was 95% and 92%, respectively. Bile was the most discriminative parameter. The addition of FS did not improve the overall accuracy. Sensitivity and specificity was not hampered by neo-adjuvant chemotherapy; sensitivity and specificity after neo-adjuvant chemotherapy were 92% and 100%, respectively. We have successfully integrated spectroscopy technology into a disposable 15 Gauge optical needle and we have shown that DRS and FS can accurately discriminate CRLM from normal liver tissue in the in vivo setting regardless of whether the patient was pre-treated with systemic therapy. This technique makes in vivo guidance accessible for common surgical practice. Lasers Surg. Med. 48:820-827, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Adrenohepatic fusion: Adhesion or invasion in primary virilizant giant adrenal carcinoma? Implications for surgical resection. Two case report and review of the literature.

PubMed

Alastrué Vidal, Antonio; Navinés López, Jordi; Julián Ibáñez, Juan Francisco; De la Ossa Merlano, Napoleón; Botey Fernandez, Mireia; Sampere Moragues, Jaume; Sánchez Torres, Maria Del Carmen; Barluenga Torres, Eva; Fernández-Llamazares Rodríguez, Jaime

2016-01-01

Adrenohepatic fusion means union between the adrenal gland and the liver, intermingling its parenchymas. It is not possible to identify this condition by image tests. Its presence implies radical and multidisciplinar approach. We report two female cases of 45 and 50 years old with clinical virilization and palpable mass on the abdominal right upper quadrant corresponding to adrenocortical carcinoma with hepatic fusion. The contrast-enhanced tomography showed an indistinguishable mass involving the liver and the right adrenal gland. In the first case, the patient had a two-time operation, the former removing only the adrenal carcinoma, and the second performing a radical surgery after an early relapse. In the second case, a radical right en bloc adrenohepatectomy was performed. Both cases were pathologically reported as liver-infiltrating adrenal carcinoma. Only in the second case the surgery was radical effective as first intention to treat, with 3 years of disease-free survival. ACC is a rare entity with poor prognosis. The major indicators of malignancy are tumour diameter over 6cm, local invasion or metastasis, secretion of corticosteroids, virilization and hypertension and hypokalaemia. The parenchymal fusion of the adrenal cortical layer can be misdiagnosed as hepatocellular carcinoma with adhesion with the Glisson capsule. AHF in such cases may be misinterpreted during surgery, what may impair its resectability, and therefore the survival. The surgical treatment must be performed en bloc, often using liver vascular control. Postoperative treatment must be offered immediately after surgery. We report two consecutive rare cases of adrenohepatic fusion in giant right adrenocortical carcinoma, not detectable by imaging, what has important implications for the surgical decision-making. As radical surgery is the best choice to offer a curative treatment, it has to be performed by a multidisciplinary well-assembled team, counting with endocrine and liver surgeons, and transplant surgeons in case of vena cava involvement, in order to maximize the disease-free survival. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Quantitative assessment of the hepatic metabolic volume product in patients with diffuse hepatic steatosis and normal controls through use of FDG-PET and MR imaging: a novel concept.

PubMed

Bural, Gonca G; Torigian, Drew A; Burke, Anne; Houseni, Mohamed; Alkhawaldeh, Khaled; Cucchiara, Andrew; Basu, Sandip; Alavi, Abass

2010-06-01

The aim of this study was to compare hepatic standardized uptake values (SUVs) and hepatic metabolic volumetric products (HMVP) between patients of diffuse hepatic steatosis and control subjects with normal livers. Twenty-seven subjects were included in the study (13 men and 14 women; age range, 34-72 years). All had 18F-2-fluoro-2-D-deoxyglucose-positron emission tomography (FDG-PET) and magnetic resonance imaging (MRI) scans with an interscan interval of 0-5 months. Twelve of 27 subjects had diffuse hepatic steatosis on MRI. The remaining 15 were selected as age-matched controls based on normal liver parenchyma on MRI. Mean and maximum hepatic SUVs were calculated for both patient groups on FDG-PET images. Hepatic volumes were measured from MRI. HMVP in each subject was subsequently calculated by multiplication of hepatic volume by mean hepatic SUV. HMVPs as well as mean and maximum hepatic SUVs were compared between the two study groups. HMVPs, mean hepatic SUVs, and maximum hepatic SUVs were greater (statistically significant, p < 0.05) in subjects with diffuse hepatic steatosis compared to those in the control group. The increase in HMVP is the result of increased hepatic metabolic activity likely related to the diffuse hepatic steatosis. The active inflammatory process related to the diffuse hepatic steatosis is the probable explanation for the increase in hepatic metabolic activity on FDG-PET study.

Expression patterns of STAT3, ERK and estrogen-receptor α are associated with development and histologic severity of hepatic steatosis: a retrospective study.

PubMed

Choi, Euno; Kim, Won; Joo, Sae Kyung; Park, Sunyoung; Park, Jeong Hwan; Kang, Yun Kyung; Jin, So-Young; Chang, Mee Soo

2018-04-03

Hepatic steatosis renders hepatocytes vulnerable to injury, resulting in the progression of preexisting liver disease. Previous animal and cell culture studies implicated mammalian target of rapamycin (mTOR), signal transducer and activator of transcription-3 (STAT3), extracellular signal-regulated kinase (ERK) and estrogen-receptor α in the pathogenesis of hepatic steatosis and disease progression. However, to date there have been few studies performed using human liver tissue to study hepatic steatosis. We examined the expression patterns of mTOR, STAT3, ERK and estrogen-receptor α in liver tissues from patients diagnosed with hepatic steatosis. We reviewed the clinical and histomorphological features of 29 patients diagnosed with hepatic steatosis: 18 with non-alcoholic fatty liver disease (NAFLD), 11 with alcoholic fatty acid disease (AFLD), and a control group (16 biliary cysts and 22 hepatolithiasis). Immunohistochemistry was performed on liver tissue using an automated immunostainer. The histologic severity of hepatic steatosis was evaluated by assessing four key histomorphologic parameters common to NAFLD and AFLD: steatosis, lobular inflammation, ballooning degeneration and fibrosis. mTOR, phosphorylated STAT3, phosphorylated pERK, estrogen-receptor α were found to be more frequently expressed in the hepatic steatosis group than in the control group. Specifically, mTOR was expressed in 78% of hepatocytes, and ERK in 100% of hepatic stellate cells, respectively, in patients with NAFLD. Interestingly, estrogen-receptor α was diffusely expressed in hepatocytes in all NALFD cases. Phosphorylated (active) STAT3 was expressed in 73% of hepatocytes and 45% of hepatic stellate cells in patients with AFLD, and phosphorylated (active) ERK was expressed in hepatic stellate cells in all AFLD cases. Estrogen-receptor α was expressed in all AFLD cases (focally in 64% of AFLD cases, and diffusely in 36%). Phosphorylated STAT3 expression in hepatocytes and hepatic stellate cells correlated with severe lobular inflammation, severe ballooning degeneration and advanced fibrosis, whereas diffusely expressed estrogen-receptor α correlated with a mild stage of fibrosis. Our data indicate ERK activation and estrogen-receptor α may be relevant in the development of hepatic steatosis. However, diffuse expression of estrogen-receptor α would appear to impede disease progression, including hepatic fibrosis. Finally, phosphorylated STAT3 may also contribute to disease progression.

Basic investigation on acoustic velocity change imaging method for quantitative assessment of fat content in human liver

NASA Astrophysics Data System (ADS)

Mano, Kazune; Tanigawa, Shohei; Hori, Makoto; Yokota, Daiki; Wada, Kenji; Matsunaka, Toshiyuki; Morikawa, Hiroyasu; Horinaka, Hiromichi

2016-07-01

Fatty liver is a disease caused by the excess accumulation of fat in the human liver. The early diagnosis of fatty liver is very important, because fatty liver is the major marker linked to metabolic syndrome. We already proposed the ultrasonic velocity change imaging method to diagnose fatty liver by using the fact that the temperature dependence of ultrasonic velocity is different in water and in fat. For the diagonosis of a fatty liver stage, we attempted a feasibility study of the quantitative assessment of the fat content in the human liver using our ultrasonic velocity change imaging method. Experimental results showed that the fat content in the tissue mimic phantom containing lard was determined by its ultrasonic velocity change in the flat temperature region formed by a circular warming ultrasonic transducer with an acoustic lens having an appropriate focal length. By considering the results of our simulation using a thermal diffusion equation, we determined whether this method could be applied to fatty liver assessment under the condition that the tissue had the thermal relaxation effect caused by blood flow.

Factors predicting non-alcoholic steatohepatitis (NASH) and advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD).

PubMed

Tasneem, Abbas Ali; Luck, Nasir Hassan; Majid, Zain

2018-04-01

Introduction To determine the factors predicting non-alcoholic steatohepatitis (NASH) and advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Methodology All patients aged >18 years and having a fatty liver on abdominal ultrasound (US), presenting from January 2011 to January 2017, were included. A liver biopsy was performed on all the patients. Results Of 96 patients undergoing liver biopsy for non-alcoholic fatty liver disease (NAFLD), 76 (79.2%) were men. On liver US, diffuse fatty liver (DFL) was noted in 68 (70.8%) patients. Liver biopsy showed non-alcoholic steatohepatitis (NASH) in 78 (81.3%) patients. Factors associated with NASH were male gender, body mass index (BMI) > 27 kg/m 2 , DFL and raised alanine aminotransferase (ALT). A GULAB score (based on gender, US liver findings, lipid (fasting) levels, ALT level and BMI) of ≥5 predicted NASH with 82.05% sensitivity. Factors associated with advanced fibrosis in NAFLD were age >40 years, diabetes mellitus, AST/ALT ratio > 1 and raised GGT. Conclusion NASH is common in patients with male gender, high BMI, DFL on liver US, raised ALT and GULAB score ≥5.

Histopathological and biochemical assessment of d-limonene-induced liver injury in rats.

PubMed

Ramos, Carlos Alberto F; Sá, Rita de Cássia da S; Alves, Mateus F; Benedito, Rubens B; de Sousa, Damião P; Diniz, Margareth de Fátima F M; Araújo, Maria Salete T; de Almeida, Reinaldo N

2015-01-01

The aim of the present work was to develop a biochemical, histologic and immunohistochemical study about the potential hepatotoxic effect of d-limonene - a component of volatile oils extracted from citrus plants. Blood alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) from d-limonene-treated animals were determined and compared to morphologic hepatic lesions in order to investigate the possible physiopathologic mechanisms involved in the liver toxicity, in experimental animals treated with d-limonene. Wistar rats were randomly divided into seven groups: two control groups (untreated or receiving only vehicle, tween-80); one positive control (vehicle); two experimental groups treated with d-limonene at doses of 25 mg/kg/day and 75 mg/kg/day for 45 days, and two other groups treated with the same doses for 30 days and kept under observation during 30 more days. Biochemical data showed significant reduction in ALT levels in the animals treated with 75 mg/kg of d-limonene. Histological analysis revealed some hepatocyte morphological lesions, including hydropic degeneration, microvesicular steatosis and necrosis, Kupffer cell hyperplasia and incipient fibrosis. By immunohistochemistry, influx of T (CD3+) and cytotoxic (CD8+) lymphocytes was observed in the rats treated with d-limonene at both dose levels. In conclusion, it is possible that d-limonene has been directly responsible for hepatic parenchymal and matrix damage following subchronic treatment with d-limonene.

Differential toxic effects of azathioprine, 6-mercaptopurine and 6-thioguanine on human hepatocytes.

PubMed

Petit, Elise; Langouet, Sophie; Akhdar, Hanane; Nicolas-Nicolaz, Christophe; Guillouzo, André; Morel, Fabrice

2008-04-01

Thiopurines (azathioprine, 6-mercaptopurine and 6-thioguanine) are therapeutic compounds widely administered in the clinic for their multiple uses (autoimmune diseases, post-transplant immunosuppression and cancer). Despite these advantages, their therapeutic potential is limited by occasional adverse effects (myelotoxicity and hepatotoxicity) and by a relatively frequent lack of efficacy. Previous studies have demonstrated that azathioprine decreased the viability of rat hepatocytes. In order to investigate cytotoxic effects of thiopurines in human liver, we used primary human hepatocytes and a highly differentiated human hepatoma cell line, HepaRG, treated or not with azathioprine, 6-mercaptopurine and 6-thioguanine. In parallel, expression of the genes involved in the metabolism of thiopurines, glutathione synthesis and antioxidant defences was measured by quantitative PCR. We clearly demonstrate that human liver parenchymal cells were much less sensitive than rat hepatocytes to thiopurine treatments. The toxic effects appeared after 96 h of treatment while ATP depletion was observed after a 24 h incubation with azathioprine and 6-mercaptopurine. Toxic effects were more pronounced for azathioprine and 6-mercaptopurine, when compared to 6-thioguanine, and might explain glutathione synthesis and antioxidant enzyme induction only by these two drugs. Finally, we also demonstrate for the first time an up-regulation by azathioprine and 6-mercaptopurine of inosine monophosphate dehydrogenase which might have consequences on the de novo biosynthesis of guanine nucleotides and thiopurines metabolism.

Evaluation of stapler hepatectomy during a laparoscopic liver resection

PubMed Central

Buell, Joseph F; Gayet, Brice; Han, Ho-Seong; Wakabayashi, Go; Kim, Ki-Hun; Belli, Giulio; Cannon, Robert; Saggi, Bob; Keneko, Hiro; Koffron, Alan; Brock, Guy; Dagher, Ibrahim

2013-01-01

Methods An international database of 1499 laparoscopic liver resections was analysed using multivariate and Kaplan–Meier analysis. Results In total, 764 stapler hepatectomies (SH) were compared with 735 electrosurgical resections (ER). SH was employed in larger tumours (4.5 versus 3.8 cm; P < 0.003) with decreased operative times (2.6 versus 3.1 h; P < 0.001), blood loss (100 versus 200 cc; P < 0.001) and length of stay (3.0 versus 7.0 days; P < 0.001). SH incurred a trend towards higher complications (16% versus 13%; P = 0.057) including bile leaks (26/764, 3.4% versus 16/735, 2.2%: P = 0.091). To address group homogeneity, a subset analysis of lobar resections confirmed the benefits of SH. Kaplan–Meier analysis in non-cirrhotic and cirrhotic patients confirmed equivalent patient (P = 0.290 and 0.118) and disease-free survival (P = 0.120 and 0.268). Multivariate analysis confirmed the parenchymal transection technique did not increase the risk of cancer recurrence, whereas tumour size, the presence of cirrhosis and concomitant operations did. Conclusions A SH provides several advantages including: diminished blood loss, transfusion requirements and shorter operative times. In spite of the smaller surgical margins in the SH group, equivalent recurrence and survival rates were observed when matched for parenchyma and extent of resection. PMID:23458439

Idiopathic portal hypertension and extrahepatic portal venous obstruction.

PubMed

Khanna, Rajeev; Sarin, Shiv Kumar

2018-02-01

Idiopathic portal hypertension (IPH) and extrahepatic portal venous obstruction (EHPVO) are non-cirrhotic vascular causes of portal hypertension (PHT). Variceal bleed and splenomegaly are the commonest presentations. The present review is intended to provide the existing literature on etiopathogenesis, clinical profile, diagnosis, natural history and management of IPH and EHPVO. IPH and EHPVO are both characterized by normal hepatic venous pressure gradient, moderate to massive splenomegaly with preserved liver synthetic functions. While the level of block in IPH is presinusoidal, in EHPVO it is at prehepatic level. Infections, autoimmunity, drugs, immunodeficiency and prothrombotic states are possible etiological agents in IPH. Contrastingly in EHPVO, prothrombotic disorders and local factors around the portal vein are the incriminating factors. Diagnosis is often clinical, supported by simple radiological tools. Natural history is defined by episodes of variceal bleed and symptoms related to enlarged spleen. Growth failure, portal biliopathy and minimal hepatic encephalopathy are additional concerns in EHPVO. Long-term survival is reasonably good with endoscopic surveillance; however, parenchymal extinction leading to decompensation is seen in a minority of patients in both the disorders. Surgical shunts revert the complications secondary to PHT. Meso-Rex shunt has become the standard surgery in children with EHPVO. This review gives a detailed summary of these two vascular conditions of liver-IPH and EHPVO. Further research is needed to understand the pathogenesis and natural history of these disorders.

Dietary cancer risk from conditional cancerogens in produce of livestock fed on species of spurge (Euphorbiaceae). II. Pathophysiological investigations in lactating goats fed on the skin irritant herb Euphorbia peplus and in their milk-raised kids.

PubMed

Nawito, M; Ahmed, Y F; Zayed, S M; Hecker, E

1998-01-01

Lactating goats were fed on aerial parts of the herb Euphorbia peplus L. admixed with their usual green fodder. During the experimental feeding period they showed symptoms of general poisoning. In necropsy the main toxic effects were seen in the heart, lung and liver. Histopathological examinations revealed that the primary toxic effects originated from degenerative changes in parenchymal and endothelial cells. Adverse symptoms in the liver and kidney were also reflected in an alteration of the levels of certain serum enzymes and of blood urea nitrogen. The milk of the goats fed on E. peplus, consumed by their young kids, caused poisoning and even death, with signs similar to those observed in the adult dams. These observations support the hypothesis that the poisoning observed in both milk-raised kids and mother goats is caused by diterpene ester type toxins present in the aerial parts of the herb contaminating the dams fodder. Generally, such skin irritant and hyperplasiogenic toxins are known to be highly active tumour promoters of skin and other organ, e.g. in mice. Lactating goats--as an important source of milk around the world--in a setting similar to that described, may provide a valid experimental etiological model for investigation of food polluted by tumour-promoting diterpene ester toxins.

Ultrasound imaging in an experimental model of fatty liver disease and cirrhosis in rats

PubMed Central

2010-01-01

Background Domestic dogs and cats are very well known to develop chronic hepatic diseases, including hepatic lipidosis and cirrhosis. Ultrasonographic examination is extensively used to detect them. However, there are still few reports on the use of the ultrasound B-mode scan in correlation with histological findings to evaluate diffuse hepatic changes in rodents, which represent the most important animal group used in experimental models of liver diseases. The purpose of this study was to determine the reliability of ultrasound findings in the assessment of fatty liver disease and cirrhosis when compared to histological results in Wistar rats by following up a murine model of chronic hepatic disease. Results Forty Wistar rats (30 treated, 10 controls) were included. Liver injury was induced by dual exposure to CCl4 and ethanol for 4, 8 and 15 weeks. Liver echogenicity, its correlation to the right renal cortex echogenicity, measurement of portal vein diameter (PVD) and the presence of ascites were evaluated and compared to histological findings of hepatic steatosis and cirrhosis. Liver echogenicity correlated to hepatic steatosis when it was greater or equal to the right renal cortex echogenicity, with a sensitivity of 90%, specificity of 100%, positive and negative predictive values of 100% and 76.9% respectively, and accuracy of 92.5%. Findings of heterogeneous liver echogenicity and irregular surface correlated to liver cirrhosis with a sensitivity of 70.6%, specificity of 100%, positive and negative predictive values of 100% and 82.1% respectively, and accuracy of 87.5%. PVD was significantly increased in both steatotic and cirrhotic rats; however, the later had greater diameters. PVD cut-off point separating steatosis from cirrhosis was 2.1 mm (sensitivity of 100% and specificity of 90.5%). One third of cirrhotic rats presented with ascites. Conclusion The use of ultrasound imaging in the follow-up of murine diffuse liver disease models is feasible and efficient, especially when the studied parameters are used in combination. The potential implication of this study is to provide a non-invasive method that allows follow-up studies of fatty liver disease and cirrhosis of individual rats for pre-clinical drug or cell based therapies. PMID:20113491

Hilar Parenchymal Oversew: a novel technique for robotic partial nephrectomy hilar tumor renorrhaphy.

PubMed

Chavali, Jaya Sai S; Nelson, Ryan; Maurice, Matthew J; Kara, Onder; Mouracade, Pascal; Dagenais, Julien; Reese, Jeremy; Bayona, Pilar; Haber, Georges-Pascal; Stein, Robert J

2018-01-01

A renorrhaphy technique which is effective for hemostasis but does not place undue tension on the branch vessels of the renal sinus remains one of the challenging steps after hilar tumor resection during robotic partial nephrectomy (RPN). The published V-hilar suture (VHS) technique is one option for reconstruction after an RPN involving the hilum. The objective of this video is to show a novel renorrhaphy technique, Hilar Parenchymal Oversew that has been effective for such cases. We present two cases of RPN for renal hilar tumors. The first case depicts use of the VHS renorrhaphy technique for a tumor that abuts the renal hilum along 20% of its diameter. The second case demonstrates tumor resection and reconstruction for a tumor that has >50% involvement of the hilum along its diameter. After tumor resection, individual sinus vessels can be selectively oversewn with 2-0 Vicryl suture on SH needle. The remaining exposed parenchyma is controlled using the Hilar Parenchymal Oversew technique with a #0 Vicryl on CT-1 needle. For the Hilar Parenchymal Oversew surgery operative time was 225 min, estimated blood loss was 140 ml, warm ischemia time was 19 minutes, and there were no intraoperative complications. Pathology was consistent with clear cell renal cancer with negative margins. Robotic partial nephrectomy with the Hilar Parenchymal Oversew technique is a good alternative to VHS renorrhaphy in the management of renal hilar tumors "bulging" into the renal sinus with >50% of the tumor diameter abutting the hilum. Copyright® by the International Brazilian Journal of Urology.

Evidence for differential changes of junctional complex proteins in murine neurocysticercosis dependent upon CNS vasculature.

PubMed

Alvarez, Jorge I; Teale, Judy M

2007-09-12

The delicate balance required to maintain homeostasis of the central nervous system (CNS) is controlled by the blood-brain barrier (BBB). Upon injury, the BBB is disrupted compromising the CNS. BBB disruption has been represented as a uniform event. However, our group has shown in a murine model of neurocysticercosis (NCC) that BBB disruption varies depending upon the anatomical site/vascular bed analyzed. In this study further understanding of the mechanisms of BBB disruption was explored in blood vessels located in leptomeninges (pial vessels) and brain parenchyma (parenchymal vessels) by examining the expression of junctional complex proteins in murine brain infected with Mesocestoides corti. Both pial and parenchymal vessels from mock infected animals showed significant colocalization of junctional proteins and displayed an organized architecture. Upon infection, the patterned organization was disrupted and in some cases, particular tight junction and adherens junction proteins were undetectable or appeared to be undergoing proteolysis. The extent and timing of these changes differed between both types of vessels (pial vessel disruption within days versus weeks for parenchymal vessels). To approach potential mechanisms, the expression and activity of matrix metalloproteinase-9 (MMP-9) were evaluated by in situ zymography. The results indicated an increase in MMP-9 activity at sites of BBB disruption exhibiting leukocyte infiltration. Moreover, the timing of MMP activity in pial and parenchymal vessels correlated with the timing of permeability disruption. Thus, breakdown of the BBB is a mutable process despite the similar structure of the junctional complex between pial and parenchymal vessels and involvement of MMP activity.

Quantitative CT characterization of pediatric lung development using routine clinical imaging

PubMed Central

Stein, Jill M.; Walkup, Laura L.; Brody, Alan S.; Fleck, Robert J.

2016-01-01

Background The use of quantitative CT analysis in children is limited by lack of normal values of lung parenchymal attenuation. These characteristics are important because normal lung development yields significant parenchymal attenuation changes as children age. Objective To perform quantitative characterization of normal pediatric lung parenchymal X-ray CT attenuation under routine clinical conditions in order to establish a baseline comparison to that seen in pathological lung conditions. Materials and methods We conducted a retrospective query of normal CT chest examinations in children ages 0–7 years from 2004 to 2014 using standard clinical protocol. During these examinations semi-automated lung parenchymal segmentation was performed to measure lung volume and mean lung attenuation. Results We analyzed 42 CT examinations in 39 children, ages 3 days to 83 months (mean ± standard deviation [SD] = 42±27 months). Lung volume ranged 0.10–1.72 liters (L). Mean lung attenuation was much higher in children younger than 12 months, with values as high as −380 Hounsfield units (HU) in neonates (lung volume 0.10 L). Lung volume decreased to approximately −650 HU by age 2 years (lung volume 0.47 L), with subsequently slower exponential decrease toward a relatively constant value of −860 HU as age and lung volume increased. Conclusion Normal lung parenchymal X-ray CT attenuation decreases with increasing lung volume and age; lung attenuation decreases rapidly in the first 2 years of age and more slowly thereafter. This change in normal lung attenuation should be taken into account as quantitative CT methods are translated to pediatric pulmonary imaging. PMID:27576458

Tubeless percutaneous nephrolithotomy with non-absorbable hemostatic sealant (Quikclot®) versus nephrostomy tube placement: a propensity score-matched analysis.

PubMed

Koo, Kyo Chul; Park, Sang Un; Jang, Ho Sung; Hong, Chang-Hee

2015-11-01

The purpose of this study was to determine the efficacy and safety of tubeless percutaneous nephrolithotomy (PNL) using a non-absorbable hemostatic sealant (Quikclot(®)) as an adjunct compared to nephrostomy tube placement in patients exhibiting significant parenchymal bleeding following PNL. We identified 113 PNL cases performed between May 2011 and October 2014. For patients with insignificant parenchymal bleeding following stone removal, defined as a clear visualization of the surgical field at full irrigation of the nephroscope, tubeless PNL was performed. For patients with significant parenchymal bleeding, we introduced the tubeless Quikclot(®) technique as of September 2013 and have performed it ever since. Formerly, nephrostomy placement PNL was performed. In this study, 40 Quikclot(®) applied PNL cases were matched with an equal number of nephrostomy placement cases by propensity scoring based on body mass index, stone size, and Guy's stone score. The mean postoperative drop in hematocrit was comparative between the Quikclot(®) group and the nephrostomy group on both postoperative days 1 (p = 0.459) and 2 (p = 0.325). Quikclot(®) application was associated with lower VAS scores throughout the postoperative period, lower cumulative analgesic requirement (p = 0.025), and with shorter hospitalization (p = 0.002). Complication rates were comparable with no need for blood transfusions in any patients. Tubeless Quikclot(®) PNL was safe and provided effective hemostasis of significant parenchymal bleeding. By avoiding nephrostomy placement, we were able to reduce postoperative pain, analgesic requirements, and hospitalization. Application of Quikclot(®) may be considered prior to nephrostomy placement in patients with significant parenchymal bleeding.

Stereotactic Radiofrequency Ablation (SRFA) of Liver Lesions: Technique Effectiveness, Safety, and Interoperator Performance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Widmann, Gerlig, E-mail: gerlig.widmann@i-med.ac.at; Schullian, Peter, E-mail: peter.schullian@i-med.ac.at; Haidu, Marion, E-mail: marion.haidu@i-med.ac.at

Purpose: To evaluate technique effectiveness, safety, and interoperator performance of stereotactic radiofrequency ablation (SRFA) of liver lesions. Methods: Retrospective review including 90 consecutive patients from January 2008 to January 2010 with 106 computed tomography-guided SRFA sessions using both single and multiple electrodes for the treatment of 177 lesions: 72 hepatocellular carcinoma (HCC) and 105 metastases with a mean size of 2.9 cm (range 0.5-11 cm). Technique effectiveness and 1-year local recurrence were evaluated by computed tomographic scans. Complications, mortality, and hospital days were recorded. The performance between an experienced and inexperienced interventional radiologist was compared. Results: The overall technique effectivenessmore » after a single SRFA was 95.5% (93.1% for HCC and 97.1% for metastases). Four of the eight unsuccessfully treated lesions could be retreated (secondary technique effectiveness of 97.7%). Local recurrence at 1 year was 2.9%. Technique effectiveness was significantly different for lesions <5 cm (96.7%) and >5 cm (87.5%) (P = 0.044) but not for lesions <3 cm (95.9%) and 3-5 cm (100%). Compared to clear parenchymal property (97.3%), vessel vicinity (93.3%) (P = 0.349) and subcapsular (95.2%) (P = 0.532) had no, but hollow viscera vicinity (83.3%) had a significantly lower technique effectiveness (P = 0.020). Mortality rate was 0.9%. Major complications and hospital days were higher for cirrhosis Child-Pugh B (20%, 7.2 days) than Child-Pugh A (3.1%, 4.7 days) patients and for metastases (5.1%, 4.3 days). There was no significant difference in interoperator performance. Conclusions: RFA allowed for efficient, reliable, and safe ablation of large-volume liver disease.« less

Three members of the iodothyronine deiodinase family, dio1, dio2 and dio3, are expressed in spatially and temporally specific patterns during metamorphosis of the flounder, Paralichthys olivaceus.

PubMed

Itoh, Kae; Watanabe, Kohei; Wu, Xiaoming; Suzuki, Tohru

2010-07-01

Flounder metamorphosis, marked by eye migration, lateralized pigmentation, and tissue differentiation in the stomach and skeletal muscle, is stimulated by thyroid hormone (TH). It is known that tri-iodothyronine (T3) produced by iodothyronine deiodinase type-1 (Dio1) from thyroxine (T4) enters the blood, whereas T3 produced by Dio2 penetrates into the nucleus of the Dio2-expressing cells, and then Dio3 inactivates both T4 and T3. To better understand the distinct functions of these three deiodinases in T3 regulation during flounder metamorphosis, we examined the tissue expression patterns of dio1, dio2, and dio3 in larvae of the Japanese flounder, Paralichthys olivaceus, by section in situ hybridization (SISH). We found that each deiodinase is expressed in a spatially and temporally specific pattern. dio1 is expressed in liver parenchymal cells from pro-metamorphosis to early climax, while dio2 is expressed in limited regions of the eyes, tectum, and skeletal muscles from pro-metamorphosis to post-climax. Considering these findings together with reports on other vertebrates, we predict that the liver cells expressing dio1 supply T3 to the blood, and that this systemic T3 synchronizes metamorphosis of differentiating tissues throughout the larval body, whereas the eyes, tectum, and skeletal muscles autonomously produce additional T3 for local tissue differentiation. Finally, dio3 expression is detected in skeletal muscle and gastric gland blastemas, which both undergo marked tissue differentiation at metamorphic climax. We hypothesize that dio3 expression protects these tissues from basal T3 levels early in metamorphosis, ensuring, together with the T3 surge from the liver, the synchronization of tissue differentiation at metamorphic climax.

Phenobarbital Induces Alterations in the Proteome of Hepatocytes and Mesenchymal Cells of Rat Livers

PubMed Central

Klepeisz, Philip; Sagmeister, Sandra; Haudek-Prinz, Verena; Pichlbauer, Melanie; Grasl-Kraupp, Bettina; Gerner, Christopher

2013-01-01

Preceding studies on the mode of action of non-genotoxic hepatocarcinogens (NGCs) have concentrated on alterations induced in hepatocytes (HCs). A potential role of non-parenchymal liver cells (NPCs) in NGC-driven hepatocarcinogenesis has been largely neglected so far. The aim of this study is to characterize NGC-induced alterations in the proteome profiles of HCs as well as NPCs. We chose the prototypic NGC phenobarbital (PB) which was applied to male rats for a period of 14 days. The livers of PB-treated rats were perfused by collagenase and the cell suspensions obtained were subjected to density gradient centrifugation to separate HCs from NPCs. In addition, HCs and NPC isolated from untreated animals were treated with PB in vitro. Proteome profiling was done by CHIP-HPLC and ion trap mass spectrometry. Proteome analyses of the in vivo experiments showed many of the PB effects previously described in HCs by other methods, e.g. induction of phase I and phase II drug metabolising enzymes. In NPCs proteins related to inflammation and immune regulation such as PAI-1 and S100-A10, ADP-ribosyl cyclase 1 and to cell migration such as kinesin-1 heavy chain, myosin regulatory light chain RLC-A and dihydropyrimidinase-related protein 1 were found to be induced, indicating major PB effects on these cells. Remarkably, in vitro treatment of HCs and NPCs with PB hardly reproduced the proteome alterations observed in vivo, indicating differences of NGC induced responses of cells at culture conditions compared to the intact organism. To conclude, the present study clearly demonstrated that PB induces proteome alterations not only in HCs but also in NPCs. Thus, any profound molecular understanding on the mode of action of NGCs has to consider effects on cells of the hepatic mesenchyme. PMID:24204595

Comparison of a pocket-size ultrasound device with a premium ultrasound machine: diagnostic value and time required in bedside ultrasound examination.

PubMed

Stock, Konrad Friedrich; Klein, Bettina; Steubl, Dominik; Lersch, Christian; Heemann, Uwe; Wagenpfeil, Stefan; Eyer, Florian; Clevert, Dir-Andre

2015-10-01

Time savings and clinical accuracy of a new miniature ultrasound device was investigated utilizing comparison with conventional high-end ultrasound instruments. Our objective was to determine appropriate usage and limitations of this diagnostic tool in internal medicine. We investigated 28 patients from the internal-medicine department. Patients were examined with the Acuson P10 portable device and a Sonoline Antares instrument in a cross-over design. All investigations were carried out at the bedside; the results were entered on a standardized report form. The time for the ultrasound examination (transfer time, setting up and disassembly, switching on and off, and complete investigation time) was recorded separately. Mean time for overall examination per patient with the portable ultrasound device was shorter (25.0 ± 4.5 min) than with the high-end machine (29.4 ± 4.4 min; p < 0.001). When measuring the size of liver, spleen, and kidneys, the values obtained differed significantly between portable device and the high-end instrument. In our study, we identified 113 pathological ultrasound findings with the high-end ultrasound machine, while 82 pathological findings (73%) were concordantly detected with the portable ultrasound device. The main diagnostic strengths of the portable device were in the detection of ascites (sensitivity 80%), diagnosis of fatty liver, and identification of severe parenchymal liver damage. The clinical utility of portable ultrasound machines is limited. There will be clinical roles for distinct clinical questions such as detection of ascites or pleural effusion when used by experienced examiners. However, sensitivity in detecting multiple pathologies is not comparable to high-end ultrasound machines.

Superselective intra-arterial hepatic injection of indocyanine green (ICG) for fluorescence image-guided segmental positive staining: experimental proof of the concept.

PubMed

Diana, Michele; Liu, Yu-Yin; Pop, Raoul; Kong, Seong-Ho; Legnèr, Andras; Beaujeux, Remy; Pessaux, Patrick; Soler, Luc; Mutter, Didier; Dallemagne, Bernard; Marescaux, Jacques

2017-03-01

Intraoperative liver segmentation can be obtained by means of percutaneous intra-portal injection of a fluorophore and illumination with a near-infrared light source. However, the percutaneous approach is challenging in the minimally invasive setting. We aimed to evaluate the feasibility of fluorescence liver segmentation by superselective intra-hepatic arterial injection of indocyanine green (ICG). Eight pigs (mean weight: 26.01 ± 5.21 kg) were involved. Procedures were performed in a hybrid experimental operative suite equipped with the Artis Zeego ® , multiaxis robotic angiography system. A pneumoperitoneum was established and four laparoscopic ports were introduced. The celiac trunk was catheterized, and a microcatheter was advanced into different segmental hepatic artery branches. A near-infrared laparoscope (D-Light P, Karl Storz) was used to detect the fluorescent signal. To assess the correspondence between arterial-based fluorescence demarcation and liver volume, metallic markers were placed along the fluorescent border, followed by a 3D CT-scanning, after injecting intra-arterial radiological contrast (n = 3). To assess the correspondence between arterial and portal supplies, percutaneous intra-portal angiography and intra-arterial angiography were performed simultaneously (n = 1). Bright fluorescence signal enhancing the demarcation of target segments was obtained from 0.1 mg/mL, in matter of seconds. Correspondence between the volume of hepatic segments and arterial territories was confirmed by CT angiography. Higher background fluorescence noise was found after positive staining by intra-portal ICG injection, due to parenchymal accumulation and porto-systemic shunting. Intra-hepatic arterial ICG injection, rapidly highlights hepatic target segment borders, with a better signal-to-background ratio as compared to portal vein injection, in the experimental setting.

Hepatic Histology and Morphometric Measurements in Idiopathic Extrahepatic Portal Vein Thrombosis in Children, Correlated to Clinical Outcome of Meso-Rex Bypass.

PubMed

Tantemsapya, Niramol; Superina, Riccardo; Wang, Deli; Kronauer, Grace; Whitington, Peter F; Melin-Aldana, Hector

2018-06-01

The aim of this study was to correlate clinical, histologic, and morphometric features of the liver in children with extrahepatic portal vein thrombosis (EHPVT), with surgical outcome after Meso-Rex bypass (MRB). Idiopathic EHPVT, a significant cause of portal hypertension, is surgically corrected by MRB. Correlation of histologic and morphometric features of the liver with outcome has not been reported in children. We retrospectively reviewed clinical and intraoperative data of 45 children with idiopathic EHPVT. Liver samples were obtained at the time of MRB. Morphometric measurements of portal tract structures were performed and correlated with surgical outcome. Median follow-up was 3.65 years after surgery (range 1.5 to 10 years). Thirty-seven (82.2%) children had successful MRB. There was no association between age, sex, and suture material with surgical outcome. Average patient age was higher in patients with postoperative complications (P = NS). Portal fibrosis, bridging, parenchymal nodules, portal inflammation, hepatocellular swelling, steatosis, dilatation of portal lymphatics, and periductal fibrosis did not show a significant difference between the 2 groups. Portal vein and bile duct area index were significantly smaller in the unsuccessful group (P = 0.004 and 0.003, respectively). A portal vein area index <0.08 had a lower chance of successful surgical outcome. Hepatic artery area index was not significantly different. Measured intraoperative portal blood inflow was the only significant clinical factor affecting surgical outcome (P = 0.0003). Low portal vein area index and intraoperative portal blood inflow may be negative prognostic factors for MRB outcome in children with idiopathic EHPVT. Average patient age was higher, although not statistically significant, in patients with postoperative complications.

Characterization of CD133+ parenchymal cells in the liver: histology and culture.

PubMed

Yoshikawa, Seiichi; Zen, Yoh; Fujii, Takahiko; Sato, Yasunori; Ohta, Tetsuo; Aoyagi, Yutaka; Nakanuma, Yasuni

2009-10-21

To reveal the characteristics of CD133(+) cells in the liver. This study examined the histological characteristics of CD133(+) cells in non-neoplastic and neoplastic liver tissues by immunostaining, and also analyzed the biological characteristics of CD133(+) cells derived from human hepatocellular carcinoma (HCC) or cholangiocarcinoma cell lines. Immunostaining revealed constant expression of CD133 in non-neoplastic and neoplastic biliary epithelium, and these cells had the immunophenotype CD133(+)/CK19(+)/HepPar-1(-). A small number of CD133(+)/CK19(-)/HepPar-1(+) cells were also identified in HCC and combined hepatocellular and cholangiocarcinoma. In addition, small ductal structures, resembling the canal of Hering, partly surrounded by hepatocytes were positive for CD133. CD133 expression was observed in three HCC (HuH7, PLC5 and HepG2) and two cholangiocarcinoma cell lines (HuCCT1 and CCKS1). Fluorescence-activated cell sorting (FACS) revealed that CD133(+) and CD133(-) cells derived from HuH7 and HuCCT1 cells similarly produced CD133(+) and CD133(-) cells during subculture. To examine the relationship between CD133(+) cells and the side population (SP) phenotype, FACS was performed using Hoechst 33342 and a monoclonal antibody against CD133. The ratios of CD133(+)/CD133(-) cells were almost identical in the SP and non-SP in HuH7. In addition, four different cellular populations (SP/CD133(+), SP/CD133(-), non-SP/CD133(+), and non-SP/CD133(-)) could similarly produce CD133(+) and CD133(-) cells during subculture. This study revealed that CD133 could be a biliary and progenitor cell marker in vivo. However, CD133 alone is not sufficient to detect tumor-initiating cells in cell lines.

Normal sonographic anatomy of the abdomen of coatis (Nasua nasua Linnaeus 1766).

PubMed

Ribeiro, Rejane G; Costa, Ana Paula A; Bragato, Nathália; Fonseca, Angela M; Duque, Juan C M; Prado, Tales D; Silva, Andrea C R; Borges, Naida C

2013-06-23

The use of ultrasound in veterinary medicine is widespread as a diagnostic supplement in the clinical routine of small animals, but there are few reports in wild animals. The objective of this study was to describe the anatomy, topography and abdominal sonographic features of coatis. The urinary bladder wall measured 0.11 ± 0.03 cm. The symmetrical kidneys were in the left and right cranial quadrant of the abdomen and the cortical, medullary and renal pelvis regions were recognized and in all sections. The medullary rim sign was visualized in the left kidney of two coatis. The liver had homogeneous texture and was in the cranial abdomen under the rib cage. The gallbladder, rounded and filled with anechoic content was visualized in all coatis, to the right of the midline. The spleen was identified in the left cranial abdomen following the greater curvature of the stomach. The parenchyma was homogeneous and hyperechogenic compared to the liver and kidney cortex. The stomach was in the cranial abdomen, limited cranially by the liver and caudo-laterally by the spleen. The left adrenal glands of five coatis were seen in the cranial pole of the left kidney showing hypoechogenic parenchyma without distinction of cortex and medulla. The pancreas was visualized in only two coatis. The left ovary (0.92 cm x 0.56 cm) was visualized on a single coati in the caudal pole of the kidney. The uterus, right adrenal, right ovary and intestines were not visualized. Ultrasound examination of the abdomen of coatis may be accomplished by following the recommendations for dogs and cats. It is possible to evaluate the anatomical and topographical relationships of the abdominal organs together with the knowledge of the peculiarities of parenchymal echogenicity and echotexture of the viscera.

Intersex and liver alterations induced by long-term sublethal exposure to 17α-ethinylestradiol in adult male Cnesterodon decemmaculatus (Pisces: Poeciliidae).

PubMed

Young, Brian Jonathan; López, Gabriela Carina; Cristos, Diego Sebastián; Crespo, Diana Cristina; Somoza, Gustavo Manuel; Carriquiriborde, Pedro

2017-07-01

The aim of the present study was to assess the responses of the gonopodium morphology and the gonadal and liver histology of adult male Cnesterodon decemmaculatus to sublethal long-term exposure concentrations of 17α-ethinylestradiol (EE2). Two experiments were conducted exposing the fish to waterborne concentrations of EE2 ranging from 20 ng/L to 200 ng/L for 8 wk, 12 wk, and 16 wk. Intersex gonads were observed after 8 wk and 16 wk in fish exposed to 200 ng EE2/L and 100 ng EE2/L, respectively. Oocytes' development from testis germ cells and replacement of the efferent duct periodic acid-Schiff-positive secretion surrounding spermatozeugmata by parenchymal tissue and duct structure alterations were the major observed changes in the gonads. In contrast, no response was observed in the gonopodium morphology. Liver histology was also altered, showing increasing steatosis, single-cell necrosis to generalized necrosis, and disruption of acinar organization from 100 ng EE2/L to 200 ng EE2/L. In summary, the present results showed that although EE2 was not able to alter the morphology of a developed gonopodium, it was capable of inducing development of testicular oocytes in adult male C. decemmaculatus at environmentally relevant concentrations. Thus, externally normal but intersex C. decemmaculatus males would be expected in the wastewater-receiving streams that the species inhabits. According to the literature, the present study would be the first indicating estrogen-induced intersex in adult male poeciliid. Environ Toxicol Chem 2017;36:1738-1745. © 2016 SETAC. © 2016 SETAC.

Automated two-point dixon screening for the evaluation of hepatic steatosis and siderosis: comparison with R2-relaxometry and chemical shift-based sequences.

PubMed

Henninger, B; Zoller, H; Rauch, S; Schocke, M; Kannengiesser, S; Zhong, X; Reiter, G; Jaschke, W; Kremser, C

2015-05-01

To evaluate the automated two-point Dixon screening sequence for the detection and estimated quantification of hepatic iron and fat compared with standard sequences as a reference. One hundred and two patients with suspected diffuse liver disease were included in this prospective study. The following MRI protocol was used: 3D-T1-weighted opposed- and in-phase gradient echo with two-point Dixon reconstruction and dual-ratio signal discrimination algorithm ("screening" sequence); fat-saturated, multi-gradient-echo sequence with 12 echoes; gradient-echo T1 FLASH opposed- and in-phase. Bland-Altman plots were generated and correlation coefficients were calculated to compare the sequences. The screening sequence diagnosed fat in 33, iron in 35 and a combination of both in 4 patients. Correlation between R2* values of the screening sequence and the standard relaxometry was excellent (r = 0.988). A slightly lower correlation (r = 0.978) was found between the fat fraction of the screening sequence and the standard sequence. Bland-Altman revealed systematically lower R2* values obtained from the screening sequence and higher fat fraction values obtained with the standard sequence with a rather high variability in agreement. The screening sequence is a promising method with fast diagnosis of the predominant liver disease. It is capable of estimating the amount of hepatic fat and iron comparable to standard methods. • MRI plays a major role in the clarification of diffuse liver disease. • The screening sequence was introduced for the assessment of diffuse liver disease. • It is a fast and automated algorithm for the evaluation of hepatic iron and fat. • It is capable of estimating the amount of hepatic fat and iron.

Characterizing focal hepatic lesions by free-breathing intravoxel incoherent motion MRI at 3.0 T.

PubMed

Watanabe, Haruo; Kanematsu, Masayuki; Goshima, Satoshi; Kajita, Kimihiro; Kawada, Hiroshi; Noda, Yoshifumi; Tatahashi, Yukichi; Kawai, Nobuyuki; Kondo, Hiroshi; Moriyama, Noriyuki

2014-12-01

Diffusion-weighted (DW) imaging is commonly used to distinguish between benign and malignant liver lesions. To prospectively evaluate the true molecular-diffusion coefficient (D), perfusion-related diffusion coefficient (D*), perfusion fraction (f), and ADC of focal hepatic lesions using a free-breathing intravoxel incoherent motion (IVIM) DW sequence, and to determine if these parameters are useful for characterizing focal hepatic lesions. One hundred and twenty hepatic lesions (34 metastases, 32 hepatocellular carcinoma [HCC], 33 hemangiomas, and 21 liver cysts) in 74 patients were examined. Mean D, D*, f, and ADC values of hepatic lesions were compared among pathologies. ROC curve analyses were performed to assess the performances of D, D*, f, and ADC values for the characterization of liver lesions as benign or malignant. The mean D and ADC values of benign lesions were greater than those of malignant lesions (P < 0.001). Although the mean D and ADC values of liver cysts were greater than those of hemangiomas (P < 0.001), and these values were not significantly different between metastases and HCCs (P = 0.99). Area under the ROC curve for ADC values (0.98) was significantly greater (P = 0.048) than that for D values (0.96) for the differentiation of benign and malignant lesions. Sensitivity and specificity for the detection of malignant lesion were 89% and 98%, respectively, when an ADC cut-off value of 1.40 was applied. D and ADC values have more potential for characterizing focal hepatic lesions than D* or f values, and for the differentiation of malignancy and benignity. © The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Concurrent gall bladder, liver lobe torsion, and bile peritonitis in a German shepherd dog 2 months after gastric dilatation/volvulus gastropexy and splenectomy.

PubMed

Tubby, Kurtis G

2013-08-01

Postmortem examination of a 7-year-old German shepherd dog which had gastric dilatation/volvulus and splenectomy 2 months earlier revealed that the right middle and quadrate liver lobes were diffusely congested and torsed. The gall bladder was grossly distended and torsed along its long axis and there was evidence of bile peritonitis.

Concurrent gall bladder, liver lobe torsion, and bile peritonitis in a German shepherd dog 2 months after gastric dilatation/volvulus gastropexy and splenectomy

PubMed Central

Tubby, Kurtis G.

2013-01-01

Postmortem examination of a 7-year-old German shepherd dog which had gastric dilatation/volvulus and splenectomy 2 months earlier revealed that the right middle and quadrate liver lobes were diffusely congested and torsed. The gall bladder was grossly distended and torsed along its long axis and there was evidence of bile peritonitis. PMID:24155480

Research and development of a new RF-assisted device for bloodless rapid transection of the liver: Computational modeling and in vivo experiments

PubMed Central

Burdío, Fernando; Berjano, Enrique J; Navarro, Ana; Burdío, José M; Grande, Luis; Gonzalez, Ana; Cruz, Ignacio; Güemes, Antonio; Sousa, Ramón; Subirá, Jorge; Castiella, Tomás; Poves, Ignasi; Lequerica, Juan L

2009-01-01

Background Efficient and safe transection of biological tissue in liver surgery is strongly dependent on the ability to address both parenchymal division and hemostasis simultaneously. In addition to the conventional clamp crushing or finger fracture methods other techniques based on radiofrequency (RF) currents have been extensively employed to reduce intraoperative blood loss. In this paper we present our broad research plan for a new RF-assisted device for bloodless, rapid resection of the liver. Methods Our research plan includes computer modeling and in vivo studies. Computer modeling was based on the Finite Element Method (FEM) and allowed us to estimate the distribution of electrical power deposited in the tissue, along with assessing the effect of the characteristics of the device on the temperature profiles. Studies based on in vivo pig liver models provided a comparison of the performance of the new device with other techniques (saline-linked technology) currently employed in clinical practice. Finally, the plan includes a pilot clinical trial, in which both the new device and the accessory equipment are seen to comply with all safety requirements. Results The FEM results showed a high electrical gradient around the tip of the blade, responsible for the maximal increase of temperature at that point, where temperature reached 100°C in only 3.85 s. Other hot points with lower temperatures were located at the proximal edge of the device. Additional simulations with an electrically insulated blade produced more uniform and larger lesions (assessed as the 55°C isotherm) than the electrically conducting blade. The in vivo study, in turn, showed greater transection speed (3 ± 0 and 3 ± 1 cm2/min for the new device in the open and laparoscopic approaches respectively) and also lower blood loss (70 ± 74 and 26 ± 34 mL) during transection of the liver, as compared to saline-linked technology (2 ± 1 cm2/min with P = 0.002, and 527 ± 273 mL with P = 0.001). Conclusion A new RF-assisted device for bloodless, rapid liver resection was designed, built and tested. The results demonstrate the potential advantages of this device over others currently employed. PMID:19296852

Sodium 4-phenylbutyrate protects against liver ischemia reperfusion injury by inhibition of endoplasmic reticulum-stress mediated apoptosis.

PubMed

Vilatoba, Mario; Eckstein, Christopher; Bilbao, Guadalupe; Smyth, Cheryl A; Jenkins, Stacie; Thompson, J Anthony; Eckhoff, Devin E; Contreras, Juan L

2005-08-01

Evidence is emerging that the endoplasmic reticulum (ER) participates in initiation of apoptosis induced by the unfolded protein response and by aberrant Ca(++) signaling during cellular stress such as ischemia/reperfusion injury (I/R injury). ER-induced apoptosis involves the activation of caspase-12 and C/EBP homologous protein (CHOP), and the shutdown of translation initiated by phosphorylation of eIF2alpha. Sodium 4-phenylbutyrate (PBA) is a low molecular weight fatty acid that acts as a chemical chaperone reducing the load of mutant or unfolded proteins retained in the ER during cellular stress and also exerting anti-inflammatory activity. It has been used successfully for treatment of urea cycle disorders and sickle cell disease. Thus, we hypothesized that PBA may reduce ER-induced apoptosis triggered by I/R injury to the liver. Groups of male C57BL/6 mice were subjected to warm ischemia (70% of the liver mass, 45 minutes). Serum aspartate aminotransferase was assessed 6 hours after reperfusion; apoptosis was evaluated by enzyme-linked immunosorbent assays of caspase-12 and plasma tumor necrosis factor alpha, Western blot analyses of eIF2alpha, and reverse transcriptase-polymerase chain reaction of CHOP expression. A dose-dependent decrease in aspartate aminotransferase was demonstrated in mice given intraperitoneal PBA (1 hour before and 12 hours after reperfusion), compared with vehicle-treated controls; this effect was associated with reduced pyknosis, parenchymal hemorrhages, and neutrophil infiltrates in PBA-treated mice, compared with controls. In a lethal model of total liver I/R injury, all vehicle-treated controls died within 3 days after reperfusion. In contrast, 50% survival (>30 days) was observed in animals given PBA. The beneficial effects of PBA were associated with a greater than 45% reduction in apoptosis, decreased ER-mediated apoptosis characterized by significant reduction in caspase-12 activation, and reduced levels of both phosphorylated eIF2alpha and CHOP. Significant reductions in plasma levels of tumor necrosis factor alpha and liver myeloperoxidase content were demonstrated after PBA treatment. Reduction in ER stress-induced hepatocellular injury was achieved by the administration of PBA. Targeting the ER-associated cell death pathway might offer a novel approach to reduce I/R injury to the liver.

Diffusion-weighted MR imaging of the liver at 3.0 Tesla using TRacking Only Navigator echo (TRON): a feasibility study.

PubMed

Ivancevic, Marko K; Kwee, Thomas C; Takahara, Taro; Ogino, Tetsuo; Hussain, Hero K; Liu, Peter S; Chenevert, Thomas L

2009-11-01

To assess the feasibility of TRacking Only Navigator echo (TRON) for diffusion-weighted magnetic resonance imaging (DWI) of the liver at 3.0T. Ten volunteers underwent TRON, respiratory triggered, and free breathing DWI of the liver at 3.0 Tesla (T). Scan times were measured. Image sharpness, degree of stair-step and stripe artifacts for the three methods were assessed by two observers. Mean scan times of TRON and respiratory triggered DWI relative to free breathing DWI were 34% and 145% longer respectively. In four of eight comparisons (two observers, two b-values, two slice orientations), TRON DWI image sharpness was significantly better than free breathing DWI, but inferior to respiratory triggered DWI. In two of four comparisons (two observers, two b-values), degree of stair-step artifacts in TRON DWI was significantly lower than in respiratory triggered DWI. Degree of stripe artifacts between the three methods was not significantly different. DWI of the liver at 3.0T using TRON is feasible. Image sharpness in TRON DWI is superior to that in free breathing DWI. Although image sharpness of respiratory triggered DWI is still better, TRON DWI requires less scan time and reduces stair-step artifacts.

In vivo characterization of colorectal metastases in human liver using diffuse reflectance spectroscopy: toward guidance in oncological procedures

NASA Astrophysics Data System (ADS)

Spliethoff, Jarich W.; de Boer, Lisanne L.; Meier, Mark A. J.; Prevoo, Warner; de Jong, Jeroen; Kuhlmann, Koert; Bydlon, Torre M.; Sterenborg, Henricus J. C. M.; Hendriks, Benno H. W.; Ruers, Theo J. M.

2016-09-01

There is a strong need to develop clinical instruments that can perform rapid tissue assessment at the tip of smart clinical instruments for a variety of oncological applications. This study presents the first in vivo real-time tissue characterization during 24 liver biopsy procedures using diffuse reflectance (DR) spectroscopy at the tip of a core biopsy needle with integrated optical fibers. DR measurements were performed along each needle path, followed by biopsy of the target lesion using the same needle. Interventional imaging was coregistered with the DR spectra. Pathology results were compared with the DR spectroscopy data at the final measurement position. Bile was the primary discriminator between normal liver tissue and tumor tissue. Relative differences in bile content matched with the tissue diagnosis based on histopathological analysis in all 24 clinical cases. Continuous DR measurements during needle insertion in three patients showed that the method can also be applied for biopsy guidance or tumor recognition during surgery. This study provides an important validation step for DR spectroscopy-based tissue characterization in the liver. Given the feasibility of the outlined approach, it is also conceivable to make integrated fiber-optic tools for other clinical procedures that rely on accurate instrument positioning.

3.0 Tesla magnetic resonance imaging: A new standard in liver imaging?

PubMed Central

Girometti, Rossano

2015-01-01

An ever-increasing number of 3.0 Tesla (T) magnets are installed worldwide. Moving from the standard of 1.5 T to higher field strength implies a number of potential advantage and drawbacks, requiring careful optimization of imaging protocols or implementation of novel hardware components. Clinical practice and literature review suggest that state-of-the-art 3.0 T is equivalent to 1.5 T in the assessment of focal liver lesions and diffuse liver disease. Therefore, further technical improvements are needed in order to fully exploit the potential of higher field strength. PMID:26244063

3.0 Tesla magnetic resonance imaging: A new standard in liver imaging?

PubMed

Girometti, Rossano

2015-07-28

An ever-increasing number of 3.0 Tesla (T) magnets are installed worldwide. Moving from the standard of 1.5 T to higher field strength implies a number of potential advantage and drawbacks, requiring careful optimization of imaging protocols or implementation of novel hardware components. Clinical practice and literature review suggest that state-of-the-art 3.0 T is equivalent to 1.5 T in the assessment of focal liver lesions and diffuse liver disease. Therefore, further technical improvements are needed in order to fully exploit the potential of higher field strength.

Liver diffusion-weighted MR imaging: reproducibility comparison of ADC measurements obtained with multiple breath-hold, free-breathing, respiratory-triggered, and navigator-triggered techniques.

PubMed

Chen, Xin; Qin, Lei; Pan, Dan; Huang, Yanqi; Yan, Lifen; Wang, Guangyi; Liu, Yubao; Liang, Changhong; Liu, Zaiyi

2014-04-01

To prospectively compare the reproducibility of normal liver apparent diffusion coefficient (ADC) measurements by using different respiratory motion compensation techniques with multiple breath-hold (MBH), free-breathing (FB), respiratory-triggered (RT), and navigator-triggered (NT) diffusion-weighted (DW) imaging and to compare the ADCs at different liver anatomic locations. The study protocol was approved by the institutional review board, and written informed consent was obtained from each participant. Thirty-nine volunteers underwent liver DW imaging twice. Imaging was performed with a 1.5-T MR imager with MBH, FB, RT, and NT techniques (b = 0, 100, and 500 sec/mm(2)). Three representative sections--superior, central, and inferior--were selected on left and right liver lobes, respectively. On each selected section, three regions of interest were drawn, and ADCs were measured. Analysis of variance was used to assess ADCs among the four techniques and various anatomic locations. Reproducibility of ADCs was assessed with the Bland-Altman method. ADCs obtained with MBH (range: right lobe, [1.641-1.662] × 10(-3)mm(2)/sec; left lobe, [2.034-2.054] ×10(-3)mm(2)/sec) were higher than those obtained with FB (right, [1.349-1.391] ×10(-3)mm(2)/sec; left, [1.630-1.700] ×10(-3)mm(2)/sec), RT (right, [1.439-1.455] ×10(-3)mm(2)/sec; left, [1.720-1.755] ×10(-3)mm(2)/sec), or NT (right, [1.387-1.400] ×10(-3)mm(2)/sec; left, [1.661-1.736] ×10(-3)mm(2)/sec) techniques (P < .001); however, no significant difference was observed between ADCs obtained with FB, RT, and NT techniques (P = .130 to P >.99). ADCs showed a trend to decrease moving from left to right. Reproducibility in the left liver lobe was inferior to that in the right, and the central middle segment in the right lobe had the most reproducible ADC. Statistical differences in ADCs were observed in the left-right direction in the right lobe (P < .001), but they were not observed in the superior-inferior direction (P = .144-.450). However, in the left liver lobe, statistical differences existed in both directions (P = .001 to P = .016 in the left-right direction, P < .001 in the superior-inferior direction). Both anatomic location and DW imaging technique influence liver ADC measurements and their reproducibility. FB DW imaging is recommended for liver DW imaging because of its good reproducibility and shorter acquisition time compared with that of MBH, RT, and NT techniques. RSNA, 2014

Quantitative microscopy of the lung: a problem-based approach. Part 2: stereological parameters and study designs in various diseases of the respiratory tract.

PubMed

Mühlfeld, Christian; Ochs, Matthias

2013-08-01

Design-based stereology provides efficient methods to obtain valuable quantitative information of the respiratory tract in various diseases. However, the choice of the most relevant parameters in a specific disease setting has to be deduced from the present pathobiological knowledge. Often it is difficult to express the pathological alterations by interpretable parameters in terms of volume, surface area, length, or number. In the second part of this companion review article, we analyze the present pathophysiological knowledge about acute lung injury, diffuse parenchymal lung diseases, emphysema, pulmonary hypertension, and asthma to come up with recommendations for the disease-specific application of stereological principles for obtaining relevant parameters. Worked examples with illustrative images are used to demonstrate the work flow, estimation procedure, and calculation and to facilitate the practical performance of equivalent analyses.

Hypervitaminosis A-induced hepatic fibrosis in a cat.

PubMed

Guerra, Juliana M; Daniel, Alexandre G T; Aloia, Thiago P A; de Siqueira, Adriana; Fukushima, André R; Simões, Denise M N; Reche-Júior, Archivaldo; Cogliati, Bruno

2014-03-01

The excessive intake of vitamin A in the form of vitamin concentrate, supplement or vitamin-rich liver can result in hypervitaminosis A in man and animals. Although osteopathologies resulting from chronic vitamin A intoxication in cats are well characterized, no information is available concerning feline hypervitaminosis A-induced liver disease. We report the first case of hepatic stellate cell lipidosis and hepatic fibrosis in a domestic cat that had been fed a diet based on raw beef liver. Radiographic examination revealed exostoses and ankylosis between vertebrae C1 and T7, compatible with deforming cervical spondylosis. Necropsy showed a slightly enlarged and light yellow to bronze liver. Microscopic and ultrastructural analyses of liver tissues revealed diffuse and severe liver fibrosis associated with hepatic stellate cell hyperplasia and hypertrophy. These cells showed immunopositive staining for α-smooth muscle actin and desmin markers. The necropsy findings of chronic liver disease coupled with osteopathology supported the diagnosis of hypervitaminosis A. As in human hepatology, if there is dietary evidence to support increased intake of vitamin A, then hypervitaminosis A should be considered in the differential diagnosis of chronic liver disease in cats.

Frontal parenchymal atrophy measures in multiple sclerosis.

PubMed

Locatelli, Laura; Zivadinov, Robert; Grop, Attilio; Zorzon, Marino

2004-10-01

The aim of this study was to establish whether, in a cross-sectional study, the normalized measures of whole and regional brain atrophy correlate better with tests assessing the cognitive function than the absolute brain atrophy measures. The neuropsychological performances and disability have been assessed in 39 patients with relapsing-remitting multiple sclerosis (MS). T1- and T2-lesion load (LL) of total brain and frontal lobes (FLs) were measured using a reproducible semiautomated technique. The whole brain volume and the regional brain parenchymal volume (RBPV) of FLs were obtained using a computerized interactive program, which incorporates semiautomated and automated segmentation processes. Normalized measures of brain atrophy, i.e., brain parenchymal fraction (BPF) and regional brain parenchymal fraction (RBPF) of FLs, were calculated. The scan-rescan, inter- and intrarater coefficient of variation (COV) and intraclass correlation coefficient (ICC) have been estimated. The RBPF of FLs showed an acceptable level of reproducibility which ranged from 1.7% for intrarater variability to 3.2% for scan-rescan variability. The mean ICC was 0.88 (CI 0.82-0.93). The RBPF of FLs demonstrated stronger magnitudes of correlation with neuropsychological functioning, disability and quantitative MRI lesion measures than RBPV. These differences were statistically significant: P<0.001 for Stroop Color Word Interference test, P<0.001 for Paced Auditory Serial Addition Test, P=0.04 for Standard Raven Progressive Matrices, P=0.049 for Expanded Disability Status Scale, P=0.01 for T2-LL of FLs and P<0.001 for T1-LL of FLs. BPF demonstrated significant correlations with tests assessing cognitive functions, whereas BPAV did not. The correlation analysis results were supported by the results of multiple regression analysis which showed that only the normalized brain atrophy measures were associated with tests exploring the cognitive functions. These data suggest that RBPF is a reproducible and sensitive method for measuring frontal parenchymal atrophy. The normalized measures of whole and regional brain parenchymal atrophy should be preferred to absolute measures in future studies that correlate neuropsychological performances and brain atrophy measures in patients with MS.

Diffuse vascular damage in a transplanted kidney: an indication for nuclear magnetic resonance?

PubMed

Burdese, M; Consiglio, V; Mezza, E; Savio, D; Guarena, C; Rossetti, M; Messina, M; Soragna, G; Suriani, C; Rabbia, C; Segoloni, G P; Piccoli, G B

2005-06-01

Vascular lesions are an increasing challenge after renal transplantation due to the wider indications for recipients and acceptance criteria for donors. Diagnostic approach and prognostic interpretation are still matter of controversy. The case reported herein may summarize some of the issues in this regard. A 54-year-old woman, on renal replacement therapy since 1974, and a kidney graft recipient from 1975 to 1999, received a second graft in 2001. The donor age was 65 years (cold ischemia 22 hours; two mismatches). The early posttransplant follow-up was characterized by delayed graft function, hypertension, and diabetes. During the initial hypertension workup, renal graft ultrasound (US) Doppler demonstrated increased vascular resistances, stable over time (resistance index 0.74 to 0.77); renal scintiscan displayed homogeneously parenchymoa and angio-magnetic resonance imaging (MRI), an homogeneous parenchymal vascularization. Initial immunosuppression with tacrolimus and steroids was modulated by adding mycophenolate mofetil to taper tacrolimus (to reduce nephrotoxicity and hypertension). Despite this, kidney function slowly deteriorated; serum creatinine reached 3 to 3.5 mg/dL by the second year. After a severe hypertensive crisis with unchanged scintiscan and US doppler examinations, angio-MRI revealed the almost complete disappearance of parenchymal enhancement beyond the lobar arteries. A renal biopsy confirmed the severe vascular damage. The patient was switched to rapamycine and a low-dose of an angiotension converting enzyme (ACE) inhibitor. She did relatively well (serum creatinine 2.2 to 3 mg/dL) for 6 months, when rapid functional impairment forced her to restart hemodialysis. This case, almost paradigmatic of the problems occurring when the rigid vasculature of long-term dialysis patients is matched with "marginal kidneys," suggests that MRI may be a sensible good to define vascular damage in the grafted kidney.

Non-invasive assessment of vasospasm following aneurysmal SAH using C-arm FDCT parenchymal blood volume measurement in the neuro-interventional suite: Technical feasibility

PubMed Central

Downer, Jonathan; Corkill, Rufus; Byrne, James V

2015-01-01

Introduction Cerebral vasospasm is the leading cause of morbidity and mortality in patients with aneurysmal subarachnoid haemorrhage (SAH) surviving the initial ictus. Commonly used techniques for vasospasm assessment are digital subtraction angiography and transcranial Doppler sonography. These techniques can reliably identify only the major vessel spasm and fail to estimate its haemodynamic significance. To overcome these issues and to enable comprehensive non-invasive assessment of vasospasm inside the interventional suite, a novel protocol involving measurement of parenchymal blood volume (PBV) using C-arm flat detector computed tomography (FDCT) was implemented. Materials and methods Patients from the neuro-intensive treatment unit (ITU) with suspected vasospasm following aneurysmal SAH were scanned with a biplane C-arm angiography system using an intravenous contrast injection protocol. The PBV maps were generated using prototype software. Contemporaneous clinically indicated MR scan including the diffusion- and perfusion-weighted sequences was performed. C-arm PBV maps were compared against the MR perfusion maps. Results Distribution of haemodynamic impairment on C-arm PBV maps closely matched the pattern of abnormality on MR perfusion maps. On visual comparison between the two techniques, the extent of abnormality indicated PBV to be both cerebral blood flow and cerebral blood volume weighted. Conclusion C-arm FDCT PBV measurements allow an objective assessment of the severity and localisation of cerebral hypoperfusion resulting from vasospasm. The technique has proved feasible and useful in very sick patients after aneurysmal SAH. The promise shown in this early study indicates that it deserves further evaluation both for post-SAH vasospasm and in other relevant clinical settings. PMID:26017197

Non-invasive assessment of vasospasm following aneurysmal SAH using C-arm FDCT parenchymal blood volume measurement in the neuro-interventional suite: Technical feasibility.

PubMed

Kamran, Mudassar; Downer, Jonathan; Corkill, Rufus; Byrne, James V

2015-08-01

Cerebral vasospasm is the leading cause of morbidity and mortality in patients with aneurysmal subarachnoid haemorrhage (SAH) surviving the initial ictus. Commonly used techniques for vasospasm assessment are digital subtraction angiography and transcranial Doppler sonography. These techniques can reliably identify only the major vessel spasm and fail to estimate its haemodynamic significance. To overcome these issues and to enable comprehensive non-invasive assessment of vasospasm inside the interventional suite, a novel protocol involving measurement of parenchymal blood volume (PBV) using C-arm flat detector computed tomography (FDCT) was implemented. Patients from the neuro-intensive treatment unit (ITU) with suspected vasospasm following aneurysmal SAH were scanned with a biplane C-arm angiography system using an intravenous contrast injection protocol. The PBV maps were generated using prototype software. Contemporaneous clinically indicated MR scan including the diffusion- and perfusion-weighted sequences was performed. C-arm PBV maps were compared against the MR perfusion maps. Distribution of haemodynamic impairment on C-arm PBV maps closely matched the pattern of abnormality on MR perfusion maps. On visual comparison between the two techniques, the extent of abnormality indicated PBV to be both cerebral blood flow and cerebral blood volume weighted. C-arm FDCT PBV measurements allow an objective assessment of the severity and localisation of cerebral hypoperfusion resulting from vasospasm. The technique has proved feasible and useful in very sick patients after aneurysmal SAH. The promise shown in this early study indicates that it deserves further evaluation both for post-SAH vasospasm and in other relevant clinical settings. © The Author(s) 2015.

Mammographic parenchymal texture as an imaging marker of hormonal activity: a comparative study between pre- and post-menopausal women

NASA Astrophysics Data System (ADS)

Daye, Dania; Bobo, Ezra; Baumann, Bethany; Ioannou, Antonios; Conant, Emily F.; Maidment, Andrew D. A.; Kontos, Despina

2011-03-01

Mammographic parenchymal texture patterns have been shown to be related to breast cancer risk. Yet, little is known about the biological basis underlying this association. Here, we investigate the potential of mammographic parenchymal texture patterns as an inherent phenotypic imaging marker of endogenous hormonal exposure of the breast tissue. Digital mammographic (DM) images in the cranio-caudal (CC) view of the unaffected breast from 138 women diagnosed with unilateral breast cancer were retrospectively analyzed. Menopause status was used as a surrogate marker of endogenous hormonal activity. Retroareolar 2.5cm2 ROIs were segmented from the post-processed DM images using an automated algorithm. Parenchymal texture features of skewness, coarseness, contrast, energy, homogeneity, grey-level spatial correlation, and fractal dimension were computed. Receiver operating characteristic (ROC) curve analysis was performed to evaluate feature classification performance in distinguishing between 72 pre- and 66 post-menopausal women. Logistic regression was performed to assess the independent effect of each texture feature in predicting menopause status. ROC analysis showed that texture features have inherent capacity to distinguish between pre- and post-menopausal statuses (AUC>0.5, p<0.05). Logistic regression including all texture features yielded an ROC curve with an AUC of 0.76. Addition of age at menarche, ethnicity, contraception use and hormonal replacement therapy (HRT) use lead to a modest model improvement (AUC=0.78) while texture features maintained significant contribution (p<0.05). The observed differences in parenchymal texture features between pre- and post- menopausal women suggest that mammographic texture can potentially serve as a surrogate imaging marker of endogenous hormonal activity.

Predictive value of flat-panel CT for haemorrhagic transformations in patients with acute stroke treated with thrombectomy.

PubMed

Rouchaud, Aymeric; Pistocchi, Silvia; Blanc, Raphaël; Engrand, Nicolas; Bartolini, Bruno; Piotin, Michel

2014-03-01

Haemorrhagic transformations are pejorative for patients with acute ischaemic stroke (AIS). We estimated flat-panel CT performances to detect brain parenchymal hyperdense lesions immediately after mechanical thrombectomy directly on the angiography table in patients with AIS, and its ability to predict haemorrhagic transformation. We also evaluated an easy-reading protocol for post-procedure flat-panel CT evaluation by clinicians to enable them to determine the potential risk of haemorrhage. Two neuroradiologists retrospectively reviewed post-procedural flat-panel CT and 24 h follow-up imaging. We evaluated hyperdense lesions on flat-panel CT to predict the occurrence of haemorrhagic transformation within 24 h detected with conventional imaging. Of 63 patients, 60.3% presented post-procedural parenchymal hyperdensity and 54.0% had haemorrhagic transformation. Significantly more patients with hyperdense lesions on post-thrombectomy flat-panel CT presented haemorrhagic transformation (84.2% vs 8.0%; p<0.0001). No significant haemorrhagic transformations were detected for patients without parenchymal hyperdensity. Sensitivity and specificity of hyperdense lesions on flat-panel CT for the prediction of haemorrhagic transformation were 94.1% (80.3-99.3%) and 79.3% (60.3-92.0%), respectively. The positive and negative predictive values for the occurrence of haemorrhage were 84.2% (68.8-94.0%) and 92.0% (74.0-99.0%), respectively. For significant parenchymal haemorrhage type 2, sensitivity and negative predictive values were 100%. We observed good homogeneity between the different readers. Hyperdensity on post-procedural flat-panel CT was associated with a tendency for higher risk of death and lower risk of good clinical outcome. Flat-panel CT appears to be a good tool to detect brain parenchymal hyperdensities after mechanical thrombectomy in patients with AIS and to predict haemorrhagic transformation.

Effect of bovine somatotropin and rumen-undegradable protein on mammary growth of prepubertal dairy heifers and subsequent milk production.

PubMed

Capuco, A V; Dahl, G E; Wood, D L; Moallem, U; Erdman, R E

2004-11-01

Rapid body growth during the prepubertal period may be associated with reductions in mammary parenchymal growth and subsequent milk yield. The objective of this study was to test effects of dietary rumen-undegradable protein (RUP) and administration of recombinant bovine somatotropin (bST) during the prepubertal period on mammary growth and milk yield of dairy heifers. Seventy-two Holstein heifers were used in the experiment. At 90 d of age, 8 heifers were slaughtered before initiation of treatment. Remaining heifers were assigned randomly to 1 of 4 treatments. Treatments consisted of a control diet (5.9% RUP, 14.9% CP, DM basis) or RUP-supplemented diet (control diet plus 2% added RUP) with or without 0.1 mg of bST/kg of BW per day applied in a 2 x 2 factorial design. A total of 6 heifers per treatment (3 each at 5 and 10 mo of age) were slaughtered for mammary tissue analysis. Remaining heifers were bred to evaluate impact of treatment on subsequent milk yield and composition. Mammary parenchymal growth was not affected by RUP or bST treatment. Total parenchymal mass increased from 16 to 364 g, and parenchymal DNA from 58 to 1022 mg from 3 to 10 mo of age, respectively. Furthermore, number of mammary epithelial cells likely was not affected by diet or bST because the epithelial cell proliferation index, assessed by Ki-67 labeling, was not affected by treatment, nor was total parenchymal DNA and lipid content. Neither deleterious effects of increased rates of gain nor positive effects of bST were evident in prepubertal mammary growth. Subsequent milk production and composition was not different among treatments.

Robot-assisted laparoscopic partial nephrectomy versus laparoscopic partial nephrectomy: A propensity score-matched comparative analysis of surgical outcomes and preserved renal parenchymal volume.

PubMed

Tachibana, Hidekazu; Takagi, Toshio; Kondo, Tsunenori; Ishida, Hideki; Tanabe, Kazunari

2018-04-01

To compare surgical outcomes, including renal function and the preserved renal parenchymal volume, between robot-assisted laparoscopic partial nephrectomy and laparoscopic partial nephrectomy using propensity score-matched analyses. In total, 253 patients, with a normal contralateral kidney, who underwent laparoscopic partial nephrectomy (n = 131) or robot-assisted laparoscopic partial nephrectomy (n = 122) with renal arterial clamping between 2010 and 2015, were included. Patients' background and tumor factors were adjusted by propensity score matching. Surgical outcomes, including postoperative renal function, complications, warm ischemia time and preserved renal parenchymal volume, evaluated by volumetric analysis, were compared between the surgical procedures. After matching, 64 patients were assigned to each group. The mean age was 56-57 years, and the mean tumor size was 22 mm. Approximately 50% of patients had low complexity tumors (RENAL nephrometry score 4-7). The incidence rate of acute kidney failure was significantly lower in the robot-assisted laparoscopic partial nephrectomy (11%) than laparoscopic partial nephrectomy (23%) group (P = 0.049), and warm ischemia time shorter in the robot-assisted laparoscopic partial nephrectomy (17 min) than laparoscopic partial nephrectomy (25 min) group (P < 0.0001). The preservation rate of renal function, measured by the estimated glomerular filtration rate, at 6 months post-surgery was 96% for robot-assisted laparoscopic partial nephrectomy and 90% for laparoscopic partial nephrectomy (P < 0.0001). The preserved renal parenchymal volume was higher for robot-assisted laparoscopic partial nephrectomy (89%) than laparoscopic partial nephrectomy (77%; P < 0.0001). The rate of perioperative complications, surgical margin status and length of hospital stay were equivalent for both techniques. Robot-assisted laparoscopic partial nephrectomy allows to achieve better preservation of renal function and parenchymal volume than laparoscopic partial nephrectomy. © 2018 The Japanese Urological Association.

Relative enhanced diffusivity: noise sensitivity, protocol optimization, and the relation to intravoxel incoherent motion.

PubMed

While, Peter T; Teruel, Jose R; Vidić, Igor; Bathen, Tone F; Goa, Pål Erik

2018-06-01

To explore the relationship between relative enhanced diffusivity (RED) and intravoxel incoherent motion (IVIM), as well as the impact of noise and the choice of intermediate diffusion weighting (b value) on the RED parameter. A mathematical derivation was performed to cast RED in terms of the IVIM parameters. Noise analysis and b value optimization was conducted by using Monte Carlo calculations to generate diffusion-weighted imaging data appropriate to breast and liver tissue at three different signal-to-noise ratios. RED was shown to be approximately linearly proportional to the IVIM parameter f, inversely proportional to D and to follow an inverse exponential decay with respect to D*. The choice of intermediate b value was shown to be important in minimizing the impact of noise on RED and in maximizing its discriminatory power. RED was shown to be essentially a reparameterization of the IVIM estimates for f and D obtained with three b values. RED imaging in the breast and liver should be performed with intermediate b values of 100 and 50 s/mm 2 , respectively. Future clinical studies involving RED should also estimate the IVIM parameters f and D using three b values for comparison.

Prognostic value of three-dimensional ultrasound for fetal hydronephrosis

PubMed Central

WANG, JUNMEI; YING, WEIWEN; TANG, DAXING; YANG, LIMING; LIU, DONGSHENG; LIU, YUANHUI; PAN, JIAOE; XIE, XING

2015-01-01

The present study evaluated the prognostic value of three-dimensional ultrasound for fetal hydronephrosis. Pregnant females with fetal hydronephrosis were enrolled and a novel three-dimensional ultrasound indicator, renal parenchymal volume/kidney volume, was introduced to predict the postnatal prognosis of fetal hydronephrosis in comparison with commonly used ultrasound indicators. All ultrasound indicators of fetal hydronephrosis could predict whether postnatal surgery was required for fetal hydronephrosis; however, the predictive performance of renal parenchymal volume/kidney volume measurements as an individual indicator was the highest. In conclusion, ultrasound is important in predicting whether postnatal surgery is required for fetal hydronephrosis, and the three-dimensional ultrasound indicator renal parenchymal volume/kidney volume has a high predictive performance. Furthermore, the majority of cases of fetal hydronephrosis spontaneously regress subsequent to birth, and the regression time is closely associated with ultrasound indicators. PMID:25667626

Imaging patterns and focal lesions in fatty liver: a pictorial review.

PubMed

Venkatesh, Sudhakar K; Hennedige, Tiffany; Johnson, Geoffrey B; Hough, David M; Fletcher, Joel G

2017-05-01

Non-alcoholic fatty liver disease is the most common cause of chronic liver disease and affects nearly one-third of US population. With the increasing trend of obesity in the population, associated fatty change in the liver will be a common feature observed in imaging studies. Fatty liver causes changes in liver parenchyma appearance on imaging modalities including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) and may affect the imaging characteristics of focal liver lesions (FLLs). The imaging characteristics of FLLs were classically described in a non-fatty liver. In addition, focal fatty change and focal fat sparing may also simulate FLLs. Knowledge of characteristic patterns of fatty change in the liver (diffuse, geographical, focal, subcapsular, and perivascular) and their impact on the detection and characterization of FLL is therefore important. In general, fatty change may improve detection of FLLs on MRI using fat suppression sequences, but may reduce sensitivity on a single-phase (portal venous) CT and conventional ultrasound. In patients with fatty liver, MRI is generally superior to ultrasound and CT for detection and characterization of FLL. In this pictorial essay, we describe the imaging patterns of fatty change in the liver and its effect on detection and characterization of FLLs on ultrasound, CT, MRI, and PET.

[Intracranial granulocytic sarcoma extending from the posterior fossa to the carotid space via the jugular foramen: a case report].

PubMed

Baba, Shiro; Matsuo, Takayuki; Ishizaka, Shunsuke; Morikawa, Minoru; Suyama, Kazuhiko; Nagata, Izumi

2010-01-01

Granulocytic sarcoma consists of neoplastic granulocytic precursors and myeloblasts. It is a focal lesion seen in 2-10.9% of acute myelogenous leukaemia (AML) patients. It usually develops either concurrently with the AML or after a remission. On rare occasions, it may be an initial manifestation of AML. Most common involvement sites are bone, periostium, soft tissue, lymph nodes and skin. Intracranial granulocytic sarcoma rarely occurs in meningeal or parenchymal form. We present an extremely rare case of intracranial granulocytic sarcoma extending from the posterior fossa to the carotid space via the jugular foramen in a 69 year old female. This form of involvement has not been previously reported. On MRI, the lesion appears isointense compared with normal grey matter in T1 and T2 weighted images and shows homogeneous contrast enhancement. With these findings, it is difficult to differentiate the lesion from other extraaxial tumours such as meningioma, paraganglioma, schwannoma, carcinoma, metastatic tumor, malignant lymphoma. However, granulocytic sarcoma, densely increased tumour cells restrict diffusion and reduce the extracellular volume fraction, tends to be markedly hyperintense on diffusion-weighted MR images and exhibits a marked decrease in ADC values. Therefore, DWI may be helpful in differentiating granulocytic sarcoma from other intracranial lesions.

Development and maintenance of the brain's immune toolkit: Microglia and non-parenchymal brain macrophages.

PubMed

Lopez-Atalaya, Jose P; Askew, Katharine E; Sierra, Amanda; Gomez-Nicola, Diego

2018-06-01

Microglia and non-parenchymal macrophages located in the perivascular space, the meninges and the choroid plexus are independent immune populations that play vital roles in brain development, homeostasis, and tissue healing. Resident macrophages account for a significant proportion of cells in the brain and their density remains stable throughout the lifespan thanks to constant turnover. Microglia develop from yolk sac progenitors, later evolving through intermediate progenitors in a fine-tuned process in which intrinsic factors and external stimuli combine to progressively sculpt their cell type-specific transcriptional profiles. Recent evidence demonstrates that non-parenchymal macrophages are also generated during early embryonic development. In recent years, the development of powerful fate mapping approaches combined with novel genomic and transcriptomic methodologies have greatly expanded our understanding of how brain macrophages develop and acquire specialized functions, and how cell population dynamics are regulated. Here, we review the transcription factors, epigenetic remodeling, and signaling pathways orchestrating the embryonic development of microglia and non-parenchymal macrophages. Next, we describe the dynamics of the macrophage populations of the brain and discuss the role of progenitor cells, to gain a better understanding of their functions in the healthy and diseased brain. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 561-579, 2018. © 2017 The Authors Developmental Neurobiology Published by Wiley Periodicals, Inc.

Subarachnoid Hemorrhage Severely Impairs Brain Parenchymal Cerebrospinal Fluid Circulation in Nonhuman Primate.

PubMed

Goulay, Romain; Flament, Julien; Gauberti, Maxime; Naveau, Michael; Pasquet, Nolwenn; Gakuba, Clement; Emery, Evelyne; Hantraye, Philippe; Vivien, Denis; Aron-Badin, Romina; Gaberel, Thomas

2017-08-01

Subarachnoid hemorrhage (SAH) is a devastating form of stroke with neurological outcomes dependent on the occurrence of delayed cerebral ischemia. It has been shown in rodents that some of the mechanisms leading to delayed cerebral ischemia are related to a decreased circulation of the cerebrospinal fluid (CSF) within the brain parenchyma. Here, we evaluated the cerebral circulation of the CSF in a nonhuman primate in physiological condition and after SAH. We first evaluated in physiological condition the circulation of the brain CSF in Macaca facicularis , using magnetic resonance imaging of the temporal DOTA-Gd distribution after its injection into the CSF. Then, animals were subjected to a minimally invasive SAH before an MRI evaluation of the impact of SAH on the brain parenchymal CSF circulation. We first demonstrate that the CSF actively penetrates the brain parenchyma. Two hours after injection, almost the entire brain is labeled by DOTA-Gd. We also show that our model of SAH in nonhuman primate displays the characteristics of SAH in humans and leads to a dramatic impairment of the brain parenchymal circulation of the CSF. The CSF actively penetrates within the brain parenchyma in the gyrencephalic brain, as described for the glymphatic system in rodent. This parenchymal CSF circulation is severely impaired by SAH. © 2017 American Heart Association, Inc.

One-month apparent diffusion coefficient correlates with response to radiofrequency ablation of hepatocellular carcinoma.

PubMed

Barat, Maxime; Fohlen, Audrey; Cassinotto, Christophe; Jannot, Anne Sophie; Dautry, Raphael; Pelage, Jean-Pierre; Boudiaf, Mourad; Pocard, Marc; Eveno, Clarisse; Taouli, Bachir; Soyer, Philippe; Dohan, Anthony

2017-06-01

To assess whether apparent diffusion coefficient (ADC) values at 1 and 3 months after radiofrequency ablation (RFA) may be associated with a favorable response to therapy for hepatocellular carcinoma (HCC) and liver metastases. Fifty-nine patients with HCC (n = 35) or liver metastases (n = 24) who underwent 1.5T diffusion-weighted magnetic resonance imaging (DWMRI) at 1 and 3 months post-RFA were included. ADC values of patients with local tumor recurrence were compared to those without local recurrence. A subgroup analysis was performed for HCC and metastases. Thirty-eight HCC and 27 metastases were evaluated. The ADC value of HCC at 1 month after RFA was lower in recurrent tumors (0.957 ± 0.229 [SD] × 10 -3 mm 2 ) compared to tumors with complete response (1.414 ± 0.322 [SD] × 10 -3 mm 2 /s, P = 0.006). At multivariate analysis, ADC at 1 month was the single independent variable associated with recurrence for HCC (area under the receiver operating characteristic curve = 0.860). No significant association was observed for liver metastases (P = 0.089). A low ADC value at 1 month after RFA is associated with an early local recurrence of HCC. This study does not confirm that such association exists for hepatic metastases. 3 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;45:1648-1658. © 2016 International Society for Magnetic Resonance in Medicine.

[A case of fulminant hepatic failure secondary to hepatic metastasis of small cell lung carcinoma].

PubMed

Hwang, Young Tae; Shin, Jung Woo; Lee, Jun Ho; Hwang, Dae Sung; Eum, Jun Bum; Choi, Hye Jeong; Park, Neung Hwa

2007-12-01

Although liver metastasis is commonly found in cancer patients, fulminant hepatic failure secondary to diffuse cancer infiltration into the liver is rare. Liver metastasis-induced fulminant hepatic failure has been reported in patients with primary cancer of the gastrointestinal tract, breast and uroepithelium, and in patients with melanoma and hematologic malignancy. Small cell lung cancer is so highly invasive that hepatic metastasis is common, but rapid progression to fulminant hepatic failure is extremely rare. We report here on a case of a patient who died because of rapid progression to fulminant hepatic failure as a result of hepatic metastasis of small cell lung carcinoma.

Hepatic gas gangrene following orthotopic liver transplantation: three cases treated with re-transplantation and a review of the literature.

PubMed

Doblecki-Lewis, S; Palaios, E; Bejarano, P A; Tzakis, A G; Selvaggi, G; Morris, M I

2008-07-01

Gas gangrene is a rare and devastating infectious process that can occur after liver transplantation, most often following hepatic artery thrombosis. We here report 3 cases of gas gangrene following orthotopic liver transplantation. Blood cultures were positive for Clostridium clostridiiforme in one case. In 2 other cases liver tissue from explanted specimens was positive for Enterobacter cloacae. Ultrasound demonstrated hepatic artery thrombosis and computed tomography imaging revealed diffuse liver necrosis with gas formation in each case. All 3 patients were successfully treated with a combination of antibiotics and emergent re-transplantation. We review previously published cases of gas gangrene after liver transplant and emphasize the importance of hepatic artery thrombosis in the development of this syndrome as well as the frequent involvement of non-clostridial organisms. Early diagnosis and aggressive combined medical and surgical treatment including re-transplantation are essential for successful treatment of these rare and catastrophic infections.

Liver lesions produced by aflatoxins in Rana catesbeiana (bullfrog).

PubMed

Grassi, Tony Fernando; Pires, Paulo Wagner; Barbisan, Luis Fernando; Pai-Silva, Maeli Dal; Said, Roueda Abou; de Camargo, João Lauro Viana

2007-09-01

This study describes alterations induced in Rana catesbeiana (bullfrog) liver after extended dietary exposure to aflatoxins (AFs). Bullfrogs of both sexes were fed for 120 days a commercial chow blended with a rice bran-based mixture of AFs containing 667.0, 11.65, 141.74, and 3.53 mg/kg of AFs B1, B2, G1, and G2, respectively. Animals were sacrificed on study days 45, 90, and 120. Severe and progressive liver lesions with structural collapse, increased hepatocyte and biliary duct cell proliferation, appearance of basophilic hepatocytes, and diffuse scarring, were observed at all time points. There were no quantitative alterations in the liver melanomacrophage centers of the AFs-exposed animals. Increased amounts of lipid hydroperoxides, indicative of ongoing oxidative stress, were more evident in the Addutor magnum muscle than in the AFs-damaged livers. No tumors were found in the R. catesbeiana livers after 120 days of exposure to relatively high doses of AFs.

Combining diffusion-weighted MRI with Gd-EOB-DTPA-enhanced MRI improves the detection of colorectal liver metastases.

PubMed

Koh, D-M; Collins, D J; Wallace, T; Chau, I; Riddell, A M

2012-07-01

To compare the diagnostic accuracy of gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced MRI, diffusion-weighted MRI (DW-MRI) and a combination of both techniques for the detection of colorectal hepatic metastases. 72 patients with suspected colorectal liver metastases underwent Gd-EOB-DTPA MRI and DW-MRI. Images were retrospectively reviewed with unenhanced T(1) and T(2) weighted images as Gd-EOB-DTPA image set, DW-MRI image set and combined image set by two independent radiologists. Each lesion detected was scored for size, location and likelihood of metastasis, and compared with surgery and follow-up imaging. Diagnostic accuracy was compared using receiver operating characteristics and interobserver agreement by kappa statistics. 417 lesions (310 metastases, 107 benign) were found in 72 patients. For both readers, diagnostic accuracy using the combined image set was higher [area under the curve (Az)=0.96, 0.97] than Gd-EOB-DTPA image set (Az=0.86, 0.89) or DW-MRI image set (Az=0.93, 0.92). Using combined image set improved identification of liver metastases compared with Gd-EOB-DTPA image set (p<0.001) or DW-MRI image set (p<0.001). There was very good interobserver agreement for lesion classification (κ=0.81-0.88). Combining DW-MRI with Gd-EOB-DTPA-enhanced T(1) weighted MRI significantly improved the detection of colorectal liver metastases.

Non invasive tools for the diagnosis of liver cirrhosis.

PubMed

Soresi, Maurizio; Giannitrapani, Lydia; Cervello, Melchiorre; Licata, Anna; Montalto, Giuseppe

2014-12-28

Liver cirrhosis (LC), the end stage of many forms of chronic hepatitis of different etiologies is a diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules surrounded by annular fibrosis. This chronic progressive clinical condition, leads to liver cell failure and portal hypertension, which can favour the onset of hepatocellular carcinoma. Defining the phase of the natural history is crucial for therapeutic choice and prognosis. Liver biopsy is currently considered the best available standard of reference but it has some limits, so alternative tools have been developed to substitute liver biopsy when assessing liver fibrosis. Serum markers offer a cost-effective alternative to liver biopsy being less invasive and theoretically without complications. They can be classified into direct and indirect markers which may be used alone or in combination to produce composite scores. Diagnostic imaging includes a number of instruments and techniques to estimate liver fibrosis and cirrhosis like ultrasound (US), US Doppler, contrast enhanced US and Elastography. US could be used for the diagnosis of advanced LC while is not able to evaluate progression of fibrosis, in this case Elastography is more reliable. This review aims to revise the most recent data from the literature about non invasive methods useful in defining liver fibrosis.

Non invasive tools for the diagnosis of liver cirrhosis

PubMed Central

Soresi, Maurizio; Giannitrapani, Lydia; Cervello, Melchiorre; Licata, Anna; Montalto, Giuseppe

2014-01-01

Liver cirrhosis (LC), the end stage of many forms of chronic hepatitis of different etiologies is a diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules surrounded by annular fibrosis. This chronic progressive clinical condition, leads to liver cell failure and portal hypertension, which can favour the onset of hepatocellular carcinoma. Defining the phase of the natural history is crucial for therapeutic choice and prognosis. Liver biopsy is currently considered the best available standard of reference but it has some limits, so alternative tools have been developed to substitute liver biopsy when assessing liver fibrosis. Serum markers offer a cost-effective alternative to liver biopsy being less invasive and theoretically without complications. They can be classified into direct and indirect markers which may be used alone or in combination to produce composite scores. Diagnostic imaging includes a number of instruments and techniques to estimate liver fibrosis and cirrhosis like ultrasound (US), US Doppler, contrast enhanced US and Elastography. US could be used for the diagnosis of advanced LC while is not able to evaluate progression of fibrosis, in this case Elastography is more reliable. This review aims to revise the most recent data from the literature about non invasive methods useful in defining liver fibrosis. PMID:25561782

Quantitative Assessment of Liver Fat with Magnetic Resonance Imaging and Spectroscopy

PubMed Central

Reeder, Scott B.; Cruite, Irene; Hamilton, Gavin; Sirlin, Claude B.

2011-01-01

Hepatic steatosis is characterized by abnormal and excessive accumulation of lipids within hepatocytes. It is an important feature of diffuse liver disease, and the histological hallmark of non-alcoholic fatty liver disease (NAFLD). Other conditions associated with steatosis include alcoholic liver disease, viral hepatitis, HIV and genetic lipodystrophies, cystic fibrosis liver disease, and hepatotoxicity from various therapeutic agents. Liver biopsy, the current clinical gold standard for assessment of liver fat, is invasive and has sampling errors, and is not optimal for screening, monitoring, clinical decision making, or well-suited for many types of research studies. Non-invasive methods that accurately and objectively quantify liver fat are needed. Ultrasound (US) and computed tomography (CT) can be used to assess liver fat but have limited accuracy as well as other limitations. Magnetic resonance (MR) techniques can decompose the liver signal into its fat and water signal components and therefore assess liver fat more directly than CT or US. Most magnetic resonance (MR) techniques measure the signal fat-fraction (the fraction of the liver MR signal attributable to liver fat), which may be confounded by numerous technical and biological factors and may not reliably reflect fat content. By addressing the factors that confound the signal fat-fraction, advanced MR techniques measure the proton density fat-fraction (the fraction of the liver proton density attributable to liver fat), which is a fundamental tissue property and a direct measure of liver fat content. These advanced techniques show promise for accurate fat quantification and are likely to be commercially available soon. PMID:22025886

Spatio-temporal Model of Xenobiotic Distribution and Metabolism in an in Silico Mouse Liver Lobule

NASA Astrophysics Data System (ADS)

Fu, Xiao; Sluka, James; Clendenon, Sherry; Glazier, James; Ryan, Jennifer; Dunn, Kenneth; Wang, Zemin; Klaunig, James

Our study aims to construct a structurally plausible in silico model of a mouse liver lobule to simulate the transport of xenobiotics and the production of their metabolites. We use a physiologically-based model to calculate blood-flow rates in a network of mouse liver sinusoids and simulate transport, uptake and biotransformation of xenobiotics within the in silico lobule. Using our base model, we then explore the effects of variations of compound-specific (diffusion, transport and metabolism) and compound-independent (temporal alteration of blood flow pattern) parameters, and examine their influence on the distribution of xenobiotics and metabolites. Our simulations show that the transport mechanism (diffusive and transporter-mediated) of xenobiotics and blood flow both impact the regional distribution of xenobiotics in a mouse hepatic lobule. Furthermore, differential expression of metabolic enzymes along each sinusoid's portal to central axis, together with differential cellular availability of xenobiotics, induce non-uniform production of metabolites. Thus, the heterogeneity of the biochemical and biophysical properties of xenobiotics, along with the complexity of blood flow, result in different exposures to xenobiotics for hepatocytes at different lobular locations. We acknowledge support from National Institute of Health GM 077138 and GM 111243.

Elastase-Induced Parenchymal Disruption and Airway Hyper Responsiveness in Mouse Precision Cut Lung Slices: Toward an Ex vivo COPD Model.

PubMed

Van Dijk, Eline M; Culha, Sule; Menzen, Mark H; Bidan, Cécile M; Gosens, Reinoud

2016-01-01

Background: COPD is a progressive lung disease characterized by emphysema and enhanced bronchoconstriction. Current treatments focused on bronchodilation can delay disease progression to some extent, but recovery or normalization of loss of lung function is impossible. Therefore, novel therapeutic targets are needed. The importance of the parenchyma in airway narrowing is increasingly recognized. In COPD, the parenchyma and extracellular matrix are altered, possibly affecting airway mechanics and enhancing bronchoconstriction. Our aim was to set up a comprehensive ex vivo Precision Cut Lung Slice (PCLS) model with a pathophysiology resembling that of COPD and integrate multiple readouts in order to study the relationship between parenchyma, airway functionality, and lung repair processes. Methods: Lungs of C57Bl/6J mice were sliced and treated ex vivo with elastase (2.5 μg/ml) or H 2 O 2 (200 μM) for 16 h. Following treatment, parenchymal structure, airway narrowing, and gene expression levels of alveolar Type I and II cell repair were assessed. Results: Following elastase, but not H 2 O 2 treatment, slices showed a significant increase in mean linear intercept (Lmi), reflective of emphysema. Only elastase-treated slices showed disorganization of elastin and collagen fibers. In addition, elastase treatment lowered both alveolar Type I and II marker expression, whereas H 2 O 2 stimulation lowered alveolar Type I marker expression only. Furthermore, elastase-treated slices showed enhanced methacholine-induced airway narrowing as reflected by increased pEC50 (5.87 at basal vs. 6.50 after elastase treatment) and Emax values (47.96 vs. 67.30%), and impaired chloroquine-induced airway opening. The increase in pEC50 correlated with an increase in mean Lmi. Conclusion: Using this model, we show that structural disruption of elastin fibers leads to impaired alveolar repair, disruption of the parenchymal compartment, and altered airway biomechanics, enhancing airway contraction. This finding may have implications for COPD, as the amount of elastin fiber and parenchymal tissue disruption is associated with disease severity. Therefore, we suggest that PCLS can be used to model certain aspects of COPD pathophysiology and that the parenchymal tissue damage observed in COPD contributes to lung function decline by disrupting airway biomechanics. Targeting the parenchymal compartment may therefore be a promising therapeutic target in the treatment of COPD.

Modes of action and species-specific effects of di-(2-ethylhexyl)phthalate in the liver.

PubMed

Rusyn, Ivan; Peters, Jeffrey M; Cunningham, Michael L

2006-05-01

The industrial plasticizer di-(2-ethylhexyl)phthalate (DEHP) is used in manufacturing of a wide variety of polyvinyl chloride (PVC)-containing medical and consumer products. DEHP belongs to a class of chemicals known as peroxisome proliferators (PPs). PPs are a structurally diverse group of compounds that share many (but perhaps not all) biological effects and are characterized as non-genotoxic rodent carcinogens. This review focuses on the effect of DEHP in liver, a primary target organ for the pleiotropic effects of DEHP and other PPs. Specifically, liver parenchymal cells, identified herein as hepatocytes, are a major cell type that are responsive to exposure to PPs, including DEHP; however, other cell types in the liver may also play a role. The PP-induced increase in the number and size of peroxisomes in hepatocytes, so called 'peroxisome proliferation' that results in elevation of fatty acid metabolism, is a hallmark response to these compounds in the liver. A link between peroxisome proliferation and tumor formation has been a predominant, albeit questioned, theory to explain the cause of a hepatocarcinogenic effect of PPs. Other molecular events, such as induction of cell proliferation, decreased apoptosis, oxidative DNA damage, and selective clonal expansion of the initiated cells have been also been proposed to be critically involved in PP-induced carcinogenesis in liver. Considerable differences in the metabolism and molecular changes induced by DEHP in the liver, most predominantly the activation of the nuclear receptor peroxisome proliferator-activated receptor (PPAR)alpha, have been identified between species. Both sexes of rats and mice develop adenomas and carcinomas after prolonged feeding with DEHP; however, limited DEHP-specific human data are available, even though exposure to DEHP and other phthalates is common in the general population. This likely constitutes the largest gap in our knowledge on the potential for DEHP to cause liver cancer in humans. Overall, it is believed that the sequence of key events that are relevant to DEHP-induced liver carcinogenesis in rodents involves the following events whereby the combination of the molecular signals and multiple pathways, rather than a single hallmark event (such as induction of PPARalpha and peroxisomal genes, or cell proliferation) contribute to the formation of tumors: (i) rapid metabolism of the parental compound to primary and secondary bioactive metabolites that are readily absorbed and distributed throughout the body; (ii) receptor-independent activation of hepatic macrophages and production of oxidants; (iii) activation of PPARalpha in hepatocytes and sustained increase in expression of peroxisomal and non-peroxisomal metabolism-related genes; (iv) enlargement of many hepatocellular organelles (peroxisomes, mitochondria, etc.); (v) rapid but transient increase in cell proliferation, and a decrease in apoptosis; (vi) sustained hepatomegaly; (vii) chronic low-level oxidative stress and accumulation of DNA damage; (viii) selective clonal expansion of the initiated cells; (ix) appearance of the pre-neoplastic nodules; (x) development of adenomas and carcinomas.

Comparison of magnetic resonance elastography and diffusion-weighted imaging for differentiating benign and malignant liver lesions.

PubMed

Hennedige, Tiffany P; Hallinan, James Thomas Patrick Decourcy; Leung, Fiona P; Teo, Lynette Li San; Iyer, Sridhar; Wang, Gang; Chang, Stephen; Madhavan, Krishna Kumar; Wee, Aileen; Venkatesh, Sudhakar K

2016-02-01

Comparison of magnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI) for differentiating malignant and benign focal liver lesions (FLLs). Seventy-nine subjects with 124 FLLs (44 benign and 80 malignant) underwent both MRE and DWI. MRE was performed with a modified gradient-echo sequence and DWI with a free breathing technique (b = 0.500). Apparent diffusion coefficient (ADC) maps and stiffness maps were generated. FLL mean stiffness and ADC values were obtained by placing regions of interest over the FLLs on stiffness and ADC maps. The accuracy of MRE and DWI for differentiation of benign and malignant FLL was compared using receiver operating curve (ROC) analysis. There was a significant negative correlation between stiffness and ADC (r = -0.54, p < 0.0001) of FLLs. Malignant FLLs had significantly higher mean stiffness (7.9kPa vs. 3.1kPa, p < 0.001) and lower mean ADC (129 vs. 200 × 10(-3)mm(2)/s, p < 0.001) than benign FLLs. The sensitivity/specificity/positive predictive value/negative predictive value for differentiating malignant from benign FLLs with MRE (cut-off, >4.54kPa) and DWI (cut-off, <151 × 10(-3)mm(2)/s) were 96.3/95.5/97.5/93.3% (p < 0.001) and 85/81.8/88.3/75% (p < 0.001), respectively. ROC analysis showed significantly higher accuracy for MRE than DWI (0.986 vs. 0.82, p = 0.0016). MRE is significantly more accurate than DWI for differentiating benign and malignant FLLs. • MRE is superior to DWI for differentiating benign and malignant focal liver lesions. • Benign lesions with large fibrous components may have higher stiffness with MRE. • Cholangiocarcinomas tend to have higher stiffness than hepatocellular carcinomas. • Hepatocellular adenomas tend to have lower stiffness than focal nodular hyperplasia. • MRE is superior to conventional MRI in differentiating benign and malignant liver lesions.

Liver Function Assessment by Magnetic Resonance Imaging.

PubMed

Ünal, Emre; Akata, Deniz; Karcaaltincaba, Musturay

2016-12-01

Liver function assessment by hepatocyte-specific contrast-enhanced magnetic resonance imaging is becoming a new biomarker. Liver function can be assessed by T1 mapping (reduction rate) and signal intensity measurement (relative enhancement ratio) before and after GD-EOB-DTPA (gadoxetic acid) administration, as alternative to Tc-99m galactosyl serum albumin scintigraphy, 99m Tc-labeled mebrofenin scintigraphy, and indocyanine green clearance test. Magnetic resonance imaging assessment of liver function can enable diagnosis of cirrhosis, nonalcoholic fatty liver disease associated fibrosis and steatohepatitis, primary sclerosing cholangitis, toxic hepatitis, and chemotherapy and radiotherapy-related changes, which may be only visible on hepatobiliary phase images. Simple visual assessment of signal intensity at hepatobiliary phase images is important for the diagnosis of different patterns of liver dysfunction including diffuse, lobar, segmental, and subsegmental forms. Furthermore, preoperative assessment of liver function is feasible before oncologic hepatic surgery, which may be important to prevent posthepatectomy liver failure and to estimate future remnant volume. Functional magnetic resonance cholangiography obtained by T1-weighted images at hepatobiliary phase can allow diagnosis of acalculous cholecystitis, biliary leakage, bile reflux to the stomach, sphincter of oddi dysfunction, and lesions with communication to biliary tree. Functional information can be easily obtained when Gd-EOB-DTPA is used for liver magnetic resonance imaging. Copyright © 2016 Elsevier Inc. All rights reserved.

IMPACT OF VENTILATION FREQUENCY AND PARENCHYMAL STIFFNESS ON FLOW AND PRESSURE DISTRIBUTION IN A CANINE LUNG MODEL

PubMed Central

Amini, Reza; Kaczka, David W.

2013-01-01

To determine the impact of ventilation frequency, lung volume, and parenchymal stiffness on ventilation distribution, we developed an anatomically-based computational model of the canine lung. Each lobe of the model consists of an asymmetric branching airway network subtended by terminal, viscoelastic acinar units. The model allows for empiric dependencies of airway segment dimensions and parenchymal stiffness on transpulmonary pressure. We simulated the effects of lung volume and parenchymal recoil on global lung impedance and ventilation distribution from 0.1 to 100 Hz, with mean transpulmonary pressures from 5 to 25 cmH2O. With increasing lung volume, the distribution of acinar flows narrowed and became more synchronous for frequencies below resonance. At higher frequencies, large variations in acinar flow were observed. Maximum acinar flow occurred at first antiresonance frequency, where lung impedance achieved a local maximum. The distribution of acinar pressures became very heterogeneous and amplified relative to tracheal pressure at the resonant frequency. These data demonstrate the important interaction between frequency and lung tissue stiffness on the distribution of acinar flows and pressures. These simulations provide useful information for the optimization of frequency, lung volume, and mean airway pressure during conventional ventilation or high frequency oscillation (HFOV). Moreover our model indicates that an optimal HFOV bandwidth exists between the resonant and antiresonant frequencies, for which interregional gas mixing is maximized. PMID:23872936