Predictors of Liver Toxicity Following Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma

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

Velec, Michael; Haddad, Carol R.; Craig, Tim

Purpose: To identify risk factors associated with a decline in liver function after stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma. Methods and Materials: Data were analyzed from patients with hepatocellular carcinoma treated on clinical trials of 6-fraction SBRT. Liver toxicity was defined as an increase in Child-Pugh (CP) score ≥2 three months after SBRT. Clinical factors, SBRT details, and liver dose-volume histogram (DVH) parameters were tested for association with toxicity using logistic regression. CP class B patients were analyzed separately. Results: Among CP class A patients, 101 were evaluable, with a baseline score of A5 (72%) or A6 (28%).more » Fifty-three percent had portal vein thrombus. The median liver volume was 1286 cc (range, 766-3967 cc), and the median prescribed dose was 36 Gy (range, 27-54 Gy). Toxicity was seen in 26 patients (26%). Thrombus, baseline CP of A6, and lower platelet count were associated with toxicity on univariate analysis, as were several liver DVH-based parameters. Absolute and spared liver volumes were not significant. On multivariate analysis for CP class A patients, significant associations were found for baseline CP score of A6 (odds ratio [OR], 4.85), lower platelet count (OR, 0.90; median, 108 × 10{sup 9}/L vs 150 × 10{sup 9}/L), higher mean liver dose (OR, 1.33; median, 16.9 Gy vs 14.7 Gy), and higher dose to 800 cc of liver (OR, 1.11; median, 14.3 Gy vs 6.0 Gy). With 13 CP-B7 patients included or when dose to 800 cc of liver was replaced with other DVH parameters (eg, dose to 700 or 900 cc of liver) in the multivariate analysis, effective volume and portal vein thrombus were associated with an increased risk. Conclusions: Baseline CP scores and higher liver doses (eg, mean dose, effective volume, doses to 700-900 cc) were strongly associated with liver function decline 3 months after SBRT. A lower baseline platelet count and portal vein thrombus were also associated with an increased risk.« less

Living Liver Donor Selection and Resection at the University of Tokyo Hospital.

PubMed

Akamatsu, N; Kokudo, N

2016-05-01

Donor selection and operative procedures for adult-to-adult living donor liver transplantation at the University of Tokyo are presented. Donor selection criteria are as follows: age between 20 and 65 years, within 3 degrees of consanguinity, without coercion, free from any major comorbidities, body mass index (BMI) < 30, and ABO blood type identical or compatible. Liver biopsy is indicated for BMI > 25 kg/m(2) or any liver function abnormality, and those with macroscopic steatosis >10% are rejected. Thereafter, an indocyanine green retention test and dynamic computed tomography are evaluated. Graft type is determined based on computed tomography volumetry. An estimated graft volume of 40% to recipient standard liver volume ratio is the lower limit. For donor safety, the left liver is the first choice, provided that it satisfies the lower limit. Otherwise, right liver harvesting is indicated, providing that the estimated remnant liver volume is >30% of the donor's total liver volume. A posterior sector graft is a possible option. Between 1996 and 2014, 462 donor hepatectomies were performed, with 257 right livers, 179 left livers, and 26 posterior sectors. There was no mortality, and the incidence of morbidity grades I, II, IIIa, and IIIb was 16%, 5%, 5%, and 3%, respectively, without a difference between right and left liver grafts. The left liver was used without impairing recipient outcome. Two aborted hepatectomies (0.4%) and 3 near-miss events (0.6%) were encountered. Maximal effort should be applied to donor selection and operation for donor safety. Copyright © 2016 Elsevier Inc. All rights reserved.

Functional image-guided stereotactic body radiation therapy planning for patients with hepatocellular carcinoma

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

Tsegmed, Uranchimeg; Kimura, Tomoki, E-mail: tkkimura@hiroshima-u.ac.jp; Nakashima, Takeo

The aim of the current planning study is to evaluate the ability of gadoxetate disodium-enhanced magnetic resonance imaging (EOB-MRI)–guided stereotactic body radiation therapy (SBRT) planning by using intensity-modulated radiation therapy (IMRT) techniques in sparing the functional liver tissues during SBRT for hepatocellular carcinoma. In this study, 20 patients with hepatocellular carcinoma were enrolled. Functional liver tissues were defined according to quantitative liver-spleen contrast ratios ≥ 1.5 on a hepatobiliary phase scan. Functional images were fused with the planning computed tomography (CT) images; the following 2 SBRT plans were designed using a “step-and-shoot” static IMRT technique for each patient: (1) an anatomicalmore » SBRT plan optimization based on the total liver; and (2) a functional SBRT plan based on the functional liver. The total prescribed dose was 48 gray (Gy) in 4 fractions. Dosimetric parameters, including dose to 95% of the planning target volume (PTV D{sub 95%}), percentages of total and functional liver volumes, which received doses from 5 to 30 Gy (V5 to V30 and fV5 to fV30), and mean doses to total and functional liver (MLD and fMLD, respectively) of the 2 plans were compared. Compared with anatomical plans, functional image-guided SBRT plans reduced MLD (mean: plan A, 5.5 Gy; and plan F, 5.1 Gy; p < 0.0001) and fMLD (mean: plan A, 5.4 Gy; and plan F, 4.9 Gy; p < 0.0001), as well as V5 to V30 and fV5 to fV30. No differences were noted in PTV coverage and nonhepatic organs at risk (OARs) doses. In conclusion, EOB-MRI–guided SBRT planning using the IMRT technique may preserve functional liver tissues in patients with hepatocellular carcinoma (HCC).« less

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.

The use of a projection method to simplify portal and hepatic vein segmentation in liver anatomy.

PubMed

Huang, Shaohui; Wang, Boliang; Cheng, Ming; Huang, Xiaoyang; Ju, Ying

2008-12-01

In living donor liver transplantation, the volume of the potential graft must be measured to ensure sufficient liver function after surgery. Couinaud divided the liver into 8 functionally independent segments. However, this method is not simple to perform in 3D space directly. Thus, we propose a rapid method to segment the liver based on the hepatic vessel tree. The most important step of this method is vascular projection. By carefully selecting a projection plane, a 3D point can be fixed in the projection plane. This greatly helps in rapid classification. This method was validated by applying it to a 3D liver depicted on CT images, and the result was in good agreement with Couinaud's classification.

Computational Modeling in Liver Surgery

PubMed Central

Christ, Bruno; Dahmen, Uta; Herrmann, Karl-Heinz; König, Matthias; Reichenbach, Jürgen R.; Ricken, Tim; Schleicher, Jana; Ole Schwen, Lars; Vlaic, Sebastian; Waschinsky, Navina

2017-01-01

The need for extended liver resection is increasing due to the growing incidence of liver tumors in aging societies. Individualized surgical planning is the key for identifying the optimal resection strategy and to minimize the risk of postoperative liver failure and tumor recurrence. Current computational tools provide virtual planning of liver resection by taking into account the spatial relationship between the tumor and the hepatic vascular trees, as well as the size of the future liver remnant. However, size and function of the liver are not necessarily equivalent. Hence, determining the future liver volume might misestimate the future liver function, especially in cases of hepatic comorbidities such as hepatic steatosis. A systems medicine approach could be applied, including biological, medical, and surgical aspects, by integrating all available anatomical and functional information of the individual patient. Such an approach holds promise for better prediction of postoperative liver function and hence improved risk assessment. This review provides an overview of mathematical models related to the liver and its function and explores their potential relevance for computational liver surgery. We first summarize key facts of hepatic anatomy, physiology, and pathology relevant for hepatic surgery, followed by a description of the computational tools currently used in liver surgical planning. Then we present selected state-of-the-art computational liver models potentially useful to support liver surgery. Finally, we discuss the main challenges that will need to be addressed when developing advanced computational planning tools in the context of liver surgery. PMID:29249974

Cross-sectional and longitudinal evaluation of liver volume and total liver fat burden in adults with nonalcoholic steatohepatitis

PubMed Central

Tang, An; Chen, Joshua; Le, Thuy-Anh; Changchien, Christopher; Hamilton, Gavin; Middleton, Michael S.; Loomba, Rohit; Sirlin, Claude B.

2014-01-01

Purpose To explore the cross-sectional and longitudinal relationships between fractional liver fat content, liver volume, and total liver fat burden. Methods In 43 adults with non-alcoholic steatohepatitis participating in a clinical trial, liver volume was estimated by segmentation of magnitude-based low-flip-angle multiecho GRE images. The liver mean proton density fat fraction (PDFF) was calculated. The total liver fat index (TLFI) was estimated as the product of liver mean PDFF and liver volume. Linear regression analyses were performed. Results Cross-sectional analyses revealed statistically significant relationships between TLFI and liver mean PDFF (R2 = 0.740 baseline/0.791 follow-up, P < 0.001 baseline/P < 0.001 follow-up), and between TLFI and liver volume (R2 = 0.352/0.452, P < 0.001/< 0.001). Longitudinal analyses revealed statistically significant relationships between liver volume change and liver mean PDFF change (R2 = 0.556, P < 0.001), between TLFI change and liver mean PDFF change (R2 = 0.920, P < 0.001), and between TLFI change and liver volume change (R2 = 0.735, P < 0.001). Conclusion Liver segmentation in combination with MRI-based PDFF estimation may be used to monitor liver volume, liver mean PDFF, and TLFI in a clinical trial. PMID:25015398

Protective effect of aqueous extract of Feronia elephantum correa leaves on thioacetamide induced liver necrosis in diabetic rats

PubMed Central

Sharma, Prashant; Bodhankar, Subhash L; Thakurdesai, Prasad A

2012-01-01

Objective To evalueate hepatoprotective effects Feronia elephantum (F. elephantum) correa against thioacetamide (TA) induced liver necrosis in diabetic rats. Methods Male wistar rats were made diabetic with alloxan (160 mg/kg) on day 0 of the study. They were intoxicated with hepatotoxicant (thioacetamide, 300 mg/kg, ip) on day 9 of study to produce liver necrosis. Effects of 7 day daily once administration (day 2 to day 9) of EF (400 and 800 mg/kg, po) were evaluated on necorosis of liver in terms of mortality, liver volume, liver weight, serum aspartate aminotransferase (AST) and serum alanine transaminase (ALT), and histopathology of liver sections (for signs of necorosis and inflammation) on day-9 of the study. Separate groups of rats with treated only with alloxan (DA control), thioacetamide (TA control) and both (TA+DA control) were maintained. Results FE significantly lowered the mortality rate and showed improvement in liver function parameters in TA-induced diabetic rats without change in liver weight, volume and serum glucose levels. Conclusions FE showed promising activity against TA-induced liver necorsis in diabetic rats and so might be useful for prevention of liver complications in DM. PMID:23569996

Abnormal Liver Function Tests in an Anorexia Nervosa Patient and an Atypical Manifestation of Refeeding Syndrome.

PubMed

Vootla, Vamshidhar R; Daniel, Myrta

2015-01-01

Refeeding syndrome is defined as electrolyte and fluid abnormalities that occur in significantly malnourished patients when they are refed orally, enterally, or parenterally. The principal manifestations include hypophosphatemia, hypokalemia, vitamin deficiencies, volume overload and edema. This can affect multiple organ systems, such as the cardiovascular, pulmonary, or neurological systems, secondary to the above-mentioned abnormalities. Rarely, patients may develop gastrointestinal symptoms and show abnormal liver function test results. We report the case of a 52-year-old woman with anorexia nervosa who developed refeeding syndrome and simultaneous elevations of liver function test results, which normalized upon the resolution of the refeeding syndrome.

Liver Function Tests Following Irreversible Electroporation of Liver Tumors: Experience in 174 Procedures.

PubMed

Froud, Tatiana; Venkat, Shree R; Barbery, Katuzka J; Gunjan, Arora; Narayanan, Govindarajan

2015-09-01

Irreversible electroporation (IRE) is a relatively new ablation modality that uses electric currents to cause cell death. It is commonly used to treat primary and secondary liver tumors in patients with normal liver function and preexisting cirrhosis. Retrospective analysis of 205 procedures sought to evaluate changes in liver function after IRE. Liver function tests (LFTs) results before and after IRE were evaluated from 174 procedures in 124 patients. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase (ALKP), and total bilirubin levels were analyzed. The study was Health Insurance Portability and Accountability Act compliant and institutional review board approved. Informed consent was waived. Changes in LFT results after IRE were compared with baseline and were followed up over time to see if they resolved. Changes were compared with volume of ablation. The greatest perturbations were in transaminase levels. The levels increased sharply within 24 hours after IRE in 129 (74.1%) procedures to extreme levels (more than 20 times the upper limit of normal in one-third of cases). Resolution occurred in 95% and was demonstrated to have occurred by a mean of approximately 10 weeks, many documented as early as 7 days after procedure. ALKP levels elevated in 10% procedures, was slower to increase, and was less likely to resolve. Total bilirubin level demonstrated 2 different patterns of elevation--early and late--and similar to ALKP, it was more likely to remain elevated. There was no increased risk in patients with cirrhosis or cholangiocarcinoma. There was no correlation of levels with volume of ablation. IRE results in significant abnormalities in LFT results, but in most of the cases, these are self-limiting, do not preclude treatment, and are similar to the changes seen after radiofrequency and cryoablation in the liver. Copyright © 2015. Published by Elsevier Inc.

Volumetric analysis and indocyanine green retention rate at 15 min as predictors of post-hepatectomy liver failure

PubMed Central

Kim, Hee Joon; Kim, Choong Young; Park, Eun Kyu; Hur, Young Hoe; Koh, Yang Seok; Kim, Hyun Jong; Cho, Chol Kyoon

2015-01-01

Objectives The actual future liver remnant (aFLR) is calculated as the ratio of remnant liver volume (RLV) to total functional liver volume (TFLV). The standardized future liver remnant (sFLR) is calculated as the ratio of RLV to standard liver volume (SLV). The aims of this study were to compare the aFLR with the sFLR and to determine criteria for safe hepatectomy using computed tomography volumetry and indocyanine green retention rate at 15 min (ICG R15). Methods Medical records and volumetric measurements were obtained retrospectively for 81 patients who underwent right hemi-hepatectomy for malignant hepatic tumours from January 2010 to November 2013. The sFLR was compared with the aFLR, and a ratio of sFLR to ICG R15 as a predictor of postoperative hepatic function was established. Results In patients without cirrhosis, the sFLR showed a stronger correlation with the total serum bilirubin level than the aFLR (R2 = 0.499 versus R2 = 0.239). Post-hepatectomy liver failure developed only in the group with an sFLR of <25%, regardless of ICG R15. In patients with cirrhosis, the aFLR and sFLR had no correlation with postoperative total serum bilirubin. An sFLR : ICG R15 ratio of >1.9 showed 66.7% sensitivity and 100% specificity. Conclusions Regardless of ICG R15, an sFLR of ≥25% in patients without cirrhosis, and an sFLR of ≥25% with an sFLR : ICG R15 ratio of >1.9 in patients with cirrhosis indicate acceptable levels of safety in major hepatectomy. PMID:24964188

Liver Function Assessment Using Technetium 99m-Galactosyl Single-Photon Emission Computed Tomography/CT Fusion Imaging: A Prospective Trial.

PubMed

Okabayashi, Takehiro; Shima, Yasuo; Morita, Sojiro; Shimada, Yasuhiro; Sumiyoshi, Tatsuaki; Sui, Kenta; Iwata, Jun; Iiyama, Tatsuo

2017-12-01

The prediction of postoperative liver function remains a largely subjective practice based on CT volumetric analysis. However, future liver volume after a hepatectomy is not the only factor that contributes to postoperative liver function and outcomes. In this prospective trial, 185 consecutive patients who underwent liver operations between 2014 and 2015 were studied. Volumetric and functional rates of remnant liver were measured using technetium 99m-galactosyl human serum albumin single-photon emission computed tomography/CT fusion imaging to evaluate post-hepatectomy remnant liver function. Remnant indocyanine green clearance rate using galactosyl (KGSA) (KGSA × functional rate) was used to predict future remnant liver function. Hepatectomy was considered safe for patients with remnant KGSA values ≥0.05, and the primary end point was to determine the accuracy and reliability of this criteria. The prediction of the 90-day major complication and mortality rates was assessed. Median hospital stay was 9 days and median ICU stay was 1 day, with only 1 in-hospital death (90-day mortality rate 0.5%). Overall morbidity rate evaluated according to the Clavien-Dindo classification was 9%. For post-hepatectomy liver failure definitions, the International Study Group of Liver Surgery definition was fulfilled in 14 patients (8%), with the majority being grade B (50%), compared with 2 patients (1%) fulfilling the "50-50" criteria, and 0 patients (0%) fulfilling the Peak Bili >7 criteria. Results of this study showed that remnant KGSA provided information that allowed us to predict remnant liver function. This information will be important for surgeons when deciding on a treatment plan for patients with liver diseases. (ClinicalTrials.gov ID: NCT02013895). Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Surgical Strategy Based on Indocyanine Green Test for Chemotherapy-Associated Liver Injury and Long-Term Outcome in Colorectal Liver Metastases.

PubMed

Takamoto, Takeshi; Hashimoto, Takuya; Ichida, Akihiko; Shimada, Kei; Maruyama, Yoshikazu; Makuuchi, Masatoshi

2018-06-01

It remains unclear whether the presence of chemotherapy-induced liver injury (CALI) or impaired liver functional reserve affects the long-term outcome. This study assessed the applicability and long-term effects of using criteria based on the indocyanine green (ICG) test results in selecting the operative procedure among patients with colorectal liver metastases (CRLM) who had a risk of CALI. CRLM patients who received preoperative chemotherapy including oxaliplatin and/or irinotecan prior to a curative hepatectomy between 2007 and 2017 were included. For each case, the minimum required future remnant liver volume and operative procedure were decided based on the ICG retention rate at 15 min (ICG R15). Patients with an ICG R15 > 10% and who had undergone a major hepatectomy were categorized in a marginal liver functional reserve (MHML) group. Overall, 161 patients were included; 77 of them had an ICG R15 > 10%, and 57 had pathological liver injury (PLI). After the median follow-up time of 30.9 months, the 5-year overall survival rate was 36.1%. The presence of an impaired ICG test result or CALI did not negatively impact the overall and recurrence-free survival outcomes. A multivariate analysis revealed that the presence of four or more nodules of liver metastases was the only independent predictor of a poor overall survival. A significantly larger proportion of patients in the MHML group (n = 37) had a 25% or larger increase in splenic volume (30 vs. 13%; P = 0.024). The presence of an impaired ICG test result or PLI did not affect the long-term outcome after individually selected operative procedure. However, patients undergoing MHML had a higher possibility of developing a > 25% splenic volume increase after hepatectomy.

Indocyanine green: A test of hepatic function and a measure of plasma volume in the duck

USGS Publications Warehouse

Patton, J.F.

1978-01-01

1. The exponential removal of ICG from the plasma by the mallard duck liver made possible the measurement of fractional dye clearance (K), plasma volume (PV) and plasma clearance (PC).2. Values obtained for K (14.9%/min), PV (39.2 ml/kg) and PC (5.8 ml/min per kg) agreed with those obtained by other techniques used in a number of species.3. Sex did not affect the removal of ICG by the liver. However, increases in K, PV and PC were noted in hen mallards in laying condition.4. The data should prove useful as baseline values for physiological and pathological studies on the avian liver

Effects of the liver volume and donor steatosis on errors in the estimated standard liver volume.

PubMed

Siriwardana, Rohan Chaminda; Chan, See Ching; Chok, Kenneth Siu Ho; Lo, Chung Mau; Fan, Sheung Tat

2011-12-01

An accurate assessment of donor and recipient liver volumes is essential in living donor liver transplantation. Many liver donors are affected by mild to moderate steatosis, and steatotic livers are known to have larger volumes. This study analyzes errors in liver volume estimation by commonly used formulas and the effects of donor steatosis on these errors. Three hundred twenty-five Asian donors who underwent right lobe donor hepatectomy were the subjects of this study. The percentage differences between the liver volumes from computed tomography (CT) and the liver volumes estimated with each formula (ie, the error percentages) were calculated. Five popular formulas were tested. The degrees of steatosis were categorized as follows: no steatosis [n = 178 (54.8%)], ≤ 10% steatosis [n = 128 (39.4%)], and >10% to 20% steatosis [n = 19 (5.8%)]. The median errors ranged from 0.6% (7 mL) to 24.6% (360 mL). The lowest was seen with the locally derived formula. All the formulas showed a significant association between the error percentage and the CT liver volume (P < 0.001). Overestimation was seen with smaller liver volumes, whereas underestimation was seen with larger volumes. The locally derived formula was most accurate when the liver volume was 1001 to 1250 mL. A multivariate analysis showed that the estimation error was dependent on the liver volume (P = 0.001) and the anthropometric measurement that was used in the calculation (P < 0.001) rather than steatosis (P ≥ 0.07). In conclusion, all the formulas have a similar pattern of error that is possibly related to the anthropometric measurement. Clinicians should be aware of this pattern of error and the liver volume with which their formula is most accurate. Copyright © 2011 American Association for the Study of Liver Diseases.

Volumetric Growth of the Liver in the Human Fetus: An Anatomical, Hydrostatic, and Statistical Study.

PubMed

Szpinda, Michał; Paruszewska-Achtel, Monika; Woźniak, Alina; Mila-Kierzenkowska, Celestyna; Elminowska-Wenda, Gabriela; Dombek, Małgorzata; Szpinda, Anna; Badura, Mateusz

2015-01-01

Using anatomical, hydrostatic, and statistical methods, liver volumes were assessed in 69 human fetuses of both sexes aged 18-30 weeks. No sex differences were found. The median of liver volume achieved by hydrostatic measurements increased from 6.57 cm(3) at 18-21 weeks through 14.36 cm(3) at 22-25 weeks to 20.77 cm(3) at 26-30 weeks, according to the following regression: y = -26.95 + 1.74 × age ± Z × (-3.15 + 0.27 × age). The median of liver volume calculated indirectly according to the formula liver volume = 0.55 × liver length × liver transverse diameter × liver sagittal diameter increased from 12.41 cm(3) at 18-21 weeks through 28.21 cm(3) at 22-25 weeks to 49.69 cm(3) at 26-30 weeks. There was a strong relationship (r = 0.91, p < 0.001) between the liver volumes achieved by hydrostatic (x) and indirect (y) methods, expressed by y = -0.05 + 2.16x ± 7.26. The liver volume should be calculated as follows liver volume = 0.26 × liver length × liver transverse diameter × liver sagittal diameter. The age-specific liver volumes are of great relevance in the evaluation of the normal hepatic growth and the early diagnosis of fetal micro- and macrosomias.

3-Dimensional liver volume assessment in patients with hepatitis B virus-related liver cirrhosis during long-term oral nucleos(t)ide analogues therapy.

PubMed

Lee, Chang Hun; Kim, In Hee; Moon, Jin Chang; Seo, Seung Young; Kim, Seong Hun; Kim, Sang Wook; Lee, Seung Ok; Lee, Soo Teik; Kim, Dae Ghon; Yang, Jae Do; Yu, Hee Chul

2017-01-14

To assess the effect of long-term oral nucleos(t)ide analogues (NUCs) therapy on liver volume change in patients with suppress hepatitis B virus (HBV)-related liver cirrhosis. We reviewed the data of naïve patients with HBV-related liver cirrhosis, who had taken oral NUCs therapy, between 2003 and 2007 at Chonbuk University Hospital. We analyzed two consecutive sets of abdominal computerized tomography scans-one at the time of treatment initiation and another at the second-year follow-up. Liver volume was calculated by 3-dimensional liver extraction volumetry program. A total of 55 patients (34 males) were included. There was 114.3 mL ± 167.8 mL (12.9% ± 17.9%) of increase in liver volume during the two years of NUCs therapy (993.8 mL ± 242.8 mL at baseline vs 1108.1 mL ± 263.3 mL at two-year follow-up, P < 0.001). The ratio of the measured baseline liver volume to the estimated standard liver volume was improved from 70.8% to 78.0%. An increase in liver volume was shown not only in patients with compensated cirrhosis ( P = 0.046) but also in those with decompensated cirrhosis ( P < 0.001). Significant factors for volume increases were Child-Turcotte-Pugh grade and model for end-stage liver disease score improvement without virological breakthrough. In multiple linear regression analysis, delta albumin and delta alanine aminotransferase levels showed a significant association with the increase in liver volume ( P = 0.002 and 0.005, respectively). Long-term oral NUCs therapy in patients with HBV-related liver cirrhosis lead to significant increase in liver volume assessed with 3-dimensional liver extraction volumetry program.

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.

Abnormal Liver Function Tests in an Anorexia Nervosa Patient and an Atypical Manifestation of Refeeding Syndrome

PubMed Central

Vootla, Vamshidhar R.; Daniel, Myrta

2015-01-01

Refeeding syndrome is defined as electrolyte and fluid abnormalities that occur in significantly malnourished patients when they are refed orally, enterally, or parenterally. The principal manifestations include hypophosphatemia, hypokalemia, vitamin deficiencies, volume overload and edema. This can affect multiple organ systems, such as the cardiovascular, pulmonary, or neurological systems, secondary to the above-mentioned abnormalities. Rarely, patients may develop gastrointestinal symptoms and show abnormal liver function test results. We report the case of a 52-year-old woman with anorexia nervosa who developed refeeding syndrome and simultaneous elevations of liver function test results, which normalized upon the resolution of the refeeding syndrome. PMID:26351414

Technical aspects of virtual liver resection planning.

PubMed

Glombitza, G; Lamadé, W; Demiris, A M; Göpfert, M R; Mayer, A; Bahner, M L; Meinzer, H P; Richter, G; Lehnert, T; Herfarth, C

1998-01-01

Operability of a liver tumor is depending on its three dimensional relation to the intrahepatic vascular trees which define autonomously functioning liver (sub-)segments. Precise operation planning is complicated by anatomic variability, distortion of the vascular trees by the tumor or preceding liver resections. Because of the missing possibility to track the deformation of the liver during the operation an integration of the resection planning system into an intra-operative navigation system is not feasible. So the main task of an operation planning system in this domain is a quantifiable patient selection by exact prediction of post-operative liver function and a quantifiable resection proposal. The system quantifies the organ structures and resection volumes by means of absolute and relative values. It defines resection planes depending on security margins and the vascular trees and presents the data in visualized form as a 3D movie. The new 3D operation planning system offers quantifiable liver resection proposals based on individualized liver anatomy. The results are visualized in digital movies as well as in quantitative reports.

The Predictive Value of the Maximal Liver Function Capacity Test for the Isolation of Primary Human Hepatocytes.

PubMed

Major, Rebeka D; Kluge, Martin; Jara, Maximilian; Nösser, Maximilian; Horner, Rosa; Gassner, Joseph; Struecker, Benjamin; Tang, Peter; Lippert, Steffen; Reutzel-Selke, Anja; Geisel, Dominik; Denecke, Timm; Stockmann, Martin; Pratschke, Johann; Sauer, Igor M; Raschzok, Nathanael

2018-03-01

The need for primary human hepatocytes is constantly growing for basic research, as well as for therapeutic applications. However, the isolation outcome strongly depends on the quality of liver tissue, and we are still lacking a preoperative test that allows the prediction of the hepatocyte isolation outcome. In this study, we evaluated the "maximal liver function capacity test" (LiMAx) as predictive test for the quantitative and qualitative outcome of hepatocyte isolation. This test is already used in clinical routine to measure preoperative and to predict postoperative liver function. The patient's preoperative mean LiMAx was obtained from the patient records, and preoperative computed tomography and magnetic resonance images were used to calculate the whole liver volume to adjust the mean LiMAx. The outcome parameters of the hepatocyte isolation procedures were analyzed in correlation with the adjusted mean LiMAx. Primary human hepatocytes were isolated from partial hepatectomies (n = 64). From these 64 hepatectomies we included 48 to our study and correlated their isolation outcome parameters with volume corrected LiMAx values. From a total of 11 hepatocyte isolation procedures, metabolic parameters (albumin, urea, and aspartate aminotransferase or AST) were assessed during the hepatocyte cultivation period of 5 days. The volume adjusted mean LiMAx showed a significant positive correlation with the total cell yield (p = 0.049; r = 0.242; n = 48). The correlations of volume adjusted LiMAx values with viable cell yield and cell viability did not reach statistical significance. To create a more homogenous study group regarding tumor entities, subgroup analyses were performed. A subgroup analysis of isolations from patients with colorectal metastasis revealed a significant correlation between volume adjusted mean LiMAx and total cell yield (p = 0.012; r = 0.488; n = 21) and viable cell yield (p = 0.034; r = 0.405; n = 21), whereas a subgroup analysis of isolations of patients with carcinoma of the biliary tree showed significant correlations of volume adjusted mean LiMAx with cell viability (r = 0.387; p = 0.046; n = 20) and lacked significant correlations with total cell yield (r = -0.060; p = 0.401; n = 20) and viable cell yield (r = 0.012; p = 0.480; n = 20). The volume-adjusted mean LiMAx did not show a significant correlation with any of the metabolic parameters. In conclusion, the LiMAx test might be a useful tool to predict the quantitative outcome of hepatocyte isolation, as long as underlying liver disease is taken into consideration.

Volumetric Growth of the Liver in the Human Fetus: An Anatomical, Hydrostatic, and Statistical Study

PubMed Central

Szpinda, Michał; Paruszewska-Achtel, Monika; Mila-Kierzenkowska, Celestyna; Elminowska-Wenda, Gabriela; Dombek, Małgorzata; Szpinda, Anna; Badura, Mateusz

2015-01-01

Using anatomical, hydrostatic, and statistical methods, liver volumes were assessed in 69 human fetuses of both sexes aged 18–30 weeks. No sex differences were found. The median of liver volume achieved by hydrostatic measurements increased from 6.57 cm3 at 18–21 weeks through 14.36 cm3 at 22–25 weeks to 20.77 cm3 at 26–30 weeks, according to the following regression: y = −26.95 + 1.74 × age ± Z  × (−3.15 + 0.27 × age). The median of liver volume calculated indirectly according to the formula liver volume = 0.55 × liver length × liver transverse diameter × liver sagittal diameter increased from 12.41 cm3 at 18–21 weeks through 28.21 cm3 at 22–25 weeks to 49.69 cm3 at 26–30 weeks. There was a strong relationship (r = 0.91, p < 0.001) between the liver volumes achieved by hydrostatic (x) and indirect (y) methods, expressed by y = −0.05 + 2.16x  ± 7.26. The liver volume should be calculated as follows liver volume = 0.26 × liver length × liver transverse diameter × liver sagittal diameter. The age-specific liver volumes are of great relevance in the evaluation of the normal hepatic growth and the early diagnosis of fetal micro- and macrosomias. PMID:26413551

Evaluation of Liver Function After Proton Beam Therapy for Hepatocellular Carcinoma

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

Mizumoto, Masashi; Okumura, Toshiyuki; Hashimoto, Takayuki

Purpose: Our previous results for treatment of hepatocellular carcinoma with proton beam therapy (PBT) revealed excellent local control. In this study, we focused on the impact of PBT on normal liver function. Methods and Materials: The subjects were 259 patients treated with PBT at University of Tsukuba between January 2001 and December 2007. We evaluated the Child-Pugh score pretreatment, on the final day of PBT, and 6, 12, and 24 months after treatment with PBT. Patients who had disease progression or who died with tumor progression at each evaluation point were excluded from the analysis to rule out an effectmore » of tumor progression. An increase in the Child-Pugh score of 1 or more was defined as an adverse event. Results: Of the 259 patients, 241 had no disease progression on the final day of PBT, and 91 had no progression within 12 months after PBT. In univariate analysis, the percentage volumes of normal liver receiving at least 0, 10, 20, and 30 GyE in PBT (V0, 10, 20, and 30) were significantly associated with an increase of Child-Pugh score at 12 months after PBT. Of the 91 patients evaluated at 12 months, 66 had no increase of Child-Pugh score, 15 had a 1-point increase, and 10 had an increase of {>=}2 points. For the Youden index, the optimal cut-offs for V0, V10, V20, and V30 were 30%, 20%, 26%, and 18%, respectively. Conclusion: Our findings indicate that liver function after PBT is significantly related to the percentage volume of normal liver that is not irradiated. This suggests that further study of the relationship between liver function and PBT is required.« less

Gd-EOB-DTPA-enhanced MRI for monitoring future liver remnant function after portal vein embolization and extended hemihepatectomy: A prospective trial.

PubMed

Geisel, Dominik; Raabe, Philip; Lüdemann, Lutz; Malinowski, Maciej; Stockmann, Martin; Seehofer, Daniel; Pratschke, Johann; Hamm, Bernd; Denecke, Timm

2017-07-01

To evaluate changes in liver function after right portal vein embolization (PVE) and extended right hemihepatectomy using gadolinium ethoxybenzyl-DTPA-enhanced (Gd-EOB-DTPA) MRI. In this prospective trial, 37 patients undergoing PVE were examined before and 14 and 28 days after PVE and 10 days after extended hemihepatectomy using Gd-EOB-DTPA-enhanced MRI. Lobar volume, kinetic growth rate (KGR), relative enhancement (RE) as well as hepatocellular uptake index (HUI) and fat signal fraction (FSF) were calculated for each lobe. RE of the left liver lobe (LLL) was steadily increasing after PVE and decreased to 0.48 ± 0.19 10 days after surgery, which is significantly lower than 14 days and 28 days post PVE (P < 0.05). KGR was 14.06 ± 9.82%/week for the period from PVE to 14 days after PVE. HUI of the LLL increased steadily after PVE and was significantly higher at both 14 and 28 days after PVE compared to pre PVE (P < 0.05). HUI of the residual liver after surgery was lower than before. Gd-EOB-DTPA-enhanced MRI may be used to monitor the functional increase in the FLR after PVE and to depict the intraoperative liver injury leading to a decrease in liver remnant function. • The most significant FLR volume increase happens within the first 14 days. • No MRI parameter was able to predict the success of FLR growth. • Our data suggest an early resection about 14 days after PVE. • Routine Gd-EOB-DTPA-enhanced MRI might be suitable to replace ICG-test.

Stepwise approach to curative surgery using percutaneous transhepatic cholangiodrainage and portal vein embolization for severe bile duct injury during laparoscopic cholecystectomy: a case report.

PubMed

Honmyo, Naruhiko; Kuroda, Shintaro; Kobayashi, Tsuyoshi; Ishiyama, Kohei; Ide, Kentaro; Tahara, Hiroyuki; Ohira, Masahiro; Ohdan, Hideki

2016-12-01

Laparoscopic cholecystectomy (LC) has been recently adapted to acute cholecystitis. Major bile duct injury during LC, especially Strasberg-Bismuth classification type E, can be a critical problem sometimes requiring hepatectomy. Safety and definitive treatment without further morbidities, such as posthepatectomy liver failure, is required. Here, we report a case of severe bile duct injury treated with a stepwise approach using (99m)Tc-galactosyl human serum albumin ((99m)Tc-GSA) single-photon emission computed tomography (SPECT)/CT fusion imaging to accurately estimate liver function.A 52-year-old woman diagnosed with acute cholecystitis underwent LC at another hospital and was transferred to our university hospital for persistent bile leakage on postoperative day 20. She had no jaundice or infection, although an intraperitoneal drainage tube discharged approximately 500 ml of bile per day. Recorded operation procedure showed removal of the gallbladder with a part of the common bile duct due to its misidentification, and each of the hepatic ducts and right hepatic artery was injured. Abdominal enhanced CT revealed obstructive jaundice of the left liver and arterial shunt through the hilar plate to the right liver. Magnetic resonance cholangiopancreatography revealed type E4 or more advanced bile duct injury according to the Bismuth-Strasberg classification. We planned a stepwise approach using percutaneous transhepatic cholangiodrainage (PTCD) and portal vein embolization (PVE) for secure right hemihepatectomy and biliary-jejunum reconstruction and employed (99m)Tc-GSA SPECT/CT fusion imaging to estimate future remnant liver function. The left liver function rate had changed from 26.2 % on admission to 26.3 % after PTCD and 54.5 % after PVE, while the left liver volume rate was 33.8, 33.3, and 49.6 %, respectively. The increase of liver function was higher than that of volume (28.3 vs. 15.8 %). On postoperative day 63, the curative operation, right hemihepatectomy and biliary-jejunum reconstruction, was performed, and posthepatectomy liver failure could be avoided.Careful consideration of treatment strategy for each case is necessary for severe bile duct injury with arterial injury requiring hepatectomy. The stepwise approach using PTCD and PVE could enable hemihepatectomy, and (99m)Tc-GSA SPECT/CT fusion imaging was useful to estimate heterogeneous liver function.

Estimation of standard liver volume in Chinese adult living donors.

PubMed

Fu-Gui, L; Lu-Nan, Y; Bo, L; Yong, Z; Tian-Fu, W; Ming-Qing, X; Wen-Tao, W; Zhe-Yu, C

2009-12-01

To determine a formula predicting the standard liver volume based on body surface area (BSA) or body weight in Chinese adults. A total of 115 consecutive right-lobe living donors not including the middle hepatic vein underwent right hemi-hepatectomy. No organs were used from prisoners, and no subjects were prisoners. Donor anthropometric data including age, gender, body weight, and body height were recorded prospectively. The weights and volumes of the right lobe liver grafts were measured at the back table. Liver weights and volumes were calculated from the right lobe graft weight and volume obtained at the back table, divided by the proportion of the right lobe on computed tomography. By simple linear regression analysis and stepwise multiple linear regression analysis, we correlated calculated liver volume and body height, body weight, or body surface area. The subjects had a mean age of 35.97 +/- 9.6 years, and a female-to-male ratio of 60:55. The mean volume of the right lobe was 727.47 +/- 136.17 mL, occupying 55.59% +/- 6.70% of the whole liver by computed tomography. The volume of the right lobe was 581.73 +/- 96.137 mL, and the estimated liver volume was 1053.08 +/- 167.56 mL. Females of the same body weight showed a slightly lower liver weight. By simple linear regression analysis and stepwise multiple linear regression analysis, a formula was derived based on body weight. All formulae except the Hong Kong formula overestimated liver volume compared to this formula. The formula of standard liver volume, SLV (mL) = 11.508 x body weight (kg) + 334.024, may be applied to estimate liver volumes in Chinese adults.

Management of Liver Cancer Argon-helium Knife Therapy with Functional Computer Tomography Perfusion Imaging.

PubMed

Wang, Hongbo; Shu, Shengjie; Li, Jinping; Jiang, Huijie

2016-02-01

The objective of this study was to observe the change in blood perfusion of liver cancer following argon-helium knife treatment with functional computer tomography perfusion imaging. Twenty-seven patients with primary liver cancer treated with argon-helium knife and were included in this study. Plain computer tomography (CT) and computer tomography perfusion (CTP) imaging were conducted in all patients before and after treatment. Perfusion parameters including blood flows, blood volume, hepatic artery perfusion fraction, hepatic artery perfusion, and hepatic portal venous perfusion were used for evaluating therapeutic effect. All parameters in liver cancer were significantly decreased after argon-helium knife treatment (p < 0.05 to all). Significant decrease in hepatic artery perfusion was also observed in pericancerous liver tissue, but other parameters kept constant. CT perfusion imaging is able to detect decrease in blood perfusion of liver cancer post-argon-helium knife therapy. Therefore, CTP imaging would play an important role for liver cancer management followed argon-helium knife therapy. © The Author(s) 2014.

Functional liver image guided hepatic therapy (FLIGHT) with hepatobiliary iminodiacetic acid (HIDA) scans.

PubMed

Long, David E; Tann, Mark; Huang, Ke Colin; Bartlett, Gregory; Galle, James O; Furukawa, Yukie; Maluccio, Mary; Cox, John A; Kong, Feng-Ming Spring; Ellsworth, Susannah G

2018-05-01

Hepatobiliary iminodiacetic acid (HIDA) scans provide global and regional assessments of liver function that can serve as a road map for functional avoidance in stereotactic body radiation therapy (SBRT) planning. Functional liver image guided hepatic therapy (FLIGHT), an innovative planning technique, is described and compared with standard planning using functional dose-volume histograms. Thresholds predicting for decompensation during follow up are evaluated. We studied 17 patients who underwent HIDA scans before SBRT. All SBRT cases were replanned using FLIGHT. The following dosimetric endpoints were compared for FLIGHT versus standard SBRT planning: functional residual capacity <15 Gy (FRC 15 HIDA), mean liver dose (MLD), equivalent uniform dose (EUD), and functional EUD (FEUD). Receiver operating characteristics curves were used to evaluate whether baseline HIDA values, standard cirrhosis scoring, and/or dosimetric data predicted clinical decompensation. Compared with standard planning, FLIGHT significantly improved FRC 15 HIDA (mean improvement: 5.3%) as well as MLD, EUD, and FEUD (P < .05). Considerable interindividual variations in the extent of benefit were noted. Decompensation during follow-up was associated with baseline global HIDA <2.915%/min/m 2 , FRC 15 HIDA <2.11%/min/m 2 , and MELD ≥11 (P < .05). FLIGHT with HIDA-based parameters may complement blood chemistry-based assessments of liver function and facilitate individualized, adaptive liver SBRT planning. Copyright © 2018. Published by Elsevier Inc.

Severe leptospirosis with multiple organ failure successfully treated by plasma exchange and high-volume hemofiltration.

PubMed

Bourquin, Vincent; Ponte, Belén; Hirschel, Bernard; Pugin, Jérôme; Martin, Pierre-Yves; Saudan, Patrick

2011-01-01

Background. Leptospirosis is a spirochetal zoonosis with complex clinical features including renal and liver failure. Case report. We report the case of a Swiss fisherman presenting with leptospirosis. After initial improvement, refractory septic shock and severe liver and kidney failure developed. The expected mortality was estimated at 90% with clinical scores. The patient underwent plasma exchanges and high-volume hemofiltration (HVHF) with complete recovery of hepatic and kidney functions. Discussion. Plasma exchanges and HVHF may confer survival benefit on patients with severe leptospirosis, refractory septic shock, and multiple-organ failure.

The prognostic value of functional and anatomical parameters for the selection of patients receiving yttrium-90 microspheres for the treatment of liver cancer

NASA Astrophysics Data System (ADS)

Mesoloras, Geraldine

Yttrium-90 (90Y) microsphere therapy is being utilized as a treatment option for patients with primary and metastatic liver cancer due to its ability to target tumors within the liver. The success of this treatment is dependent on many factors, including the extent and type of disease and the nature of prior treatments received. Metabolic activity, as determined by PET imaging, may correlate with the number of viable cancer cells and reflect changes in viable cancer cell volume. However, contouring of PET images by hand is labor intensive and introduces an element of irreproducibility into the determination of functional target/tumor volume (FTV). A computer-assisted method to aid in the automatic contouring of FTV has the potential to substantially improve treatment individualization and outcome assessment. Commercial software to determine FTV in FDG-avid primary and metastatic liver tumors has been evaluated and optimized. Volumes determined using the automated technique were compared to those from manually drawn contours identified using the same cutoff in the standard uptake value (SUV). The reproducibility of FTV is improved through the introduction of an optimal threshold value determined from phantom experiments. Application of the optimal threshold value from the phantom experiments to patient scans was in good agreement with hand-drawn determinations of the FTV. It is concluded that computer-assisted contouring of the FTV for primary and metastatic liver tumors improves reproducibility and increases accuracy, especially when combined with the selection of an optimal SUV threshold determined from phantom experiments. A method to link the pre-treatment assessment of functional (PET based) and anatomical (CT based) parameters to post-treatment survival and time to progression was evaluated in 22 patients with colorectal cancer liver metastases treated using 90Y microspheres and chemotherapy. The values for pre-treatment parameters that were the best predictors of response were determined for FTV, anatomical tumor volume, total lesion glycolysis, and the tumor marker, CEA. Of the parameters considered, the best predictors of response were found to be pre-treatment FTV ≤153 cm3, ATV ≤163 cm3, TLG ≤144 g in the chemo-SIRT treated field, and CEA ≤11.6 ng/mL.

Effects of dietary interventions on liver volume in humans.

PubMed

Bian, Hua; Hakkarainen, Antti; Lundbom, Nina; Yki-Järvinen, Hannele

2014-04-01

To compare effects of similar weight loss induced either by a short-term low-carbohydrate or by a long-term hypocaloric diet, and to determine effects of high carbohydrate overfeeding on liver total, lean, and fat volumes. Liver total, lean, and fat volumes were measured before and after (i) a 6-day low-carbohydrate diet (n = 17), (ii) a 7-month standard hypocaloric diet (n = 26), and (iii) a 3-week high-carbohydrate diet (n = 17), by combining magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy ((1) H-MRS) techniques. At baseline, three groups were comparable with respect to age, body mass index, liver volumes and the liver fat content. Body weight decreased similarly by the short-term and long-term hypocaloric diets. Liver total volume decreased significantly more during the short-term low-carbohydrate (-22 ± 2%) than the long-term (-7 ± 2%) hypocaloric diet (P < 0.001). This was due to a greater decrease in liver lean volume in the short-term (-20 ± 2%) than the long-term (-4 ± 2%) weight loss group (P < 0.001). Decreases in liver fat were comparable. Liver volume increased by 9 ± 3% due to overfeeding (P< 0.02 for before vs. after). These data support the use of a short-term low-carbohydrate diet whenever a reduction in liver volume is desirable. Overeating carbohydrate is harmful because it increases liver volume. Copyright © 2013 The Obesity Society.

Japanese-style intensive medical care improves prognosis for acute liver failure and the perioperative management of liver transplantation.

PubMed

Inoue, K; Watanabe, T; Maruoka, N; Kuroki, Y; Takahashi, H; Yoshiba, M

2010-12-01

The Japanese style of intensive medical care for acute liver failure has yielded high survival rates. The care system comprises artificial liver support (ALS) together with treatment for the underlying disease. Plasma exchange in combination with high-volume hemodiafiltration using an high performance membrane has become the standard ALS system. It is safe, efficiently removing more low and middle molecular weight toxic substances than other methods because of the large volumes of buffer (more than 200 L per session), resulting in recovery from coma in patients with severe fulminant hepatitis, a status comparable with the ahepatic state. This ALS is therefore an effective tool to sustain patients with fulminant hepatitis in a favorable condition until liver function recovers or liver transplantation becomes available. The accompanying treatment for underlying disease serves to limit the liver destruction that hampers regeneration. The treatment has remarkably improved the prognosis for patients with subacute types of fulminant hepatitis, which generally carry a less favorable prognosis than the acute type. This treatment system thus provides more time for physicians to assess the indications for liver transplantation as well as giving the patient a greater chance of undergoing transplantation. Copyright © 2010 Elsevier Inc. All rights reserved.

[Liver volume, intrahepatic fat and body weight in the course of a lifestyle interventional study: Analysis with quantitative MR-based methods].

PubMed

Bongers, M N; Stefan, N; Fritsche, A; Häring, H-U; Nikolaou, K; Schick, F; Machann, J

2015-04-01

The aim of this study was to investigate potential associations between changes in liver volume, the amount of intrahepatic lipids (IHL) and body weight during lifestyle interventions. In a prospective study 150 patients with an increased risk for developing type 2 diabetes mellitus were included who followed a caloric restriction diet for 6 months. In the retrospective analysis 18 women and 9 men (age range 22-71 years) with an average body mass index (BMI) of 32 kg/m(2) were enrolled. The liver volume was determined at the beginning and after 6 months by three-dimensional magnetic resonance imaging (3D-MRI, echo gradient, opposed-phase) and IHLs were quantified by volume-selective MR spectroscopy in single voxel stimulated echo acquisition mode (STEAM). Univariable and multivariable correlation analyses between changes of liver volume (Δliver volume), intrahepatic lipids (ΔIHL) and body weight (ΔBW) were performed. Univariable correlation analysis in the whole study cohort showed associations between ΔIHL and ΔBW (r = 0.69; p < 0.0001), ΔIHL and Δliver volume (r = 0.66; p = 0.0002) as well as ΔBW and Δliver volume (r = 0.5; p = 0.0073). Multivariable correlation analysis revealed that changes of liver volume are primarily determined by changes in IHL independent of changes in body weight (β = 0.0272; 95% CI: 0.0155-0.034; p < 0.0001). Changes of liver volume during lifestyle interventions are independent of changes of body weight primarily determined by changes of IHL. These results show the reversibility of augmented liver volume in steatosis if it is possible to reduce IHLs during lifestyle interventions.

Correlation between liver volume, portal vascular anatomy, and hepatic perfusion in dogs with congenital portosystemic shunt before and after placement of ameroid constrictors.

PubMed

Zwingenberger, Allison L; Daniel, Leticia; Steffey, Michele A; Mayhew, Philipp D; Mayhew, Kelli N; Culp, William T N; Hunt, Geraldine B

2014-11-01

To correlate changes in hepatic volume, hepatic perfusion, and vascular anatomy of dogs with congenital extrahepatic portosystemic shunts, before and after attenuation with an ameroid constrictor. Prospective study. Dogs (n = 22) with congenital extrahepatic portosystemic shunts. CT angiography and perfusion scans were performed before and after attenuation of a portosystemic shunt with an ameroid constrictor. Changes in hepatic volume, hepatic perfusion, and vascular anatomy were measured. Portal scintigraphy was performed in 8 dogs preoperatively and 22 dogs postoperatively. Dogs with smaller preoperative liver volumes had greater increases in liver volume postoperatively compared with those with larger preoperative liver volumes. Hepatic arterial fraction was increased in dogs preoperatively and returned to normal range after shunt attenuation, and was correlated with increase in liver size and decreased shunt fraction. Three dogs with no visible portal vasculature preoperatively developed portal branches postoperatively. Dogs with smaller preoperative liver volumes had the largest postoperative increase in liver volume. Hepatic arterial perfusion and portal scintigraphy correlate with liver volume and are indicators of successful shunt attenuation. Dogs without visible vasculature on CT angiography had visible portal vasculature postoperatively. © Copyright 2014 by The American College of Veterinary Surgeons.

Liver remnant regeneration in donors after living donor liver transplantation: long-term follow-up using CT and MR imaging.

PubMed

Klink, T; Simon, P; Knopp, C; Ittrich, H; Fischer, L; Adam, G; Koops, A

2014-06-01

To assess liver remnant volume regeneration and maintenance, and complications in the long-time follow-up of donors after living donor liver transplantation using CT and MRI. 47 donors with a mean age of 33.5 years who donated liver tissue for transplantation and who were available for follow-up imaging were included in this retrospective study. Contrast-enhanced CT and MR studies were acquired for routine follow-up. Two observers evaluated pre- and postoperative images regarding anatomy and pathological findings. Volumes were manually measured on contrast-enhanced images in the portal venous phase, and potential postoperative complications were documented. Pre- and postoperative liver volumes were compared for evaluating liver remnant regeneration. 47 preoperative and 89 follow-up studies covered a period of 22.4 months (range: 1 - 84). After right liver lobe (RLL) donation, the mean liver remnant volume was 522.0 ml (± 144.0; 36.1 %; n = 18), after left lateral section (LLS) donation 1,121.7 ml (± 212.8; 79.9 %; n = 24), and after left liver lobe (LLL) donation 1,181.5 ml (± 279.5; 72.0 %; n = 5). Twelve months after donation, the liver remnant volume were 87.3 % (RLL; ± 11.8; n = 11), 95.0 % (LS; ± 11.6; n = 18), and 80.1 % (LLL; ± 2.0; n = 2 LLL) of the preoperative total liver volume. Rapid initial regeneration and maintenance at 80 % of the preoperative liver volume were observed over the total follow-up period.  Minor postoperative complications were found early in 4 patients. No severe or late complications or mortality occurred. Rapid regeneration of liver remnant volumes in all donors and volume maintenance over the long-term follow-up period of up to 84 months without severe or late complications are important observations for assessing the safety of LDLT donors. Liver remnant volumes of LDLT donors rapidly regenerated after donation and volumes were maintained over the long-term follow-up period of up to 84 months without severe or late complications. © Georg Thieme Verlag KG Stuttgart · New York.

Haemodynamic changes in hepatocellular carcinoma and liver parenchyma under balloon occlusion of the hepatic artery.

PubMed

Sugihara, Fumie; Murata, Satoru; Ueda, Tatsuo; Yasui, Daisuke; Yamaguchi, Hidenori; Miki, Izumi; Kawamoto, Chiaki; Uchida, Eiji; Kumita, Shin-Ichiro

2017-06-01

To investigate haemodynamic changes in hepatocellular carcinoma (HCC) and liver under hepatic artery occlusion. Thirty-eight HCC nodules in 25 patients were included. Computed tomography (CT) during hepatic arteriography (CTHA) with and without balloon occlusion of the hepatic artery was performed. CT attenuation and enhancement volume of HCC and liver with and without balloon occlusion were measured on CTHA. Influence of balloon position (segmental or subsegmental branch) was evaluated based on differences in HCC-to-liver attenuation ratio (H/L ratio) and enhancement volume of HCC and liver. In the segmental group (n = 20), H/L ratio and enhancement volume of HCC and liver were significantly lower with balloon occlusion than without balloon occlusion. However, in the subsegmental group (n = 18), H/L ratio was significantly higher and liver enhancement volume was significantly lower with balloon occlusion; HCC enhancement volume was similar with and without balloon occlusion. Rate of change in H/L ratio and enhancement volume of HCC and liver were lower in the segmental group than in the subsegmental group. There were significantly more perfusion defects in HCC in the segmental group. Hepatic artery occlusion causes haemodynamic changes in HCC and liver, especially with segmental occlusion. • Hepatic artery occlusion causes haemodynamic changes in hepatocellular carcinoma and liver. • Segmental occlusion decreased rate of change in hepatocellular carcinoma-to-liver attenuation ratio. • Subsegmental occlusion increased rate of change in hepatocellular carcinoma-to-liver attenuation ratio. • Hepatic artery occlusion decreased enhancement volume of hepatocellular carcinoma and liver. • Hepatic artery occlusion causes perfusion defects in hepatocellular carcinoma.

Endoscopic stenting in bile duct cancer increases liver volume.

PubMed

Lee, Chang Hun; Kim, Seong Hun; Kim, In Hee; Kim, Sang Wook; Lee, Soo Teik; Kim, Dae Ghon; Yang, Jae Do; Yu, Hee Chul; Cho, Baik Hwan; Lee, Seung Ok

2014-09-01

Objective evaluation tools for assessing the effectiveness of stenting in palliative treatment of malignant biliary obstruction are not satisfactory. Effects of biliary stenting on liver volume change have never been studied. We aimed to use volumetry to analyze liver volume changes after endoscopic stenting in bile duct cancer according to the location and number of stents. Retrospective review. University hospital. Patients with a diagnosis of hilar or distal bile duct cancer and who underwent biliary metal stenting. ERCP with self-expandable metal stent placement. Liver volume change after biliary stenting and its comparison according to the location (hilar vs distal common bile duct) and number (hilar bilateral vs hilar unilateral). There were 60 patients; 31 were treated for hilar bile duct cancer (13 for bilateral stent and 18 for unilateral stent) and 29 for distal bile duct cancer. Overall mean follow-up duration was 11.7 ± 4.9 weeks. Liver volume increased 17.4 ± 24.1%. The rate of liver growth was rapid during the early period from 4 to 8 weeks. Stenting in hilar bile duct cancer tended to increase liver volume more than distal biliary stents (22.5% vs 11.9%, P = .091). In hilar bile duct cancer, unilateral and bilateral stents showed similar liver volume increases (20.1% and 25.8%, respectively; P = .512). Single center, retrospective. Biliary stenting markedly increased liver volume in both hilar and distal bile duct cancer. Our data suggest that liver volume assessment could be a useful tool for evaluating stent efficacy. Copyright © 2014 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Feasibility of Percutaneous Intrahepatic Split by Microwave Ablation (PISA) After Portal Vein Embolization for Hypertrophy of Future Liver Remnant: The Radiological Stage-1 ALPPS.

PubMed

Lunardi, Alessandro; Cervelli, Rosa; Volterrani, Duccio; Vitali, Saverio; Lombardo, Carlo; Lorenzoni, Giulia; Crocetti, Laura; Bargellini, Irene; Campani, Daniela; Pollina, Luca Emanuele; Cioni, Roberto; Caramella, Davide; Boggi, Ugo

2018-05-01

To assess the feasibility of radiological stage-1 ALPPS, associating liver partition and portal vein ligation for staged hepatectomy, by combining portal vein embolization (PVE) with percutaneous intrahepatic split by ablation (PISA). Three patients (mean age 65.0 ± 7.3 years) underwent PVE and PISA. PISA was performed 21 days after PVE by microwave ablation to create a continuous intrahepatic cutting plane. Abdominal CT examinations were performed before and after PVE and PISA. The future liver remnant (FLR) volume was calculated by semiautomatic segmentation, and increase was reported as a percentage of the pre-procedural volume. The FLR/body weight (FLR/BW) ratio was calculated; a ratio greater than 0.8% was considered sufficient for guaranteeing adequate liver function after surgery. The liver function before and after PISA was also evaluated by 99mTc-mebrofenin hepatobiliary scintigraphy. Patients' laboratory tests, performance status, ability to walk were assessed before and after PVE and PISA procedures. No procedure-related complications were recorded. The FLR volume increase in each patient was 42.0, 33.1 and 30.4% within 21 days of PVE and 109.3, 68.1 and 71.7% within 10 days after PISA. The FLR/BW ratios were 0.76, 0.66, 0.63% and 1.13, 0.83, 0.83% after PVE and PISA procedures, respectively. Two patients underwent successful right hepatectomy; in one patient, despite 1.13% FLR/BW, surgery was not performed because of the absolute rejection of blood transfusion due to the patient's religious convictions. Radiological stage-1 ALPPS is a feasible, minimally invasive option to be further investigated to become an effective alternative to surgical stage-1 ALPPS.

Computerized Liver Volumetry on MRI by Using 3D Geodesic Active Contour Segmentation

PubMed Central

Huynh, Hieu Trung; Karademir, Ibrahim; Oto, Aytekin; Suzuki, Kenji

2014-01-01

OBJECTIVE Our purpose was to develop an accurate automated 3D liver segmentation scheme for measuring liver volumes on MRI. SUBJECTS AND METHODS Our scheme for MRI liver volumetry consisted of three main stages. First, the preprocessing stage was applied to T1-weighted MRI of the liver in the portal venous phase to reduce noise and produce the boundary-enhanced image. This boundary-enhanced image was used as a speed function for a 3D fast-marching algorithm to generate an initial surface that roughly approximated the shape of the liver. A 3D geodesic-active-contour segmentation algorithm refined the initial surface to precisely determine the liver boundaries. The liver volumes determined by our scheme were compared with those manually traced by a radiologist, used as the reference standard. RESULTS The two volumetric methods reached excellent agreement (intraclass correlation coefficient, 0.98) without statistical significance (p = 0.42). The average (± SD) accuracy was 99.4% ± 0.14%, and the average Dice overlap coefficient was 93.6% ± 1.7%. The mean processing time for our automated scheme was 1.03 ± 0.13 minutes, whereas that for manual volumetry was 24.0 ± 4.4 minutes (p < 0.001). CONCLUSION The MRI liver volumetry based on our automated scheme agreed excellently with reference-standard volumetry, and it required substantially less completion time. PMID:24370139

Computerized liver volumetry on MRI by using 3D geodesic active contour segmentation.

PubMed

Huynh, Hieu Trung; Karademir, Ibrahim; Oto, Aytekin; Suzuki, Kenji

2014-01-01

Our purpose was to develop an accurate automated 3D liver segmentation scheme for measuring liver volumes on MRI. Our scheme for MRI liver volumetry consisted of three main stages. First, the preprocessing stage was applied to T1-weighted MRI of the liver in the portal venous phase to reduce noise and produce the boundary-enhanced image. This boundary-enhanced image was used as a speed function for a 3D fast-marching algorithm to generate an initial surface that roughly approximated the shape of the liver. A 3D geodesic-active-contour segmentation algorithm refined the initial surface to precisely determine the liver boundaries. The liver volumes determined by our scheme were compared with those manually traced by a radiologist, used as the reference standard. The two volumetric methods reached excellent agreement (intraclass correlation coefficient, 0.98) without statistical significance (p = 0.42). The average (± SD) accuracy was 99.4% ± 0.14%, and the average Dice overlap coefficient was 93.6% ± 1.7%. The mean processing time for our automated scheme was 1.03 ± 0.13 minutes, whereas that for manual volumetry was 24.0 ± 4.4 minutes (p < 0.001). The MRI liver volumetry based on our automated scheme agreed excellently with reference-standard volumetry, and it required substantially less completion time.

Portal vein embolization with plug/coils improves hepatectomy outcome.

PubMed

Malinowski, Maciej; Geisel, Dominik; Stary, Victoria; Denecke, Timm; Seehofer, Daniel; Jara, Maximillian; Baron, Annekathrin; Pratschke, Johann; Gebauer, Bernhard; Stockmann, Martin

2015-03-01

Portal vein embolization (PVE) has become the standard of care before extended hepatectomy. Various PVE methods using different embolization materials have been described. In this study, we compared PVE with polyvinyl alcohol particles alone (PVA only) versus PVA with plug or coils (PVA + plug/coils). Patients undergoing PVE before hepatectomy were included. PVA alone was used until December 2013, thereafter plug or coils were placed in addition. The volume of left lateral liver lobe (LLL), clinical parameters, and liver function tests were measured before PVE and resection. A total of 43 patients were recruited into the PVA only group and 42 were recruited into the PVA + plug/coils group. There were no major differences between groups except significantly higher total bilirubin level before PVE in the PVA only group, which improved before hepatectomy. Mean LLL volume increased by 25.7% after PVE in the PVA only group and by 44% in the PVA + plug/coils group (P < 0.001). Recanalization was significantly less common in the PVA + plug/coils group. In multivariate regression, initial LLL volume and use of plug or coils were the only parameters influencing LLL volume increase. The postoperative liver failure rate was significantly reduced in PVA + plug/coils group (P = <0.001). PVE using PVA particles together with plug or coils is a safe and efficient method to increase future liver remnant volume. The additional central embolization with plug or coils led to an increased hypertrophy, due to lower recanalization rates, and subsequently decreased incidence of postoperative liver failure. No additional procedure-specific complications were observed in this series. Copyright © 2015 Elsevier Inc. All rights reserved.

Impact of Graft Selection on Donor and Recipient Outcomes After Living Donor Liver Transplantation.

PubMed

Braun, Hillary J; Dodge, Jennifer L; Roll, Garrett R; Freise, Chris E; Ascher, Nancy L; Roberts, John P

2016-06-01

Balancing donor and recipient risks in living donor liver transplantation remains an issue of debate. This study assessed the impact of graft selection on outcomes and complications for left lobe (LL) versus right lobe (RL) donors and recipients. The medical records of donors and recipients, who underwent living donor liver transplantation at our institution between 2003 and 2015, were reviewed. For donors, we evaluated graft volume, residual liver volume per standard liver volume, length of hospital stay (LOS), complications, and readmissions. For recipients, we looked at graft and patient survival, graft function at postoperative days 7 and 14, graft volume, LOS, biliary complications, Model for End-Stage Liver Disease at transplant, and hepatitis C virus status. At 5 years posttransplant, there were no significant differences in graft survival for LL recipients (86% [95% confidence interval, 74-93]) compared with 82% (95% confidence interval, 69-89) for RL recipients (P = 0.85) or recipient survival (90% vs 84%; P = 0.44). In LL recipients, postoperative days 7 and 14 median international normalized ratio (1.5 and 1.2, respectively) and total bilirubin (4.6 and 2.7) were significantly greater compared with RL recipients (7 and 14 days international normalized ratio [1.2, P < 0.001; 1.1, P = 0.001] and total bilirubin (2.7, P = 0.001; 2.1, P = 0.05)). The LL recipients also had a significantly greater median LOS (14 vs 10, P = 0.008). Median donor LOS was significantly greater for RL donors (7 [interquartile range, 7-8] vs 7 [interquartile range, 6-7] days, P < 0.001). The RL and LL grafts provide comparable long-term outcomes in properly selected donor-recipient pairs and the appropriate use of LL grafts does not impact graft or patient survival at 5 years posttransplant.

Association between Helicobacter pylori and liver-to-spleen ratio: a randomized-controlled single-blind study.

PubMed

Doğan, Zeynal; Filik, Levent; Ergül, Bilal; Sarikaya, Murat; Akbal, Erdem

2013-01-01

Helicobacter pylori infection is reported to be associated with some extragastrointestinal manifestations, such as hematological diseases (thrombocytopenia, anemia), obesity, and fatty liver disease. The length or the volume ratio of liver to spleen was suggested to be changed in some hematological and hepatobiliary disorders. We hypothesized that the liver-to-spleen ratio may be affected in H. pylori-positive patients. In this respect, we aimed to evaluate the effect of H. pylori infection on the liver-to-spleen ratio and platelet indices. A total of 174 patients with functional dyspepsia were included in the study. Patients were divided into group 1 (H. pylori-positive gastritis) (n=95) and group 2 (H. pylori negative, control group) (n=79). Liver, spleen length measurement, and liver steatosis scores were performed by ultrasonography by the same physicians who were blinded to the H. pylori results. Blood count values including the platelet count and the mean platelet volume (MPV) were compared between the two groups. BMI was also evaluated as a potential confounding factor for fatty liver. The liver-to-spleen ratio, platelet-to-spleen ratio, MPV-to-spleen ratio, and the MPV-to-liver ratio were significantly lower in the H. pylori-positive group compared with the H. pylori-negative group (P<0.001, <0.001, <0.001, and 0.038, respectively). Fatty liver was significantly more frequent in H. pylori-positive patients. Liver-to-spleen ratio and the MPV-to-spleen ratio are important indices in the pathogenesis of H. pylori-linked liver and spleen manifestations, and thrombocytopenia.

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

Wang, Hesheng, E-mail: hesheng@umich.edu; Feng, Mary; Jackson, Andrew

Purpose: To develop a local and global function model in the liver based on regional and organ function measurements to support individualized adaptive radiation therapy (RT). Methods and Materials: A local and global model for liver function was developed to include both functional volume and the effect of functional variation of subunits. Adopting the assumption of parallel architecture in the liver, the global function was composed of a sum of local function probabilities of subunits, varying between 0 and 1. The model was fit to 59 datasets of liver regional and organ function measures from 23 patients obtained before, during, andmore » 1 month after RT. The local function probabilities of subunits were modeled by a sigmoid function in relating to MRI-derived portal venous perfusion values. The global function was fitted to a logarithm of an indocyanine green retention rate at 15 minutes (an overall liver function measure). Cross-validation was performed by leave-m-out tests. The model was further evaluated by fitting to the data divided according to whether the patients had hepatocellular carcinoma (HCC) or not. Results: The liver function model showed that (1) a perfusion value of 68.6 mL/(100 g · min) yielded a local function probability of 0.5; (2) the probability reached 0.9 at a perfusion value of 98 mL/(100 g · min); and (3) at a probability of 0.03 [corresponding perfusion of 38 mL/(100 g · min)] or lower, the contribution to global function was lost. Cross-validations showed that the model parameters were stable. The model fitted to the data from the patients with HCC indicated that the same amount of portal venous perfusion was translated into less local function probability than in the patients with non-HCC tumors. Conclusions: The developed liver function model could provide a means to better assess individual and regional dose-responses of hepatic functions, and provide guidance for individualized treatment planning of RT.« less

Testosterone and estradiol treatments differently affect pituitary-thyroid axis and liver deiodinase 1 activity in orchidectomized middle-aged rats.

PubMed

Šošić-Jurjević, B; Filipović, B; Renko, K; Miler, M; Trifunović, S; Ajdžanovič, V; Kӧhrle, J; Milošević, V

2015-12-01

We previously reported that orchidectomy (Orx) of middle-aged rats (15-16-month-old; MA) slightly affected pituitary-thyroid axis, but decreased liver deiodinase (Dio) type 1 and pituitary Dio2 enzyme activities. At present, we examined the effects of subsequent testosterone-propionate treatment (5mg/kg; Orx+T), and compared the effects of testosterone with the effects of estradiol-dipropionate (0.06mg/kg; Orx+E) treatment. Hormones were subcutaneously administered, daily, for three weeks, while Orx and sham-operated (SO) controls received only the vehicle. The applied dose of T did not alter serum TSH, T4 and T3 concentrations in Orx- MA, though it increased TSH when administrated to Orx young adults (2.5-month-old; Orx-YA). However, pituitaries of Orx-MA+T rats had higher relative intensity of immunofluorescence (RIF) for TSHβ; in their thyroids we found increased volume and height of follicular epithelium, decreased volume of the colloid and higher RIF for T4-bound to thyroglobulin (Tg-T4). Liver Dio1 activity was increased. E-treatment did not affect serum hormone levels, pituitary RIF for TSHβ, or liver Dio1 activity in Orx-MA rats. Thyroids had decreased relative volume and height of follicular epithelium, increased relative volume of the colloid, decreased volume of sodium-iodide symporter-immunopositive epithelium and lower RIF for Tg-T4. Detected changes were statistically significant. In conclusion, androgenization enhanced pituitary TSHβ RIF, thyroid activation and liver Dio1 enzyme activity in Orx-MA, without elevating serum TSH as in Orx-YA rats. Estrogenization induced pituitary enlargement with no effect on pituitary TSHβ RIF, serum TSH or liver Dio1 activity. E also induced alterations in thyroid histology that indicate mild suppression of its functioning, and contributed to thyroid blood vessel enlargement in Orx-MA rats. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Shen, Sui, E-mail: sshen@uabmc.edu; Jacob, Rojymon; Bender, Luvenia W.

Radiotherapy or stereotactic body radiosurgery (SBRT) requires a sufficient functional liver volume to tolerate the treatment. The current study extended the work of de Graaf et al. (2010) [3] on the use of {sup 99m}Tc-mebrofenin imaging for presurgery planning to radiotherapy planning for liver cancer or metastases. Patient was immobilized and imaged in an identical position on a single-photon emission computed tomography/computed tomography (SPECT-CT) system and a radiotherapy simulation CT system. {sup 99m}Tc-mebrofenin SPECT was registered to the planning CT through image registration of noncontrast CT from SPECT-CT system to the radiotherapy planning CT. The voxels with higher uptake ofmore » {sup 99m}Tc-mebrofenin were transferred to the planning CT as an avoidance structure in optimizing a 2-arc RapidArc plan for SBRT delivery. Excellent dose coverage to the target and sparing of the healthy remnant liver volume was achieved. This report illustrated a procedure for the use of {sup 99m}Tc-mebrofenin SPECT for optimizing radiotherapy for liver cancers and metastases.« less

CT liver volumetry using three-dimensional image data in living donor liver transplantation: Effects of slice thickness on volume calculation

PubMed Central

Hori, Masatoshi; Suzuki, Kenji; Epstein, Mark L.; Baron, Richard L.

2011-01-01

The purpose was to evaluate a relationship between slice thickness and calculated volume on CT liver volumetry by comparing the results for images with various slice thicknesses including three-dimensional images. Twenty adult potential liver donors (12 men, 8 women; mean age, 39 years; range, 24–64) underwent CT with a 64-section multi-detector row CT scanner after intra-venous injection of contrast material. Four image sets with slice thicknesses of 0.625 mm, 2.5 mm, 5 mm, and 10 mm were used. First, a program developed in our laboratory for automated liver extraction was applied to CT images, and the liver boundary was obtained automatically. Then, an abdominal radiologist reviewed all images on which automatically extracted boundaries were superimposed, and edited the boundary on each slice to enhance the accuracy. Liver volumes were determined by counting of the voxels within the liver boundary. Mean whole liver volumes estimated with CT were 1322.5 cm3 on 0.625-mm, 1313.3 cm3 on 2.5-mm, 1310.3 cm3 on 5-mm, and 1268.2 cm3 on 10-mm images. Volumes calculated for three-dimensional (0.625-mm-thick) images were significantly larger than those for thicker images (P<.0001). Partial liver volumes of right lobe, left lobe, and lateral segment were also evaluated in a similar manner. Estimated maximum differences in calculated volumes of lateral segment was −10.9 cm3 (−4.6%) between 0.625-mm and 5-mm images. In conclusion, liver volumes calculated on 2.5-mm or thicker images were significantly smaller than volumes calculated on three-dimensional images. If a maximum error of 5% in the calculated graft volume is within the range of having an insignificant clinical impact, 5-mm thick images are acceptable for CT volumetry. If not, three-dimensional images could be essential. PMID:21850689

Kinetic Growth Rate after Portal Vein Embolization Predicts Posthepatectomy Outcomes: Toward Zero Liver-Related Mortality in Patients with Colorectal Liver Metastases and Small Future Liver Remnant

PubMed Central

Shindoh, Junichi; Truty, Mark J; Aloia, Thomas A; Curley, Steven A; Zimmitti, Giuseppe; Huang, Steven Y; Mahvash, Armeen; Gupta, Sanjay; Wallace, Michael J; Vauthey, Jean-Nicolas

2013-01-01

Background Standardized future liver remnant (sFLR) volume and degree of hypertrophy after portal vein embolization (PVE) have been recognized as significant predictors of surgical outcomes after major liver resection. However, regeneration rate of the FLR after PVE varies among individuals and its clinical significance is unknown. Study Design Degree of hypertrophy at initial volume assessment divided by number of weeks elapsed after PVE was defined as the kinetic growth rate (KGR). In 107 consecutive patients who underwent liver resection for colorectal liver metastases with a sFLR volume of greater than 20%, the ability of the KGR to predict overall and liver-specific postoperative morbidity and mortality was compared with sFLR volume and degree of hypertrophy. Results Using receiver operating characteristic analysis, the best cut-off values for sFLR volume, degree of hypertrophy, and KGR for predicting postoperative hepatic insufficiency were estimated as, respectively, 29.6%, 7.5%, and 2.0% per week. Among these, KGR was the most accurate predictor (area under the curve, 0.830 [0.736-0.923]; asymptotic significance, 0.002). KGR of less than 2% per week vs. ≥2% per week correlate with rates of hepatic insufficiency (21.6% vs. 0%, p = 0.0001) and liver-related 90-day mortality (8.1% vs. 0%, P=0.04). The predictive value of KGR was not influenced by sFLR volume or the timing of initial volume assessment when evaluated within 8 weeks after PVE. Conclusions KGR is a better predictor of postoperative morbidity and mortality after liver resection for small FLR than conventional measured volume parameters (sFLR volume and degree of hypertrophy). PMID:23219349

Kinetic growth rate after portal vein embolization predicts posthepatectomy outcomes: toward zero liver-related mortality in patients with colorectal liver metastases and small future liver remnant.

PubMed

Shindoh, Junichi; Truty, Mark J; Aloia, Thomas A; Curley, Steven A; Zimmitti, Giuseppe; Huang, Steven Y; Mahvash, Armeen; Gupta, Sanjay; Wallace, Michael J; Vauthey, Jean-Nicolas

2013-02-01

Standardized future liver remnant (sFLR) volume and degree of hypertrophy after portal vein embolization (PVE) have been recognized as important predictors of surgical outcomes after major liver resection. However, the regeneration rate of the FLR after PVE varies among individuals and its clinical significance is unknown. Kinetic growth rate (KGR) is defined as the degree of hypertrophy at initial volume assessment divided by number of weeks elapsed after PVE. In 107 consecutive patients who underwent liver resection for colorectal liver metastases with an sFLR volume >20%, the ability of the KGR to predict overall and liver-specific postoperative morbidity and mortality was compared with sFLR volume and degree of hypertrophy. Using receiver operating characteristic analysis, the best cutoff values for sFLR volume, degree of hypertrophy, and KGR for predicting postoperative hepatic insufficiency were estimated as 29.6%, 7.5%, and 2.0% per week, respectively. Among these, KGR was the most accurate predictor (area under the curve 0.830 [95% CI, 0.736-0.923]; asymptotic significance, 0.002). A KGR of <2% per week vs ≥2% per week correlates with rates of hepatic insufficiency (21.6% vs 0%; p = 0.0001) and liver-related 90-day mortality (8.1% vs 0%; p = 0.04). The predictive value of KGR was not influenced by sFLR volume or the timing of initial volume assessment when evaluated within 8 weeks after PVE. Kinetic growth rate is a better predictor of postoperative morbidity and mortality after liver resection for small FLR than conventional measured volume parameters (ie, sFLR volume and degree of hypertrophy). Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Volumetry-based selection of right posterior sector grafts for adult living donor liver transplantation.

PubMed

Kim, Bong-Wan; Xu, Weiguang; Wang, Hee-Jung; Park, Yong-Keun; Lee, Kwangil; Kim, Myung-Wook

2011-09-01

To determine the feasibility of volumetric criteria without anatomic exclusion for the selection of right posterior sector (RPS) grafts for adult-to-adult living donor liver transplantation (LDLT), we reviewed and compared our transplant data for RPS grafts and right lobe (RL) grafts. Between January 2008 and September 2010, adult-to-adult LDLT was performed 65 times at our institute; 13 of the procedures (20%) were performed with RPS grafts [the posterior sector (PS) group], and 39 (60%) were performed with RL grafts (the RL group). The volumetry of the 13 RPS donor livers showed that the RPS volume was 39.8% ± 7.6% of the total liver volume. Ten of the 13 donors had to donate RPS grafts because the left liver volume was inadequate. All donor procedures were performed successfully, and all donors recovered from hepatectomy. However, longer operative times were required for the procurement of RPS grafts versus RL grafts (418 ± 40 versus 345 ± 48 minutes, P < 0.001). The postoperative recovery of liver function was smoother for the donors of the PS group versus the donors of the RL group. The RPS grafts had significantly smaller hepatic artery and bile duct openings than the RL grafts. All recipients with RPS grafts survived LDLT. No recipients experienced vascular graft complications or small-for-size graft dysfunction. There were no significant differences in the incidence of posttransplant complications between the donors and recipients of the PS and RL groups. The 3-year graft survival rates were favorable in both groups (100% in the PS group versus 91% in the RL group). In conclusion, the selection of RPS grafts by volume criteria is a feasible strategy for an adult-to-adult LDLT program. Copyright © 2011 American Association for the Study of Liver Diseases.

Spatial considerations during cryopreservation of a large volume sample.

PubMed

Kilbride, Peter; Lamb, Stephen; Milne, Stuart; Gibbons, Stephanie; Erro, Eloy; Bundy, James; Selden, Clare; Fuller, Barry; Morris, John

2016-08-01

There have been relatively few studies on the implications of the physical conditions experienced by cells during large volume (litres) cryopreservation - most studies have focused on the problem of cryopreservation of smaller volumes, typically up to 2 ml. This study explores the effects of ice growth by progressive solidification, generally seen during larger scale cryopreservation, on encapsulated liver hepatocyte spheroids, and it develops a method to reliably sample different regions across the frozen cores of samples experiencing progressive solidification. These issues are examined in the context of a Bioartificial Liver Device which requires cryopreservation of a 2 L volume in a strict cylindrical geometry for optimal clinical delivery. Progressive solidification cannot be avoided in this arrangement. In such a system optimal cryoprotectant concentrations and cooling rates are known. However, applying these parameters to a large volume is challenging due to the thermal mass and subsequent thermal lag. The specific impact of this to the cryopreservation outcome is required. Under conditions of progressive solidification, the spatial location of Encapsulated Liver Spheroids had a strong impact on post-thaw recovery. Cells in areas first and last to solidify demonstrated significantly impaired post-thaw function, whereas areas solidifying through the majority of the process exhibited higher post-thaw outcome. It was also found that samples where the ice thawed more rapidly had greater post-thaw viability 24 h post-thaw (75.7 ± 3.9% and 62.0 ± 7.2% respectively). These findings have implications for the cryopreservation of large volumes with a rigid shape and for the cryopreservation of a Bioartificial Liver Device. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Prediction of Liver Function by Using Magnetic Resonance-based Portal Venous Perfusion Imaging

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

Cao Yue, E-mail: yuecao@umich.edu; Department of Radiology, University of Michigan, Ann Arbor, Michigan; Wang Hesheng

2013-01-01

Purpose: To evaluate whether liver function can be assessed globally and spatially by using volumetric dynamic contrast-enhanced magnetic resonance imaging MRI (DCE-MRI) to potentially aid in adaptive treatment planning. Methods and Materials: Seventeen patients with intrahepatic cancer undergoing focal radiation therapy (RT) were enrolled in institution review board-approved prospective studies to obtain DCE-MRI (to measure regional perfusion) and indocyanine green (ICG) clearance rates (to measure overall liver function) prior to, during, and at 1 and 2 months after treatment. The volumetric distribution of portal venous perfusion in the whole liver was estimated for each scan. We assessed the correlation betweenmore » mean portal venous perfusion in the nontumor volume of the liver and overall liver function measured by ICG before, during, and after RT. The dose response for regional portal venous perfusion to RT was determined using a linear mixed effects model. Results: There was a significant correlation between the ICG clearance rate and mean portal venous perfusion in the functioning liver parenchyma, suggesting that portal venous perfusion could be used as a surrogate for function. Reduction in regional venous perfusion 1 month after RT was predicted by the locally accumulated biologically corrected dose at the end of RT (P<.0007). Regional portal venous perfusion measured during RT was a significant predictor for regional venous perfusion assessed 1 month after RT (P<.00001). Global hypovenous perfusion pre-RT was observed in 4 patients (3 patients with hepatocellular carcinoma and cirrhosis), 3 of whom had recovered from hypoperfusion, except in the highest dose regions, post-RT. In addition, 3 patients who had normal perfusion pre-RT had marked hypervenous perfusion or reperfusion in low-dose regions post-RT. Conclusions: This study suggests that MR-based volumetric hepatic perfusion imaging may be a biomarker for spatial distribution of liver function, which could aid in individualizing therapy, particularly for patients at risk for liver injury after RT.« less

Treatment Planning and Volumetric Response Assessment for Yttrium-90 Radioembolization: Semiautomated Determination of Liver Volume and Volume of Tumor Necrosis in Patients with Hepatic Malignancy

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

Monsky, Wayne L., E-mail: wayne.monsky@ucdmc.ucdavis.edu; Garza, Armando S.; Kim, Isaac

Purpose: The primary purpose of this study was to demonstrate intraobserver/interobserver reproducibility for novel semiautomated measurements of hepatic volume used for Yttrium-90 dose calculations as well as whole-liver and necrotic-liver (hypodense/nonenhancing) tumor volume after radioembolization. The secondary aim was to provide initial comparisons of tumor volumetric measurements with linear measurements, as defined by Response Evaluation Criteria in Solid Tumors criteria, and survival outcomes. Methods: Between 2006 and 2009, 23 consecutive radioembolization procedures were performed for 14 cases of hepatocellular carcinoma and 9 cases of hepatic metastases. Baseline and follow-up computed tomography obtained 1 month after treatment were retrospectively analyzed. Threemore » observers measured liver, whole-tumor, and tumor-necrosis volumes twice using semiautomated software. Results: Good intraobserver/interobserver reproducibility was demonstrated (intraclass correlation [ICC] > 0.9) for tumor and liver volumes. Semiautomated measurements of liver volumes were statistically similar to those obtained with manual tracing (ICC = 0.868), but they required significantly less time to perform (p < 0.0001, ICC = 0.088). There was a positive association between change in linear tumor measurements and whole-tumor volume (p < 0.0001). However, linear measurements did not correlate with volume of necrosis (p > 0.05). Dose, change in tumor diameters, tumor volume, and necrotic volume did not correlate with survival (p > 0.05 in all instances). However, Kaplan-Meier curves suggest that a >10% increase in necrotic volume correlated with survival (p = 0.0472). Conclusion: Semiautomated volumetric analysis of liver, whole-tumor, and tumor-necrosis volume can be performed with good intraobserver/interobserver reproducibility. In this small retrospective study, measurements of tumor necrosis were suggested to correlate with survival.« less

Effect of oral D-tagatose on liver volume and hepatic glycogen accumulation in healthy male volunteers.

PubMed

Boesch, C; Ith, M; Jung, B; Bruegger, K; Erban, S; Diamantis, I; Kreis, R; Bär, A

2001-04-01

Standard toxicity tests with high levels of D-tagatose showed a reversible enlargement of the liver in Sprague-Dawley rats without increase of liver enzymes. The present study tests the hypotheses that partial substitution of dietary sucrose by D-tagatose for 28 days increases the volume of human liver and the concentration of liver glycogen. Twelve healthy, male volunteers were studied in a double-blind crossover study with ingestion of D-tagatose (3x15 g daily) and placebo (sucrose, 3x15 g daily) for periods of 28 days each. Liver volume and glycogen concentration have been determined by magnetic resonance (MR) imaging and spectroscopy, which were accompanied by routine medical examinations. MR examinations before and after the treatments revealed no effects (P>0.05) of treatment, period, or subject for changes in liver volume or glycogen concentration. A steady increase of liver volumes, independent of the D-tagatose or placebo intake, has been observed over the study in parallel with a slight increase in body weight. The treatment with D-tagatose was not associated with clinically relevant changes of the examined clinico-chemical and hematological parameters, including liver enzymes and uric acid. Copyright 2001 Academic Press.

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.

Increase in left liver lobe function after preoperative right portal vein embolisation assessed with gadolinium-EOB-DTPA MRI.

PubMed

Geisel, Dominik; Lüdemann, Lutz; Keuchel, Thomas; Malinowski, Maciej; Seehofer, Daniel; Stockmann, Martin; Hamm, Bernd; Gebauer, Bernhard; Denecke, Timm

2013-09-01

To prospectively evaluate the early development of regional liver function after right portal vein embolisation (PVE) with Gd-EOB-DTPA-enhanced MRI in patients scheduled for extended right hemihepatectomy. Ten patients who received a PVE before an extended hemihepatectomy were examined before and 14 days after PVE using Gd-EOB-DTPA-enhanced MRI of the liver. In these sequences representative region of interest measurements were performed in the embolised right (RLL) and the non-embolised left liver lobe (LLL). The volume as well as hepatic uptake index (HUI) was calculated independently for each lobe. Relative enhancement 14 days after PVE decreased in the RLL and increased significantly in the LLL (P < 0.05). Average hepatic uptake index (HUI) for RLL was significantly lower 14 days after PVE than before PVE (P < 0.05) and significantly higher for LLL (P < 0.05). A significant shift of contrast uptake from the right to the left liver lobe can be depicted as early as 14 days after right PVE by using Gd-EOB-DTPA-enhanced MRI, which could reflect the redirected portal venous blood flow and the rapid utilisation of a hepatic functional reserve. • Preoperative portal vein embolisation (PVE) is widely performed before right-sided hepatic resection. • PVE increases intravenous contrast medium uptake in the left lobe of liver. • The hepatic uptake index for the left liver lobe increases rapidly after PVE. • Left liver lobe function increase may be visualised by Gd-EOB-DTPA-enhanced MRI.

Role of intrahepatic innervation in regulating the activity of liver cells

PubMed Central

Streba, Letitia Adela Maria; Vere, Cristin Constantin; Ionescu, Alin Gabriel; Streba, Costin Teodor; Rogoveanu, Ion

2014-01-01

Liver innervation comprises sympathetic, parasympathetic and peptidergic nerve fibers, organized as either afferent or efferent nerves with different origins and roles. Their anatomy and physiology have been studied in the past 30 years, with different results published over time. Hepatocytes are the main cell population of the liver, making up almost 80% of the total liver volume. The interaction between hepatocytes and nerve fibers is accomplished through a wealth of neurotransmitters and signaling pathways. In this short review, we have taken the task of condensing the most important data related to how the nervous system interacts with the liver and especially with the hepatocyte population, how it influences their metabolism and functions, and how different receptors and transmitters are involved in this complex process. PMID:24672643

Assessment of tumor vascularization with functional computed tomography perfusion imaging in patients with cirrhotic liver disease.

PubMed

Li, Jin-Ping; Zhao, De-Li; Jiang, Hui-Jie; Huang, Ya-Hua; Li, Da-Qing; Wan, Yong; Liu, Xin-Ding; Wang, Jin-E

2011-02-01

Hepatocellular carcinoma (HCC) is a common malignant tumor in China, and early diagnosis is critical for patient outcome. In patients with HCC, it is mostly based on liver cirrhosis, developing from benign regenerative nodules and dysplastic nodules to HCC lesions, and a better understanding of its vascular supply and the hemodynamic changes may lead to early tumor detection. Angiogenesis is essential for the growth of primary and metastatic tumors due to changes in vascular perfusion, blood volume and permeability. These hemodynamic and physiological properties can be measured serially using functional computed tomography perfusion (CTP) imaging and can be used to assess the growth of HCC. This study aimed to clarify the physiological characteristics of tumor angiogenesis in cirrhotic liver disease by this fast imaging method. CTP was performed in 30 volunteers without liver disease (control subjects) and 49 patients with liver disease (experimental subjects: 27 with HCC and 22 with cirrhosis). All subjects were also evaluated by physical examination, laboratory screening and Doppler ultrasonography of the liver. The diagnosis of HCC was made according to the EASL criteria. All patients underwent contrast-enhanced ultrasonography, pre- and post-contrast triple-phase CT and CTP study. A mathematical deconvolution model was applied to provide hepatic blood flow (HBF), hepatic blood volume (HBV), mean transit time (MTT), permeability of capillary vessel surface (PS), hepatic arterial index (HAI), hepatic arterial perfusion (HAP) and hepatic portal perfusion (HPP) data. The Mann-Whitney U test was used to determine differences in perfusion parameters between the background cirrhotic liver parenchyma and HCC and between the cirrhotic liver parenchyma with HCC and that without HCC. In normal liver, the HAP/HVP ratio was about 1/4. HCC had significantly higher HAP and HAI and lower HPP than background liver parenchyma adjacent to the HCC. The value of HBF at the tumor rim was significantly higher than that in the controls. HBF, HBV, HAI, HAP and HPP, but not MTT and PS, were significantly higher in the cirrhotic liver parenchyma involved with HCC than those of the controls. Perfusion parameters were not significantly different between the controls and the cirrhotic liver parenchyma not involved with HCC. CTP can clearly distinguish tumor from cirrhotic liver parenchyma and controls and can provide quantitative information about tumor-related angiogenesis, which can be used to assess tumor vascularization in cirrhotic liver disease.

Measuring hepatic functional reserve using low temporal resolution Gd-EOB-DTPA dynamic contrast-enhanced MRI: a preliminary study comparing galactosyl human serum albumin scintigraphy with indocyanine green retention.

PubMed

Saito, Kazuhiro; Ledsam, Joseph; Sourbron, Steven; Hashimoto, Tsuyoshi; Araki, Yoichi; Akata, Soichi; Tokuuye, Koichi

2014-01-01

To investigate if tracer kinetic modelling of low temporal resolution dynamic contrast-enhanced (DCE) MRI with Gd-EOB-DTPA could replace technetium-99 m galactosyl human serum albumin (GSA) single positron emission computed tomography (SPECT) and indocyanine green (ICG) retention for the measurement of liver functional reserve. Twenty eight patients awaiting liver resection for various cancers were included in this retrospective study that was approved by the institutional review board. The Gd-EOB-DTPA MRI sequence acquired five images: unenhanced, double arterial phase, portal phase, and 4 min after injection. Intracellular contrast uptake rate (UR) and extracellular volume (Ve) were calculated from DCE-MRI, along with the ratio of GSA radioactivity of liver to heart-plus-liver and per cent of cumulative uptake from 15-16 min (LHL15 and LU15, respectively) from GSA-scintigraphy. ICG retention at 15 min, Child-Pugh cirrhosis score (CPS) and postoperative Inuyama fibrosis criteria were also recorded. Statistical analysis was with Spearman rank correlation analysis. Comparing MRI parameters with the reference methods, significant correlations were obtained for UR and LHL15, LU15, ICG15 (all 0.4-0.6, P < 0.05); UR and CPS (-0.64, P < 0.001); Ve and Inuyama (0.44, P < 0.05). Measures of liver function obtained by routine Gd-EOB-DTPA DCE-MRI with tracer kinetic modelling may provide a suitable method for the evaluation of liver functional reserve. • Magnetic resonance imaging (MRI) provides new methods of measuring hepatic functional reserve. • DCE-MRI with Gd-EOB-DTPA offers the possibility of replacing scintigraphy. • The analysis method can be used for preoperative liver function evaluation.

Reproducibility of functional volume and activity concentration in 18F-FDG PET/CT of liver metastases in colorectal cancer.

PubMed

Heijmen, Linda; de Geus-Oei, Lioe-Fee; de Wilt, Johannes H W; Visvikis, Dimitris; Hatt, Mathieu; Visser, Eric P; Bussink, Johan; Punt, Cornelis J A; Oyen, Wim J G; van Laarhoven, Hanneke W M

2012-12-01

Several studies showed potential for monitoring response to systemic therapy in metastatic colorectal cancer patients with (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Before (18)F-FDG PET can be implemented for response evaluation the repeatability should be known. This study was performed to assess the magnitude of the changes in standardized uptake value (SUV), volume and total lesion glycolysis (TLG) in colorectal liver metastases and validate the biological basis of (18)F-FDG PET in colorectal liver metastases. Twenty patients scheduled for liver metastasectomy underwent two (18)F-FDG PET scans within 1 week. Bland-Altman analysis was performed to assess repeatability of SUV(max), SUV(mean), volume and TLG. Tumours were delineated using an adaptive threshold method (PET(SBR)) and a semiautomatic fuzzy locally adaptive Bayesian (FLAB) delineation method. Coefficient of repeatability of SUV(max) and SUV(mean) were ∼39 and ∼31 %, respectively, independent of the delineation method used and image reconstruction parameters. However, repeatability was worse in recently treated patients. The FLAB delineation method improved the repeatability of the volume and TLG measurements compared to PET(SBR), from coefficients of repeatability of over 85 % to 45 % and 57 % for volume and TLG, respectively. Glucose transporter 1 (GLUT1) expression correlated to the SUV(mean). Vascularity (CD34 expression) and tumour hypoxia (carbonic anhydrase IX expression) did not correlate with (18)F-FDG PET parameters. In conclusion, repeatability of SUV(mean) and SUV(max) was mainly affected by preceding systemic therapy. The repeatability of tumour volume and TLG could be improved using more advanced and robust delineation approaches such as FLAB, which is recommended when (18)F-FDG PET is utilized for volume or TLG measurements. Improvement of repeatability of PET measurements, for instance by dynamic PET scanning protocols, is probably necessary to effectively use PET for early response monitoring.

Experimental study of electrolysis-induced hepatic necrosis.

PubMed

Robertson, G S; Wemyss-Holden, S A; Dennison, A R; Hall, P M; Baxter, P; Maddern, G J

1998-09-01

One of the most promising but unexplored methods for treating patients with irresectable liver tumours is electrolysis. This study examined the effect of increasing 'current dose' on the volume of the lesion induced in normal rat liver. A direct current generator, connected to platinum electrodes implanted in the rat liver, was used to examine the effect of (1) varying current doses from 1 to 5 coulombs and (2) electrode separation (2 or 20 mm), on the volume of liver necrosis. There was a significant correlation (P < 0.001) between the current dose and the volume of necrosis produced for each electrode separation. Placing the electrodes 2 mm apart resulted in smaller total volumes of necrosis than placing them 20 mm apart when anode lesions were significantly larger than cathode lesions (P< 0.05). Liver enzymes (aspartate aminotransferase, alanine aminotransferase) were significantly raised 1 day after treatment (P < 0.001) and predicted the total volume of hepatic necrosis (P < 0.001). Predictable and reproducible areas of liver necrosis are produced with electrolysis. If these results extrapolate to larger animal models, this technique has potential for patients with irresectable primary and secondary liver tumours.

Quantitative Radiology: Automated CT Liver Volumetry Compared With Interactive Volumetry and Manual Volumetry

PubMed Central

Suzuki, Kenji; Epstein, Mark L.; Kohlbrenner, Ryan; Garg, Shailesh; Hori, Masatoshi; Oto, Aytekin; Baron, Richard L.

2014-01-01

OBJECTIVE The purpose of this study was to evaluate automated CT volumetry in the assessment of living-donor livers for transplant and to compare this technique with software-aided interactive volumetry and manual volumetry. MATERIALS AND METHODS Hepatic CT scans of 18 consecutively registered prospective liver donors were obtained under a liver transplant protocol. Automated liver volumetry was developed on the basis of 3D active-contour segmentation. To establish reference standard liver volumes, a radiologist manually traced the contour of the liver on each CT slice. We compared the results obtained with automated and interactive volumetry with those obtained with the reference standard for this study, manual volumetry. RESULTS The average interactive liver volume was 1553 ± 343 cm3, and the average automated liver volume was 1520 ± 378 cm3. The average manual volume was 1486 ± 343 cm3. Both interactive and automated volumetric results had excellent agreement with manual volumetric results (intraclass correlation coefficients, 0.96 and 0.94). The average user time for automated volumetry was 0.57 ± 0.06 min/case, whereas those for interactive and manual volumetry were 27.3 ± 4.6 and 39.4 ± 5.5 min/case, the difference being statistically significant (p < 0.05). CONCLUSION Both interactive and automated volumetry are accurate for measuring liver volume with CT, but automated volumetry is substantially more efficient. PMID:21940543

Quantitative radiology: automated CT liver volumetry compared with interactive volumetry and manual volumetry.

PubMed

Suzuki, Kenji; Epstein, Mark L; Kohlbrenner, Ryan; Garg, Shailesh; Hori, Masatoshi; Oto, Aytekin; Baron, Richard L

2011-10-01

The purpose of this study was to evaluate automated CT volumetry in the assessment of living-donor livers for transplant and to compare this technique with software-aided interactive volumetry and manual volumetry. Hepatic CT scans of 18 consecutively registered prospective liver donors were obtained under a liver transplant protocol. Automated liver volumetry was developed on the basis of 3D active-contour segmentation. To establish reference standard liver volumes, a radiologist manually traced the contour of the liver on each CT slice. We compared the results obtained with automated and interactive volumetry with those obtained with the reference standard for this study, manual volumetry. The average interactive liver volume was 1553 ± 343 cm(3), and the average automated liver volume was 1520 ± 378 cm(3). The average manual volume was 1486 ± 343 cm(3). Both interactive and automated volumetric results had excellent agreement with manual volumetric results (intraclass correlation coefficients, 0.96 and 0.94). The average user time for automated volumetry was 0.57 ± 0.06 min/case, whereas those for interactive and manual volumetry were 27.3 ± 4.6 and 39.4 ± 5.5 min/case, the difference being statistically significant (p < 0.05). Both interactive and automated volumetry are accurate for measuring liver volume with CT, but automated volumetry is substantially more efficient.

Automatic liver contouring for radiotherapy treatment planning

NASA Astrophysics Data System (ADS)

Li, Dengwang; Liu, Li; Kapp, Daniel S.; Xing, Lei

2015-09-01

To develop automatic and efficient liver contouring software for planning 3D-CT and four-dimensional computed tomography (4D-CT) for application in clinical radiation therapy treatment planning systems. The algorithm comprises three steps for overcoming the challenge of similar intensities between the liver region and its surrounding tissues. First, the total variation model with the L1 norm (TV-L1), which has the characteristic of multi-scale decomposition and an edge-preserving property, is used for removing the surrounding muscles and tissues. Second, an improved level set model that contains both global and local energy functions is utilized to extract liver contour information sequentially. In the global energy function, the local correlation coefficient (LCC) is constructed based on the gray level co-occurrence matrix both of the initial liver region and the background region. The LCC can calculate the correlation of a pixel with the foreground and background regions, respectively. The LCC is combined with intensity distribution models to classify pixels during the evolutionary process of the level set based method. The obtained liver contour is used as the candidate liver region for the following step. In the third step, voxel-based texture characterization is employed for refining the liver region and obtaining the final liver contours. The proposed method was validated based on the planning CT images of a group of 25 patients undergoing radiation therapy treatment planning. These included ten lung cancer patients with normal appearing livers and ten patients with hepatocellular carcinoma or liver metastases. The method was also tested on abdominal 4D-CT images of a group of five patients with hepatocellular carcinoma or liver metastases. The false positive volume percentage, the false negative volume percentage, and the dice similarity coefficient between liver contours obtained by a developed algorithm and a current standard delineated by the expert group are on an average 2.15-2.57%, 2.96-3.23%, and 91.01-97.21% for the CT images with normal appearing livers, 2.28-3.62%, 3.15-4.33%, and 86.14-93.53% for the CT images with hepatocellular carcinoma or liver metastases, and 2.37-3.96%, 3.25-4.57%, and 82.23-89.44% for the 4D-CT images also with hepatocellular carcinoma or liver metastases, respectively. The proposed three-step method can achieve efficient automatic liver contouring for planning CT and 4D-CT images with follow-up treatment planning and should find widespread applications in future treatment planning systems.

Validating New Software for Semiautomated Liver Volumetry--Better than Manual Measurement?

PubMed

Noschinski, L E; Maiwald, B; Voigt, P; Wiltberger, G; Kahn, T; Stumpp, P

2015-09-01

This prospective study compared a manual program for liver volumetry with semiautomated software. The hypothesis was that the semiautomated software would be faster, more accurate and less dependent on the evaluator's experience. Ten patients undergoing hemihepatectomy were included in this IRB approved study after written informed consent. All patients underwent a preoperative abdominal 3-phase CT scan, which was used for whole liver volumetry and volume prediction for the liver part to be resected. Two different types of software were used: 1) manual method: borders of the liver had to be defined per slice by the user; 2) semiautomated software: automatic identification of liver volume with manual assistance for definition of Couinaud segments. Measurements were done by six observers with different experience levels. Water displacement volumetry immediately after partial liver resection served as the gold standard. The resected part was examined with a CT scan after displacement volumetry. Volumetry of the resected liver scan showed excellent correlation to water displacement volumetry (manual: ρ = 0.997; semiautomated software: ρ = 0.995). The difference between the predicted volume and the real volume was significantly smaller with the semiautomated software than with the manual method (33% vs. 57%, p = 0.002). The semiautomated software was almost four times faster for volumetry of the whole liver (manual: 6:59 ± 3:04 min; semiautomated: 1:47 ± 1:11 min). Both methods for liver volumetry give an estimated liver volume close to the real one. The tested semiautomated software is faster, more accurate in predicting the volume of the resected liver part, gives more reproducible results and is less dependent on the user's experience. Both tested types of software allow exact volumetry of resected liver parts. Preoperative prediction can be performed more accurately with the semiautomated software. The semiautomated software is nearly four times faster than the tested manual program and less dependent on the user's experience. © Georg Thieme Verlag KG Stuttgart · New York.

Fully automated MR liver volumetry using watershed segmentation coupled with active contouring.

PubMed

Huynh, Hieu Trung; Le-Trong, Ngoc; Bao, Pham The; Oto, Aytek; Suzuki, Kenji

2017-02-01

Our purpose is to develop a fully automated scheme for liver volume measurement in abdominal MR images, without requiring any user input or interaction. The proposed scheme is fully automatic for liver volumetry from 3D abdominal MR images, and it consists of three main stages: preprocessing, rough liver shape generation, and liver extraction. The preprocessing stage reduced noise and enhanced the liver boundaries in 3D abdominal MR images. The rough liver shape was revealed fully automatically by using the watershed segmentation, thresholding transform, morphological operations, and statistical properties of the liver. An active contour model was applied to refine the rough liver shape to precisely obtain the liver boundaries. The liver volumes calculated by the proposed scheme were compared to the "gold standard" references which were estimated by an expert abdominal radiologist. The liver volumes computed by using our developed scheme excellently agreed (Intra-class correlation coefficient was 0.94) with the "gold standard" manual volumes by the radiologist in the evaluation with 27 cases from multiple medical centers. The running time was 8.4 min per case on average. We developed a fully automated liver volumetry scheme in MR, which does not require any interaction by users. It was evaluated with cases from multiple medical centers. The liver volumetry performance of our developed system was comparable to that of the gold standard manual volumetry, and it saved radiologists' time for manual liver volumetry of 24.7 min per case.

Liver-fat and liver-function indices derived from Gd-EOB-DTPA-enhanced liver MRI for prediction of future liver remnant growth after portal vein occlusion.

PubMed

Barth, Borna K; Fischer, Michael A; Kambakamba, Patryk; Lesurtel, Mickael; Reiner, Caecilia S

2016-04-01

To evaluate the use of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI)-derived fat- and liver function-measurements for prediction of future liver remnant (FLR) growth after portal vein occlusion (PVO) in patients scheduled for major liver resection. Forty-five patients (age, 59 ± 13.9 y) who underwent Gd-EOB-DTPA-enhanced liver MRI within 24 ± 18 days prior to PVO were included in this study. Fat-Signal-Fraction (FSF), relative liver enhancement (RLE) and corrected liver-to-spleen ratio (corrLSR) of the FLR were calculated from in- and out-of-phase (n=42) as well as from unenhanced T1-weighted, and hepatocyte-phase images (n=35), respectively. Kinetic growth rate (KGR, volume increase/week) of the FLR after PVO was the primary endpoint. Receiver operating characteristics analysis was used to determine cutoff values for prediction of impaired FLR-growth. FSF (%) showed significant inverse correlation with KGR (r=-0.41, p=0.008), whereas no significant correlation was found with RLE and corrLSR. FSF was significantly higher in patients with impaired FLR-growth than in those with normal growth (%FSF, 8.1 ± 9.3 vs. 3.0 ± 5.9, p=0.02). ROC-analysis revealed a cutoff-FSF of 4.9% for identification of patients with impaired FLR-growth with a specificity of 82% and sensitivity of 47% (AUC 0.71 [95%CI:0.54-0.87]). Patients with impaired FLR-growth according to the FSF-cutoff showed a tendency towards higher postoperative complication rates (posthepatectomy liver failure in 50% vs. 19%). Liver fat-content, but not liver function derived from Gd-EOB-DTPA-enhanced MRI is a predictor of FLR-growth after PVO. Thus, liver MRI could help in identifying patients at risk for insufficient FLR-growth, who may need re-evaluation of the therapeutic strategy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Hepatobiliary MRI: Signal intensity based assessment of liver function correlated to 13C-Methacetin breath test.

PubMed

Haimerl, Michael; Probst, Ute; Poelsterl, Stefanie; Beyer, Lukas; Fellner, Claudia; Selgrad, Michael; Hornung, Matthias; Stroszczynski, Christian; Wiggermann, Philipp

2018-06-13

Gadoxetic acid (Gd-EOB-DTPA) is a paramagnetic MRI contrast agent with raising popularity and has been used for evaluation of imaging-based liver function in recent years. In order to verify whether liver function as determined by real-time breath analysis using the intravenous administration of 13 C-methacetin can be estimated quantitatively from Gd-EOB-DTPA-enhanced MRI using signal intensity (SI) values. 110 patients underwent Gd-EOB-DTPA-enhanced 3-T MRI and, for the evaluation of liver function, a 13 C-methacetin breath test ( 13 C-MBT). SI values from before (SI pre ) and 20 min after (SI post ) contrast media injection were acquired by T1-weighted volume-interpolated breath-hold examination (VIBE) sequences with fat suppression. The relative enhancement (RE) between the plain and contrast-enhanced SI values was calculated and evaluated in a correlation analysis of 13 C-MBT values to SI post and RE to obtain a SI-based estimation of 13 C-MBT values. The simple regression model showed a log-linear correlation of 13 C-MBT values with SI post and RE (p < 0.001). Stratified by 3 different categories of 13 C-MBT readouts, there was a constant significant decrease in both SI post (p ≤ 0.002) and RE (p ≤ 0.033) with increasing liver disease progression as assessed by the 13 C-MBT. Liver function as determined using real-time 13 C-methacetin breath analysis can be estimated quantitatively from Gd-EOB-DTPA-enhanced MRI using SI-based indices.

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

Radiographic liver size in Pekingese dogs versus other dog breeds.

PubMed

Choi, Jihye; Keh, Seoyeon; Kim, Hyunwook; Kim, Junyoung; Yoon, Junghee

2013-01-01

Differential diagnoses for canine liver disease are commonly based on radiographic estimates of liver size, however little has been published on breed variations. Aims of this study were to describe normal radiographic liver size in Pekingese dogs and to compare normal measurements for this breed with other dog breeds and Pekingese dogs with liver disease. Liver measurements were compared for clinically normal Pekingese (n = 61), normal non-Pekingese brachycephalic (n = 45), normal nonbrachycephalic (n = 71), and Pekingese breed dogs with liver disease (n = 22). For each dog, body weight, liver length, T11 vertebral length, thoracic depth, and thoracic width were measured on right lateral and ventrodorsal abdominal radiographs. Liver volume was calculated using a formula and ratios of liver length/T11 vertebral length and liver volume/body weight ratio were determined. Normal Pekingese dogs had a significantly smaller liver volume/body weight ratio (16.73 ± 5.67, P < 0.05) than normal non-Pekingese brachycephalic breed dogs (19.54 ± 5.03) and normal nonbrachycephalic breed dogs (18.72 ± 6.52). The liver length/T11 vertebral length ratio in normal Pekingese (4.64 ± 0.65) was significantly smaller than normal non-Pekingese brachycephalic breed dogs (5.16 ± 0.74) and normal nonbrachycephalic breed dogs (5.40 ± 0.74). Ratios of liver volume/body weight and liver length/T11 vertebral length in normal Pekingese were significantly different from Pekingese with liver diseases (P < 0.05). Findings supported our hypothesis that Pekingese dogs have a smaller normal radiographic liver size than other breeds. We recommend using 4.64× the length of the T11 vertebra as a radiographic criterion for normal liver length in Pekingese dogs. © 2012 Veterinary Radiology & Ultrasound.

Body Fat Patterning, Hepatic Fat and Pancreatic Volume of Non-Obese Asian Indians with Type 2 Diabetes in North India: A Case-Control Study

PubMed Central

Misra, Anoop; Anoop, Shajith; Gulati, Seema; Mani, Kalaivani; Bhatt, Surya Prakash; Pandey, Ravindra Mohan

2015-01-01

Objective To evaluate body fat patterning and phenotype including hepatic fat and pancreatic volume of non-obese (BMI: < 25 kg/m2) Asian Indians with type 2 diabetes residing in North India. Methods Non-obese patients with type 2 diabetes (n = 93) and non-obese, normo-glycemic subjects (n = 40) were recruited. BMI, waist & hip circumferences, skinfold thickness at 8 sites, body fat, lean mass and detailed abdominal fat evaluation [total abdominal fat, total subcutaneous fat (superficial, deep, anterior, and posterior), total intra-abdominal fat (intra-peritoneal, retroperitoneal)], liver span, grades of fatty liver and pancreatic volume were compared. Results Waist circumference, subscapular skinfolds and total truncal fat (on DEXA) were higher whereas calf, total peripheral skinfolds and total leg fat (on DEXA) lower in patients. Specifically, the following volumes were higher in cases as compared to controls; total abdominal fat (19.4%), total intra-abdominal fat (49.7%), intra-peritoneal fat (47.7%), retroperitoneal fat (70.7%), pancreatic volume (26.6%), pancreatic volume index (21.3%) and liver span (10.8%). In cases, significant positive correlations were observed for pancreatic volume with BMI, waist and hip circumferences, W-HR, subscapular, abdominal and total truncal skinfolds, truncal, total subcutaneous, total intra-abdominal, intra-peritoneal, retroperitoneal fat depots, liver span and fatty liver. Conclusions In non-obese Asian Indians with type 2 diabetes, subcutaneous and intra-abdominal obesity, including fatty liver, and pancreatic volume were higher and peripheral subcutaneous adiposity was lower than BMI matched non-diabetic subjects. Importantly, increased pancreatic volume in patients was highly correlated with multiple measures of abdominal obesity and liver fat. PMID:26474415

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

Metabolic liver function measured in vivo by dynamic (18)F-FDGal PET/CT without arterial blood sampling.

PubMed

Horsager, Jacob; Munk, Ole Lajord; Sørensen, Michael

2015-01-01

Metabolic liver function can be measured by dynamic PET/CT with the radio-labelled galactose-analogue 2-[(18)F]fluoro-2-deoxy-D-galactose ((18)F-FDGal) in terms of hepatic systemic clearance of (18)F-FDGal (K, ml blood/ml liver tissue/min). The method requires arterial blood sampling from a radial artery (arterial input function), and the aim of this study was to develop a method for extracting an image-derived, non-invasive input function from a volume of interest (VOI). Dynamic (18)F-FDGal PET/CT data from 16 subjects without liver disease (healthy subjects) and 16 patients with liver cirrhosis were included in the study. Five different input VOIs were tested: four in the abdominal aorta and one in the left ventricle of the heart. Arterial input function from manual blood sampling was available for all subjects. K*-values were calculated using time-activity curves (TACs) from each VOI as input and compared to the K-value calculated using arterial blood samples as input. Each input VOI was tested on PET data reconstructed with and without resolution modelling. All five image-derived input VOIs yielded K*-values that correlated significantly with K calculated using arterial blood samples. Furthermore, TACs from two different VOIs yielded K*-values that did not statistically deviate from K calculated using arterial blood samples. A semicircle drawn in the posterior part of the abdominal aorta was the only VOI that was successful for both healthy subjects and patients as well as for PET data reconstructed with and without resolution modelling. Metabolic liver function using (18)F-FDGal PET/CT can be measured without arterial blood samples by using input data from a semicircle VOI drawn in the posterior part of the abdominal aorta.

Estradiol improves cardiac and hepatic function after trauma-hemorrhage: role of enhanced heat shock protein expression.

PubMed

Szalay, László; Shimizu, Tomoharu; Suzuki, Takao; Yu, Huang-Ping; Choudhry, Mashkoor A; Schwacha, Martin G; Rue, Loring W; Bland, Kirby I; Chaudry, Irshad H

2006-03-01

Although studies indicate that 17beta-estradiol administration after trauma-hemorrhage (T-H) improves cardiac and hepatic functions, the underlying mechanisms remain unclear. Because the induction of heat shock proteins (HSPs) can protect cardiac and hepatic functions, we hypothesized that these proteins contribute to the salutary effects of estradiol after T-H. To test this hypothesis, male Sprague-Dawley rats ( approximately 300 g) underwent laparotomy and hemorrhagic shock (35-40 mmHg for approximately 90 min) followed by resuscitation with four times the shed blood volume in the form of Ringer lactate. 17beta-estradiol (1 mg/kg body wt) was administered at the end of the resuscitation. Five hours after T-H and resuscitation there was a significant decrease in cardiac output, positive and negative maximal rate of left ventricular pressure. Liver function as determined by bile production and indocyanine green clearance was also compromised after T-H and resuscitation. This was accompanied by an increase in plasma alanine aminotransferase (ALT) levels and liver perfusate lactic dehydrogenase levels. Furthermore, circulating levels of TNF-alpha, IL-6, and IL-10 were also increased. In addition to decreased cardiac and hepatic function, there was an increase in cardiac HSP32 expression and a reduction in HSP60 expression after T-H. In the liver, HSP32 and HSP70 were increased after T-H. There was no change in heart HSP70 and liver HSP60 after T-H and resuscitation. Estradiol administration at the end of T-H and resuscitation increased heart/liver HSPs expression, ameliorated the impairment of heart/liver functions, and significantly prevented the increase in plasma levels of ALT, TNF-alpha, and IL-6. The ability of estradiol to induce HSPs expression in the heart and the liver suggests that HSPs, in part, mediate the salutary effects of 17beta-estradiol on organ functions after T-H.

Point-shear wave elastography predicts liver hypertrophy after portal vein embolization and postoperative liver failure.

PubMed

Hocquelet, A; Frulio, N; Gallo, G; Laurent, C; Papadopoulos, P; Salut, C; Denys, A; Trillaud, H

2018-06-01

To correlate point-shear wave elastography (SWE) with liver hypertrophy after right portal vein embolization (RPVE) and to determine its usefulness in predicting postoperative liver failure in patients undergoing partial liver resection. Point-SWE was performed the day before RPVE in 56 patients (41 men) with a median age of 66 years. The percentage (%) of future remnant liver (FRL) volume increase was defined as: %FRL post -%FRL pre %FRL pre ×100 and assessed on computed tomography performed 4 weeks after RPVE. Median (range) %FRL pre and %FRL post was respectively, 31.5% (12-48%) and 41% (23-61%) (P<0.001), with a median %FRL volume increase of 25.6% (-8; 123%). SWE correlated with %FRL volume increase (P=-0.510; P<0.001). SWV (P=0.003) and %FRL pre (P<0.001) were associated with %FRL volume increase at multivariate regression analysis. Forty-three patients (77%) were operated. Postoperative liver failure occurred in 14 patients (32.5%). Median SWE was different between the group with (1.68m/s) and without liver failure (1.07m/s) (P=0.018). The AUROC of SWE predicting liver failure was 0.724 with a best cut-off of 1.31m/s, corresponding to a sensitivity of 21%, specificity of 96%, positive predictive value 75% and negative predictive value of 72%. SWE was the single independent preoperative variable associated with liver failure. SWE assessed by point-SWE is a simple and useful tool to predict the FRL volume increase and postoperative liver failure in a population of patients with liver tumor. Copyright © 2018 Société française de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Validation of graft and standard liver size predictions in right liver living donor liver transplantation.

PubMed

Chan, See Ching; Lo, Chung Mau; Chok, Kenneth S H; Sharr, William W; Cheung, Tan To; Tsang, Simon H Y; Chan, Albert C Y; Fan, Sheung Tat

2011-12-01

To assess the accuracy of a formula derived from 159 living liver donors to estimate the liver size of a normal subject: standard liver weight (g) = 218 + body weight (kg) × 12.3 + 51 (if male). Standard liver volume (SLV) is attained by a conversion factor of 1.19 mL/g. The total liver volume (TLV) of each of the subsequent consecutive 126 living liver donors was determined using the right liver graft weight (RGW) on the back table, right/left liver volume ratio on computed tomography, and the conversion factor. The estimated right liver graft weight (ERGW) was determined by the right liver volume on computed tomography (CT) and the conversion factor. SLV and ERGW were compared with TLV and RGW, respectively, by paired sample t test. Donor characteristics of both series were similar. SLV and TLV were 1,099.6 ± 139.6 and 1,108.5 ± 175.2 mL, respectively, ( R 2  = 0.476) ( p  = 0.435). The difference between SLV and TLV was only -8.9 ± 128.2 mL (-1.0 ± 11.7%). ERGW and RGW were 601.5 ± 104.1 and 597.1 ± 102.2 g, respectively ( R 2  = 0.781) ( p  = 0.332). The conversion factor from liver weight to volume for this series was 1.20 mL/g. The difference between ERGW and RGW was 4.3 ± 49.8 g (0.3 ± 8.8%). ERGW was smaller than RGW for over 10% (range 0.21-40.66 g) in 18 of the 126 donors. None had the underestimation of RGW by over 20%. SLV and graft weight estimations were accurate using the formula and conversion factor.

Albumin and magnetic resonance imaging-liver volume to identify hepatitis B-related cirrhosis and esophageal varices

PubMed Central

Li, Hang; Chen, Tian-Wu; Li, Zhen-Lin; Zhang, Xiao-Ming; Li, Cheng-Jun; Chen, Xiao-Li; Chen, Guang-Wen; Hu, Jia-Ni; Ye, Yong-Quan

2015-01-01

AIM: To investigate whether liver lobe volume and albumin (ALB) could predict the presence and severity of liver cirrhosis, and esophageal varices. METHODS: Seventy-one cirrhotic patients with hepatitis B and 21 healthy individuals were enrolled in this study. All the participants underwent abdominal enhanced magnetic resonance imaging to measure each liver lobe volume, and biochemical workup for testing ALB and Child-Pugh class. All cirrhotic patients underwent upper gastrointestinal endoscopy to show the presence of cirrhotic esophageal varices. Right liver lobe volume (RV), left medial liver lobe volume (LMV), left lateral liver lobe volume (LLV), and caudate lobe volume (CV) were measured using enhanced magnetic resonance imaging. The ratios of RV to ALB (RV/ALB), LMV to ALB (LMV/ALB), LLV to ALB (LLV/ALB) and CV to ALB (CV/ALB) were calculated. Statistical analyses were performed to determine whether and how the combination of liver lobe volume measured using magnetic resonance imaging and albumin could predict the presence and severity of liver cirrhosis, and the presence of esophageal varices. RESULTS: RV, LMV, LLV and CV decreased (r = -0.51-0.373; all P < 0.05), while RV/ALB increased (r = 0.424; P < 0.05), with the progress of Child-Pugh class of liver cirrhosis. RV, LMV, CV, LLV/ALB and CV/ALB could identify presence of liver cirrhosis; LLV and LMV could distinguish Child-Pugh class A from B; RV, LMV, LLV, CV, RV/ALB and LLV/ALB could distinguish class A from C; RV and LLV/ALB could differentiate B from C; and RV, RV/ALB and CV/ALB could identify presence of esophageal varices (all P < 0.05). Among these parameters, CV/ALB could best identify the presence of liver cirrhosis, with an area under receiver operating characteristic curve (AUC) of 0.860, a sensitivity of 82.0% and a specificity of 83.0%. LLV could best distinguish class A from B, with an AUC of 0.761, a sensitivity of 74.4% and a specificity of 73.1%. RV could best distinguish class A from C, with an AUC of 0.900, a sensitivity of 90.3% and a specificity of 84.5%. LLV/ALB could best distinguish class B from C, with an AUC of 0.900, a sensitivity of 93.8% and a specificity of 81.5%. RV/ALB could best identify esophageal varices, with an AUC of 0.890, a sensitivity of 80.0% and a specificity of 83.5%. CONCLUSION: The combination of liver lobe volume and ALB has potential to identify presence and severity of cirrhosis, and presence of esophageal varices. PMID:25624735

There were no differences in serum HBV DNA level between HBeAg-positive and HBeAg-negative chronic hepatitis B with same liver histological necroinflammation grade but differences among grades 1, 2, 3 and 4 apportioned by the same hepatic parenchyma cell volume.

PubMed

Ke, W-M; Xie, S-B; Li, X-J; Zhang, S-Q; Lai, J; Ye, Y-N; Gao, Z-L; Chen, P-J

2011-09-01

Hepatitis B virus (HBV) DNA levels and liver histological necroinflammation grades are correlated with the antiviral efficacy. It is necessary to clarify the relationship between HBV replication levels apportioned by the same hepatic parenchyma cell volume and severity of liver histological necroinflammation grades in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative chronic hepatitis B. The serum HBV DNA levels apportioned by the same hepatic parenchyma cell volume were compared between HBeAg-positive and HBeAg-negative chronic hepatitis B as well as among liver histological necroinflammation grades 1, 2, 3 and 4, respectively. There were no differences in the serum HBV DNA levels between HBeAg-positive and HBeAg-negative chronic hepatitis B as well as among liver histological necroinflammation grades 1, 2, 3 and 4. However, there were differences in the serum HBV DNA levels apportioned by the same hepatic parenchyma cell volume among liver histological necroinflammation grades 1, 2, 3 and 4 in both HBeAg-positive and HBeAg-negative chronic hepatitis B, respectively. There were no differences in HBV DNA levels with the same liver histological necroinflammation grade activated by HBV wild-type and variant strains. After the differences in hepatic parenchyma cell volume for HBV replication of the same liver histological necroinflammation grade accompanied by different hepatic fibrosis stages were adjusted, the serum HBV DNA level apportioned by the same hepatic parenchyma cell volume was correlated with the severity of liver histological necroinflammation grade. © 2011 Blackwell Publishing Ltd.

Assessment of liver volume with computed tomography and comparison of findings with ultrasonography.

PubMed

Bora, Aydın; Alptekin, Cem; Yavuz, Alpaslan; Batur, Abdussamet; Akdemir, Zülküf; Berköz, Mehmet

2014-12-01

In this study, we aimed to investigate the impact of non-alcoholic hepatic steatosis on the liver volume. As investigating hepatic steatosis, we utilized computed tomography (CT) to determine the degree of steatosis and we utilized hepatobiliary ultrasonography (USG) for densitometry and correlation. As hepatosteatosis group, 35 patients over 18 years of age and whose abdominal CT scans were requested by several clinics and performed routinely were included in this study, and as control group, 40 healthy subjects without hepatosteatosis (clinically and radiologically) and correlated with hepatosteatosis group in terms of age and gender were included in this study. CT densitometry and liver attenuation index (LAI) of all individuals who participated in our study were calculated, and contrast images of patients were transferred to CT-Volume Software (Siemens Syngo Multimodality Workplace; Version VE52A). In this study, interactive and automated volume measurement techniques were used together. The volumes were measured separately in patient and control group. In this study for each stage in USG, there was found a direct correlation in terms of LAI and volume, and this correlation was statistically significant (p < 0.01). Furthermore, statistical significance between size and USG stage draws attention (p < 0.05). A significance relationship between USG stage and age could not be determined. As a result, we have reached the conclusion that CT densitometry can be used as an assistive technique along with USG to determine the degree of steatosis in the non-alcoholic fatty liver disease, and there is a positive linear correlation between the liver size and volume, and liver volume increases in the non-alcoholic fatty liver disease.

Relationship between vitamin A deficiency and the thyroid axis in clinically stable patients with liver cirrhosis related to hepatitis C virus.

PubMed

El-Eshmawy, Mervat M; Arafa, Mona M; Elzehery, Rasha R; Elhelaly, Rania M; Elrakhawy, Mohamed M; El-Baiomy, Azza A

2016-09-01

Vitamin A deficiency (VAD) and altered thyroid function are commonly encountered in patients with liver cirrhosis. The link between vitamin A metabolism and thyroid function has been previously identified. The aim of this study was to explore the association between VAD and the thyroid axis in clinically stable patients with cirrhosis related to hepatitis C virus (HCV). One hundred and twelve patients with clinically stable HCV-related cirrhosis and 56 healthy controls matched for age, sex, and socioeconomic status were recruited for this study. Vitamin A status, liver function, thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), reverse triiodothyronine (rT3), anti-thyroid peroxidase antibodies (anti-TPO), and thyroid volume were evaluated. The prevalence of VAD among patients with HCV-related cirrhosis was 62.5% compared with 5.4% among controls (P < 0.001). Patients with HCV-related cirrhosis had significantly higher FT4, FT3, TSH, and thyroid volume than did healthy controls. Of the 112 patients initially recruited, 18 were excluded (patients with subclinical hypothyroidism and/or anti-TPO positive), so a total of 94 patients with HCV-related cirrhosis were divided into 2 groups according to vitamin A status: VAD and normal vitamin A. Patients with VAD had significantly lower vitamin A intake and serum albumin and higher serum bilirubin, FT4, FT3, and TSH than patients with normal vitamin A status. Multiple logistic regression analysis revealed that VAD was associated with Child-Pugh score (β = 0.11, P = 0.05) and TSH (β = -1.63, P = 0.02) independently of confounding variables. We conclude that VAD may be linked to central hyperthyroidism in patients with clinically stable HCV-related liver cirrhosis.

Diffuse Reflectance Spectroscopy for Surface Measurement of Liver Pathology.

PubMed

Nilsson, Jan H; Reistad, Nina; Brange, Hannes; Öberg, Carl-Fredrik; Sturesson, Christian

2017-01-01

Liver parenchymal injuries such as steatosis, steatohepatitis, fibrosis, and sinusoidal obstruction syndrome can lead to increased morbidity and liver failure after liver resection. Diffuse reflectance spectroscopy (DRS) is an optical measuring method that is fast, convenient, and established. DRS has previously been used on the liver with an invasive technique consisting of a needle that is inserted into the parenchyma. We developed a DRS system with a hand-held probe that is applied to the liver surface. In this study, we investigated the impact of the liver capsule on DRS measurements and whether liver surface measurements are representative of the whole liver. We also wanted to confirm that we could discriminate between tumor and liver parenchyma by DRS. The instrumentation setup consisted of a light source, a fiber-optic contact probe, and two spectrometers connected to a computer. Patients scheduled for liver resection due to hepatic malignancy were included, and DRS measurements were performed on the excised liver part with and without the liver capsule and alongside a newly cut surface. To estimate the scattering parameters and tissue chromophore volume fractions, including blood, bile, and fat, the measured diffuse reflectance spectra were applied to an analytical model. In total, 960 DRS spectra from the excised liver tissue of 18 patients were analyzed. All factors analyzed regarding tumor versus liver tissue were significantly different. When measuring through the capsule, the blood volume fraction was found to be 8.4 ± 3.5%, the lipid volume fraction was 9.9 ± 4.7%, and the bile volume fraction was 8.2 ± 4.6%. No differences could be found between surface measurements and cross-sectional measurements. In measurements with/without the liver capsule, the differences in volume fraction were 1.63% (0.75-2.77), -0.54% (-2.97 to 0.32), and -0.15% (-1.06 to 1.24) for blood, lipid, and bile, respectively. This study shows that it is possible to manage DRS measurements through the liver capsule and that surface DRS measurements are representative of the whole liver. The results are consistent with data published earlier on the combination of liver chromophores. The results encourage us to proceed with in vivo measurements for further quantification of the liver's composition and assessment of parenchymal damage such as steatosis and fibrosis grade. © 2016 S. Karger AG, Basel.

PET imaging in adaptive radiotherapy of gastrointestinal tumours.

PubMed

Bulens, Philippe; Thomas, Melissa; Deroose, Christophe M; Haustermans, Karin

2018-06-04

Radiotherapy is the standard of care in the multimodality treatment of a variety of gastrointestinal (GI) tumours, such as oesophageal cancer, gastric cancer, rectal cancer and anal cancer. Additionally, radiotherapy has served as an alternative for surgery in patients with liver cancer, cancer of the biliary tract and pancreatic cancer. Positron-emission tomography (PET), generally in combination with computed tomography (CT), has an established role in the diagnosis, response assessment and (re-)staging of several GI tumours. However, the additional value of PET in adaptive radiotherapy, i.e. during the radiation treatment course and in the delineation process, is still unclear. When performed during radiotherapy, PET aims at assessing treatment-induced variations in functional tumour volumes to reduce the radiation target volume. Moreover, in the radiation treatment planning, tumour delineation could be more accurate by incorporating PET to identify the metabolic tumour volume. This review focuses on the additional value of PET for adaptive radiotherapy protocols as well as for the target volume adaptation for individualised treatment strategies in oesophageal, gastric, pancreatic, liver, biliary tract, rectal and anal neoplasms.

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.

Serial volumetric assessment of large for size liver grafts after whole cadaveric liver transplant in adults: do large liver grafts shrink in size?

PubMed

Bekheit, Mohamed; Rajakannu, Muthukumarassamy; Bucur, Petru; Adam, Rene; SaCunha, Antonio; Castaing, Denis; Cherqui, Daniel; Vibert, Eric

2016-02-01

After whole graft orthotopic liver transplantation (OLT), adaptation of the large grafts' volume to recipient weight is widely accepted despite the paucity of evidence on this subject. Thirty nine patients with GRWR > 2.5% were included in this study and subsequently divided into two groups with 3 ≥ GRWR > 3%. Patients had CT scans at three predetermined time points after OLT used for measuring the liver volume. The objective of this study is to evaluate the volumetric changes of whole large liver grafts after adult OLT. At LT, the mean graft recipient body weight ratio (GRWR) was 3.1 ± 0.4%. The mean liver weight was 1881 ± 68 g at LT, 2014 ± 99 ml at one week, 1725 ± 126 ml at 3 months, and 1632 ± 117 (ml) at >6 months. There is an initial increase at 1 week after LT and a subsequent decrease of liver volume on later measurements. None of the late volume measurements were significantly different from the initial graft volume at liver transplant in pair wise comparisons ANOVA repeated measures (p > 0.05). Similarly, the mean GRWR did not change significantly between the initial calculation at transplantation date and the subsequent measurements during the different study time points (F = 0.04, p = 0.96) with a mean of 3.1% (95% CI = 2.2-4.2). AUC ROC discriminated a cutoff of 3% for the initial GRWR above which grafts tend to decrease in size over time (c statistics = 0.74, p = 0.036). In a Clustered ANOVA repeated measures, there was no significant difference in the changes of liver volume between both groups. However, patients with GRWR > 3 showed a trend towards a latent reduction in volume over the tracing period. There was a tendency, but none significant; towards a higher bilirubin, AST, ALT levels over the first postoperative days in recipients with GRWR > 3. Large grafts do not significantly decrease in size. Nonetheless, grafts weighing >3% of the GRWR show a different trend towards decrease in size over time. Copyright © 2015. Published by Elsevier Ltd.

Home-based drainage of refractory ascites by a permanent-tunneled peritoneal catheter can safely replace large-volume paracentesis.

PubMed

Solbach, Philipp; Höner Zu Siederdissen, Christoph; Taubert, Richard; Ziegert, Szilvia; Port, Kerstin; Schneider, Andrea; Hueper, Katja; Manns, Michael P; Wedemeyer, Heiner; Jaeckel, Elmar

2017-05-01

Refractory ascites has a poor prognosis. Recurrent large-volume paracentesis is the current standard of care; however, it results in circulatory dysfunction and renal dysfunction, and hospitalization is commonly required. Transjugular intrahepatic portosystemic shunt placement is not an option in a substantial number of patients because of contraindications. The placement of a tunneled peritoneal drainage catheter has been shown to be effective in patients with malignant ascites. However, data in patients with nonmalignant refractory ascites are rare. We followed 24 consecutive patients in whom tunneled peritoneal drainage catheters were placed in the Endoscopy Unit at Hannover Medical School between June 2013 and December 2014. Catheters were placed in 24 patients with refractory ascites in end-stage liver disease and with a contraindication to transjugular intrahepatic portosystemic shunt placement. Placement was technically successful in all patients. The dosage of diuretics could be reduced significantly. The number of paracentesis decreased from 2.2±1 to 0 per week, although the volume of daily ascites removal remained stable (2 l). Despite frequent drainage of ascites, kidney function, serum sodium, and serum albumin remained stable. Seven adverse events occurred in six (25%) patients. Five patients listed for liver transplantation underwent successful transplantation without a negative impact. The tunneled peritoneal drainage catheter placement is a viable and effective treatment alternative in patients with refractory ascites because of end-stage liver disease, reducing diuretic intake and the need for paracentesis. The procedure avoids hyponatremia, worsening kidney function, and albumin infusions without an increased risk of spontaneous bacterial peritonitis.

Sebelipase alfa over 52 weeks reduces serum transaminases, liver volume and improves serum lipids in patients with lysosomal acid lipase deficiency.

PubMed

Valayannopoulos, Vassili; Malinova, Vera; Honzík, Tomas; Balwani, Manisha; Breen, Catherine; Deegan, Patrick B; Enns, Gregory M; Jones, Simon A; Kane, John P; Stock, Eveline O; Tripuraneni, Radhika; Eckert, Stephen; Schneider, Eugene; Hamilton, Gavin; Middleton, Michael S; Sirlin, Claude; Kessler, Bruce; Bourdon, Christopher; Boyadjiev, Simeon A; Sharma, Reena; Twelves, Chris; Whitley, Chester B; Quinn, Anthony G

2014-11-01

Lysosomal acid lipase deficiency is an autosomal recessive enzyme deficiency resulting in lysosomal accumulation of cholesteryl esters and triglycerides. LAL-CL04, an ongoing extension study, investigates the long-term effects of sebelipase alfa, a recombinant human lysosomal acid lipase. Sebelipase alfa (1mg/kg or 3mg/kg) was infused every-other-week to eligible subjects. Safety and tolerability assessments, including liver function, lipid profiles and liver volume assessment, were carried out at regular intervals. 216 infusions were administered to eight adult subjects through week 52 during LAL-CL04. At week 52, mean alanine aminotransferase and aspartate aminotransferase levels were normal with mean change from baseline of -58% and -40%. Mean changes for low-density lipoprotein, total cholesterol, triglyceride and high-density lipoprotein were -60%, -39%, -36%, and +29%, respectively. Mean liver volume by magnetic resonance imaging and hepatic proton density fat fraction decreased (12% and 55%, respectively). Adverse events were mainly mild and unrelated to sebelipase alfa. Infusion-related reactions were uncommon: three events of moderate severity were reported in two subjects; one patient's event was suggestive of a hypersensitivity-like reaction, but additional testing did not confirm this, and the subject has successfully re-started sebelipase alfa. Of samples tested to date, no anti-drug antibodies have been detected. Long-term dosing with sebelipase alfa in lysosomal acid lipase-deficient patients is well tolerated and produces sustained reductions in transaminases, improvements in serum lipid profile and reduction in the hepatic fat fraction. A randomized, placebo-controlled phase 3 trial in children and adults is underway (ARISE: NCT01757184). Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Medical Surveillance Monthly Report (MSMR). Volume 18, Number 03, March 2011

DTIC Science & Technology

2011-03-01

nervous system dysfunction; the diagnosis was also applicable to patients with laboratory evidence of injury to the liver , muscles, or kidneys. Th e...decrease cerebral blood fl ow and disrupt brain function (e.g., hypotonic encephalopathy , seizures, coma). Without rapid and defi nitive treatment to

[Effects of low intensity infra-red laser irradiation on ultrastructure and proliferation of liver cells in experimental hepatitis and cirrhosis].

PubMed

Baĭbekov, I M; Vorozheĭkin, V M; Artykov, Sh N

1992-04-01

With the aid of light, electron transmission and scanning electron microscopy and radioautography and stereometry, the influence of low-intensive laser irradiation (LILI) (infrared) was studied in normal rat liver and in experimental cirrhosis and hepatitis. It was revealed that arsenide-gallium laser irradiation causes the change of intracellular structure. These changes show the intensification on their specific function manifest in an increase of relative volume of intracellular structures. The changes of microvessels show the activation of microcirculation. The elevation of the index of the labelled nuclei testify to increased proliferation. The similar influences of LILI on the liver ultrastructure and proliferation in hepatitis and cirrhosis are accompanied by the reduction of the pathological changes of the liver--the hepatocytes oedema, granular, vacuolar and fatty dystrophy.

Spatially resolved assessment of hepatic function using 99mTc-IDA SPECT

PubMed Central

Wang, Hesheng; Cao, Yue

2013-01-01

Purpose: 99mTc-iminodiacetic acid (IDA) hepatobiliary imaging is usually quantified for hepatic function on the entire liver or regions of interest (ROIs) in the liver. The authors presented a method to estimate the hepatic extraction fraction (HEF) voxel-by-voxel from single-photon emission computed tomography (SPECT)/CT with a 99mTc-labeled IDA agent of mebrofenin and evaluated the spatially resolved HEF measurements with an independent physiological measurement. Methods: Fourteen patients with intrahepatic cancers were treated with radiation therapy (RT) and imaged by 99mTc-mebrofenin SPECT before and 1 month after RT. The dynamic SPECT volumes were with a resolution of 3.9 × 3.9 × 2.5 mm3. Throughout the whole liver with approximate 50 000 voxels, voxelwise HEF quantifications were estimated and compared between using arterial input function (AIF) from the heart and using vascular input function (VIF) from the spleen. The correlation between mean of the HEFs over the nontumor liver tissue and the overall liver function measured by Indocyanine green clearance half-time (T1/2) was assessed. Variation of the voxelwise estimation was evaluated in ROIs drawn in relatively homogeneous regions of the livers. The authors also examined effects of the time range parameter on the voxelwise HEF quantification. Results: Mean of the HEFs over the liver estimated using AIF significantly correlated with the physiological measurement T1/2 (r = 0.52, p = 0.0004), and the correlation was greatly improved by using VIF (r = 0.79, p < 0.0001). The parameter of time range for the retention phase did not lead to a significant difference in the means of the HEFs in the ROIs. Using VIF and a retention phase time range of 7–30 min, the relative variation of the voxelwise HEF in the ROIs was 10% ± 6% of respective mean HEF. Conclusions: The voxelwise HEF derived from 99mTc-IDA SPECT by the deconvolution analysis is feasible to assess the spatial distribution of hepatic function in the liver. PMID:24007177

Comparison of MRI segmentation techniques for measuring liver cyst volumes in autosomal dominant polycystic kidney disease.

PubMed

Farooq, Zerwa; Behzadi, Ashkan Heshmatzadeh; Blumenfeld, Jon D; Zhao, Yize; Prince, Martin R

To compare MRI segmentation methods for measuring liver cyst volumes in autosomal dominant polycystic kidney disease (ADPKD). Liver cyst volumes in 42 ADPKD patients were measured using region growing, thresholding and cyst diameter techniques. Manual segmentation was the reference standard. Root mean square deviation was 113, 155, and 500 for cyst diameter, thresholding and region growing respectively. Thresholding error for cyst volumes below 500ml was 550% vs 17% for cyst volumes above 500ml (p<0.001). For measuring volume of a small number of cysts, cyst diameter and manual segmentation methods are recommended. For severe disease with numerous, large hepatic cysts, thresholding is an acceptable alternative. Copyright © 2017 Elsevier Inc. All rights reserved.

Small for Size and Flow (SFSF) syndrome: An alternative description for posthepatectomy liver failure.

PubMed

Golriz, Mohammad; Majlesara, Ali; El Sakka, Saroa; Ashrafi, Maryam; Arwin, Jalal; Fard, Nassim; Raisi, Hanna; Edalatpour, Arman; Mehrabi, Arianeb

2016-06-01

Small for Size Syndrome (SFSS) syndrome is a recognizable clinical syndrome occurring in the presence of a reduced mass of liver, which is insufficient to maintain normal liver function. A definition has yet to be fully clarified, but it is a common clinical syndrome following partial liver transplantation and extended hepatectomy, which is characterized by postoperative liver dysfunction with prolonged cholestasis and coagulopathy, portal hypertension, and ascites. So far, this syndrome has been discussed with focus on the remnant size of the liver after partial liver transplantation or extended hepatectomy. However, the current viewpoints believe that the excessive flow of portal vein for the volume of the liver parenchyma leads to over-pressure, sinusoidal endothelial damages and haemorrhage. The new hypothesis declares that in both extended hepatectomy and partial liver transplantation, progression of Small for Size Syndrome is not determined only by the "size" of the liver graft or remnant, but by the hemodynamic parameters of the hepatic circulation, especially portal vein flow. Therefore, we suggest the term "Small for Size and Flow (SFSF)" for this syndrome. We believe that it is important for liver surgeons to know the pathogenesis and manifestation of this syndrome to react early enough preventing non-reversible tissue damages. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

17β-Estradiol protects the liver against cold ischemia/reperfusion injury through the Akt kinase pathway.

PubMed

Yang, Xiaohua; Qin, Lei; Liu, Jianxia; Tian, Liping; Qian, Haixin

2012-12-01

Hepatic ischemia-reperfusion (IR) injury occurs during liver resection and transplantation. Recent studies have shown that 17β-estradiol (E2) can protect the heart and liver against warm IR. The present study focused on the cytoprotective effects of E2 on cold IR injury to the liver. Sprague-Dawley male rats were randomly divided into three groups: sham, IR, and IR plus E2. The model of rat orthotopic liver transplantation was used. The rats in the IR plus E2 group were intraperitoneally injected with E2 (100 μg/kg/d) for 7 d before surgery. The sham and IR group received the same quantity of saline. The donor livers were then orthotopically transplanted into rats after cold ischemia preservation for 4 h at 4°C lactated Ringer's solution. After 6 h reperfusion, liver function, bile flow volume, hepatocyte apoptosis, and activation of Akt, glycogen synthase kinase-3β, and Bcl-2-associated death promoter were assessed. The survival rate of the rats was also investigated. The administration of E2 significantly prolonged the survival of liver grafts by improving liver function and decreasing hepatocyte apoptosis. Rats undergoing E2 demonstrated a greater level activation of Akt in the liver compared with the IR group. In addition, E2 also inhibited the activities of glycogen synthase kinase-3β, Bcl-2-associated death promoter, and caspase-3-induced by IR injury. E2 pretreatment attenuated the hepatocellular damage caused by hepatic cold IR injury through the Akt pathway. Estrogen therapy might be important in clinical settings associated with cold IR injury during liver transplantation. Copyright © 2012 Elsevier Inc. All rights reserved.

Evaluation of the Role of Cisplatin-conjugated-soluble Gelatin Sponge: Feasibility Study in a Swine Model

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

Ikoma, Akira; Kawai, Nobuyuki; Sato, Morio, E-mail: morisato@wakayama-med.ac.jp

2013-08-01

PurposeTo evaluate the safety and the delivery function of cisplatin-conjugated-soluble gelatin sponge in a swine model.MethodsFifteen healthy young swine were assigned into three groups: transarterial cisplatin infusion group, transarterial chemoembolization (TACE) with cisplatin-conjugated 120-min soluble gelatin sponge (TACE-120) group, and TACE with cisplatin-conjugated 360-min soluble gelatin sponge (TACE-360) group. A total volume of 0.8 mL/kg cisplatin in each group and 8 mg/kg soluble gelatin sponge in TACE-120 and TACE-360 groups were injected from the left hepatic artery in small increments for 10 min. Common hepatic angiography and whole-blood sampling via the left hepatic vein were conducted to explore recanalization immediatelymore » after the procedure and again at 10, 30, 60, 90, 120, 180, 240, 300, 360, and 420 min later. The area under the plasma concentration curve (AUC) of non-protein-bound platinum was compared among the three groups. Each liver was removed and cut into 10-cm-thick sections for calculating liver-damaged volume ratio.ResultsSequential angiography depicted gradual recanalization of the occluded hepatic artery and total recanalization at 120 and 360 min after embolization in the TACE-120 and TACE-360 groups, respectively. Of the three groups, AUC{sub 0-30}, AUC{sub 30-120}, and AUC{sub 120-420} were significantly highest in the transarterial cisplatin infusion group (p < 0.001), the TACE-120 group (p < 0.001), and the TACE-360 group (p < 0.001), respectively. The liver-damaged volume ratio in the TACE-360 group was small (8.20 %) but significantly higher than that in the TACE-120 group (2.67 %, p = 0.014).ConclusionCisplatin-conjugated soluble gelatin sponge functions as a cisplatin carrier and is associated with tolerable liver damage.« less

The prediction of radiofrequency ablation zone volume using vascular indices of 3-dimensional volumetric colour Doppler ultrasound in an in vitro blood-perfused bovine liver model

PubMed Central

Lanctot, Anthony C; McCarter, Martin D; Roberts, Katherine M; Glueck, Deborah H; Dodd, Gerald D

2017-01-01

Objective: To determine the most reliable predictor of radiofrequency (RF) ablation zone volume among three-dimensional (3D) volumetric colour Doppler vascular indices in an in vitro blood-perfused bovine liver model. Methods: 3D colour Doppler volume data of the local hepatic parenchyma were acquired from 37 areas of 13 bovine livers connected to an in vitro oxygenated blood perfusion system. Doppler vascular indices of vascularization index (VI), flow index (FI) and vascularization flow index (VFI) were obtained from the volume data using 3D volume analysis software. 37 RF ablations were performed at the same locations where the ultrasound data were obtained from. The relationship of these vascular indices and the ablation zone volumes measured from gross specimens were analyzed using a general linear mixed model fit with random effect for liver and backward stepwise regression analysis. Results: FI was significantly associated with ablation zone volumes measured on gross specimens (p = 0.0047), but explained little of the variance (Rβ2 = 0.21). Ablation zone volume decreased by 0.23 cm3 (95% confidence interval: −0.38, −0.08) for every 1 increase in FI. Neither VI nor VFI was significantly associated with ablation zone volumes (p > 0.05). Conclusion: Although FI was associated with ablation zone volumes, it could not sufficiently explain their variability, limiting its clinical applicability. VI, FI and VFI are not clinically useful in the prediction of RF ablation zone volume in the liver. Advances in knowledge: Despite a significant association of FI with ablation zone volumes, VI, FI and VFI cannot be used for their prediction. Different Doppler vascular indices need to be investigated for clinical use. PMID:27925468

The Safety and Feasibility of Three-Dimensional Visualization Technology Assisted Right Posterior Lobe Allied with Part of V and VIII Sectionectomy for Right Hepatic Malignancy Therapy.

PubMed

Hu, Min; Hu, Haoyu; Cai, Wei; Mo, Zhikang; Xiang, Nan; Yang, Jian; Fang, Chihua

2018-05-01

Hepatectomy is the optimal method for liver cancer; the virtual liver resection based on three-dimensional visualization technology (3-DVT) could provide better preoperative strategy for surgeon. We aim to introduce right posterior lobe allied with part of V and VIII sectionectomy assisted by 3-DVT as a promising treatment for massive or multiple right hepatic malignancies to retain maximum residual liver volume on the basis of R0 resection. Among 126 consecutive patients who underwent hepatectomy, 9 (7%) underwent right posterior lobe allied with part of V and VIII sectionectomy. 21 (17%) underwent right hemihepatectomy (RH). The virtual RH was performed with 3-DVT, which provided better observation of spatial position relationship between tumor and vessels, and the more accurate estimation of the remnant liver volume. If remnant liver volume was <40%, right posterior lobe allied with part of V and VIII sectionectomy should be undergone. Then, the precut line ought to be planned on the basis of protecting the portal branch of subsegment 5 and 8. The postoperative outcome of patients was compared before and after propensity score matching. Nine patients meeting the eligibility criteria received right posterior lobe allied with part of V and VIII sectionectomy. The variables, including the overall mean operation time, blood transfusion, operation length, liver function, and postoperative complications, were similar between two groups before and after propensity matching. The postoperative first, third, fifth, and seventh days mean value of aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin (ALB), and total bilirubin had no significant difference compared with preoperative value. One patient in each group had recurrence six months after surgery. Right posterior lobe allied with part of V and VIII sectionectomy based on 3-DVT is safe and feasible surgery way, and can be a very promising method in massive or multiple right hepatic malignancy therapy.

Postoperative liver volume was accurately predicted by a medical image three dimensional visualization system in hepatectomy for liver cancer.

PubMed

Cai, Wei; Fan, Yingfang; Hu, Haoyu; Xiang, Nan; Fang, Chihua; Jia, Fucang

2017-06-01

Liver cancer is the second most common cause of cancer death worldwide. The hepatectomy is the most effective and the only potentially curative treatment for patients with resectable neoplasm. Precisely preoperative assessment of remnant liver volume is essential in preventing postoperative liver failure. The aim of our study is to report our experience of using a medical image three dimensional (3D) visualization system (MI-3DVS), which was developed by our team, in assisting hepatectomy for patients with liver cancer. Between January 2010 and June 2016, 69 patients with liver cancer underwent hepatic resection based on the MI-3DVS were enrolled in this study. All patients underwent CT scan 5 days before the surgery and within 5 days after resection. CT images were reconstructed with the MI-3DVS to assist to perform hepatectomy. Simple linear regression, intra-class correlation coefficient (ICC) and Bland-Altman analysis were used to evaluate the relationship and agreement between actual excisional liver volume (AELV) and predicted excisional liver volume (PELV). Among 69 patients in this study, 62(89.85%) of them were diagnosed with hepatocellular carcinoma by histopathologic examination, and 41(59.42%) underwent major hepatectomy. The average AELV was 330.13 cm 3 and the average PELV was 287.67 cm 3 . The simple regression equation is AELV = 1.016 × PELV+30.39(r = 0.966; p < 0.0003). PELV (ICC = 0.964) achieved an excellent agreement with AELV with statistical significance (p < 0.001). 65 of 69 dots are in the range of 95% confidence interval in Bland-Altman analyses. The MI-3DVS has advantages of simple usage and convenient hold. It is accurate in assessment of postoperative liver volume and improve safety in liver resection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Forensic postmortem computed tomography: volumetric measurement of the heart and liver.

PubMed

Jakobsen, Lykke Schrøder; Lundemose, Sissel; Banner, Jytte; Lynnerup, Niels; Jacobsen, Christina

2016-12-01

The purpose of this study was to investigate the utility of postmortem computed tomography (PMCT) images in estimating organ sizes and to examine the use of the cardiothoracic ratio (CTR). We included 45 individuals (19 females), who underwent a medico-legal autopsy. Using the computer software program Mimics ® , we determined in situ heart and liver volumes derived from linear measurements (width, height and depth) on a whole body PMCT-scan, and compared the volumes with ex vivo volumes derived by CT-scan of the eviscerated heart and liver. The ex vivo volumes were also compared with the organ weights. Further, we compared the CTR with the ex vivo heart volume and a heart weight-ratio (HWR). Intra- and inter-observer analyses were performed. We found no correlation between the in situ and ex vivo volumes of the heart and liver. However, a highly significant correlation was found between the ex vivo volumes and weights of the heart and liver. No correlations between CTR and the ex vivo heart volume nor with HWR was found. Concerning cardiomegaly, we found no agreement between the CTR and HWR. The intra- and inter-observer analyses showed no significant differences. Noninvasive in situ PMCT methods for organ measuring, as performed in this study, are not useful tools in forensic pathology. The best method to estimate organ volume is a CT-scan of the eviscerated organ. PMCT-determined CTR seems to be useless for ascertaining cardiomegaly, as it neither correlated with the ex vivo heart volume nor with the HWR.

SU-E-T-402: Y-90 Microspheres (SIR Spheres) for Treatment of Liver Metastasis : Technique

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

Nair, M

2014-06-01

Purpose: The purpose of this presentation is to discuss the radiation safety and dosimetric technique used for the therapeutic procedure using Y-90 microspheres through intra -arterial administration on patients with liver metastasis Methods: The radiation dosimetry, technique and safety aspects of 14 patients with primary and metastatic liver cancer, treated with Y-90 microsphere (SIR spheres) are discussed. The liver and tumor volumes were determined using the CT and MR scans . The images were imported into the treatment planning system and the liver and tumor volumes and the volume of the liver affected were outlined and the volume calculation wasmore » performed using the software. The lung shunt fraction (LSF) and tumor to liver uptake ratio (TLR) were determined using the nuclear medicine SPECT imaging with Tc-99m MAA. The absorbed dose to the target volume in liver was calculated using the following equation:Dose ? (Gy) = C x E? x 5.92 x 10-6 (Gy/s) x T(1/2)(days) x 1.44 x 8.64 x 104 (s) The distribution of activity in the tumor bed was confirmed by post Y-90 administration imaging using the Bremsstrahlung peak at 30% window. The patient and the procedure room were surveyed and radiation safety instructions were given to the patient Results: The tumor volume ranged from 77 cc to 700 cc, tumor to liver uptake ranged from 3 to 12. The lung shunt fraction varied from 1.08% to 9.0%. The activity administered ranged from 1.0GBq to 2.5 GBq, . The radiation survey in contact with the patient ranged from 1.8 mR/hr to 2.5 mR/hr and reading at 1 meter was less than 0.2 mR/hr Conclusion: The technique for radiation dosimetry and radiation safety for Y-90 microsphere therapy is established. The post treatment imaging helped to confirm the distribution of Y-90 microspheres inside the tumor bed.« less

[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.

Is computed tomography volumetric assessment of the liver reliable in patients with cirrhosis?

PubMed Central

Goumard, Claire; Perdigao, Fabiano; Cazejust, Julien; Zalinski, Stéphane; Soubrane, Olivier; Scatton, Olivier

2014-01-01

Objectives: The estimation of liver volume (LV) has been widely studied in normal liver, the density of which is considered to be equivalent to 1 kg/l. In cirrhosis, volumetric evaluation and its correlation to liver mass remain unclear. The aim of this study was to evaluate the accuracy of computed tomography (CT) scanning to assess LV in patients with cirrhosis. Methods: Liver volume was evaluated by CT (CTLV) and correlated to the explanted liver weight (LW) in 49 patients. Liver density (LD) and its association with clinical features were analysed. Commonly used formulae for estimating LV were also evaluated. The real density of cirrhotic liver was prospectively measured in explant specimens. Results: Wide variations between CTLV (in ml) and LW (in g) were found (range: 3–748). Cirrhotic livers in patients with hepatitis B virus infection presented significantly increased LD (P = 0.001) with lower CTLV (P = 0.005). Liver volume as measured by CT was also decreased in patients with Model for End-stage Liver Disease scores of >15 (P = 0.023). Formulae estimating LV correlated poorly with CTLV and LW. The density of cirrhotic liver measured prospectively in 15 patients was 1.1 kg/l. Conclusions: In cirrhotic liver, LV assessed by CT did not correspond to real LW. Liver density changed according to the aetiology and severity of liver disease. Commonly used formulae did not accurately assess LV. PMID:23679861

Morphometric analysis of abdominal organs and rib cage: Implication for risk of solid organ injuries in children.

PubMed

Harbaugh, Calista M; Shlykov, Maksim A; Tsuchida, Ryan E; Holcombe, Sven A; Hirschl, Jake; Wang, Stewart C; Ehrlich, Peter F

2015-06-01

Motor vehicle crashes are the leading cause of injury-related mortality in children, with a higher rate of multiorgan injuries than in adults. This may be related to increased solid organ volume relative to abdominal cavity and decreased protection of an underdeveloped cartilaginous rib cage in young children. To date, these anatomic relationships have not been fully described. Our study used analytic morphomics to obtain precise measures of the pediatric liver, spleen, kidneys, and ribs. This pilot study included 215 trauma patients (aged 0-18 years) with anonymized computed tomography (CT) scans. Liver, spleen, and kidney volumes were modeled using semiautomatic algorithms (MATLAB 2013a, MathWorks Inc., Natick, MA). Thirty-one scans were adequate to model the rib cage. Pearson's r was used to correlate absolute organ volume, fractional organ volume, and organ exposure with age and weight. Spleen, right and left kidney, and liver volumes increased with age and weight (p < 0.01). Right/left kidney and liver fractional volumes decreased with age (p < 0.01), whereas spleen fractional volume remained relatively constant. Exposed surface area of the liver only significantly decreased with age in the anterior (p < 0.01), right (p < 0.01), and posterior views (p = 0.02). With this study, we have demonstrated the ability to model solid organ and rib cage anatomy of children using cross-sectional imaging. In younger children, there may be a decrease in fractional organ volume and increase in liver surface exposure, although analysis of a larger sample size is warranted. In the future, this information may be used to improve the design of safety restraints in motor vehicles.

Technetium-99m NGA functional hepatic imaging: preliminary clinical experience

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

Stadalnik, R.C.; Vera, D.R.; Woodle, E.S.

1985-11-01

Technetium-99m galactosyl-neoglycoalbumin ( (Tc)NGA) is a radiolabeled ligand to hepatic binding protein, a receptor which resides at the plasma membrane of hepatocytes. This receptor-binding radiopharmaceutical and its kinetic model provide a noninvasive method for the assessment of liver function. Eighteen patients were studied: seven with hepatoma, eight with liver metastases, four with cirrhosis, and one patient with acute fulminant non-A, non-B hepatitis. Technetium-99m NGA liver imaging provided anatomic information of diagnostic quality comparable to that obtained with other routine imaging modalities, including computed tomography, angiography, ultrasound, and (Tc)sulfur colloid scintigraphy. Kinetic modeling of dynamic (Tc)NGA data produced estimates of standardizedmore » hepatic blood flow, Q (hepatic blood flow divided by total blood volume), and hepatic binding protein concentration, (HBP). Significant rank correlation was obtained between (HBP) estimates and CTC scores. This correlation supports the hypothesis that (HBP) is a measure of functional hepatocyte mass. The combination of decreased Q and markedly reduced (HBP) may have prognostic significance; all three patients with this combination died of hepatic failure within 6 wk of imaging.« less

Correlation between melphalan pharmacokinetics and hepatic toxicity following hyperthermic isolated liver perfusion for unresectable metastatic disease.

PubMed

Mocellin, Simone; Pilati, Pierluigi; Da Pian, Pierpaolo; Forlin, Marco; Corazzina, Susanna; Rossi, Carlo Riccardo; Innocente, Federico; Ori, Carlo; Casara, Dario; Ujka, Francesca; Nitti, Donato; Lise, Mario

2007-02-01

In the present work, we report on the results of our pilot study of hyperthermic isolated hepatic perfusion (IHP) with melphalan alone for patients with unresectable metastatic liver tumors refractory to conventional treatments, with particular regard to the correlation between pharmacokinetic findings and hepatic toxicity. Inclusion criteria were unresectable liver metastases, hepatic parenchyma replacement

Functional discrepancy between two liver lobes after hemilobe biliary drainage in patients with jaundice and bile duct cancer: an appraisal using (99m)Tc-GSA SPECT/CT fusion imaging.

PubMed

Sumiyoshi, Tatsuaki; Shima, Yasuo; Okabayashi, Takehiro; Noda, Yoshihiro; Hata, Yasuhiro; Murata, Yoriko; Kozuki, Akihito; Tokumaru, Teppei; Nakamura, Toshio; Uka, Kiminori

2014-11-01

To determine the functional discrepancy between the two liver lobes using technetium 99m ((99m)Tc) diethylenetriamine-pentaacetic acid-galactosyl human serum albumin ( GSA diethylenetriamine-pentaacetic acid-galactosyl human serum albumin ) single photon emission computed tomography (SPECT)/computed tomography (CT) fusion imaging following preoperative biliary drainage and portal vein embolization ( PVE portal vein embolization ) in patients with jaundice who have bile duct cancer ( BDC bile duct cancer ). This retrospective study was approved by the institutional review board, with waiver of informed consent. Preoperative (99m)Tc- GSA diethylenetriamine-pentaacetic acid-galactosyl human serum albumin SPECT/CT fusion images from 32 patients with extrahepatic BDC bile duct cancer were retrospectively reviewed. Patients were classified into four groups according to the extent of biliary drainage and presence of a preoperative right PVE portal vein embolization : right lobe drainage group (right drainage), bilateral lobe drainage group (bilateral drainage), left lobe drainage group (left drainage), and left lobe drainage with right PVE portal vein embolization group (left drainage with right PVE portal vein embolization ). Percentage volume and percentage function were measured in each lobe using fusion imaging. The ratio between percentage function and percentage volume (the function-to-volume ratio) was calculated for each lobe, and the results were compared among the four groups. Statistical analysis was performed with Wilcoxon signed-rank tests and Mann-Whitney U tests. The median values for the function-to-volume ratio in the right drainage, bilateral drainage, left drainage, and left drainage with right PVE portal vein embolization group were 1.12, 1.05, 1.02, and 0.81 in the right lobe; and 0.51, 0.88, 0.96, and 1.17 in the left lobe. Significant differences in the function-to-volume ratio were observed among the four groups (right drainage vs bilateral drainage vs left drainage vs left drainage with right PVE portal vein embolization ; with P < .002, P = .023, and P < .002 for the right lobe and P < .001, P = .023, and P < .002 for the left lobe). Hepatic lobar function significantly differs between the two lobes, depending on the extent of biliary drainage and the presence of portal vein embolization.

Evaluation of the rabbit liver by direct portography and contrast-enhanced computed tomography: anatomical variations of the portal system and hepatic volume quantification.

PubMed

Páramo, María; García-Barquin, Paula; Santa María, Eva; Madrid, José Miguel; Caballeros, Meylin; Benito, Alberto; Sangro, Bruno; Iñarrairaegui, Mercedes; Bilbao, José Ignacio

2017-01-01

The study was aimed at: (1) describing the incidence of anatomic variations of the portal system in the rabbit using direct portography; and (2) estimating the liver volume and caudate lobe volume by using contrast-enhanced computed tomography (CECT) in the same animal model. Forty-six New Zealand white rabbits were included. All of them underwent direct portography and unenhanced CECT. Conventional liver rabbit portal system anatomy (type 1) consisted of the bifurcation of the main portal vein (MPV) into the right portal vein (RPV) and left portal vein (LPV), which subsequently divided into medial left portal vein and lateral left portal vein. Trifurcation of the LPV was considered type 2. The LPV that divides into four smaller branches was classified as type 3. Other configurations of the portal system, including particular cases of MPV branching, were grouped as type 4. Liver lobes were manually segmented. The incidence of each type of portal system anatomy was: type 1, 67.4%; type 2, 15.2%; type 3, 13.0%); and type 4, 4.3%. The mean volume of the caudate lobe was 19.1 ml ± 5.7 ml and of the cranial lobes it was 66.7 ml ± 13.7 ml, and the total liver volume was 85.7 ml ± 16.7 ml. In New Zealand white rabbits, type 1 is the prevalent type of portal system, liver volume is about 86 ml, and the caudate and cranial lobes are separated. This information could be important when planning experimental rabbit liver procedures.

Flow dynamics analyses of pathophysiological liver lobules using porous media theory

NASA Astrophysics Data System (ADS)

Hu, Jinrong; Lü, Shouqin; Feng, Shiliang; Long, Mian

2017-08-01

Blood flow inside the liver plays a key role in hepatic functions, and abnormal hemodynamics are highly correlated with liver diseases. To date, the flow field in an elementary building block of the organ, the liver lobule, is difficult to determine experimentally in humans due to its complicated structure, with radially branched microvasculature and the technical difficulties that derive from its geometric constraints. Here we established a set of 3D computational models for a liver lobule using porous media theory and analyzed its flow dynamics in normal, fibrotic, and cirrhotic lobules. Our simulations indicated that those approximations of ordinary flow in portal tracts (PTs) and the central vein, and of porous media flow in the sinusoidal network, were reasonable only for normal or fibrotic lobules. Models modified with high resistance in PTs and collateral vessels inside sinusoids were able to describe the flow features in cirrhotic lobules. Pressures, average velocities, and volume flow rates were profiled and the predictions compared well with experimental data. This study furthered our understanding of the flow dynamics features of liver lobules and the differences among normal, fibrotic, and cirrhotic lobules.

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.

3D liver volume reconstructed for palpation training.

PubMed

Tibamoso, Gerardo; Perez-Gutierrez, Byron; Uribe-Quevedo, Alvaro

2013-01-01

Virtual Reality systems for medical procedures such as the palpation of different organs, requires fast, robust, accurate and reliable computational methods for providing realism during interaction with the 3D biological models. This paper presents the segmentation, reconstruction and palpation simulation of a healthy liver volume as a tool for training. The chosen method considers the mechanical characteristics and liver properties for correctly simulating palpation interactions, which results appropriate as a complementary tool for training medical students in familiarizing with the liver anatomy.

Small animal magnetic resonance imaging: an efficient tool to assess liver volume and intrahepatic vascular anatomy.

PubMed

Melloul, Emmanuel; Raptis, Dimitri A; Boss, Andreas; Pfammater, Thomas; Tschuor, Christoph; Tian, Yinghua; Graf, Rolf; Clavien, Pierre-Alain; Lesurtel, Mickael

2014-04-01

To develop a noninvasive technique to assess liver volumetry and intrahepatic portal vein anatomy in a mouse model of liver regeneration. Fifty-two C57BL/6 male mice underwent magnetic resonance imaging (MRI) of the liver using a 4.7 T small animal MRI system after no treatment, 70% partial hepatectomy (PH), or selective portal vein embolization. The protocol consisted of the following sequences: three-dimensional-encoded spoiled gradient-echo sequence (repetition time per echo time 15 per 2.7 ms, flip angle 20°) for volumetry, and two-dimensional-encoded time-of-flight angiography sequence (repetition time per echo time 18 per 6.4 ms, flip angle 80°) for vessel visualization. Liver volume and portal vein segmentation was performed using a dedicated postprocessing software. In animals with portal vein embolization, portography served as reference standard. True liver volume was measured after sacrificing the animals. Measurements were carried out by two independent observers with subsequent analysis by the Cohen κ-test for interobserver agreement. MRI liver volumetry highly correlated with the true liver volume measurement using a conventional method in both the untreated liver and the liver remnant after 70% PH with a high interobserver correlation coefficient of 0.94 (95% confidence interval, 0.80-0.98 for untreated liver [P < 0.001] and 0.90-0.97 after 70% PH [P < 0.001]). The diagnostic accuracy of magnetic resonance angiography for the occlusion of one branch of the portal vein was 0.95 (95% confidence interval, 0.84-1). The level of agreement between the two observers for the description of intrahepatic vascular anatomy was excellent (Cohen κ value = 0.925). This protocol may be used for noninvasive liver volumetry and visualization of portal vein anatomy in mice. It will serve the dynamic study of new strategies to enhance liver regeneration in vivo. Copyright © 2014 Elsevier Inc. All rights reserved.

The effects of iterative reconstruction in CT on low-contrast liver lesion volumetry: a phantom study

NASA Astrophysics Data System (ADS)

Li, Qin; Berman, Benjamin P.; Schumacher, Justin; Liang, Yongguang; Gavrielides, Marios A.; Yang, Hao; Zhao, Binsheng; Petrick, Nicholas

2017-03-01

Tumor volume measured from computed tomography images is considered a biomarker for disease progression or treatment response. The estimation of the tumor volume depends on the imaging system parameters selected, as well as lesion characteristics. In this study, we examined how different image reconstruction methods affect the measurement of lesions in an anthropomorphic liver phantom with a non-uniform background. Iterative statistics-based and model-based reconstructions, as well as filtered back-projection, were evaluated and compared in this study. Statistics-based and filtered back-projection yielded similar estimation performance, while model-based yielded higher precision but lower accuracy in the case of small lesions. Iterative reconstructions exhibited higher signal-to-noise ratio but slightly lower contrast of the lesion relative to the background. A better understanding of lesion volumetry performance as a function of acquisition parameters and lesion characteristics can lead to its incorporation as a routine sizing tool.

The Impact of Hospital/Surgeon Volume on Acute Renal Failure and Mortality in Liver Transplantation: A Nationwide Cohort Study.

PubMed

Cheng, Chih-Wen; Liu, Fu-Chao; Lin, Jr-Rung; Tsai, Yung-Fong; Chen, Hsiu-Pin; Yu, Huang-Ping

2016-01-01

The aim of this study was to assess whether the case volume of surgeons and hospitals affects the rates of postoperative complications and survival after liver transplantation. This population-based retrospective cohort study included 2938 recipients of liver transplantation performed between 1998 and 2012, enrolled from the Taiwan National Health Insurance Research Database. They were divided into two groups, according to the cumulative case volume of their operating surgeons and the case volume of their hospitals. The duration of intensive care unit stay and post-transplantation hospitalization, postoperative complications, and mortality were analyzed. The results showed that, in the low and high case volume surgeons groups, respectively, acute renal failure occurred at the rate of 14.11% and 5.86% (p<0.0001), and the overall mortality rates were 19.61% and 12.44% (p<0.0001). In the low and high case volume hospital groups, respectively, acute renal failure occurred in 11% and 7.11% of the recipients (p = 0.0004), and the overall mortality was 18.44% and 12.86% (p<0.0001). These findings suggest that liver transplantation recipients operated on higher case volume surgeons or in higher case volume hospitals have a lower rate of acute renal failure and mortality.

Hemorrhage-induced hepatic injury and hypoperfusion can be prevented by direct peritoneal resuscitation.

PubMed

Hurt, Ryan T; Zakaria, El Rasheid; Matheson, Paul J; Cobb, Mahoney E; Parker, John R; Garrison, R Neal

2009-04-01

Crystalloid fluid resuscitation after hemorrhagic shock (HS) that restores/maintains central hemodynamics often culminates in multi-system organ failure and death due to persistent/progressive splanchnic hypoperfusion and end-organ damage. Adjunctive direct peritoneal resuscitation (DPR) using peritoneal dialysis solution reverses HS-induced splanchnic hypoperfusion and improves survival. We examined HS-mediated hepatic perfusion (galactose clearance), tissue injury (histopathology), and dysfunction (liver enzymes). Anesthetized rats were randomly assigned (n = 8/group): (1) sham (no HS); (2) HS (40% mean arterial pressure for 60 min) plus conventional i.v. fluid resuscitation (CR; shed blood + 2 volumes saline); (3) HS + CR + 30 mL intraperitoneal (IP) DPR; or (4) HS + CR + 30 mL IP saline. Hemodynamics and hepatic blood flow were measured for 2 h after CR completion. In duplicate animals, liver and splanchnic tissues were harvested for histopathology (blinded, graded), hepatocellular function (liver enzymes), and tissue edema (wet-dry ratio). Group 2 decreased liver blood flow, caused liver injuries (focal to submassive necrosis, zones 2 and 3) and tissue edema, and elevated liver enzymes (alanine aminotransferase (ALT), 149 +/- 28 microg/mL and aspartate aminotransferase (AST), 234 +/- 24 microg/mL; p < 0.05) compared to group 1 (73 +/- 9 and 119 +/- 10 microg/mL, respectively). Minimal/no injuries were observed in group 3; enzymes were normalized (ALT 89 +/- 9 microg/mL and AST 150 +/- 17 microg/mL), and tissue edema was similar to sham. CR from HS restored and maintained central hemodynamics but did not restore or maintain liver perfusion and was associated with significant hepatocellular injury and dysfunction. DPR added to conventional resuscitation (blood and crystalloid) restored and maintained liver perfusion, prevented hepatocellular injury and edema, and preserved liver function.

Pathophysiology and management of pediatric ascites.

PubMed

Sabri, Mahmoud; Saps, Miguel; Peters, John M

2003-06-01

Ascites accumulation is the product of a complex process involving hepatic, renal, systemic, hemodynamic, and neurohormonal factors. The main pathophysiologic theories of ascites formation include the "underfill," "overflow," and peripheral arterial vasodilation hypotheses. These theories are not necessarily mutually exclusive and are linked at some level by a common pathophysiologic thread: The body senses a decreased effective arterial blood volume, leading to stimulation of the sympathetic nervous system, arginine-vasopressin feedback loops, and the renin-angiotensin-aldosterone system. Cornerstones of ascites management include dietary sodium restriction and diuretics. Spironolactone is generally tried initially, with furosemide added if clinical response is suboptimal. More refractory patients require large-volume paracentesis (LVP) accompanied by volume expansion with albumin. Placement of a transjugular intrahepatic portosystemic shunt is reserved for individuals with compensated liver function who require very frequent sessions of LVP. Peritoneovenous shunts are not used in contemporary ascites management. Liver transplantation remains the definitive therapy for refractory ascites. Although treatment of ascites fails to improve survival, it benefits quality of life and limits the development of such complications as spontaneous bacterial peritonitis.

Stereotactic Robotic Body Radiotherapy for Patients With Unresectable Hepatic Oligorecurrence.

PubMed

Berkovic, Patrick; Gulyban, Akos; Nguyen, Paul Viet; Dechambre, David; Martinive, Philippe; Jansen, Nicolas; Lakosi, Ferenc; Janvary, Levente; Coucke, Philippe A

2017-12-01

The purpose of this study was to analyze local control (LC), liver progression-free survival (PFS), and distant PFS (DFS), overall survival (OS), and toxicity in a cohort of patients treated with stereotactic body radiotherapy (SBRT) with fiducial tracking for oligorecurrent liver lesions; and to evaluate the potential influence of lesion size, systemic treatment, physical and biologically effective dose (BED), treatment calculation algorithms and other parameters on the obtained results. Unoperable patients with sufficient liver function had [18F]-fluorodeoxyglucose-positron emission tomography-computed tomography and liver magnetic resonance imaging to confirm the oligorecurrent nature of the disease and to further delineate the gross tumor volume (GTV). An intended dose of 45 Gy in 3 fractions was prescribed on the 80% isodose and adapted if risk-related. Treatment was executed with the CyberKnife system (Accuray Inc) platform using fiducials tracking. Initial plans were recalculated using the Monte Carlo algorithm. Patient and treatment data were processed using the Kaplan-Meier method and log rank test for survival analysis. Between 2010 and 2015, 42 patients (55 lesions) were irradiated. The mean GTV and planning target volume (PTV) were 30.5 cc and 96.8 cc, respectively. Treatments were delivered 3 times per week in a median of 3 fractions to a PTV median dose of 54.6 Gy. The mean GTV and PTV D98% were 51.6 Gy and 51.2 Gy, respectively. Heterogeneity corrections did not influence dose parameters. After a median follow-up of 18.9 months, the 1- and 2-year LC/liver PFS/DFS/OS were 81.3%/55%/62.4%/86.9%, and 76.3%/42.3%/52%/78.3%, respectively. Performance status and histology had a significant effect on LC, whereas age (older than 65 years) marginally influenced liver PFS. Clinical target volume physical dose V45 Gy > 95%, generalized equivalent uniform dose (a = -30) > 45 Gy and a BED (α/β = 10) V105 Gy > 96% showed statistically significant effect on the LC. Acute Grade 3 gastrointestinal (GI) and late Grade 2 GI and fatigue toxicity were found in 5% and 11% patients, respectively. Favorable survival and toxicity results support the potential paradigm shift in which the use of SBRT in oligorecurrent liver disease could benefit patients with unresectable or resectable liver metastases. Copyright © 2017 Elsevier Inc. All rights reserved.

Interfraction Liver Shape Variability and Impact on GTV Position During Liver Stereotactic Radiotherapy Using Abdominal Compression

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

Eccles, Cynthia L., E-mail: cynthia.eccles@rob.ox.ac.uk; Dawson, Laura A.; Moseley, Joanne L.

2011-07-01

Purpose: For patients receiving liver stereotactic body radiotherapy (SBRT), abdominal compression can reduce organ motion, and daily image guidance can reduce setup error. The reproducibility of liver shape under compression may impact treatment delivery accuracy. The purpose of this study was to measure the interfractional variability in liver shape under compression, after best-fit rigid liver-to-liver registration from kilovoltage (kV) cone beam computed tomography (CBCT) scans to planning computed tomography (CT) scans and its impact on gross tumor volume (GTV) position. Methods and Materials: Evaluable patients were treated in a Research Ethics Board-approved SBRT six-fraction study with abdominal compression. Kilovoltage CBCTmore » scans were acquired before treatment and reconstructed as respiratory sorted CBCT scans offline. Manual rigid liver-to-liver registrations were performed from exhale-phase CBCT scans to exhale planning CT scans. Each CBCT liver was contoured, exported, and compared with the planning CT scan for spatial differences, by use of in house-developed finite-element model-based deformable registration (MORFEUS). Results: We evaluated 83 CBCT scans from 16 patients with 30 GTVs. The mean volume of liver that deformed by greater than 3 mm was 21.7%. Excluding 1 outlier, the maximum volume that deformed by greater than 3 mm was 36.3% in a single patient. Over all patients, the absolute maximum deformations in the left-right (LR), anterior-posterior (AP), and superior-inferior directions were 10.5 mm (SD, 2.2), 12.9 mm (SD, 3.6), and 5.6 mm (SD, 2.7), respectively. The absolute mean predicted impact of liver volume displacements on GTV by use of center of mass displacements was 0.09 mm (SD, 0.13), 0.13 mm (SD, 0.18), and 0.08 mm (SD, 0.07) in the left-right, anterior-posterior, and superior-inferior directions, respectively. Conclusions: Interfraction liver deformations in patients undergoing SBRT under abdominal compression after rigid liver-to-liver registrations on respiratory sorted CBCT scans were small in most patients (<5 mm).« less

A prospective single-institute study of the impact of Daikenchuto on the early postoperative outcome after living donor liver transplantation.

PubMed

Takatsuki, Mitsuhisa; Hidaka, Masaaki; Soyama, Akihiko; Hara, Takanobu; Okada, Satomi; Ono, Shinichiro; Adachi, Tomohiko; Eguchi, Susumu

2018-01-20

The aim of this study was to investigate the impact of Daikenchuto (DKT) on early postoperative outcomes after living donor liver transplantation (LDLT), focusing on the prevention of abdominal distension and bacterial translocation. Adult LDLT recipients were prospectively divided into 2 groups, who were administered DKT (n = 20, group A) or not (n = 20, group B). The area of bowel gas defined as gas volume score (GVS) 7 days after LDLT was calculated. Postoperative liver function tests, the development of bacterial, viral, and fungal infections, and GVS after LDLT were reviewed. There were no significant differences in liver function tests and ammonia level after LDLT. Also, the rates of infection and the result of culture study were not different between groups. The median GVS 7 days after LDLT was not significantly different between groups A (0.26 (range, 0.12-0.58)) and B (0.23 (range, 0.15-0.42)). No positive impact was observed for 14-day DKT administration after LDLT, in terms of preventing infection or abdominal distension. Copyright © 2018. Published by Elsevier Taiwan.

Predictors of renal function recovery among patients undergoing renal replacement therapy following orthotopic liver transplantation.

PubMed

Andreoli, Maria Claudia Cruz; Souza, Nádia Karina Guimarães de; Ammirati, Adriano Luiz; Matsui, Thais Nemoto; Carneiro, Fabiana Dias; Ramos, Ana Claudia Mallet de Souza; Iizuca, Ilson Jorge; Coelho, Maria Paula Vilela; Afonso, Rogério Carballo; Ferraz-Neto, Ben-Hur; Almeida, Marcio Dias de; Durão, Marcelino; Batista, Marcelo Costa; Monte, Julio Cesar; Pereira, Virgílio Gonçalves; Santos, Oscar Pavão Dos; Santos, Bento Cardoso Dos

2017-01-01

Renal dysfunction frequently occurs during the periods preceding and following orthotopic liver transplantation (OLT), and in many cases, renal replacement therapy (RRT) is required. Information regarding the duration of RRT and the rate of kidney function recovery after OLT is crucial for transplant program management. We evaluated a sample of 155 stable patients undergoing post-intensive care hemodialysis (HD) from a patient population of 908 adults who underwent OLT. We investigated the average time to renal function recovery (duration of RRT required) and determined the risk factors for remaining on dialysis > 90 days after OLT. Log-rank tests were used for univariate analysis, and Cox proportional hazards models were used to identify factors associated with the risk of remaining on HD. The results of our analysis showed that of the 155 patients, 28% had pre-OLT diabetes mellitus, 21% had pre-OLT hypertension, and 40% had viral hepatitis. Among the patients, the median MELD (Model for End-Stage Liver Disease) score was 27 (interquartile range [IQR] 22-35). When they were listed for liver transplantation, 32% of the patients had serum creatinine (Scr) levels > 1.5 mg/dL or were on HD, and 50% had serum creatinine (Scr) levels > 1.5 mg/dL or were on HD at the time of OLT. Of the transplanted patients, 25% underwent pre-OLT intermittent HD, and 14% and 41% underwent continuous renal replacement therapy (CRRT) pre-OLT and post-OLT, respectively. At 90 days post-OLT, 118 (76%) patients had been taken off dialysis, and 16 (10%) patients had died while undergoing HD. The median recovery time of these post-OLT patients was 33 (IQR 27-39) days. In the multivariate analysis, fulminant hepatic failure as the cause of liver disease (p<0.001), the absence of pre-OLT hypertension (p = 0.016), a lower intraoperative fresh-frozen plasma (FFP) transfusion volume (p = 0.019) and not undergoing pre-OLT intermittent HD (p = 0.032) were associated with performing RRT for less than 90 days. Therefore, a high proportion of OLT patients showed improved renal function after OLT, and those who were diagnosed with fulminant hepatic failure, had no pre-OLT hypertension, received a lower transfused volume of intraoperative FFP and did not undergo pre-OLT intermittent HD had a higher probability of recovery.

Predictors of renal function recovery among patients undergoing renal replacement therapy following orthotopic liver transplantation

PubMed Central

de Souza, Nádia Karina Guimarães; Ammirati, Adriano Luiz; Matsui, Thais Nemoto; Carneiro, Fabiana Dias; Ramos, Ana Claudia Mallet de Souza; Iizuca, Ilson Jorge; Afonso, Rogério Carballo; Ferraz-Neto, Ben-Hur; de Almeida, Marcio Dias; Durão, Marcelino; Batista, Marcelo Costa; Monte, Julio Cesar; Pereira, Virgílio Gonçalves; dos Santos, Oscar Pavão

2017-01-01

Renal dysfunction frequently occurs during the periods preceding and following orthotopic liver transplantation (OLT), and in many cases, renal replacement therapy (RRT) is required. Information regarding the duration of RRT and the rate of kidney function recovery after OLT is crucial for transplant program management. We evaluated a sample of 155 stable patients undergoing post-intensive care hemodialysis (HD) from a patient population of 908 adults who underwent OLT. We investigated the average time to renal function recovery (duration of RRT required) and determined the risk factors for remaining on dialysis > 90 days after OLT. Log-rank tests were used for univariate analysis, and Cox proportional hazards models were used to identify factors associated with the risk of remaining on HD. The results of our analysis showed that of the 155 patients, 28% had pre-OLT diabetes mellitus, 21% had pre-OLT hypertension, and 40% had viral hepatitis. Among the patients, the median MELD (Model for End-Stage Liver Disease) score was 27 (interquartile range [IQR] 22-35). When they were listed for liver transplantation, 32% of the patients had serum creatinine (Scr) levels > 1.5 mg/dL or were on HD, and 50% had serum creatinine (Scr) levels > 1.5 mg/dL or were on HD at the time of OLT. Of the transplanted patients, 25% underwent pre-OLT intermittent HD, and 14% and 41% underwent continuous renal replacement therapy (CRRT) pre-OLT and post-OLT, respectively. At 90 days post-OLT, 118 (76%) patients had been taken off dialysis, and 16 (10%) patients had died while undergoing HD. The median recovery time of these post-OLT patients was 33 (IQR 27–39) days. In the multivariate analysis, fulminant hepatic failure as the cause of liver disease (p<0.001), the absence of pre-OLT hypertension (p = 0.016), a lower intraoperative fresh-frozen plasma (FFP) transfusion volume (p = 0.019) and not undergoing pre-OLT intermittent HD (p = 0.032) were associated with performing RRT for less than 90 days. Therefore, a high proportion of OLT patients showed improved renal function after OLT, and those who were diagnosed with fulminant hepatic failure, had no pre-OLT hypertension, received a lower transfused volume of intraoperative FFP and did not undergo pre-OLT intermittent HD had a higher probability of recovery. PMID:28574999

Ascites, a New Cause for Bilateral Hydronephrosis: Case Report

PubMed Central

Jain, Deepika; Dorairajan, Smrita; Misra, Madhukar

2009-01-01

Bilateral hydronephrosis secondary to urinary obstruction leads to a buildup of back pressure in the urinary tract and may lead to impairment of renal function. We present a case of a 57-year-old male with a history of alcoholic liver cirrhosis, who presented with tense ascites and acute renal failure. Bilateral hydronephrosis was seen on abdominal ultrasound. Multiple large-volume paracenteses resulted in resolution of hydronephrosis and prompt improvement in renal function. PMID:19802498

The correlation between preoperative volumetry and real graft weight: comparison of two volumetry programs.

PubMed

Mussin, Nadiar; Sumo, Marco; Lee, Kwang-Woong; Choi, YoungRok; Choi, Jin Yong; Ahn, Sung-Woo; Yoon, Kyung Chul; Kim, Hyo-Sin; Hong, Suk Kyun; Yi, Nam-Joon; Suh, Kyung-Suk

2017-04-01

Liver volumetry is a vital component in living donor liver transplantation to determine an adequate graft volume that meets the metabolic demands of the recipient and at the same time ensures donor safety. Most institutions use preoperative contrast-enhanced CT image-based software programs to estimate graft volume. The objective of this study was to evaluate the accuracy of 2 liver volumetry programs (Rapidia vs . Dr. Liver) in preoperative right liver graft estimation compared with real graft weight. Data from 215 consecutive right lobe living donors between October 2013 and August 2015 were retrospectively reviewed. One hundred seven patients were enrolled in Rapidia group and 108 patients were included in the Dr. Liver group. Estimated graft volumes generated by both software programs were compared with real graft weight measured during surgery, and further classified into minimal difference (≤15%) and big difference (>15%). Correlation coefficients and degree of difference were determined. Linear regressions were calculated and results depicted as scatterplots. Minimal difference was observed in 69.4% of cases from Dr. Liver group and big difference was seen in 44.9% of cases from Rapidia group (P = 0.035). Linear regression analysis showed positive correlation in both groups (P < 0.01). However, the correlation coefficient was better for the Dr. Liver group (R 2 = 0.719), than for the Rapidia group (R 2 = 0.688). Dr. Liver can accurately predict right liver graft size better and faster than Rapidia, and can facilitate preoperative planning in living donor liver transplantation.

Graft selection strategy in adult-to-adult living donor liver transplantation: When both hemiliver grafts meet volumetric criteria.

PubMed

Kurihara, Takeshi; Yoshizumi, Tomoharu; Yoshida, Yoshihiro; Ikegami, Toru; Itoh, Shinji; Harimoto, Norifumi; Ninomiya, Mizuki; Uchiyama, Hideaki; Okabe, Hirohisa; Kimura, Koichi; Kawanaka, Hirofumi; Shirabe, Ken; Maehara, Yoshihiko

2016-07-01

To ensure donor safety in living donor liver transplantation (LDLT), the left and caudate lobe (LL) is the preferred graft choice. However, patient prognosis may still be poor even if graft volume (GV) selection criteria are met. Our aim was to evaluate the effects of right lobe (RL) donation when the LL graft selection criteria are met. Consecutive donors (n = 135) with preoperative LL graft volumetric GV/standard liver volume (SLV) of ≥35% and RL remnant of ≥35% were retrospectively studied. Patients were divided into 2 groups: LL graft and RL graft. Recipient's body surface area (BSA), Model for End-Stage Liver Disease (MELD) score, and the donor's age were higher in the RL group. The donor's BSA and preoperative volumetric GV/SLV of the LL graft were smaller in the RL group. The predicted score (calculated using data for graft size, donor age, MELD score, and the presence of portosystemic shunt, which correlated well with graft function and with 6-month graft survival) of the RL group, was significantly lower if the LL graft were used, but using the actual RL graft improved the score equal to that of the LL group. Six-month and 12-month graft survival rates did not differ between the 2 groups. In patients with a poor prognosis, a larger RL graft improved the predicted score and survival was equal to that of patients who received LL grafts. In conclusion, graft selection by GV, donor age, and recipient MELD score improves outcomes in LDLT. Liver Transplantation 22 914-922 2016 AASLD. © 2016 American Association for the Study of Liver Diseases.

High mortality after ALPPS for perihilar cholangiocarcinoma: case-control analysis including the first series from the international ALPPS registry

PubMed Central

Olthof, Pim B.; Coelen, Robert J.S.; Wiggers, Jimme K.; Koerkamp, Bas Groot; Malago, Massimo; Hernandez-Alejandro, Roberto; Topp, Stefan A.; Vivarelli, Marco; Aldrighetti, Luca A.; Campos, Ricardo Robles; Oldhafer, Karl J.; Jarnagin, William R.; van Gulik, Thomas M.

2017-01-01

Introduction Resection of perihilar cholangiocarcinoma (PHC) entails high-risk surgery with substantial postoperative mortality reported up to 18%, even in specialized centers. The aim of this study was to compare outcomes of PHC patients who underwent associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) to patients with a small functional liver remnant who underwent resection without ALPSS. Methods All patients who underwent ALPPS for PHC were identified from the international ALPPS registry and matched controls were selected from a standard resection cohort from two centers based on future remnant liver size. Outcomes included morbidity, mortality, and overall survival. Results Of the 37 patients who had undergone ALPPS for PHC in the registry, 29 had sufficient data for analyses. ALPPS for PHC was associated with a 48% (14/29) 90-day mortality and median OS of 6 months. A total of 257 patients underwent major liver resection for PHC without ALPPS. The 90-day mortality was 13% and median OS 46 months. The 29 ALPPS patients were matched to 29 patients resected without ALPPS, with similar future liver remnant volume (P=0.480). Mortality in the matched control group was 24% (P=0.100) and median OS was 27 months (P = 0.064). Discussion Outcomes of ALPPS for PHC appear inferior when compared to standard extended resections in high-risk patients. Considering these outcomes, portal vein embolization should remain the preferred method to increase future remnant liver volume in PHC patients. ALPPS is not recommended for PHC due to the 48% 90-day mortality in expert centers. PMID:28279621

PREOPERATIVE COMPUTED TOMOGRAPHY VOLUMETRY AND GRAFT WEIGHT ESTIMATION IN ADULT LIVING DONOR LIVER TRANSPLANTATION

PubMed Central

PINHEIRO, Rafael S.; CRUZ-JR, Ruy J.; ANDRAUS, Wellington; DUCATTI, Liliana; MARTINO, Rodrigo B.; NACIF, Lucas S.; ROCHA-SANTOS, Vinicius; ARANTES, Rubens M; LAI, Quirino; IBUKI, Felicia S.; ROCHA, Manoel S.; D´ALBUQUERQUE, Luiz A. C.

2017-01-01

ABSTRACT Background: Computed tomography volumetry (CTV) is a useful tool for predicting graft weights (GW) for living donor liver transplantation (LDLT). Few studies have examined the correlation between CTV and GW in normal liver parenchyma. Aim: To analyze the correlation between CTV and GW in an adult LDLT population and provide a systematic review of the existing mathematical models to calculate partial liver graft weight. Methods: Between January 2009 and January 2013, 28 consecutive donors undergoing right hepatectomy for LDLT were retrospectively reviewed. All grafts were perfused with HTK solution. Estimated graft volume was estimated by CTV and these values were compared to the actual graft weight, which was measured after liver harvesting and perfusion. Results: Median actual GW was 782.5 g, averaged 791.43±136 g and ranged from 520-1185 g. Median estimated graft volume was 927.5 ml, averaged 944.86±200.74 ml and ranged from 600-1477 ml. Linear regression of estimated graft volume and actual GW was significantly linear (GW=0.82 estimated graft volume, r2=0.98, slope=0.47, standard deviation of 0.024 and p<0.0001). Spearman Linear correlation was 0.65 with 95% CI of 0.45 - 0.99 (p<0.0001). Conclusion: The one-to-one rule did not applied in patients with normal liver parenchyma. A better estimation of graft weight could be reached by multiplying estimated graft volume by 0.82. PMID:28489167

Exacerbation of erythropoietic protoporphyria by hyperthyroidism.

PubMed

Minder, Elisabeth I; Haldemann, Andreas R; Schneider-Yin, Xiaoye

2010-12-01

Erythropoietic protoporphyria (EPP) is a hereditary disorder caused by deficiency of ferrochelatase, the last enzyme in the heme biosynthetic pathway. The majority of EPP patients present with a clinical symptom of painful phototoxicity. Liver damage, the most serious complication of EPP, occurs in <5% of the patients. This report describes a case of an EPP patient who complained of worsening cutaneous symptoms, nervousness, and insomnia. Laboratory tests showed highly increased protoporphyrin concentration in erythrocytes and elevated serum transaminases that are indicative of EPP-related liver damage. The subsequent finding of decreased serum thyroid-stimulating hormone (TSH) and increased free triiodothyronine (FT3) and free thyroxine (FT4) concentrations, as well antibodies against both thyroid peroxidase (TPO) and TSH receptors, led to the diagnosis of Graves' disease. The patient received 500 MBq of radioiodine (I(131)). Three months after the radioactive iodine therapy, the thyroid volume was reduced to 30% of pretherapeutic volume. Although the patient was slightly hypothyroidic, his liver enzymes returned to normal, his erythrocytic protoporphyrin concentration dropped fivefold, and his skin symptoms improved dramatically. The coexistence of Graves' disease and EPP is a statistically rare event as, besides our patient, there was one additional case reported in the literature. Although the exact mechanism whereby Graves' disease interacts with EPP is yet to be explored, we recommend testing thyroid function in EPP patients with liver complication to exclude hyperthyroidism as a potential cause.

Market Competition and Density in Liver Transplantation: Relationship to Volume and Outcomes.

PubMed

Adler, Joel T; Yeh, Heidi; Markmann, James F; Nguyen, Louis L

2015-08-01

Liver transplantation centers are unevenly distributed within the Donor Service Areas (DSAs) of the United States. This study assessed how market competition and liver transplantation center density are associated with liver transplantation volume within individual DSAs. We conducted a retrospective cohort study of 53,156 adult liver transplants in 45 DSAs with 110 transplantation centers identified from the Scientific Registry of Transplant Recipients between 2003 and 2012. The following measures were derived annually for each DSA: market competition using the Herfindahl Hirschman Index, transplantation center density by the Average Nearest Neighbor method, liver quality by the Liver Donor Risk Index, and patient risk by the Model for End-Stage Liver Disease. A hierarchical mixed effects negative binomial regression model of the relationship between liver transplants and market factors was created annually. Patient and graft survival were investigated with a Cox proportional hazards model. Transplantation center density was associated with market competition (p < 0.0001), listings for organ transplantation (p < 0.0001), and Model for End-Stage Liver Disease at transplantation (p = 0.0005). More liver transplantation centers (incidence rate ratio [IRR] = 1.03; p = 0.04), greater market competition (IRR = 1.36; p = 0.02), increased listings (IRR = 1.14; p < 0.0001), more donors (IRR = 1.24; p < 0.0001), and higher Liver Donor Risk Index (IRR = 3.35; p < 0.0001) were associated with more transplants. No market variables were associated with increased mortality after transplantation. After controlling for demographic and market factors, a greater concentration of centers was associated with more liver transplants without impacting overall survival. These results warrant additional investigation into the relationship between geospatial factors and liver transplantation volume with consideration for the optimization of scarce resources. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Ultrasonic assessment of hepatic blood flow as a marker of mouse hepatocarcinoma.

PubMed

Bonnin, Philippe; Villemain, Aude; Vincent, François; Debbabi, Haythem; Silvestre, Jean Sébastien; Contreres, Jean Olivier; Levy, Bernard I; Tobelem, Gérard; Dupuy, Evelyne

2007-04-01

Two-dimensional color-coded pulsed Doppler ultrasonography (US) with a 12-MHz linear transducer was used to follow tumor growth and neoangiogenesis development in 12 transgenic mice developing a whole liver hepatocellular carcinoma (HCC) induced by the expression of SV40-T antigen. In this model, male mice developed HCC at various temporal and histologic stages (hyperplastic, four-eight wk; nodular, 12 wk; diffuse carcinoma, 16-20 wk), whereas female mice remained tumor free. Seven age-matched tumor-free mice were used as controls. Liver volume was calculated from B-mode images of the abdomen. Blood flow waveforms were recorded from the hepatic tumor-feeding artery upstream from the tumor vessels, allowing quantitative blood flow velocity measurements. Measurements were performed every four weeks from four to 20 weeks. As early as the hyperplastic stage (eight weeks), liver volume was increased by 2.7-fold, hepatic artery peak-systolic blood flow velocities (BFV) by 1.5-fold, end-diastolic BFV by 1.6-fold and mean BFV by 2.0-fold compared with control values (p < 0.001). Differences increased until 20 weeks and peak-systolic reached 90 +/- 6, end-diastolic 54 +/- 5 and mean BFV 48 +/- 5 cm s(-1). Successive measurements of BFV were reproducible and intraobserver repeatability coefficient values were <3 cm s(-1). In contrast, mesenteric artery BFV, which did not supply tumor region, did not show any significant difference with respect to control values. Thus, an increase in BFV constitutes a functional evaluation of tumor vascularity. In preclinical studies in small animals, measurements of liver volume and blood flow velocities in hepatic tumor-feeding artery provide a useful, reproducible, noninvasive, easy-to-repeat tool to monitor tumor growth and neoangiogenesis in hepatocellular carcinoma in mice.

Sebelipase alfa over 52 weeks reduces serum transaminases, liver volume and improves serum lipids in patients with lysosomal acid lipase deficiency

PubMed Central

Valayannopoulos, Vassili; Malinova, Vera; Honzík, Tomas; Balwani, Manisha; Breen, Catherine; Deegan, Patrick B.; Enns, Gregory M.; Jones, Simon A.; Kane, John P.; Stock, Eveline O.; Tripuraneni, Radhika; Eckert, Stephen; Schneider, Eugene; Hamilton, Gavin; Middleton, Michael S.; Sirlin, Claude; Kessler, Bruce; Bourdon, Christopher; Boyadjiev, Simeon A.; Sharma, Reena; Twelves, Chris; Whitley, Chester B.; Quinn, Anthony G.

2014-01-01

Background and aims Lysosomal Acid Lipase Deficiency is an autosomal recessive enzyme deficiency resulting in lysosomal accumulation of cholesteryl esters and triglycerides. LAL-CL04, an ongoing extension study, investigates the long-term effects of sebelipase alfa, a recombinant human lysosomal acid lipase. Methods Sebelipase alfa (1 mg/kg or 3 mg/kg) was infused every-other-week to eligible subjects. Safety and tolerability assessments, including liver function, lipid profiles and liver volume assessment, were carried out at regular intervals. Results 216 infusions were administered to eight adult subjects through Week 52 during LAL-CL04. At Week 52, mean alanine aminotransferase and aspartate aminotransferase were normal with mean change from baseline of −58% and −40%. Mean change for low density lipoprotein, total cholesterol, triglyceride and high-density lipoprotein were −60%, −39%, −36%, and +29%, respectively. Mean liver volume by magnetic resonance imaging and hepatic proton density fat fraction decreased (12% and 55%, respectively). Adverse events were mainly mild and unrelated to sebelipase alfa. Infusion-related reactions were uncommon: three events of moderate severity were reported in two subjects; one patient's event was suggestive of hypersensitivity-like reaction, but additional testing did not confirm this, and the subject has successfully re-started sebelipase alfa. Of samples tested to date, no anti-drug antibodies have been detected. Conclusions Long-term dosing with sebelipase alfa in Lysosomal Acid Lipase-Deficient patients is well tolerated and produces sustained reductions in transaminases, improvements in serum lipid profile and reduction in hepatic fat fraction. A randomized, placebo-controlled phase 3 trial in children and adults is underway (ARISE: NCT01757184). PMID:24993530

Preoperative Cholangitis and Future Liver Remnant Volume Determine the Risk of Liver Failure in Patients Undergoing Resection for Hilar Cholangiocarcinoma

PubMed Central

Aloia, Thomas A; Shindoh, Junichi; Fabio, Forchino; Amisano, Marco; Passot, Guillaume; Ferrero, Alessandro; Vauthey, Jean-Nicolas

2016-01-01

Background The highest mortality rates after liver surgery are reported in patients who undergo resection for hilar cholangiocarcinoma (HCCA). In these patients, postoperative death usually follows the development of hepatic insufficiency. We sought to determine the factors associated with postoperative hepatic insufficiency and death due to liver failure in patients undergoing hepatectomy for HCCA. Study Design This study included all consecutive patients who underwent hepatectomy with curative intent for HCCA at two centers from 1996 through 2013. Preoperative clinical and operative data were analyzed to identify independent determinants of i) hepatic insufficiency and ii) liver failure–related death. Results The study included 133 patients with right or left major (n=67) or extended (n=66) hepatectomy. Preoperative biliary drainage was performed in 98 patients and was complicated by cholangitis in 40 cases. In all these patients, cholangitis was controlled before surgery. Major (Dindo III-IV) postoperative complications occurred in 73 patients (55%), with 29 suffering from hepatic insufficiency. Fifteen patients (11%) died within 90 days after surgery, 10 of them of liver failure. On multivariate analysis, predictors of postoperative hepatic insufficiency (all p<0.05) were preoperative cholangitis (odds ratio [OR]=3.2), future liver remnant (FLR) volume <30% (OR=3.5), preoperative total bilirubin level >3 mg/dl (OR=4), and albumin level <3.5 mg/dl (OR=3.3). Only preoperative cholangitis (OR=7.5, p=.016) and FLR volume <30% (OR=7.2, p=.019) predicted postoperative liver failure–related death. Conclusions Preoperative cholangitis and insufficient FLR volume are major determinants of hepatic insufficiency and postoperative liver failure–related death. Given the association between biliary drainage and cholangitis, the preoperative approach to patients with HCCA should be optimized to minimize the risk of cholangitis. PMID:27049784

Tracking fuzzy borders using geodesic curves with application to liver segmentation on planning CT

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

Yuan, Yading, E-mail: yading.yuan@mssm.edu; Chao, Ming; Sheu, Ren-Dih

Purpose: This work aims to develop a robust and efficient method to track the fuzzy borders between liver and the abutted organs where automatic liver segmentation usually suffers, and to investigate its applications in automatic liver segmentation on noncontrast-enhanced planning computed tomography (CT) images. Methods: In order to track the fuzzy liver–chestwall and liver–heart borders where oversegmentation is often found, a starting point and an ending point were first identified on the coronal view images; the fuzzy border was then determined as a geodesic curve constructed by minimizing the gradient-weighted path length between these two points near the fuzzy border.more » The minimization of path length was numerically solved by fast-marching method. The resultant fuzzy borders were incorporated into the authors’ automatic segmentation scheme, in which the liver was initially estimated by a patient-specific adaptive thresholding and then refined by a geodesic active contour model. By using planning CT images of 15 liver patients treated with stereotactic body radiation therapy, the liver contours extracted by the proposed computerized scheme were compared with those manually delineated by a radiation oncologist. Results: The proposed automatic liver segmentation method yielded an average Dice similarity coefficient of 0.930 ± 0.015, whereas it was 0.912 ± 0.020 if the fuzzy border tracking was not used. The application of fuzzy border tracking was found to significantly improve the segmentation performance. The mean liver volume obtained by the proposed method was 1727 cm{sup 3}, whereas it was 1719 cm{sup 3} for manual-outlined volumes. The computer-generated liver volumes achieved excellent agreement with manual-outlined volumes with correlation coefficient of 0.98. Conclusions: The proposed method was shown to provide accurate segmentation for liver in the planning CT images where contrast agent is not applied. The authors’ results also clearly demonstrated that the application of tracking the fuzzy borders could significantly reduce contour leakage during active contour evolution.« less

A Formula to Calculate Standard Liver Volume Using Thoracoabdominal Circumference.

PubMed

Shaw, Brian I; Burdine, Lyle J; Braun, Hillary J; Ascher, Nancy L; Roberts, John P

2017-12-01

With the use of split liver grafts as well as living donor liver transplantation (LDLT) it is imperative to know the minimum graft volume to avoid complications. Most current formulas to predict standard liver volume (SLV) rely on weight-based measures that are likely inaccurate in the setting of cirrhosis. Therefore, we sought to create a formula for estimating SLV without weight-based covariates. LDLT donors underwent computed tomography scan volumetric evaluation of their livers. An optimal formula for calculating SLV using the anthropomorphic measure thoracoabdominal circumference (TAC) was determined using leave-one-out cross-validation. The ability of this formula to correctly predict liver volume was checked against other existing formulas by analysis of variance. The ability of the formula to predict small grafts in LDLT was evaluated by exact logistic regression. The optimal formula using TAC was determined to be SLV = (TAC × 3.5816) - (Age × 3.9844) - (Sex × 109.7386) - 934.5949. When compared to historic formulas, the current formula was the only one which was not significantly different than computed tomography determined liver volumes when compared by analysis of variance with Dunnett posttest. When evaluating the ability of the formula to predict small for size syndrome, many (10/16) of the formulas tested had significant results by exact logistic regression, with our formula predicting small for size syndrome with an odds ratio of 7.94 (95% confidence interval, 1.23-91.36; P = 0.025). We report a formula for calculating SLV that does not rely on weight-based variables that has good ability to predict SLV and identify patients with potentially small grafts.

Postoperative Mortality after Liver Resection for Perihilar Cholangiocarcinoma: Development of a Risk Score and Importance of Biliary Drainage of the Future Liver Remnant

PubMed Central

Wiggers, Jimme K; Koerkamp, Bas Groot; Cieslak, Kasia P; Doussot, Alexandre; van Klaveren, David; Allen, Peter J; Besselink, Marc G; Busch, Olivier R; D’Angelica, Michael I; DeMatteo, Ronald P; Gouma, Dirk J; Kingham, T Peter; van Gulik, Thomas M; Jarnagin, William R

2016-01-01

Background Liver surgery for perihilar cholangiocarcinoma (PHC) is associated with postoperative mortality ranging from 5% to 18%. The aim of this study was to develop a preoperative risk score for postoperative mortality after liver resection for PHC, and to assess the effect of biliary drainage of the future liver remnant (FLR). Study design A consecutive series of 287 patients submitted to major liver resection for presumed PHC between 1997 and 2014 at two Western centers was analyzed; 228 patients (79%) underwent preoperative drainage for jaundice. FLR volumes were calculated with CT volumetry, and completeness of FLR drainage was assessed on imaging. Logistic regression was used to develop a mortality risk score. Results Postoperative mortality at 90-days was 14%, and was independently predicted by age (Odds ratio [OR] per 10 years 2.1), preoperative cholangitis (OR 4.1), FLR volume below 30% (OR 2.9), portal vein reconstruction (OR 2.3), and incomplete FLR drainage in patients with FLR volume below 50% (OR 2.8). The risk score showed good discrimination (AUC 0.75 after bootstrap validation), and ranking patients in tertiles identified three (low-intermediate-high) risk subgroups with predicted mortalities of 2%, 11%, and 37%. No postoperative mortality was observed in 33 undrained patients with FLR volumes above 50%, including 10 jaundiced patients (median bilirubin level 11 mg/dL). Conclusions The mortality risk score for patients with resectable PHC can be used for patient counseling and identification of modifiable risk factors, which include FLR volume, FLR drainage status, and preoperative cholangitis. We found no evidence to support preoperative biliary drainage in patients with an FLR volume above 50%. PMID:27063572

Pulmonary function in individuals who underwent liver transplantation: from the US cystic fibrosis foundation registry.

PubMed

Miller, Melissa R; Sokol, Ronald J; Narkewicz, Michael R; Sontag, Marci K

2012-05-01

Severe liver disease affects 4.5% to 10% of individuals with cystic fibrosis (CF) and is the third-leading cause of death. Liver transplantation (LT) is an accepted therapy, but the effects of liver disease and LT on pulmonary function in patients with CF are controversial. Our aim was to characterize changes in pulmonary function in LT patients with CF. Using mixed effect models, we analyzed pulmonary function before and after transplantation in 168 LT patients and 840 non-LT patients with CF who were matched by age, sex, pancreatic status, infections with US CF Foundation Patient Registry data (1989-2007). The primary outcome was the change in the forced expiratory volume in 1 second (FEV(1); percent predicted) in LT and non-LT in the 3-years periods before or after transplantation; second we compared FEV(1) changes. In the 3 years before transplantation, LT had lower initial FEV(1) values (71.5% ± 1.9%, P < 0.001) and a slower decline (+0.1% ± 0.4%/year, P < 0.001) than non-LT (79.6% ± 1.3% and -1.3% ± 0.2%/year, respectively). There was no difference in the FEV(1) decline after transplantation (-1.4% ± 0.4%/year for LT versus -2.1% ± 0.2%/year for non-LT, P = 0.14). Both the (P = 0.003) and (P = 0.001) had a slower FEV(1) decline in the period before transplantation versus after transplantation. In conclusion, pulmonary function is lower and declines more slowly in patients with CF before LT versus, but parallels the decline in non-LT after transplantation. LT is neither beneficial nor detrimental to pulmonary function in CF but returns FEV(1) decline to the same trajectory found for matched non-LT individuals with CF. Copyright © 2012 American Association for the Study of Liver Diseases.

Feasibility study on image guided patient positioning for stereotactic body radiation therapy of liver malignancies guided by liver motion.

PubMed

Heinz, Christian; Gerum, Sabine; Freislederer, Philipp; Ganswindt, Ute; Roeder, Falk; Corradini, Stefanie; Belka, Claus; Niyazi, Maximilian

2016-06-27

Fiducial markers are the superior method to compensate for interfractional motion in liver SBRT. However this method is invasive and thereby limits its application range. In this retrospective study, the compensation method for the interfractional motion using fiducial markers (gold standard) was compared to a new non-invasive approach, which does rely on the organ motion of the liver and the relative tumor position within this volume. We analyzed six patients (3 m, 3f) treated with SBRT in 2014. After fiducial marker implantation, all patients received a treatment CT (free breathing, without abdominal compression) and a 4D-CT (consisting of 10 respiratory phases). For all patients the gross tumor volumes (GTVs), internal target volume (ITV), planning target volume (PTV), internal marker target volumes (IMTVs) and the internal liver target volume (ILTV) were delineated based on the CT and 4D-CT images. CBCT imaging was used for the standard treatment setup based on the fiducial markers. According to the patient coordinates the 3 translational compensation values (t x , t y , t z ) for the interfractional motion were calculated by matching the blurred fiducial markers with the corresponding IMTV structures. 4 observers were requested to recalculate the translational compensation values for each CBCT (31) based on the ILTV structures. The differences of the translational compensation values between the IMTV and ILTV approach were analyzed. The magnitude of the mean absolute 3D registration error with regard to the gold standard overall patients and observers was 0.50 cm ± 0.28 cm. Individual registration errors up to 1.3 cm were observed. There was no significant overall linear correlation between the respiratory motion and the registration error of the ILTV approach. Two different methods to calculate the translational compensation values for interfractional motion in stereotactic liver therapy were evaluated. The registration accuracy of the ILTV approach is mainly limited by the non-rigid behavior of the liver and the individual registration experience of the observer. The ILTV approach lacks the accuracy that would be desired for stereotactic radiotherapy of the liver.

Ursodeoxycholic acid in advanced polycystic liver disease: A phase 2 multicenter randomized controlled trial.

PubMed

D'Agnolo, Hedwig M A; Kievit, Wietske; Takkenberg, R Bart; Riaño, Ioana; Bujanda, Luis; Neijenhuis, Myrte K; Brunenberg, Ellen J L; Beuers, Ulrich; Banales, Jesus M; Drenth, Joost P H

2016-09-01

Ursodeoxycholic acid (UDCA) inhibits proliferation of polycystic human cholangiocytes in vitro and hepatic cystogenesis in a rat model of polycystic liver disease (PLD) in vivo. Our aim was to test whether UDCA may beneficially affect liver volume in patients with advanced PLD. We conducted an international, multicenter, randomized controlled trial in symptomatic PLD patients from three tertiary referral centers. Patients with PLD and total liver volume (TLV) ⩾2500ml were randomly assigned to UDCA treatment (15-20mg/kg/day) for 24weeks, or to no treatment. Primary endpoint was proportional change in TLV. Secondary endpoints were change in symptoms and health-related quality of life. We performed a post-hoc analysis of the effect of UDCA on liver cyst volume (LCV). We included 34 patients and were able to assess primary endpoint in 32 patients, 16 with autosomal dominant polycystic kidney disease (ADPKD) and 16 with autosomal dominant polycystic liver disease (ADPLD). Proportional TLV increased by 4.6±7.7% (mean TLV increased from 6697ml to 6954ml) after 24weeks of UDCA treatment compared to 3.1±3.8% (mean TLV increased from 5512ml to 5724ml) in the control group (p=0.493). LCV was not different after 24weeks between controls and UDCA treated patients (p=0.848). However, UDCA inhibited LCV growth in ADPKD patients compared to ADPKD controls (p=0.049). UDCA administration for 24weeks did not reduce TLV in advanced PLD, but UDCA reduced LCV growth in ADPKD patients. Future studies might explore whether ADPKD and ADPLD patients respond differently to UDCA treatment. Current therapies for polycystic liver disease are invasive and have high recurrence risks. Our trial showed that the drug, ursodeoxycholic acid, was not able to reduce liver volume in patients with polycystic liver disease. However, a subgroup analysis in patients that have kidney cysts as well showed that liver cyst volume growth was reduced in patients who received ursodeoxycholic acid in comparison to patients who received no treatment. Trial registration number https://www.clinicaltrials.gov/: NCT02021110. EudraCT Number https://www.clinicaltrialsregister.eu/: 2013-003207-19. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Anatomical parameterization for volumetric meshing of the liver

NASA Astrophysics Data System (ADS)

Vera, Sergio; González Ballester, Miguel A.; Gil, Debora

2014-03-01

A coordinate system describing the interior of organs is a powerful tool for a systematic localization of injured tissue. If the same coordinate values are assigned to specific anatomical landmarks, the coordinate system allows integration of data across different medical image modalities. Harmonic mappings have been used to produce parametric coordinate systems over the surface of anatomical shapes, given their flexibility to set values at specific locations through boundary conditions. However, most of the existing implementations in medical imaging restrict to either anatomical surfaces, or the depth coordinate with boundary conditions is given at sites of limited geometric diversity. In this paper we present a method for anatomical volumetric parameterization that extends current harmonic parameterizations to the interior anatomy using information provided by the volume medial surface. We have applied the methodology to define a common reference system for the liver shape and functional anatomy. This reference system sets a solid base for creating anatomical models of the patient's liver, and allows comparing livers from several patients in a common framework of reference.

The correlation between preoperative volumetry and real graft weight: comparison of two volumetry programs

PubMed Central

Mussin, Nadiar; Sumo, Marco; Choi, YoungRok; Choi, Jin Yong; Ahn, Sung-Woo; Yoon, Kyung Chul; Kim, Hyo-Sin; Hong, Suk Kyun; Yi, Nam-Joon; Suh, Kyung-Suk

2017-01-01

Purpose Liver volumetry is a vital component in living donor liver transplantation to determine an adequate graft volume that meets the metabolic demands of the recipient and at the same time ensures donor safety. Most institutions use preoperative contrast-enhanced CT image-based software programs to estimate graft volume. The objective of this study was to evaluate the accuracy of 2 liver volumetry programs (Rapidia vs. Dr. Liver) in preoperative right liver graft estimation compared with real graft weight. Methods Data from 215 consecutive right lobe living donors between October 2013 and August 2015 were retrospectively reviewed. One hundred seven patients were enrolled in Rapidia group and 108 patients were included in the Dr. Liver group. Estimated graft volumes generated by both software programs were compared with real graft weight measured during surgery, and further classified into minimal difference (≤15%) and big difference (>15%). Correlation coefficients and degree of difference were determined. Linear regressions were calculated and results depicted as scatterplots. Results Minimal difference was observed in 69.4% of cases from Dr. Liver group and big difference was seen in 44.9% of cases from Rapidia group (P = 0.035). Linear regression analysis showed positive correlation in both groups (P < 0.01). However, the correlation coefficient was better for the Dr. Liver group (R2 = 0.719), than for the Rapidia group (R2 = 0.688). Conclusion Dr. Liver can accurately predict right liver graft size better and faster than Rapidia, and can facilitate preoperative planning in living donor liver transplantation. PMID:28382294

Feasibility of semiautomated MR volumetry using gadoxetic acid-enhanced MRI at hepatobiliary phase for living liver donors.

PubMed

Lee, Jeongjin; Kim, Kyoung Won; Kim, So Yeon; Kim, Bohyoung; Lee, So Jung; Kim, Hyoung Jung; Lee, Jong Seok; Lee, Moon Gyu; Song, Gi-Won; Hwang, Shin; Lee, Sung-Gyu

2014-09-01

To assess the feasibility of semiautomated MR volumetry using gadoxetic acid-enhanced MRI at the hepatobiliary phase compared with manual CT volumetry. Forty potential live liver donor candidates who underwent MR and CT on the same day, were included in our study. Semiautomated MR volumetry was performed using gadoxetic acid-enhanced MRI at the hepatobiliary phase. We performed the quadratic MR image division for correction of the bias field inhomogeneity. With manual CT volumetry as the reference standard, we calculated the average volume measurement error of the semiautomated MR volumetry. We also calculated the mean of the number and time of the manual editing, edited volume, and total processing time. The average volume measurement errors of the semiautomated MR volumetry were 2.35% ± 1.22%. The average values of the numbers of editing, operation times of manual editing, edited volumes, and total processing time for the semiautomated MR volumetry were 1.9 ± 0.6, 8.1 ± 2.7 s, 12.4 ± 8.8 mL, and 11.7 ± 2.9 s, respectively. Semiautomated liver MR volumetry using hepatobiliary phase gadoxetic acid-enhanced MRI with the quadratic MR image division is a reliable, easy, and fast tool to measure liver volume in potential living liver donors. Copyright © 2013 Wiley Periodicals, Inc.

Correlation between liver cell necrosis and circulating alanine aminotransferase after ischaemia/reperfusion injuries in the rat liver.

PubMed

Knudsen, Anders R; Andersen, Kasper J; Hamilton-Dutoit, Stephen; Nyengaard, Jens R; Mortensen, Frank V

2016-04-01

Circulating liver enzymes such as alanine transaminase are often used as markers of hepatocellular damage. Ischaemia/reperfusion (I/R) injury is an inevitable consequence of prolonged liver ischaemia. The aim of this study was to examine the correlation between liver enzymes and volume of liver cell necrosis after ischaemia/reperfusion injuries, using design-unbiased stereological methods. Forty-seven male Wistar rats were subjected to 1 h of partial liver ischaemia, followed by either 4 or 24 h of reperfusion. Within each group, one-third of animals were subjected to ischaemic preconditioning and one-third to ischaemic postconditioning. At the end of reperfusion, blood and liver samples were collected for analysis. The volume of necrotic liver tissue was subsequently correlated to circulating markers of I/R injury. Correlation between histological findings and circulating markers was performed using Pearson's correlation coefficient. Alanine transferase peaked after 4 h of reperfusion; however, at this time-point, only mild necrosis was observed, with a Pearson's correlation coefficient of 0.663 (P = 0.001). After 24 h of reperfusion, alanine aminotransferase was found to be highly correlated to the degree of hepatocellular necrosis R = 0.836 (P = 0.000). Furthermore, alkaline phosphatase (R = 0.806) and α-2-macroglobulin (R = 0.655) levels were also correlated with the degree of necrosis. We show for the first time that there is a close correlation between the volume of hepatocellular necrosis and alanine aminotransferase levels in a model of I/R injury. This is especially apparent after 24 h of reperfusion. Similarly, increased levels of alkaline phosphatase and α-2-macroglobulin are correlated to the volume of liver necrosis. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

Radiation-Induced Liver Injury in Three-Dimensional Conformal Radiation Therapy (3D-CRT) for Postoperative or Locoregional Recurrent Gastric Cancer: Risk Factors and Dose Limitations.

PubMed

Li, Guichao; Wang, Jiazhou; Hu, Weigang; Zhang, Zhen

2015-01-01

This study examined the status of radiation-induced liver injury in adjuvant or palliative gastric cancer radiation therapy (RT), identified risk factors of radiation-induced liver injury in gastric cancer RT, analysed the dose-volume effects of liver injury, and developed a liver dose limitation reference for gastric cancer RT. Data for 56 post-operative gastric cancer patients and 6 locoregional recurrent gastric cancer patients treated with three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) from Sep 2007 to Sep 2009 were analysed. Forty patients (65%) were administered concurrent chemotherapy. Pre- and post-radiation chemotherapy were given to 61 patients and 43 patients, respectively. The radiation dose was 45-50.4 Gy in 25-28 fractions. Clinical parameters, including gender, age, hepatic B virus status, concurrent chemotherapy, and the total number of chemotherapy cycles, were included in the analysis. Univariate analyses with a non-parametric rank test (Mann-Whitney test) and logistic regression test and a multivariate analysis using a logistic regression test were completed. We also analysed the correlation between RT and the changes in serum chemistry parameters [including total bilirubin, (TB), direct bilirubin (D-TB), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and serum albumin (ALB)] after RT. The Child-Pugh grade progressed from grade A to grade B after radiotherapy in 10 patients. A total of 16 cases of classic radiation-induced liver disease (RILD) were observed, and 2 patients had both Child-Pugh grade progression and classic RILD. No cases of non-classic radiation liver injury occurred in the study population. Among the tested clinical parameters, the total number of chemotherapy cycles correlated with liver function injury. V35 and ALP levels were significant predictive factors for radiation liver injury. In 3D-CRT for gastric cancer patients, radiation-induced liver injury may occur and affect the overall treatment plan. The total number of chemotherapy cycles correlated with liver function injury, and V35 and ALP are significant predictive factors for radiation-induced liver injury. Our dose limitation reference for liver protection is feasible.

Induction of Inducible Nitric Oxide Synthase by Lipopolysaccharide and the Influences of Cell Volume Changes, Stress Hormones and Oxidative Stress on Nitric Oxide Efflux from the Perfused Liver of Air-Breathing Catfish, Heteropneustes fossilis

PubMed Central

Choudhury, Mahua G.; Saha, Nirmalendu

2016-01-01

The air-breathing singhi catfish (Heteropneustes fossilis) is frequently being challenged by bacterial contaminants, and different environmental insults like osmotic, hyper-ammonia, dehydration and oxidative stresses in its natural habitats throughout the year. The main objectives of the present investigation were to determine (a) the possible induction of inducible nitric oxide synthase (iNOS) gene with enhanced production of nitric oxide (NO) by intra-peritoneal injection of lipopolysaccharide (LPS) (a bacterial endotoxin), and (b) to determine the effects of hepatic cell volume changes due to anisotonicity or by infusion of certain metabolites, stress hormones and by induction of oxidative stress on production of NO from the iNOS-induced perfused liver of singhi catfish. Intra-peritoneal injection of LPS led to induction of iNOS gene and localized tissue specific expression of iNOS enzyme with more production and accumulation of NO in different tissues of singhi catfish. Further, changes of hydration status/cell volume, caused either by anisotonicity or by infusion of certain metabolites such as glutamine plus glycine and adenosine, affected the NO production from the perfused liver of iNOS-induced singhi catfish. In general, increase of hydration status/cell swelling due to hypotonicity caused decrease, and decrease of hydration status/cell shrinkage due to hypertonicity caused increase of NO efflux from the perfused liver, thus suggesting that changes in hydration status/cell volume of hepatic cells serve as a potent modulator for regulating the NO production. Significant increase of NO efflux from the perfused liver was also observed while infusing the liver with stress hormones like epinephrine and norepinephrine, accompanied with decrease of hydration status/cell volume of hepatic cells. Further, oxidative stress, caused due to infusion of t-butyl hydroperoxide and hydrogen peroxide separately, in the perfused liver of singhi catfish, resulted in significant increase of NO efflux accompanied with decrease of hydration status/cell volume of hepatic cells. However, the reasons for these cell volume-sensitive changes of NO efflux from the liver of singhi catfish are not fully understood with the available data. Nonetheless, enhanced or decreased production of NO from the perfused liver under osmotic stress, in presence of stress hormones and oxidative stress reflected its potential role in cellular homeostasis and also for better adaptations under environmental challenges. This is the first report of osmosensitive and oxidative stress-induced changes of NO production and efflux from the liver of any teleosts. Further, the level of expression of iNOS in this singhi catfish could also serve as an important indicator to determine the pathological status of the external environment. PMID:26950213

Induction of Inducible Nitric Oxide Synthase by Lipopolysaccharide and the Influences of Cell Volume Changes, Stress Hormones and Oxidative Stress on Nitric Oxide Efflux from the Perfused Liver of Air-Breathing Catfish, Heteropneustes fossilis.

PubMed

Choudhury, Mahua G; Saha, Nirmalendu

2016-01-01

The air-breathing singhi catfish (Heteropneustes fossilis) is frequently being challenged by bacterial contaminants, and different environmental insults like osmotic, hyper-ammonia, dehydration and oxidative stresses in its natural habitats throughout the year. The main objectives of the present investigation were to determine (a) the possible induction of inducible nitric oxide synthase (iNOS) gene with enhanced production of nitric oxide (NO) by intra-peritoneal injection of lipopolysaccharide (LPS) (a bacterial endotoxin), and (b) to determine the effects of hepatic cell volume changes due to anisotonicity or by infusion of certain metabolites, stress hormones and by induction of oxidative stress on production of NO from the iNOS-induced perfused liver of singhi catfish. Intra-peritoneal injection of LPS led to induction of iNOS gene and localized tissue specific expression of iNOS enzyme with more production and accumulation of NO in different tissues of singhi catfish. Further, changes of hydration status/cell volume, caused either by anisotonicity or by infusion of certain metabolites such as glutamine plus glycine and adenosine, affected the NO production from the perfused liver of iNOS-induced singhi catfish. In general, increase of hydration status/cell swelling due to hypotonicity caused decrease, and decrease of hydration status/cell shrinkage due to hypertonicity caused increase of NO efflux from the perfused liver, thus suggesting that changes in hydration status/cell volume of hepatic cells serve as a potent modulator for regulating the NO production. Significant increase of NO efflux from the perfused liver was also observed while infusing the liver with stress hormones like epinephrine and norepinephrine, accompanied with decrease of hydration status/cell volume of hepatic cells. Further, oxidative stress, caused due to infusion of t-butyl hydroperoxide and hydrogen peroxide separately, in the perfused liver of singhi catfish, resulted in significant increase of NO efflux accompanied with decrease of hydration status/cell volume of hepatic cells. However, the reasons for these cell volume-sensitive changes of NO efflux from the liver of singhi catfish are not fully understood with the available data. Nonetheless, enhanced or decreased production of NO from the perfused liver under osmotic stress, in presence of stress hormones and oxidative stress reflected its potential role in cellular homeostasis and also for better adaptations under environmental challenges. This is the first report of osmosensitive and oxidative stress-induced changes of NO production and efflux from the liver of any teleosts. Further, the level of expression of iNOS in this singhi catfish could also serve as an important indicator to determine the pathological status of the external environment.

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.

High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial.

PubMed

Larsen, Fin Stolze; Schmidt, Lars Ebbe; Bernsmeier, Christine; Rasmussen, Allan; Isoniemi, Helena; Patel, Vishal C; Triantafyllou, Evangelos; Bernal, William; Auzinger, Georg; Shawcross, Debbie; Eefsen, Martin; Bjerring, Peter Nissen; Clemmesen, Jens Otto; Hockerstedt, Krister; Frederiksen, Hans-Jørgen; Hansen, Bent Adel; Antoniades, Charalambos G; Wendon, Julia

2016-01-01

Acute liver failure (ALF) often results in cardiovascular instability, renal failure, brain oedema and death either due to irreversible shock, cerebral herniation or development of multiple organ failure. High-volume plasma exchange (HVP), defined as exchange of 8-12 or 15% of ideal body weight with fresh frozen plasma in case series improves systemic, cerebral and splanchnic parameters. In this prospective, randomised, controlled, multicentre trial we randomly assigned 182 patients with ALF to receive either standard medical therapy (SMT; 90 patients) or SMT plus HVP for three days (92 patients). The baseline characteristics of the groups were similar. The primary endpoint was liver transplantation-free survival during hospital stay. Secondary-endpoints included survival after liver transplantation with or without HVP with intention-to-treat analysis. A proof-of-principle study evaluating the effect of HVP on the immune cell function was also undertaken. For the entire patient population, overall hospital survival was 58.7% for patients treated with HVP vs. 47.8% for the control group (hazard ratio (HR), with stratification for liver transplantation: 0.56; 95% confidence interval (CI), 0.36-0.86; p=0.0083). HVP prior to transplantation did not improve survival compared with patients who received SMT alone (CI 0.37 to 3.98; p=0.75). The incidence of severe adverse events was similar in the two groups. Systemic inflammatory response syndrome (SIRS) and sequential organ failure assessment (SOFA) scores fell in the treated group compared to control group, over the study period (p<0.001). Treatment with HVP improves outcome in patients with ALF by increasing liver transplant-free survival. This is attributable to attenuation of innate immune activation and amelioration of multi-organ dysfunction. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

A model of hydraulic interactions in liver parenchyma as forces behind the intrahepatic bile flow.

PubMed

Kurbel, S; Kurbel, B; Dmitrovic, B; Wagner, J

2001-05-01

The small diameters of bile canaliculi and interlobular bile ducts make it hard to attribute the bile flow solely to the process of secretion. In the model liver within its capsule is considered a limited space in which volume expansions of one part are possible only through the shrinking of other parts. The liver capsule allows only very slow volume changes. The rate of blood flow through the sinusoides is governed by the Poisseuill-Hagen law. The model is based on a concept of circulatory liver units. A unit would contain a group of acini sharing the same conditions of arterial flow. We can imagine them as an acinar group behind the last pressure reducer on one arterial branch. Acini from neighboring units compose liver lobules and drain through the same central venule. One lobule can contain acini from several neighboring circulatory units. The perfusion cycle in one unit begins with a transient tide in the arterial flow, governed by local mediators. Corresponding acini expand, grabbing the space by compressing their neighbors in the same lobules. Vascular resistance is reduced in dilated and increased in compressed acini. Portal blood flows through the dilated acini, bypassing the compressed neighbors. The cycle ends when the portal tide slowly diminishes and acinar volume is back on the interphase value until the new perfusion cycle is started in another circulatory unit. Each cycle probably takes minutes to complete. Increased pressures both in dilated and in compressed acini force the bile to move from acinar canalicules. Both up and down changes in acinar volume might force the acinar biliary flow. In cases of arterial vasoconstriction, increased activity of vasoactive substances would keep most of the circulatory units in the interphase and increased liver resistance can be expected. Liver fibrosis makes all acini to be of fixed volume and result in increased resistance. Because of that, low pressure portal flow would be more compromised, as reported. In livers without arterial blood flow, although some slow changes in the portal flows can be expected, acinar volume changes should be reduced. In acute liver injury, enlarged hepatocytes would diminish sinusoidal diameter and increase acinar resistance. In liver tumors, areas of neovascularization with reduced resistance would divert the arterial flow from the normal tissue, while in the compressed perifocal areas, increased vascular resistance should diminish mainly the portal flow. Copyright 2001 Harcourt Publishers Ltd.

Does hepatic steatosis have an impact on the short term hepatic response after complete attenuation of congenital extrahepatic portosystemic shunts? A prospective study of 20 dogs.

PubMed

Hunt, Geraldine B; Luff, Jennifer; Daniel, Leticia; Zwingenberger, Allison

2014-11-01

To evaluate the relationship between hepatic steatosis and increase in liver size and resolution of shunting after surgical attenuation of congenital extrahepatic portosystemic shunts in dogs. Prospective study. Dogs (n = 20) with congenital extrahepatic portosystemic shunts. Shunts were attenuated using ameroid ring constrictors. Portal blood flow and liver volume were evaluated using computed tomography before and ≥8 weeks after surgery. Hepatic steatosis was quantified by stereological point counting of lipid droplets and lipogranulomas (LG) in liver biopsies stained with Oil-red-O. Associations between steatosis and preoperative liver volume, liver growth after surgery, and development of acquired shunts were evaluated. Acquired shunts developed in 2 dogs (10%). Dogs with larger preoperative liver volumes relative to bodyweight had fewer lipid droplets per tissue point (P = .019). LG per tissue point were significantly associated with age: 0.019 ± 0.06 for dogs <12 months versus 0.25 ± 0.49 for dogs >12 months (P = .007). There was a significant positive association between liver growth after surgery and the number of LG/month of age in dogs >12 months (P = .003). There was no association between steatosis, presence of macrosteatosis, the number of LG or development of acquired shunts. This preliminary study suggests that the presence of hepatic lipidosis and LG has no demonstrable effect on development of acquired shunts or the magnitude of increase in liver volume after attenuation of congenital extrahepatic portosystemic shunts in dogs. © Copyright 2014 by The American College of Veterinary Surgeons.

Physiological and biochemical basis of clinical liver function tests: a review.

PubMed

Hoekstra, Lisette T; de Graaf, Wilmar; Nibourg, Geert A A; Heger, Michal; Bennink, Roelof J; Stieger, Bruno; van Gulik, Thomas M

2013-01-01

To review the literature on the most clinically relevant and novel liver function tests used for the assessment of hepatic function before liver surgery. Postoperative liver failure is the major cause of mortality and morbidity after partial liver resection and develops as a result of insufficient remnant liver function. Therefore, accurate preoperative assessment of the future remnant liver function is mandatory in the selection of candidates for safe partial liver resection. A MEDLINE search was performed using the key words "liver function tests," "functional studies in the liver," "compromised liver," "physiological basis," and "mechanistic background," with and without Boolean operators. Passive liver function tests, including biochemical parameters and clinical grading systems, are not accurate enough in predicting outcome after liver surgery. Dynamic quantitative liver function tests, such as the indocyanine green test and galactose elimination capacity, are more accurate as they measure the elimination process of a substance that is cleared and/or metabolized almost exclusively by the liver. However, these tests only measure global liver function. Nuclear imaging techniques ((99m)Tc-galactosyl serum albumin scintigraphy and (99m)Tc-mebrofenin hepatobiliary scintigraphy) can measure both total and future remnant liver function and potentially identify patients at risk for postresectional liver failure. Because of the complexity of liver function, one single test does not represent overall liver function. In addition to computed tomography volumetry, quantitative liver function tests should be used to determine whether a safe resection can be performed. Presently, (99m)Tc-mebrofenin hepatobiliary scintigraphy seems to be the most valuable quantitative liver function test, as it can measure multiple aspects of liver function in, specifically, the future remnant liver.

IMPROVED DERIVATION OF INPUT FUNCTION IN DYNAMIC MOUSE [18F]FDG PET USING BLADDER RADIOACTIVITY KINETICS

PubMed Central

Wong, Koon-Pong; Zhang, Xiaoli; Huang, Sung-Cheng

2013-01-01

Purpose Accurate determination of the plasma input function (IF) is essential for absolute quantification of physiological parameters in positron emission tomography (PET). However, it requires an invasive and tedious procedure of arterial blood sampling that is challenging in mice because of the limited blood volume. In this study, a hybrid modeling approach is proposed to estimate the plasma IF of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) in mice using accumulated radioactivity in urinary bladder together with a single late-time blood sample measurement. Methods Dynamic PET scans were performed on nine isoflurane-anesthetized male C57BL/6 mice after a bolus injection of [18F]FDG at the lateral caudal vein. During a 60- or 90-min scan, serial blood samples were taken from the femoral artery. Image data were reconstructed using filtered backprojection with CT-based attenuation correction. Total accumulated radioactivity in the urinary bladder was fitted to a renal compartmental model with the last blood sample and a 1-exponential function that described the [18F]FDG clearance in blood. Multiple late-time blood sample estimates were calculated by the blood [18F]FDG clearance equation. A sum of 4-exponentials was assumed for the plasma IF that served as a forcing function to all tissues. The estimated plasma IF was obtained by simultaneously fitting the [18F]FDG model to the time-activity curves (TACs) of liver and muscle and the forcing function to early (0–1 min) left-ventricle data (corrected for delay, dispersion, partial-volume effects and erythrocytes uptake) and the late-time blood estimates. Using only the blood sample acquired at the end of the study to estimate the IF and the use of liver TAC as an alternative IF were also investigated. Results The area under the plasma TACs calculated for all studies using the hybrid approach was not significantly different from that using all blood samples. [18F]FDG uptake constants in brain, myocardium, skeletal muscle and liver computed by the Patlak analysis using estimated and measured plasma TACs were in excellent agreement (slope ~ 1; R2 > 0.938). The IF estimated using only the last blood sample acquired at the end of the study and the use of liver TAC as plasma IF provided less reliable results. Conclusions The estimated plasma IFs obtained with the hybrid model agreed well with those derived from arterial blood sampling. Importantly, the proposed method obviates the need of arterial catheterization, making it possible to perform repeated dynamic [18F]FDG PET studies on the same animal. Liver TAC is unsuitable as an input function for absolute quantification of [18F]FDG PET data. PMID:23322346

Monitoring of Total and Regional Liver Function after SIRT.

PubMed

Bennink, Roelof J; Cieslak, Kasia P; van Delden, Otto M; van Lienden, Krijn P; Klümpen, Heinz-Josef; Jansen, Peter L; van Gulik, Thomas M

2014-01-01

Selective internal radiation therapy (SIRT) is a promising treatment modality for advanced hepatocellular carcinoma or metastatic liver cancer. SIRT is usually well tolerated. However, in most patients, SIRT will result in a (temporary) decreased liver function. Occasionally patients develop radioembolization-induced liver disease (REILD). In case of a high tumor burden of the liver, it could be beneficial to perform SIRT in two sessions enabling the primary untreated liver segments to guarantee liver function until function in the treated segments has recovered or functional hypertrophy has occurred. Clinically used liver function tests provide evidence of only one of the many liver functions, though all of them lack the possibility of assessment of segmental (regional) liver function. Hepatobiliary scintigraphy (HBS) has been validated as a tool to assess total and regional liver function in liver surgery. It is also used to assess segmental liver function before and after portal vein embolization. HBS is considered as a valuable quantitative liver function test enabling assessment of segmental liver function recovery after regional intervention and determination of future remnant liver function. We present two cases in which HBS was used to monitor total and regional liver function in a patient after repeated whole liver SIRT complicated with REILD and a patient treated unilaterally without complications.

Chronic CCl4 intoxication causes liver and bone damage similar to the human pathology of hepatic osteodystrophy: a mouse model to analyse the liver-bone axis.

PubMed

Nussler, Andreas K; Wildemann, Britt; Freude, Thomas; Litzka, Christian; Soldo, Petra; Friess, Helmut; Hammad, Seddik; Hengstler, Jan G; Braun, Karl F; Trak-Smayra, Viviane; Godoy, Patricio; Ehnert, Sabrina

2014-04-01

Patients with chronic liver diseases frequently exhibit decreased bone mineral densities (BMD), which is defined as hepatic osteodystrophy (HOD). HOD is a multifactorial disease whose regulatory mechanisms are barely understood. Thus, an early diagnosis and therapy is hardly possible. Therefore, the aim of our study consisted in characterizing a mouse model reflecting the human pathomechanism. Serum samples were collected from patients with chronic liver diseases and 12-week old C57Bl6/N mice after 6-week treatment with carbon tetrachloride (CCl4). Repetitive injections of CCl4 induced liver damage in mice, resembling liver fibrosis in patients, as assessed by serum analysis and histological staining. Although CCl4 did not affect primary osteoblast cultures, μCT analysis revealed significantly decreased BMD, bone volume, trabecular number and thickness in CCl4-treated mice. In both HOD patients and CCl4-treated mice, an altered vitamin D metabolism with decreased CYP27A1, CYP2R1, vitamin D-binding protein GC and increased 7-dehydrocholesterol reductase hepatic gene expression, results in decreased 25-OH vitamin D serum levels. Moreover, both groups exhibit excessively high active transforming growth factor-beta (TGF-β) serum levels, inhibiting osteoblast function in vitro. Summarizing, our mouse model presents possible mediators of HOD, e.g. altered vitamin D metabolism and increased active TGF-β. Liver damage and significant changes in bone structure and mineralization are already visible by μCT analysis after 6 weeks of CCl4 treatment. This fast response and easy transferability makes it an ideal model to investigate specific gene functions in HOD.

A variational approach to liver segmentation using statistics from multiple sources

NASA Astrophysics Data System (ADS)

Zheng, Shenhai; Fang, Bin; Li, Laquan; Gao, Mingqi; Wang, Yi

2018-01-01

Medical image segmentation plays an important role in digital medical research, and therapy planning and delivery. However, the presence of noise and low contrast renders automatic liver segmentation an extremely challenging task. In this study, we focus on a variational approach to liver segmentation in computed tomography scan volumes in a semiautomatic and slice-by-slice manner. In this method, one slice is selected and its connected component liver region is determined manually to initialize the subsequent automatic segmentation process. From this guiding slice, we execute the proposed method downward to the last one and upward to the first one, respectively. A segmentation energy function is proposed by combining the statistical shape prior, global Gaussian intensity analysis, and enforced local statistical feature under the level set framework. During segmentation, the shape of the liver shape is estimated by minimization of this function. The improved Chan-Vese model is used to refine the shape to capture the long and narrow regions of the liver. The proposed method was verified on two independent public databases, the 3D-IRCADb and the SLIVER07. Among all the tested methods, our method yielded the best volumetric overlap error (VOE) of 6.5 +/- 2.8 % , the best root mean square symmetric surface distance (RMSD) of 2.1 +/- 0.8 mm, the best maximum symmetric surface distance (MSD) of 18.9 +/- 8.3 mm in 3D-IRCADb dataset, and the best average symmetric surface distance (ASD) of 0.8 +/- 0.5 mm, the best RMSD of 1.5 +/- 1.1 mm in SLIVER07 dataset, respectively. The results of the quantitative comparison show that the proposed liver segmentation method achieves competitive segmentation performance with state-of-the-art techniques.

Impaired Cell Volume Regulation in Intestinal Crypt Epithelia of Cystic Fibrosis Mice

NASA Astrophysics Data System (ADS)

Valverde, M. A.; O'Brien, J. A.; Sepulveda, F. V.; Ratcliff, R. A.; Evans, M. J.; Colledge, W. H.

1995-09-01

Cystic fibrosis is a disease characterized by abnormalities in the epithelia of the lungs, intestine, salivary and sweat glands, liver, and reproductive systems, often as a result of inadequate hydration of their secretions. The primary defect in cystic fibrosis is the altered activity of a cAMP-activated Cl^- channel, the cystic fibrosis transmembrane conductance regulator (CFTR) channel. However, it is not clear how a defect in the CFTR Cl^- channel function leads to the observed pathological changes. Although much is known about the structural properties and regulation of the CFTR, little is known of its relationship to cellular functions other than the cAMP-dependent Cl^- secretion. Here we report that cell volume regulation after hypotonic challenge is also defective in intestinal crypt epithelial cells isolated from CFTR -/- mutant mice. Moreover, the impairment of the regulatory volume decrease in CFTR -/- crypts appears to be related to the inability of a K^+ conductance to provide a pathway for the exit of this cation during the volume adjustments. This provides evidence that the lack of CFTR protein may have additional consequences for the cellular function other than the abnormal cAMP-mediated Cl^- secretion.

Liver volume measurement: reason of the difference between in vivo CT-volumetry and intraoperative ex vivo determination and how to cope it.

PubMed

Niehues, Stefan M; Unger, J K; Malinowski, M; Neymeyer, J; Hamm, B; Stockmann, M

2010-08-20

Volumetric assessment of the liver regularly yields discrepant results between pre- and intraoperatively determined volumes. Nevertheless, the main factor responsible for this discrepancy remains still unclear. The aim of this study was to systematically determine the difference between in vivo CT-volumetry and ex vivo volumetry in a pig animal model. Eleven pigs were studied. Liver density assessment, CT-volumetry and water displacement volumetry was performed after surgical removal of the complete liver. Known possible errors of volume determination like resection or segmentation borders were eliminated in this model. Regression analysis was performed and differences between CT-volumetry and water displacement determined. Median liver density was 1.07g/ml. Regression analysis showed a high correlation of r(2) = 0.985 between CT-volumetry and water displacement. CT-volumetry was found to be 13% higher than water displacement volumetry (p<0.0001). In this study the only relevant factor leading to the difference between in vivo CT-volumetry and ex vivo water displacement volumetry seems to be blood perfusion of the liver. The systematic difference of 13 percent has to be taken in account when dealing with those measures.

An evaluation of the protective role of α-tocopherol on free radical induced hepatotoxicity and nephrotoxicity due to chromium in rats

PubMed Central

Balakrishnan, Rajendran; Satish Kumar, Chitturi Sree; Rani, Matukumalli Usha; Srikanth, Mylaram Kistaiah; Boobalan, Gopu; Reddy, Alla Gopala

2013-01-01

Aim: To avert the health problems induced by many environmental pollutants, available antioxidants have been evaluated. The present study was aimed to investigate whether α-tocopherol could protect the hexavalent chromium (Cr VI)-induced peroxidation in the liver and kidney and to explore the underlying mechanism of the same. Materials and Methods: A total of 24 Wistar adult female rats were equally divided into four groups. Group 1 served as control while Groups 2 and 3 were administered K2Cr2O7(10 mg/kg b.wt. s.c. single dose). In addition to (Cr VI), Group 3 also received α-tocopherol (125 mg/kg, daily) by oral gavage for 14 days. Group 4 was maintained as α-tocopherol control (dose as above). At the end of 14 days, blood samples were drawn for hematology. Subsequently, all the rats were sacrificed to collect liver and kidney samples for assay of tissue peroxidation markers, antioxidant markers and functional markers and histopathology. Results: Administration of chromium (Cr VI) in Group 2 significantly (P < 0.05) reduced the antioxidant markers such as superoxide dismutase and reduced glutathione along with significant (P < 0.05) increase in peroxidation markers such as malondialdehyde and protein carbonyls in the liver and kidney as compared with other groups. The functional markers in serum such as total protein was decreased significantly (P < 0.05), whereas other functional markers viz. alanine transaminase, blood urea nitrogen and creatinine were increased significantly (P < 0.05) in Group 2 as compared with the other groups. Significant (P < 0.05) decrease in hemoglobin, packed cell volume, total erythrocyte count, mean corpuscular volume, mean corpuscular hemoglobin and total leukocyte count were observed in Cr VI treated Group 2 rats. Prominent pathological changes were observed in the liver and kidney of Group 2. Co-treatment with α-tocopherol in Group 3 rats significantly (P < 0.05) reversed the Cr VI induced changes. The parameters in the study in Group 4 did not differ as compared with Group 1. Conclusions: α–tocopherol exhibited protective effect against Cr VI-induced damage to the liver and kidney by inhibition of lipid peroxidation owing its antioxidant activity. PMID:24130385

Preoperative Cholangitis and Future Liver Remnant Volume Determine the Risk of Liver Failure in Patients Undergoing Resection for Hilar Cholangiocarcinoma.

PubMed

Ribero, Dario; Zimmitti, Giuseppe; Aloia, Thomas A; Shindoh, Junichi; Fabio, Forchino; Amisano, Marco; Passot, Guillaume; Ferrero, Alessandro; Vauthey, Jean-Nicolas

2016-07-01

The highest mortality rates after liver surgery are reported in patients who undergo resection for hilar cholangiocarcinoma (HCCA). In these patients, postoperative death usually follows the development of hepatic insufficiency. We sought to determine the factors associated with postoperative hepatic insufficiency and death due to liver failure in patients undergoing hepatectomy for HCCA. This study included all consecutive patients who underwent hepatectomy with curative intent for HCCA at 2 centers, from 1996 through 2013. Preoperative clinical and operative data were analyzed to identify independent determinants of hepatic insufficiency and liver failure-related death. The study included 133 patients with right or left major (n = 67) or extended (n = 66) hepatectomy. Preoperative biliary drainage was performed in 98 patients and was complicated by cholangitis in 40 cases. In all these patients, cholangitis was controlled before surgery. Major (Dindo III to IV) postoperative complications occurred in 73 patients (55%), with 29 suffering from hepatic insufficiency. Fifteen patients (11%) died within 90 days after surgery, 10 of them from liver failure. On multivariate analysis, predictors of postoperative hepatic insufficiency (all p < 0.05) were preoperative cholangitis (odds ratio [OR] 3.2), future liver remnant (FLR) volume < 30% (OR 3.5), preoperative total bilirubin level >3 mg/dL (OR 4), and albumin level < 3.5 mg/dL (OR 3.3). Only preoperative cholangitis (OR 7.5, p = 0.016) and FLR volume < 30% (OR 7.2, p = 0.019) predicted postoperative liver failure-related death. Preoperative cholangitis and insufficient FLR volume are major determinants of hepatic insufficiency and postoperative liver failure-related death. Given the association between biliary drainage and cholangitis, the preoperative approach to patients with HCCA should be optimized to minimize the risk of cholangitis. Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

SU-E-T-300: Dosimetric Comparision of 4D Radiation Therapy and 3D Radiation Therapy for the Liver Tumor Based On 4D Medical Image

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

Ma, C; Yin, Y

Purpose: The purpose of this work was to determine the dosimetric benefit to normal tissues by tracking liver tumor dose in four dimensional radiation therapy (4DRT) on ten phases of four dimensional computer tomagraphy(4DCT) images. Methods: Target tracking each phase with the beam aperture for ten liver cancer patients were converted to cumulative plan and compared to the 3D plan with a merged target volume based on 4DCT image in radiation treatment planning system (TPS). The change in normal tissue dose was evaluated in the plan by using the parameters V5, V10, V15, V20,V25, V30, V35 and V40 (volumes receivingmore » 5, 10, 15, 20, 25, 30, 35 and 40Gy, respectively) in the dose-volume histogram for the liver; mean dose for the following structures: liver, left kidney and right kidney; and maximum dose for the following structures: bowel, duodenum, esophagus, stomach and heart. Results: There was significant difference between 4D PTV(average 115.71cm3 )and ITV(169.86 cm3). When the planning objective is 95% volume of PTV covered by the prescription dose, the mean dose for the liver, left kidney and right kidney have an average decrease 23.13%, 49.51%, and 54.38%, respectively. The maximum dose for bowel, duodenum,esophagus, stomach and heart have an average decrease 16.77%, 28.07%, 24.28%, 4.89%, and 4.45%, respectively. Compared to 3D RT, radiation volume for the liver V5, V10, V15, V20, V25, V30, V35 and V40 by using the 4D plans have a significant decrease(P≤0.05). Conclusion: The 4D plan method creates plans that permit better sparing of the normal structures than the commonly used ITV method, which delivers the same dosimetric effects to the target.« less

A study on risk factors and diagnostic efficiency of posthepatectomy liver failure in the nonobstructive jaundice.

PubMed

Wang, He; Lu, Shi-Chun; He, Lei; Dong, Jia-Hong

2018-02-01

Liver failure remains as the most common complication and cause of death after hepatectomy, and continues to be a challenge for doctors.t test and χ test were used for single factor analysis of data-related variables, then results were introduced into the model to undergo the multiple factors logistic regression analysis. Pearson correlation analysis was performed for related postoperative indexes, and a diagnostic evaluation was performed using the receiver operating characteristic (ROC) of postoperative indexes.Differences in age, body mass index (BMI), portal vein hypertension, bile duct cancer, total bilirubin, alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), operation time, cumulative portal vein occlusion time, intraoperative blood volume, residual liver volume (RLV)/entire live rvolume, ascites volume at postoperative day (POD)3, supplemental albumin amount at POD3, hospitalization time after operation, and the prothrombin activity (PTA) were statistically significant. Furthermore, there were significant differences in total bilirubin and the supplemental albumin amount at POD3. ROC analysis of the average PTA, albumin amounts, ascites volume at POD3, and their combined diagnosis were performed, which had diagnostic value for postoperative liver failure (area under the curve (AUC): 0.895, AUC: 0.798, AUC: 0.775, and AUC: 0.903).Preoperative total bilirubin level and the supplemental albumin amount at POD3 were independent risk factors. PTA can be used as the index of postoperative liver failure, and the combined diagnosis of the indexes can improve the early prediction of postoperative liver failure.

Donor recruitment and selection for adult-to-adult living donor liver transplantation in urgent and elective circumstances.

PubMed

Ben-Haim, Menahem; Carmiel, Michal; Lubezky, Nir; Keidar, Rivka; Katz, Paulina; Blachar, Arye; Nimrod, Adi; Sorkine, Patrick; Oren, Ran; Klausner, Joseph M; Nakache, Richard

2005-03-01

Adult-to-adult living donor liver transplantation is becoming an alternative to cadaveric transplantation in urgent and elective settings. Donor selection crucially affects donor safety and recipient outcome. To present our algorithm of urgent and elective donor selection. Urgent selection is expeditious and protocol-based. Elective selection permits a comprehensive process. Both include medical, psychosocial and surgical-anatomic evaluations. Liver volumes and vascular anatomy are evaluated with computerized tomographic angiography. Informed consent is obtained after painstaking explanations. Independent institutional committees review and approve all cases. Between July 2003 and June 2004 we evaluated 43 potential live donors for 12 potential recipients (fulminant hepatic failure, n = 5; chronic end-stage liver disease, n = 6; primary graft non-function, n = 1). Thirty-three candidates (76%) were excluded due to blood type incompatibility (n = 14, 42%), incompatible anatomy (n = 8, 24%)--including problematic volume distribution (n = 2) or vascular anatomy (n = 6)--psychosocial issues (n = 4, 12%), or medical co-morbidity (n = 7, 22%). Five recipients (FHF, n = 4; chronic ESLD, n = 1) were successfully transplanted from living donors. In the acute setting, two patients (FHF, PGNF) died in the absence of an appropriate donor (cadaveric or living donor). In the elective group, one patient died of unexpected variceal bleeding and one received a cadaveric graft just before the planned living donor transplantation was performed. One candidate was transplanted overseas and two cases are scheduled. The ratio of compatibility for donation was 34% (10/29) for blood type-compatible candidates. Donor selection for living donor liver transplantation is a complex, labor-intensive multidisciplinary process. Most exclusions are due to blood type incompatibility or anatomic details. Psychosocial aspects of these donations warrant special attention.

Liver transplantation around the world.

PubMed

Trotter, James F

2017-04-01

In the past few years, there have been important changes in the development of liver transplantation around the world. In particular, several emerging countries have rapidly developed transplant programs. There have also been important changes in liver allocation, utilization of donors by cardiac death, and living donors. A review of the practices in different countries around the world will help provide the reader with a better appreciation of their own program as well as the recognition of potential areas of improvement based on the experience of their colleagues. A recent series of articles has been published in the journal Liver Transplantation summarizing the practice of liver transplantation from representative countries around the world. The volume of liver transplant varies widely by country and there has been an important growth in volume in emerging countries. Most liver transplant candidates are prioritized for surgery by the Model for Endstage Liver Disease score and with the exception of Germany and the USA most patients are transplanted at Model for Endstage Liver Disease score from 18 to 20. Hepatitis C is the most common indication for liver transplant with the notable exception of several European countries. Innovative strategies to incentivize donation have been developed in several countries.

Automatic liver volume segmentation and fibrosis classification

NASA Astrophysics Data System (ADS)

Bal, Evgeny; Klang, Eyal; Amitai, Michal; Greenspan, Hayit

2018-02-01

In this work, we present an automatic method for liver segmentation and fibrosis classification in liver computed-tomography (CT) portal phase scans. The input is a full abdomen CT scan with an unknown number of slices, and the output is a liver volume segmentation mask and a fibrosis grade. A multi-stage analysis scheme is applied to each scan, including: volume segmentation, texture features extraction and SVM based classification. Data contains portal phase CT examinations from 80 patients, taken with different scanners. Each examination has a matching Fibroscan grade. The dataset was subdivided into two groups: first group contains healthy cases and mild fibrosis, second group contains moderate fibrosis, severe fibrosis and cirrhosis. Using our automated algorithm, we achieved an average dice index of 0.93 ± 0.05 for segmentation and a sensitivity of 0.92 and specificity of 0.81for classification. To the best of our knowledge, this is a first end to end automatic framework for liver fibrosis classification; an approach that, once validated, can have a great potential value in the clinic.

Computerized tomography-based anatomic description of the porcine liver.

PubMed

Bekheit, Mohamed; Bucur, Petru O; Wartenberg, Mylene; Vibert, Eric

2017-04-01

The knowledge of the anatomic features is imperative for successful modeling of the different surgical situations. This study aims to describe the anatomic features of the porcine using computerized tomography (CT) scan. Thirty large, white, female pigs were included in this study. The CT image acquisition was performed in four-phase contrast study. Subsequently, analysis of the images was performed using syngo.via software (Siemens) to subtract mainly the hepatic artery and its branches. Analysis of the portal and hepatic veins division pattern was performed using the Myrian XP-Liver 1.14.1 software (Intrasense). The mean total liver volume was 915 ± 159 mL. The largest sector in the liver was the right medial one representing around 28 ± 5.7% of the total liver volume. Next in order is the right lateral sector constituting around 24 ± 5%. Its volume is very close to the volume of the left medial sector, which represents around 22 ± 4.7% of the total liver volume. The caudate lobe represents around 8 ± 2% of the total liver volume.The portal vein did not show distinct right and left divisions rather than consecutive branches that come off the main trunk. The hepatic artery frequently trifurcates into left trunk that gives off the right gastric artery and the artery to the left lateral sector, the middle hepatic artery that supplies both the right and the left medial sectors and the right hepatic artery trunk that divides to give anterior branch to the right lateral lobe, branch to the right medial lobe, and at least a branch to the caudate lobe. Frequently, there is a posterior branch that crosses behind the portal vein to the right lateral lobe. The suprahepatic veins join the inferior vena cava in three distinct openings. There are communications between the suprahepatic veins that drain the adjacent sectors. The vein from the right lateral and the right medial sectors drains into a common trunk. The vein from the left lateral and from the left medial sectors drains into a common trunk. A separate opening is usually encountered draining the right medial sector. The caudate lobe drains separately into inferior vena cava caudal to the other veins. Knowledge of the anatomic features of the porcine liver is crucial to the performance of a successful surgical procedure. We herein describe the CT-depicted anatomic features of the porcine liver. Copyright © 2016 Elsevier Inc. All rights reserved.

Living donor right liver lobes: preoperative CT volumetric measurement for calculation of intraoperative weight and volume.

PubMed

Lemke, Arne-Jörn; Brinkmann, Martin Julius; Schott, Thomas; Niehues, Stefan Markus; Settmacher, Utz; Neuhaus, Peter; Felix, Roland

2006-09-01

To prospectively develop equations for the calculation of expected intraoperative weight and volume of a living donor's right liver lobe by using preoperative computed tomography (CT) for volumetric measurement. After medical ethics committee and state medical board approval, informed consent was obtained from eight female and eight male living donors (age range, 18-63 years) for participation in preoperative CT volumetric measurement of the right liver lobes by using the summation-of-area method. Intraoperatively, the graft was weighed, and the volume of the graft was determined by means of water displacement. Distributions of pre- and intraoperative data were depicted as Tukey box-and-whisker diagrams. Then, linear regressions were calculated, and the results were depicted as scatterplots. On the basis of intraoperative data, physical density of the parenchyma was calculated by dividing weight by volume of the graft. Preoperative measurement of grafts resulted in a mean volume of 929 mL +/- 176 (standard deviation); intraoperative mean weight and volume of the grafts were 774 g +/- 138 and 697 mL +/- 139, respectively. All corresponding pre- and intraoperative data correlated significantly (P < .001) with each other. Intraoperatively expected volume (V(intraop)) in millilliters and weight (W(intraop)) in grams can be calculated with the equations V(intra)(op) = (0.656 . V(preop)) + 87.629 mL and W(intra)(op) = (0.678 g/mL . V(preop)) + 143.704 g, respectively, where preoperative volume is V(preop) in milliliters. Physical density of transplanted liver lobes was 1.1172 g/mL +/- 0.1015. By using two equations developed from the data obtained in this study, expected intraoperative weight and volume can properly be determined from CT volumetric measurements. (c) RSNA, 2006.

Metastases to the Liver from Neuroendocrine Tumors: Effect of Duration of Scan Acquisition on CT Perfusion Values

PubMed Central

Hobbs, Brian P.; Chandler, Adam G.; Anderson, Ella F.; Herron, Delise H.; Charnsangavej, Chusilp; Yao, James

2013-01-01

Purpose To assess the effects of acquisition duration on computed tomographic (CT) perfusion parameter values in neuroendocrine liver metastases and normal liver tissue. Materials and Methods This retrospective study was institutional review board approved, with waiver of informed consent. CT perfusion studies in 16 patients (median age, 57.5 years; range, 42.0–69.7 years), including six men (median, 54.1 years; range, 42.0–69.7), and 10 women (median, 59.3 years; range 43.6–66.3), with neuroendocrine liver metastases were analyzed by means of distributed parametric modeling to determine tissue blood flow, blood volume, mean transit time, permeability, and hepatic arterial fraction for tumors and normal liver tissue. Analyses were undertaken with acquisition time of 12–590 seconds. Nonparameteric regression analyses were used to evaluate the functional relationships between CT perfusion parameters and acquisition duration. Evidence for time invariance was evaluated for each parameter at multiple time points by inferring the fitted derivative to assess its proximity to zero as a function of acquisition time by using equivalence tests with three levels of confidence (20%, 70%, and 90%). Results CT perfusion parameter values varied, approaching stable values with increasing acquisition duration. Acquisition duration greater than 160 seconds was required to obtain at least low confidence stability in any of the CT perfusion parameters. At 160 seconds of acquisition, all five CT perfusion parameters stabilized with low confidence in tumor and normal tissues, with the exception of hepatic arterial fraction in tumors. After 220 seconds of acquisition, there was stabilization with moderate confidence for blood flow, blood volume, and hepatic arterial fraction in tumors and normal tissue, and for mean transit time in tumors; however, permeability values did not satisfy the moderate stabilization criteria in both tumors and normal tissue until 360 seconds of acquisition. Blood flow, mean transit time, permeability, and hepatic arterial fraction were significantly different between tumor and normal tissue at 360 seconds (P < .001). Conclusion CT perfusion parameter values are affected by acquisition duration and approach progressively stable values with increasing acquisition times. © RSNA, 2013 Online supplemental material is available for this article. PMID:23824990

Automated liver sampling using a gradient dual-echo Dixon-based technique.

PubMed

Bashir, Mustafa R; Dale, Brian M; Merkle, Elmar M; Boll, Daniel T

2012-05-01

Magnetic resonance spectroscopy of the liver requires input from a physicist or physician at the time of acquisition to insure proper voxel selection, while in multiecho chemical shift imaging, numerous regions of interest must be manually selected in order to ensure analysis of a representative portion of the liver parenchyma. A fully automated technique could improve workflow by selecting representative portions of the liver prior to human analysis. Complete volumes from three-dimensional gradient dual-echo acquisitions with two-point Dixon reconstruction acquired at 1.5 and 3 T were analyzed in 100 subjects, using an automated liver sampling algorithm, based on ratio pairs calculated from signal intensity image data as fat-only/water-only and log(in-phase/opposed-phase) on a voxel-by-voxel basis. Using different gridding variations of the algorithm, the average correct liver volume samples ranged from 527 to 733 mL. The average percentage of sample located within the liver ranged from 95.4 to 97.1%, whereas the average incorrect volume selected was 16.5-35.4 mL (2.9-4.6%). Average run time was 19.7-79.0 s. The algorithm consistently selected large samples of the hepatic parenchyma with small amounts of erroneous extrahepatic sampling, and run times were feasible for execution on an MRI system console during exam acquisition. Copyright © 2011 Wiley Periodicals, Inc.

Preoperative selective desensitization of live donor liver transplant recipients considering the degree of T lymphocyte cross-match titer, model for end-stage liver disease score, and graft liver volume.

PubMed

Hong, Geun; Yi, Nam-Joon; Suh, Suk-won; Yoo, Tae; Kim, Hyeyoung; Park, Min-Su; Choi, YoungRok; Lee, Kyungbun; Lee, Kwang-Woong; Park, Myoung Hee; Suh, Kyung-Suk

2014-05-01

Several studies have suggested that a positive lymphocyte cross-matching (XM) is associated with low graft survival rates and a high prevalence of acute rejection after adult living donor liver transplantations (ALDLTs) using a small-for-size graft. However, there is still no consensus on preoperative desensitization. We adopted the desensitization protocol from ABO-incompatible LDLT. We performed desensitization for the selected patients according to the degree of T lymphocyte cross-match titer, model for end-stage liver disease (MELD) score, and graft liver volume. We retrospectively evaluated 230 consecutive ALDLT recipients for 5 yr. Eleven recipients (4.8%) showed a positive XM. Among them, five patients with the high titer (> 1:16) by antihuman globulin-augmented method (T-AHG) and one with a low titer but a high MELD score of 36 were selected for desensitization: rituximab injection and plasmapheresis before the transplantation. There were no major side effects of desensitization. Four of the patients showed successful depletion of the T-AHG titer. There was no mortality and hyperacute rejection in lymphocyte XM-positive patients, showing no significant difference in survival outcome between two groups (P=1.000). In conclusion, this desensitization protocol for the selected recipients considering the degree of T lymphocyte cross-match titer, MELD score, and graft liver volume is feasible and safe.

Biomarkers of Exposure to Toxic Substances: Volume 4: Metabonomics Biomarkers to Liver and Organ Damage

DTIC Science & Technology

2009-05-01

examined the urinary metabolite profiles from rats following a single exposure to the kidney toxicants D- serine, puromycin, hippuric acid and...15. SUBJECT TERMS Amphotericin B, bioinformatics, cell cycle regulation, clinical, clustering analysis, D-serine, glomerular injury, hippuric acid ...puromycin, hippuric acid and amphotericin B at various doses, and as a function of time post-dose. In toxicology, such dose-time metabonomics studies are

Characteristics of Congenital Hepatic Fibrosis in a Large Cohort of Patients With Autosomal Recessive Polycystic Kidney Disease

PubMed Central

Gunay–Aygun, Meral; Font–Montgomery, Esperanza; Lukose, Linda; Gerstein, Maya Tuchman; Piwnica–Worms, Katie; Choyke, Peter; Daryanani, Kailash T.; Turkbey, Baris; Fischer, Roxanne; Bernardini, Isa; Sincan, Murat; Zhao, Xiongce; Sandler, Netanya G.; Roque, Annelys; Douek, Daniel C.; Graf, Jennifer; Huizing, Marjan; Bryant, Joy C.; Mohan, Parvathi; Gahl, William A.; Heller, Theo

2013-01-01

BACKGROUND & AIMS Autosomal recessive polycystic kidney disease (ARPKD), the most common ciliopathy of childhood, is characterized by congenital hepatic fibrosis and progressive cystic degeneration of kidneys. We aimed to describe congenital hepatic fibrosis in patients with ARPKD, confirmed by detection of mutations in PKHD1. METHODS Patients with ARPKD and congenital hepatic fibrosis were evaluated at the National Institutes of Health from 2003 to 2009. We analyzed clinical, molecular, and imaging data from 73 patients (age, 1–56 years; average, 12.7 ± 13.1 years) with kidney and liver involvement (based on clinical, imaging, or biopsy analyses) and mutations in PKHD1. RESULTS Initial symptoms were liver related in 26% of patients, and others presented with kidney disease. One patient underwent liver and kidney transplantation, and 10 others received kidney transplants. Four presented with cholangitis and one with variceal bleeding. Sixty-nine percent of patients had enlarged left lobes on magnetic resonance imaging, 92% had increased liver echogenicity on ultrasonography, and 65% had splenomegaly. Splenomegaly started early in life; 60% of children younger than 5 years had enlarged spleens. Spleen volume had an inverse correlation with platelet count and prothrombin time but not with serum albumin level. Platelet count was the best predictor of spleen volume (area under the curve of 0.88905), and spleen length corrected for patient’s height correlated inversely with platelet count (R2 = 0.42, P < .0001). Spleen volume did not correlate with renal function or type of PKHD1 mutation. Twenty-two of 31 patients who underwent endoscopy were found to have varices. Five had variceal bleeding, and 2 had portosystemic shunts. Forty-percent had Caroli syndrome, and 30% had an isolated dilated common bile duct. CONCLUSIONS Platelet count is the best predictor of the severity of portal hypertension, which has early onset but is underdiagnosed in patients with ARPKD. Seventy percent of patients with ARPKD have biliary abnormalities. Kidney and liver disease are independent, and variability in severity is not explainable by type of PKHD1 mutation; PMID:23041322

A new formula for estimation of standard liver volume using computed tomography-measured body thickness.

PubMed

Ma, Ka Wing; Chok, Kenneth S H; Chan, Albert C Y; Tam, Henry S C; Dai, Wing Chiu; Cheung, Tan To; Fung, James Y Y; Lo, Chung Mau

2017-09-01

The objective of this article is to derive a more accurate and easy-to-use formula for finding estimated standard liver volume (ESLV) using novel computed tomography (CT) measurement parameters. New formulas for ESLV have been emerging that aim to improve the accuracy of estimation. However, many of these formulas contain body surface area measurements and logarithms in the equations that lead to a more complicated calculation. In addition, substantial errors in ESLV using these old formulas have been shown. An improved version of the formula for ESLV is needed. This is a retrospective cohort of consecutive living donor liver transplantations from 2005 to 2016. Donors were randomly assigned to either the formula derivation or validation groups. Total liver volume (TLV) measured by CT was used as the reference for a linear regression analysis against various patient factors. The derived formula was compared with the existing formulas. There were 722 patients (197 from the derivation group, 164 from the validation group, and 361 from the recipient group) involved in the study. The donor's body weight (odds ratio [OR], 10.42; 95% confidence interval [CI], 7.25-13.60; P < 0.01) and body thickness (OR, 2.00; 95% CI, 0.36-3.65; P = 0.02) were found to be independent factors for the TLV calculation. A formula for TLV (cm 3 ) was derived: 2 × thickness (mm) + 10 × weight (kg) + 190 with R 2 0.48, which was the highest when compared with the 4 other most often cited formulas. This formula remained superior to other published formulas in the validation set analysis (R 2 , 5.37; interclass correlation coefficient, 0.74). Graft weight/ESLV values calculated by the new formula were shown to have the highest correlation with delayed graft function (C-statistic, 0.79; 95% CI, 0.69-0.90; P < 0.01). The new formula (2 × thickness + 10 × weight + 190) represents the first study proposing the use of CT-measured body thickness which is novel, easy to use, and the most accurate for ESLV. Liver Transplantation 23 1113-1122 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

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.

Application of modified dynamic conformal arc (MDCA) technique on liver stereotactic body radiation therapy (SBRT) planning following RTOG 0438 guideline

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

Shi, Chengyu, E-mail: shicy1974@yahoo.com; Chen, Yong; Fang, Deborah

2015-04-01

Liver stereotactic body radiation therapy (SBRT) is a feasible treatment method for the nonoperable, patient with early-stage liver cancer. Treatment planning for the SBRT is very important and has to consider the simulation accuracy, planning time, treatment efficiency effects etc. The modified dynamic conformal arc (MDCA) technique is a 3-dimensional conformal arc planning method, which has been proposed for liver SBRT planning at our center. In this study, we compared the MDCA technique with the RapidArc technique in terms of planning target volume (PTV) coverage and sparing of organs at risk (OARs). The results show that the MDCA technique hasmore » comparable plan quality to RapidArc considering PTV coverage, hot spots, heterogeneity index, and effective liver volume. For the 5 PTVs studied among 4 patients, the MDCA plan, when compared with the RapidArc plan, showed 9% more hot spots, more heterogeneity effect, more sparing of OARs, and lower liver effective volume. The monitor unit (MU) number for the MDCA plan is much lower than for the RapidArc plans. The MDCA plan has the advantages of less planning time, no-collision treatment, and a lower MU number.« less

Acoustically accessible window determination for ultrasound mediated treatment of glycogen storage disease type Ia patients

NASA Astrophysics Data System (ADS)

Wang, Shutao; Raju, Balasundar I.; Leyvi, Evgeniy; Weinstein, David A.; Seip, Ralf

2012-10-01

Glycogen storage disease type Ia (GSDIa) is caused by an inherited single-gene defect resulting in an impaired glycogen to glucose conversion pathway. Targeted ultrasound mediated delivery (USMD) of plasmid DNA (pDNA) to liver in conjunction with microbubbles may provide a potential treatment for GSDIa patients. As the success of USMD treatments is largely dependent on the accessibility of the targeted tissue by the focused ultrasound beam, this study presents a quantitative approach to determine the acoustically accessible liver volume in GSDIa patients. Models of focused ultrasound beam profiles for transducers of varying aperture and focal lengths were applied to abdomen models reconstructed from suitable CT and MRI images. Transducer manipulations (simulating USMD treatment procedures) were implemented via transducer translations and rotations with the intent of targeting and exposing the entire liver to ultrasound. Results indicate that acoustically accessible liver volumes can be as large as 50% of the entire liver volume for GSDIa patients and on average 3 times larger compared to a healthy adult group due to GSDIa patients' increased liver size. Detailed descriptions of the evaluation algorithm, transducer-and abdomen models are presented, together with implications for USMD treatments of GSDIa patients and transducer designs for USMD applications.

Increased size of solid organs in patients with Chuvash polycythemia and in mice with altered expression of HIF-1α and HIF-2α

PubMed Central

Yoon, Donghoon; Okhotin, David V.; Kim, Bumjun; Okhotina, Yulia; Okhotin, Daniel J.; Miasnikova, Galina Y.; Sergueeva, Adelina I.; Polyakova, Lydia A.; Maslow, Alexei; Lee, Yonggu; Semenza, Gregg L.; Prchal, Josef T.

2010-01-01

Chuvash polycythemia, the first hereditary disease associated with dysregulated oxygen-sensing to be recognized, is characterized by a homozygous germ-line loss-of-function mutation of the VHL gene (VHLR200W) resulting in elevated hypoxia inducible factor (HIF)-1α and HIF-2α levels, increased red cell mass and propensity to thrombosis. Organ volume is determined by the size and number of cells, and the underlying molecular control mechanisms are not fully elucidated. Work from several groups has demonstrated that the proliferation of cells is regulated in opposite directions by HIF-1α and HIF-2α. HIF-1α inhibits cell proliferation by displacing MYC from the promoter of the gene encoding the cyclin-dependent kinase inhibitor, p21Cip1, thereby inducing its expression. In contrast, HIF-2α promotes MYC activity and cell proliferation. Here we report that the volumes of liver, spleen, and kidneys relative to body mass were larger in 30 individuals with Chuvash polycythemia than in 30 matched Chuvash controls. In Hif1a+/− mice, which are heterozygous for a null (knockout) allele at the locus encoding HIF-1α, hepatic HIF-2α mRNA was increased (2-fold) and the mass of the liver was increased, compared with wild-type littermates, without significant difference in cell volume. Hepatic p21Cip1 mRNA levels were 9.5-fold lower in Hif1a+/− mice compared with wild-type littermates. These data suggest that, in addition to increased red cell mass, the sizes of liver, spleen, and kidneys are increased in Chuvash polycythemia. At least in the liver, this phenotype may result from increased HIF-2α and decreased p21Cip1 levels leading to increased hepatocyte proliferation. PMID:20140661

Preoperative bevacizumab and volumetric recovery after resection of colorectal liver metastases.

PubMed

Margonis, Georgios Antonios; Buettner, Stefan; Andreatos, Nikolaos; Sasaki, Kazunari; Pour, Manijeh Zargham; Deshwar, Ammar; Wang, Jane; Ghasebeh, Mounes Aliyari; Damaskos, Christos; Rezaee, Neda; Pawlik, Timothy M; Wolfgang, Christopher L; Kamel, Ihab R; Weiss, Matthew J

2017-12-01

While preoperative treatment is frequently administered to CRLM patients, the impact of chemotherapy, with or without bevacizumab, on liver regeneration remains controversial. The early and late regeneration indexes were defined as the relative increase in liver volume (RLV) within 2 and 9 months from surgery. Regeneration rates of the preoperative treatment groups were compared. Preoperative chemotherapy details and volumetric data were available for 185 patients; 78 (42.2%) received preoperative chemotherapy with bevacizumab (Bev+), 46 (24.8%) received chemotherapy only (Bev-), and 61 (33%) received no chemotherapy. Patients in the Bev+ and Bev- groups received similar chemotherapy cycles (4 [3-6] vs 4 [4-6]; P = 0.499). Despite the comparable clinicopathological characteristics and Resected Volume/Total Liver Volume (TLV) at surgery (P = 0.944) of both groups, Bev+ group had higher early and late regeneration (17.2% vs 4.3%; P = 0.035 and 14.0% vs 9.4%; P = 0.091, respectively). Of note, early and late regeneration rates (3.7% and 10.9% vs 6.6% and 5.5%, respectively) were comparable between the no chemotherapy and Bev- groups (all P > 0.05). In multivariable analysis -adjusted for gender, age, portal vein embolization, preoperative chemotherapy, resected liver volume, tumor number, postoperative chemotherapy, fibrosis, steatosis- bevacizumab independently predicted early liver regeneration (P = 0.019). Our findings suggest that preoperative bevacizumab administered along with chemotherapy was associated with enhanced volumetric restoration. Interestingly, this effect was more pronounced among patients who received oxaliplatin-based regimens and bevacizumab compared to those treated with irinotecan-based regimens and bevacizumab. © 2017 Wiley Periodicals, Inc.

Extraction of liver volumetry based on blood vessel from the portal phase CT dataset

NASA Astrophysics Data System (ADS)

Maklad, Ahmed S.; Matsuhiro, Mikio; Suzuki, Hidenobu; Kawata, Yoshiki; Niki, Noboru; Utsunomiya, Tohru; Shimada, Mitsuo

2012-02-01

At liver surgery planning stage, the liver volumetry would be essential for surgeons. Main problem at liver extraction is the wide variability of livers in shapes and sizes. Since, hepatic blood vessels structure varies from a person to another and covers liver region, the present method uses that information for extraction of liver in two stages. The first stage is to extract abdominal blood vessels in the form of hepatic and nonhepatic blood vessels. At the second stage, extracted vessels are used to control extraction of liver region automatically. Contrast enhanced CT datasets at only the portal phase of 50 cases is used. Those data include 30 abnormal livers. A reference for all cases is done through a comparison of two experts labeling results and correction of their inter-reader variability. Results of the proposed method agree with the reference at an average rate of 97.8%. Through application of different metrics mentioned at MICCAI workshop for liver segmentation, it is found that: volume overlap error is 4.4%, volume difference is 0.3%, average symmetric distance is 0.7 mm, Root mean square symmetric distance is 0.8 mm, and maximum distance is 15.8 mm. These results represent the average of overall data and show an improved accuracy compared to current liver segmentation methods. It seems to be a promising method for extraction of liver volumetry of various shapes and sizes.

Liver enzyme abnormalities in taking traditional herbal medicine in Korea: A retrospective large sample cohort study of musculoskeletal disorder patients.

PubMed

Lee, Jinho; Shin, Joon-Shik; Kim, Me-Riong; Byun, Jang-Hoon; Lee, Seung-Yeol; Shin, Ye-Sle; Kim, Hyejin; Byung Park, Ki; Shin, Byung-Cheul; Lee, Myeong Soo; Ha, In-Hyuk

2015-07-01

The objective of this study is to report the incidence of liver injury from herbal medicine in musculoskeletal disease patients as large-scale studies are scarce. Considering that herbal medicine is frequently used in patients irrespective of liver function in Korea, we investigated the prevalence of liver injury by liver function test results in musculoskeletal disease patients. Of 32675 inpatients taking herbal medicine at 7 locations of a Korean medicine hospital between 2005 and 2013, we screened for liver injury in 6894 patients with liver function tests (LFTs) at admission and discharge. LFTs included t-bilirubin, AST, ALT, and ALP. Liver injury at discharge was assessed by LFT result classifications at admission (liver injury, liver function abnormality, and normal liver function). In analyses for risk factors of liver injury at discharge, we adjusted for age, sex, length of stay, conventional medicine intake, HBs antigen/antibody, and liver function at admission. A total 354 patients (prevalence 5.1%) had liver injury at admission, and 217 (3.1%) at discharge. Of the 354 patients with liver injury at admission, only 9 showed a clinically significant increase after herbal medicine intake, and 225 returned to within normal range or showed significant liver function recovery. Out of 4769 patients with normal liver function at admission, 27 (0.6%) had liver injury at discharge. In multivariate analyses for risk factors, younger age, liver function abnormality at admission, and HBs antigen positive were associated with injury at discharge. The prevalence of liver injury in patients with normal liver function taking herbal medicine for musculoskeletal disease was low, and herbal medicine did not exacerbate liver injury in most patients with injury prior to intake. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Fibrosis in nonalcoholic fatty liver disease: Noninvasive assessment using computed tomography volumetry.

PubMed

Fujita, Nobuhiro; Nishie, Akihiro; Asayama, Yoshiki; Ishigami, Kousei; Ushijima, Yasuhiro; Takayama, Yukihisa; Okamoto, Daisuke; Shirabe, Ken; Yoshizumi, Tomoharu; Kotoh, Kazuhiro; Furusyo, Norihiro; Hida, Tomoyuki; Oda, Yoshinao; Fujioka, Taisuke; Honda, Hiroshi

2016-10-28

To evaluate the diagnostic performance of computed tomography (CT) volumetry for discriminating the fibrosis stage in patients with nonalcoholic fatty liver disease (NAFLD). A total of 38 NAFLD patients were enrolled. On the basis of CT imaging, the volumes of total, left lateral segment (LLS), left medial segment, caudate lobe, and right lobe (RL) of the liver were calculated with a dedicated liver application. The relationship between the volume percentage of each area and fibrosis stage was analyzed using Spearman's rank correlation coefficient. A receiver operating characteristic (ROC) curve analysis was performed to determine the accuracy of CT volumetry for discriminating fibrosis stage. The volume percentages of the caudate lobe and the LLS significantly increased with the fibrosis stage ( r = 0.815, P < 0.001; and r = 0.465, P = 0.003, respectively). Contrarily, the volume percentage of the RL significantly decreased with fibrosis stage ( r = -0.563, P < 0.001). The volume percentage of the caudate lobe had the best diagnostic accuracy for staging fibrosis, and the area under the ROC curve values for discriminating fibrosis stage were as follows: ≥ F1, 0.896; ≥ F2, 0.929; ≥ F3, 0.955; and ≥ F4, 0.923. The best cut-off for advanced fibrosis (F3-F4) was 4.789%, 85.7% sensitivity and 94.1% specificity. The volume percentage of the caudate lobe calculated by CT volumetry is a useful diagnostic parameter for staging fibrosis in NAFLD patients.

Dynamic morphological examination and evaluation of biological characteristics of a multinodular liver cancer model in mice.

PubMed

Li, Yan-Ru; Wang, Jin-Rui; Zhang, Hai-Ying; Wu, Xiao-Fei; Li, Sheng-Nan; Wang, Lin; Wang, Xue-Yao

2014-04-01

Compared with single nodular liver cancer, the prominent biological characteristics of multinodular liver cancer include rapid progression and short survival. Here, we developed a multinodular liver cancer model in mice and assessed the biological characteristics of the resulting neoplasms. H22 hepatoma cells at a dose of 2 × 10(5)/mouse, suspended in 1.6 mL, 0.8 mL, or 200 µL saline were injected via the tail vein of BALB/c mice at a velocity of 200 µL per second. The mice were sacrificed at different time points after injection. And at the time of death the liver, lungs, spleen, kidneys and heart were removed for morphological study. The biological characteristics of the tumor nodules were evaluated by immunohistochemistry. In the mice treated with a large volume injection of H22 cells, by day 7, there was a 100% occurrence of multinodular tumors in the livers, determined by histology. At the time of death, there were 100%, 100%, 37.5% and 37.5% occurrences of tumors in the lungs, kidneys, spleen and heart, respectively. The neoplastic cells in the liver nodules showed pleomorphism, and exhibited high expression of proliferating cell nuclear antigen (PCNA), c-myc, vascular endothelial growth factor (VEGF) and matrix metalloproteinase 2 (MMP-2). In mice treated with a small or medium volume injection, no tumor cells were identified in the livers, spleen, kidneys or heart at any of the examined time points. By day 7 and at the time of death, there was a 100% occurrence of tumor in the lungs. A multinodular liver cancer model in mice was achieved using a large volume injection of H22 cells.

Parenchymal-sparing hepatectomy for deep-placed colorectal liver metastases.

PubMed

Matsuki, Ryota; Mise, Yoshihiro; Saiura, Akio; Inoue, Yosuke; Ishizawa, Takeaki; Takahashi, Yu

2016-11-01

The feasibility of parenchymal-sparing hepatectomy has yet to be assessed based on the tumor location, which affects the choice of treatment in patients with colorectal liver metastases. Sixty-three patients underwent first curative hepatectomy for deep-placed colorectal liver metastases whose center was located >30 mm from the liver surface. Operative outcomes were compared among patients who underwent parenchymal-sparing hepatectomy or major hepatectomy (≥3 segments). Parenchymal-sparing hepatectomy and major hepatectomy were performed for deep-placed colorectal liver metastases in 40 (63%) and 23 (37%) patients, respectively. Resection time was longer in the parenchymal-sparing hepatectomy than in the major hepatectomy group (57 vs 39 minutes) (P = .02) and cut-surface area was wider (120 vs 86 cm 2 ) (P < .01). Resected volume was smaller in the parenchymal-sparing hepatectomy than in the major hepatectomy group (251 vs 560 g) (P < .01). No differences were found between the 2 groups for total operation time (306 vs 328 minutes), amount of blood loss (516 vs 400 mL), rate of major complications (10% vs 13%), and positive operative margins (5% vs 4%). Overall, recurrence-free, and liver recurrence-free survivals did not differ between the 2 groups. Direct major hepatectomy without portal venous embolization could not have been performed in 40% of the parenchymal-sparing hepatectomy group (16/40) because of the small liver remnant volume. Parenchymal-sparing hepatectomy for deep-placed colorectal liver metastases was performed safely without compromising oncologic radicality. Parenchymal-sparing hepatectomy can increase the number of patients eligible for an operation by halving the resection volume and by increasing the chance of direct operative treatment in patients with ill-located colorectal liver metastases. Copyright © 2016 Elsevier Inc. All rights reserved.

Evidence against functionally significant aquaporin expression in mitochondria.

PubMed

Yang, Baoxue; Zhao, Dan; Verkman, A S

2006-06-16

Recent reports suggest the expression of aquaporin (AQP)-type water channels in mitochondria from liver (AQP8) (Calamita, G., Ferri, D., Gena, P., Liquori, G. E., Cavalier, A., Thomas, D., and Svelto, M. (2005) J. Biol. Chem. 280, 17149-17153) and brain (AQP9) (Amiry-Moghaddam, M., Lindland, H., Zelenin, S., Roberg, B. A., Gundersen, B. B., Petersen, P., Rinvik, E., Torgner, I. A., and Ottersen, O. P. (2005) FASEB J. 19, 1459-1467), where they were speculated to be involved in metabolism, apoptosis, and Parkinson disease. Here, we systematically examined the functional consequence of AQP expression in mitochondria by measurement of water and glycerol permeabilities in mitochondrial membrane preparations from rat brain, liver, and kidney and from wild-type versus knock-out mice deficient in AQPs -1, -4, or -8. Osmotic water permeability, measured by stopped-flow light scattering, was similar in all mitochondrial preparations, with a permeability coefficient P(f) approximately 0.009 cm/s. Glycerol permeability was also similar ( approximately 5 x 10(-6) cm/s) in the various preparations. HgCl(2) slowed osmotic equilibration comparably in mitochondria from wild-type and AQP-deficient mice, although the slowing was explained by altered mitochondrial size rather than reduced P(f). Immunoblot analysis of mouse liver mitochondria failed to detect AQP8 expression, with liver homogenates from wild-type/AQP8 null mice as positive/negative controls. Our results provide evidence against functionally significant AQP expression in mitochondria, which is consistent with the high mitochondrial surface-to-volume ratio producing millisecond osmotic equilibration, even when intrinsic membrane water permeability is not high.

Hepatic (Liver) Function Panel

MedlinePlus

... Educators Search English Español Blood Test: Hepatic (Liver) Function Panel KidsHealth / For Parents / Blood Test: Hepatic (Liver) ... kidneys ) is working. What Is a Hepatic (Liver) Function Panel? A liver function panel is a blood ...

Dynamic changes of portal vein pressure gradient under different degrees of liver cirrhosis and resection volume in the first week post hepatectomy.

PubMed

Lan, Xiang; Zhang, Hua; Li, Hongyu; Chen, Kefei; Liu, Fei; Wei, Yonggang; Li, Bo

2018-05-31

We set out to acquire original pathophysiologic data of dynamic changes in portal vein pressure gradient (PVPG) following liver resection (LR) during post-operation days (POD) 1-7. Portal vein pressure gradient was measured in 31 patients daily until POD 7 at our liver surgery center. Patients were divided into non-, mild, moderate, and severe cirrhosis groups according to histopathology and were also divided into subgroups according to the volume of hepatectomy. Portal vein pressure gradient reached its peak on POD 3 in mild cirrhosis (F = 7.525, P < 0.001), moderate cirrhosis (F = 11.200, P < 0.001), and severe cirrhosis groups (F = 26.634, P < 0.001). There were no significant changes in PVPG in the non-cirrhosis group (F = 1.050, P = 0.411). Moreover, PVPG on POD 3 was higher with increasing severity of cirrhosis under the same interval of LR volume (resection volume <200 cm 3 : F = 13.040, P = 0.004; ≥200 cm 3 but <400 cm 3 : F = 13.243, P = 0.004; ≥400 cm 3 : F = 43.685, P < 0.001). Finally, the LR volume had significant impact on PVPG for patients with moderate cirrhosis (F = 6.339, P = 0.033) and severe cirrhosis (t = -7.000, P = 0.020). A similar tendency was also observed when patients were divided according to the ratio of the resected liver volume to total liver volume. The increase in PVPG following LR was positively associated with the degree of cirrhosis, significantly peaking on POD 3. The LR volume only had a significant impact on PVPG for patients with moderate and severe cirrhosis. This represents the first time, to our knowledge, that dynamic changes of PVPG after LR were measured and compared to cirrhosis and resection volume. © 2018 The Japan Society of Hepatology.

Plasma disappearance of exogenous erythropoietin in mice under different experimental conditions.

PubMed

Lezón, C E; Martínez, M P; Conti, M I; Bozzini, C E

1998-06-01

Erythropoietin (EPO) is a glycoprotein hormone produced primarily in the kidneys and to a lesser extent in the liver that regulates red cell production. Most of the studies conducted in experimental animals to assess the role of EPO in the regulation of erythropoiesis were performed in mouse models. However, little is known about the in vivo metabolism of the hormone in this species. The present study was thus undertaken to measure the plasma tl/2 of radiolabeled recombinant human EPO (rh-EPO) in normal mice as well as in mice with altered erythrocyte production rates (EPR), plasma EPO (pEPO) titer, marrow responsiveness, red cell volume, or liver function. Adult CF-1 mice of both sexes were used throughout. For the EPO life-span studies, 30 mice in each experiment were intravenously injected with 600,000 cpm of 125l-rh-EPO and bled by cardiac puncture in groups of five every hour for 6 h. Trichloroacetic acid (TCA) was added to each plasma sample and the radioactivity in the precipitate measured in a gamma-counter. EPO, pEPO, marrow responsiveness, or red cell volume were altered by either injections of rh-EPO, 5-fluorouracil, or phenylhydrazine, or by bleeding, or red cell transfusion. Liver function was altered by CI4C administration. In the normal groups of mice, the estimated tl/2 was 182.75+/-14.4 (SEM) min. The estimated tl/2 of the other experimental groups was not significantly different from normal. These results, therefore, strongly suggest that the clearance rate of EPO in mice is not subjected to physiologic regulation and that pEPO titer can be really taken as the reflection of the EPO production rate, at least in the experimental conditions reported here.

Accurate method for preoperative estimation of the right graft volume in adult-to-adult living donor liver transplantation.

PubMed

Khalaf, H; Shoukri, M; Al-Kadhi, Y; Neimatallah, M; Al-Sebayel, M

2007-06-01

Accurate estimation of graft volume is crucial to avoid small-for-size syndrome following adult-to-adult living donor liver transplantation AALDLT). Herein, we combined radiological and mathematical approaches for preoperative assessment of right graft volume. The right graft volume was preoperatively estimated in 31 live donors using two methods: first, the radiological graft volume (RGV) by computed tomography (CT) volumetry and second, a calculated graft volume (CGV) obtained by multiplying the standard liver volume by the percentage of the right graft volume (given by CT). Both methods were compared to the actual graft volume (AGV) measured during surgery. The graft recipient weight ratio (GRWR) was also calculated using all three volumes (RGV, CGV, and AGV). Lin's concordance correlation coefficient (CCC) was used to assess the agreement between AGV and both RGV and CGV. This was repeated using the GRWR measurements. The mean percentage of right graft volume was 62.4% (range, 55%-68%; SD +/- 3.27%). The CCC between AGV and RGV versus CGV was 0.38 and 0.66, respectively. The CCC between GRWR using AGV and RGV versus CGV was 0.63 and 0.88, respectively (P < .05). According to the Landis and Kock benchmark, the CGV correlated better with AGV when compared to RGV. The better correlation became even more apparent when applied to GRWR. In our experience, CGV showed a better correlation with AGV compared with the RGV. Using CGV in conjunction with RGV may be of value for a more accurate estimation of right graft volume for AALDLT.

Durability of small-for-size living donor allografts.

PubMed

Au, Kin Pan; Chan, See Ching; Chok, Kenneth Siu Ho; Chan, Albert Chi Yan; Wong, Tiffany Cho Lam; Sharr, William Wei; Lo, Chung Mau

2015-11-01

Our aim was to study the long-term outcomes of living donor liver transplantation using small-for-size (SFS) grafts. From July 2002 to July 2009, 233 patients received a right liver graft with a middle hepatic vein from a living donor in our center. Recipients were stratified according to the graft weight to recipient standard liver volume (GW/SLV) ratio into 4 groups: >50% (n = 89), >40% to 50% (n = 85), >35% to 40% (n = 38), and ≤ 35% (n = 21). They were compared in terms of graft survivals, biliary stricture rates, renal function in terms of estimated glomerular filtration rate (eGFR), platelet counts, and graft function in terms of serum bilirubin and international normalized ratio (INR). The 5-year graft survivals for patients with GW/SLV of >50%, >40% to 50%, >35% to 40% and ≤ 35% were 88.8%, 88.2%, 81.5%, and 81.0%, respectively. Transplantation for hepatocellular carcinoma affected graft survivals (P = 0.02), but graft size did not (P = 0.66). There were no differences in frequency of biliary stricture (21.3% versus 17.1% versus 21.1% versus 28.6%; P = 0.75). At each year after transplant, their platelet counts (P = 0.12-0.65), eGFR (P = 0.49-0.91), bilirubin (P = 0.14-0.51), and INR (P = 0.20-0.98) remained comparable. SFS grafts with GW/SLV ≤ 35% and >35% to 40% had comparable long-term outcomes with larger liver grafts. Graft size did not affect long-term graft survivals. © 2015 American Association for the Study of Liver Diseases.

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.

Preoperative estimation of the liver graft weight in adult right lobe living donor liver transplantation using maximal portal vein diameters.

PubMed

Wang, Frank; Pan, Kuang-Tse; Chu, Sung-Yu; Chan, Kun-Ming; Chou, Hong-Shiue; Wu, Ting-Jung; Lee, Wei-Chen

2011-04-01

An accurate preoperative estimate of the graft weight is vital to avoid small-for-size syndrome in the recipient and ensure donor safety after adult living donor liver transplantation (LDLT). Here we describe a simple method for estimating the graft volume (GV) that uses the maximal right portal vein diameter (RPVD) and the maximal left portal vein diameter (LPVD). Between June 2004 and December 2009, 175 consecutive donors undergoing right hepatectomy for LDLT were retrospectively reviewed. The GV was determined with 3 estimation methods: (1) the radiological graft volume (RGV) estimated by computed tomography (CT) volumetry; (2) the computed tomography-calculated graft volume (CGV-CT), which was obtained by the multiplication of the standard liver volume (SLV) by the RGV percentage with respect to the total liver volume derived from CT; and (3) the portal vein diameter ratio-calculated graft volume (CGV-PVDR), which was obtained by the multiplication of the SLV by the portal vein diameter ratio [PVDR; ie, PVDR = RPVD(2) /(RPVD(2) + LPVD(2) )]. These values were compared to the actual graft weight (AGW), which was measured intraoperatively. The mean AGW was 633.63 ± 107.51 g, whereas the mean RGV, CGV-CT, and CGV-PVDR values were 747.83 ± 138.59, 698.21 ± 94.81, and 685.20 ± 90.88 cm(3) , respectively. All 3 estimation methods tended to overestimate the AGW (P < 0.001). The actual graft-to-recipient body weight ratio (GRWR) was 1.00% ± 0.19%, and the GRWRs calculated on the basis of the RGV, CGV-CT, and CGV-PVDR values were 1.19% ± 0.25%, 1.11% ± 0.22%, and 1.09% ± 0.21%, respectively. Overall, the CGV-PVDR values better correlated with the AGW and GRWR values according to Lin's concordance correlation coefficient and the Landis and Kock benchmark. In conclusion, the PVDR method is a simple estimation method that accurately predicts GVs and GRWRs in adult LDLT. Copyright © 2011 American Association for the Study of Liver Diseases.

Liver Hypertrophy After Percutaneous Portal Vein Embolization: Comparison of N-Butyl-2-Cyanocrylate Versus Sodium Acrylate-Vinyl Alcohol Copolymer Particles in a Swine Model

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

Tsoumakidou, Georgia, E-mail: gtsoumakidou@yahoo.com; Theocharis, Stamatis, E-mail: theocharis@ath.forthnet.gr; Ptohis, Nikolaos, E-mail: nikptohis@yahoo.gr

2011-10-15

Purpose: Percutaneous portal vein embolization (PPVE) induces hypertrophy of the future liver remnant before hepatic resection. The ideal embolic material has not yet been determined. We compared N-butyl-2-cyanocrylate (NBCA) with sodium acrylate-vinyl alcohol copolymer particles using a swine model. Materials and Methods: Twelve pigs underwent PPVE. Six pigs (group A) were embolized with NBCA, and 6 pigs (group B) were embolized with sodium acrylate-vinyl alcohol copolymer particles. Computed tomographic volumetry of the embolized lobe (EL) and the nonembolized lobe (NEL), along with liver function tests, was performed before and at 14 and 28 days after embolization. Tissue samples from bothmore » lobes were taken 14 and 28 days after PPVE. Results: NEL-volume and NEL-ratio increases were significantly higher in group A at 14 and 28 days after PPVE (78 and 52% and 91 and 66%, respectively) than in group B (32 and 12% and 28 and 10%, respectively) (p < 0.05). Percent change of the EL-volume was significantly higher for group A at 28 days after PPVE. No statistically significant difference was found between the groups regarding hepatocyte proliferation on the NEL and apoptosis on the EL at both time intervals. Conclusion: PPVE using NBCA is more efficient and causes more NEL hypertrophy than microspheres.« less

MR-guided noninvasive thermal coagulation of in-vivo liver tissue using ultrasonic phased array

NASA Astrophysics Data System (ADS)

Daum, Douglas R.; Smith, Nadine; McDannold, Nathan; Hynynen, Kullervo H.

1999-05-01

Magnetic resonance (MR) imaging was used to guide and monitor the thermal tissue coagulation of in vivo porcine tissue using a 256 element ultrasonic phased array. The array could coagulate tissue volumes greater than 2 cm3 in liver and 0.5 cm3 in kidney using a single 20 second sonication. This sonication used multiple focus fields which were temporally cycled to heat large tissue volumes simultaneously. Estimates of the coagulated tissue using a thermal dose threshold compare well with T2-weighted images of post sonication lesions. The overlapping large focal volumes could aid in the treatment of large tumor volumes which require multiple overlapping sonications. The ability of MR to detect the presence and undesirable thermal increases at acoustic obstacle such as cartilaginous and bony ribs is demonstrated. This could have a significant impact on the ability to monitor thermal treatments of the liver and other organs which are acoustically blocked.

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.

Dynamic-thresholding level set: a novel computer-aided volumetry method for liver tumors in hepatic CT images

NASA Astrophysics Data System (ADS)

Cai, Wenli; Yoshida, Hiroyuki; Harris, Gordon J.

2007-03-01

Measurement of the volume of focal liver tumors, called liver tumor volumetry, is indispensable for assessing the growth of tumors and for monitoring the response of tumors to oncology treatments. Traditional edge models, such as the maximum gradient and zero-crossing methods, often fail to detect the accurate boundary of a fuzzy object such as a liver tumor. As a result, the computerized volumetry based on these edge models tends to differ from manual segmentation results performed by physicians. In this study, we developed a novel computerized volumetry method for fuzzy objects, called dynamic-thresholding level set (DT level set). An optimal threshold value computed from a histogram tends to shift, relative to the theoretical threshold value obtained from a normal distribution model, toward a smaller region in the histogram. We thus designed a mobile shell structure, called a propagating shell, which is a thick region encompassing the level set front. The optimal threshold calculated from the histogram of the shell drives the level set front toward the boundary of a liver tumor. When the volume ratio between the object and the background in the shell approaches one, the optimal threshold value best fits the theoretical threshold value and the shell stops propagating. Application of the DT level set to 26 hepatic CT cases with 63 biopsy-confirmed hepatocellular carcinomas (HCCs) and metastases showed that the computer measured volumes were highly correlated with those of tumors measured manually by physicians. Our preliminary results showed that DT level set was effective and accurate in estimating the volumes of liver tumors detected in hepatic CT images.

Multidisciplinary care of obese children and adolescents for one year reduces ectopic fat content in liver and skeletal muscle.

PubMed

Fonvig, Cilius Esmann; Chabanova, Elizaveta; Ohrt, Johanne Dam; Nielsen, Louise Aas; Pedersen, Oluf; Hansen, Torben; Thomsen, Henrik S; Holm, Jens-Christian

2015-12-30

Ectopic fat deposition in liver and skeletal muscle tissue is related to cardiovascular disease risk and is a common metabolic complication in obese children. We evaluated the hypotheses of ectopic fat in these organs could be diminished following 1 year of multidisciplinary care specialized in childhood obesity, and whether this reduction would associate with changes in other markers of metabolic function. This observational longitudinal study evaluated 40 overweight children and adolescents enrolled in a multidisciplinary treatment protocol at the Children's Obesity Clinic, Holbæk, Denmark. The participants were assessed by anthropometry, fasting blood samples (HbA1c, glucose, insulin, lipids, and biochemical variables of liver function), and liver and muscle fat content assessed by magnetic resonance spectroscopy at enrollment and following an average of 12.2 months of care. Univariate linear regression models adjusted for age, sex, treatment duration, baseline degree of obesity, and pubertal developmental stage were used for investigating possible associations. The standard deviation score (SDS) of baseline median body mass index (BMI) was 2.80 (range: 1.49-3.85) and the median age was 14 years (10-17). At the end of the observational period, the 40 children and adolescents (21 girls) significantly decreased their BMI SDS, liver fat, muscle fat, and visceral adipose tissue volume. The prevalence of hepatic steatosis changed from 28 to 20 % (p = 0.26) and the prevalence of muscular steatosis decreased from 75 to 45 % (p = 0.007). Changes in liver and muscle fat were independent of changes in BMI SDS, baseline degree of obesity, duration of treatment, age, sex, and pubertal developmental stage. A 1-year multidisciplinary intervention program in the setting of a childhood obesity outpatient clinic confers a biologically important reduction in liver and muscle fat; metabolic improvements that are independent of the magnitude of concurrent weight loss. ClinicalTrials.gov registration number: NCT00928473 , the Danish Childhood Obesity Biobank. Registered June 25, 2009.

A New Fluidized Bed Bioreactor Based on Diversion-Type Microcapsule Suspension for Bioartificial Liver Systems

PubMed Central

Li, Jianzhou; Yu, Liang; Chen, Ermei; Zhu, Danhua; Zhang, Yimin; Li, LanJuan

2016-01-01

A fluidized bed bioreactor containing encapsulated hepatocytes may be a valuable alternative to a hollow fiber bioreactor for achieving the improved mass transfer and scale-up potential necessary for clinical use. However, a conventional fluidized bed bioreactor (FBB) operating under high perfusion velocity is incapable of providing the desired performance due to the resulting damage to cell-containing microcapsules and large void volume. In this study, we developed a novel diversion-type microcapsule-suspension fluidized bed bioreactor (DMFBB). The void volume in the bioreactor and stability of alginate/chitosan microcapsules were investigated under different flow rates. Cell viability, synthesis and metabolism functions, and expression of metabolizing enzymes at transcriptional levels in an encapsulated hepatocyte line (C3A cells) were determined. The void volume was significantly less in the novel bioreactor than in the conventional FBB. In addition, the microcapsules were less damaged in the DMFBB during the fluidization process as reflected by the results for microcapsule retention rates, swelling, and breakage. Encapsulated C3A cells exhibited greater viability and CYP1A2 and CYP3A4 activity in the DMFBB than in the FBB, although the increases in albumin and urea synthesis were less prominent. The transcription levels of several CYP450-related genes and an albumin-related gene were dramatically greater in cells in the DMFBB than in those in the FBB. Taken together, our results suggest that the DMFBB is a promising alternative for the design of a bioartificial liver system based on a fluidized bed bioreactor with encapsulated hepatocytes for treating patients with acute hepatic failure or other severe liver diseases. PMID:26840840

Ethanol elimination rates in men and women in consideration of the calculated liver weight.

PubMed

Dettling, Andrea; Fischer, Florian; Böhler, Svenja; Ulrichs, Fee; Skopp, Gisela; Graw, Matthias; Haffner, Hans-Thomas

2007-09-01

The purpose of the study was to examine gender differences on the pharmacokinetics of ethanol. Sixty-eight healthy men and 64 healthy women with normal body mass indexes received between 0.79 and 0.95 g ethanol/kg body weight in the form of their choice after they had eaten a "typical" breakfast. The aimed concentration for both genders was a blood alcohol concentration C(0) of 0.104 g/dl. Blood samples in the elimination phase were taken in 10- to 20-min intervals beginning after completion of absorption. The maximum blood ethanol concentration was 0.0819+/-0.0184 g/dl for women and 0.0841+/-0.0155 g/dl for men. The hourly ethanol elimination rate, calculated over a linear function, in blood of 0.0179+/-0.0030 g/dl/h in women was significantly higher than the 0.0159+/-0.0029 g/dl/h for men (P<.0001). In relation to the liver weight, the hourly elimination rates were 5.008+/-0.678 g/kg liver/h for women and 4.854+/-0.659 g/kg liver/h for men, and were not statistically significant. The different liver masses as calculated in relation to the distribution volume account for the differing ethanol elimination rates between men and women.

The error analysis of Lobular and segmental division of right liver by volume measurement.

PubMed

Zhang, Jianfei; Lin, Weigang; Chi, Yanyan; Zheng, Nan; Xu, Qiang; Zhang, Guowei; Yu, Shengbo; Li, Chan; Wang, Bin; Sui, Hongjin

2017-07-01

The aim of this study is to explore the inconsistencies between right liver volume as measured by imaging and the actual anatomical appearance of the right lobe. Five healthy donated livers were studied. The liver slices were obtained with hepatic segments multicolor-infused through the portal vein. In the slices, the lobes were divided by two methods: radiological landmarks and real anatomical boundaries. The areas of the right anterior lobe (RAL) and right posterior lobe (RPL) on each slice were measured using Photoshop CS5 and AutoCAD, and the volumes of the two lobes were calculated. There was no statistically significant difference between the volumes of the RAL or RPL as measured by the radiological landmarks (RL) and anatomical boundaries (AB) methods. However, the curves of the square error value of the RAL and RPL measured using CT showed that the three lowest points were at the cranial, intermediate, and caudal levels. The U- or V-shaped curves of the square error rate of the RAL and RPL revealed that the lowest value is at the intermediate level and the highest at the cranial and caudal levels. On CT images, less accurate landmarks were used to divide the RAL and RPL at the cranial and caudal layers. The measured volumes of hepatic segments VIII and VI would be less than their true values, and the measured volumes of hepatic segments VII and V would be greater than their true values, according to radiological landmarks. Clin. Anat. 30:585-590, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

The in vivo performance of a novel thermal accelerant agent used for augmentation of microwave energy delivery within biologic tissues during image-guided thermal ablation: a porcine study.

PubMed

Park, William Keun Chan; Maxwell, Aaron Wilhelm Palmer; Frank, Victoria Elizabeth; Primmer, Michael Patrick; Paul, Jarod Brian; Collins, Scott Andrew; Lombardo, Kara Anne; Lu, Shaolei; Borjeson, Tiffany Marie; Baird, Grayson Luderman; Dupuy, Damian Edward

2018-02-01

To investigate the effects of a novel caesium-based thermal accelerant (TA) agent on ablation zone volumes following in vivo microwave ablation of porcine liver and skeletal muscle, and to correlate the effects of TA with target organ perfusion. This prospective study was performed following institutional animal care and use committee approval. Microwave ablation was performed in liver and resting skeletal muscle in eight Sus scrofa domesticus swine following administration of TA at concentrations of 0 mg/mL (control), 100 mg/mL and 250 mg/mL. Treated tissues were explanted and stained with triphenyltetrazolium chloride (TTC) for quantification of ablation zone volumes, which were compared between TA and control conditions. Hematoxylin and eosin (H&E) staining was also performed for histologic analysis. General mixed modelling with a log-normal distribution was used for all quantitative comparisons (p = 0.05). A total of 28 ablations were performed in the liver and 18 in the skeletal muscle. The use of TA significantly increased ablation zone volumes in a dose-dependent manner in both the porcine muscle and liver (p < 0.01). Both the absolute mean ablation zone volume and percentage increase in ablation zone volume were greater in the resting skeletal muscle than in the liver. In one swine, a qualitative mitigation of heat sink effects was observed by TTC and H&E staining. Non-lethal polymorphic ventricular tachycardia was identified in one swine, treated with intravenous amiodarone. The use of a novel TA agent significantly increased mean ablation zone volumes following microwave ablation using a porcine model. The relationship between TA administration and ablation size was dose-dependent and inversely proportional to the degree of target organ perfusion, and a qualitative reduction in heat-sink effects was observed.

Effects of Bariatric Surgery on Non-alcoholic Fatty Liver Disease: Magnetic Resonance Imaging Is an Effective, Non-invasive Method to Evaluate Changes in the Liver Fat Fraction.

PubMed

Hedderich, Dennis M; Hasenberg, Till; Haneder, Stefan; Schoenberg, Stefan O; Kücükoglu, Özlem; Canbay, Ali; Otto, Mirko

2017-07-01

Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disease worldwide and is highly associated with obesity. The prevalences of both conditions have markedly increased in the Western civilization. Bariatric surgery is the most effective treatment for morbid obesity and its comorbidities such as NAFLD. Measure postoperative liver fat fraction (LFF) in bariatric patients by using in-opposed-phase MRI, a widely available clinical tool validated for the quantification of liver fat METHODS: Retrospective analyses of participants, who underwent laparoscopic Roux-Y-gastric-bypass (17) or laparoscopic sleeve gastrectomy (2) were performed using magnetic resonance imaging (MRI), bioelectrical impedance analysis (BIA), and anthropometric measurements 1 day before surgery, as well as 6, 12, and 24 weeks after surgery, LFF was calculated from fat-only and water-only MR images. Six months after surgery, a significant decrease of LFF and liver volume has been observed along with weight loss, decreased waist circumference, and parameters obtained by body fat measured by BIA. LFF significantly correlated with liver volume in the postoperative course. MRI including in-opposed-phase imaging of the liver can detect the quantitative decrease of fatty infiltration within the liver after bariatric surgery and thus could be a valuable tool to monitor NAFLD/NASH postoperatively.

Analysis of the efficacy of portal vein embolization for patients with extensive liver malignancy and very low future liver remnant volume, including a comparison with the associating liver partition with portal vein ligation for staged hepatectomy approach.

PubMed

Shindoh, Junichi; Vauthey, Jean-Nicolas; Zimmitti, Giuzeppe; Curley, Steven A; Huang, Steven Y; Mahvash, Armeen; Gupta, Sanjay; Wallace, Michael J; Aloia, Thomas A

2013-07-01

The primary reported indication for the associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) technique is in patients with very low future liver remnant volumes. Given the elevated incidence of major morbidity (40%) and liver-related mortality (12%) with ALPPS, we sought to determine the safety and efficacy of percutaneous portal vein embolization (PVE) in a similar patient population. Tumor resectability and morbidity and mortality rates were reviewed for 144 consecutive liver tumor patients with future liver remnant to body weight ratios (LR/BW) less than 0.5%. All patients were referred for preoperative percutaneous right plus segment IV PVE using embolic microspheres, with planned reassessment of the LR/BW 30 days after PVE. Post-PVE outcomes were compared with reported outcomes for ALPPS. Percutaneous PVE was successfully performed in 141 of the 144 study patients (97.9%). Adequate regeneration was observed in 139 patients (98.5%) with median post-PVE LR/BW rising from 0.33% to 0.52% (p < 0.0001), representing a per-patient median regeneration rate of 62% (range 0.3% to 379%). In total, 104 patients underwent extended right hepatectomy (n = 102) or right hepatectomy (n = 2). The remaining 40 patients (27.8%) were not resectable due to short-interval disease progression (27 patients, 18.5%), insufficient liver regeneration (5 patients, 3.5%), and medical comorbidities (8 patients, 5.6%). After resection, the following outcomes were observed: major morbidity: 33.0% (34 of 104), liver insufficiency: 12.5% (13 of 104), and 90-day liver-related mortality: 5.8% (6 of 104). These oncologic and technical results compare favorably with those of ALPPS. Based on its ability to select oncologically resectable patients and superior safety and efficacy profiles, percutaneous right + segment IV PVE and interval surgery remains the standard of care for patients with very low future liver remnant volumes. Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Automatic liver segmentation from abdominal CT volumes using graph cuts and border marching.

PubMed

Liao, Miao; Zhao, Yu-Qian; Liu, Xi-Yao; Zeng, Ye-Zhan; Zou, Bei-Ji; Wang, Xiao-Fang; Shih, Frank Y

2017-05-01

Identifying liver regions from abdominal computed tomography (CT) volumes is an important task for computer-aided liver disease diagnosis and surgical planning. This paper presents a fully automatic method for liver segmentation from CT volumes based on graph cuts and border marching. An initial slice is segmented by density peak clustering. Based on pixel- and patch-wise features, an intensity model and a PCA-based regional appearance model are developed to enhance the contrast between liver and background. Then, these models as well as the location constraint estimated iteratively are integrated into graph cuts in order to segment the liver in each slice automatically. Finally, a vessel compensation method based on the border marching is used to increase the segmentation accuracy. Experiments are conducted on a clinical data set we created and also on the MICCAI2007 Grand Challenge liver data. The results show that the proposed intensity, appearance models, and the location constraint are significantly effective for liver recognition, and the undersegmented vessels can be compensated by the border marching based method. The segmentation performances in terms of VOE, RVD, ASD, RMSD, and MSD as well as the average running time achieved by our method on the SLIVER07 public database are 5.8 ± 3.2%, -0.1 ± 4.1%, 1.0 ± 0.5mm, 2.0 ± 1.2mm, 21.2 ± 9.3mm, and 4.7 minutes, respectively, which are superior to those of existing methods. The proposed method does not require time-consuming training process and statistical model construction, and is capable of dealing with complicated shapes and intensity variations successfully. Copyright © 2017 Elsevier B.V. All rights reserved.

High Center Volume Does Not Mitigate Risk Associated with Using High Donor Risk Organs in Liver Transplantation.

PubMed

Beal, Eliza W; Black, Sylvester M; Mumtaz, Khalid; Hayes, Don; El-Hinnawi, Ashraf; Washburn, Kenneth; Tumin, Dmitry

2017-09-01

High-risk donor allografts increase access to liver transplant, but potentially reduce patient and graft survival. It is unclear whether the risk associated with using marginal donor livers is mitigated by increasing center experience. The United Network for Organ Sharing registry was queried for adult first-time liver transplant recipients between 2/2002 and 12/2015. High donor risk was defined as donor risk index >1.9, and 1-year patient and graft survival were compared according to donor risk index in small and large centers. Multivariable Cox regression estimated the hazard ratio (HR) associated with using high-risk donor organs, according to a continuous measure of annual center volume. The analysis included 51,770 patients. In 67 small and 67 large centers, high donor risk index predicted increased mortality (p = 0.001). In multivariable analysis, high-donor risk index allografts predicted greater mortality hazard at centers performing 20 liver transplants per year (HR 1.35; 95% CI 1.22, 1.49; p < 0.001) and, similarly, at centers performing 70 per year (HR 1.35; 95% CI 1.26, 1.43; p < 0.001). The interaction between high donor risk index and center volume was not statistically significant (p = 0.747), confirming that the risk associated with using marginal donor livers was comparable between smaller and larger centers. Results were consistent when examining graft loss. At both small and large centers, high-risk donor allografts were associated with reduced patient and graft survival after liver transplant. Specific strategies to mitigate the risk of liver transplant involving high-risk donors are needed, in addition to accumulation of center expertise.

Advantages of Whole-liver Intensity Modulated Radiation Therapy in Children With Wilms Tumor and Liver Metastasis

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

Kalapurakal, John A., E-mail: j-kalapurakal@northwestern.edu; Pokhrel, Damodar; Gopalakrishnan, Mahesh

Purpose: To demonstrate the dosimetric advantages of intensity modulated radiation therapy (IMRT) in children with Wilms tumor (WT) undergoing whole-liver (WL) RT. Methods and Materials: Computed tomography simulation scans of 10 children, either 3 (3D) or 4-dimensional (4D), were used for this study. The WL PTV was determined by the 3D or 4D liver volumes, with a margin of 1 cm. A total of 40 WL RT plans were performed: 10 each for left- and right-sided WT with IMRT and anteroposterior-posteroanterior (AP-PA) techniques. The radiation dose-volume coverage of the WL planning target volume (PTV), remaining kidney, and other organs weremore » analyzed and compared. Results: The 95% dose coverage to WL PTV for left and right WT were as follows: 97% ± 4% (IMRT), 83% ± 8% (AP-PA) (P<.01) and 99% ± 1% (IMRT), 94% ± 5% (AP-PA) (P<.01), respectively. When 3D WL PTV was used for RT planning, the AP-PA technique delivered 95% of dose to only 78% ± 13% and 88% ± 8% of 4D liver volume. For left WT, the right kidney V15 and V10 for IMRT were 29% ± 7% and 55% ± 8%, compared with 61% ± 29% (P<.01) and 78% ± 25% (P<.01) with AP-PA. For right WT, the left kidney V15 and V10 were 0 ± 0 and 2% ± 3% for IMRT, compared with 25% ± 19% (P<.01) and 40% ± 31% (P<.01) for AP-PA. Conclusions: The use of IMRT and 4D treatment planning resulted in the delivery of a higher RT dose to the liver compared with the standard AP-PA technique. Whole-liver IMRT also delivered a significantly lower dose to the remaining kidney.« less

Pancreatic Cysts in Autosomal Dominant Polycystic Kidney Disease: Prevalence and Association with PKD2 Gene Mutations.

PubMed

Kim, Jin Ah; Blumenfeld, Jon D; Chhabra, Shalini; Dutruel, Silvina P; Thimmappa, Nanda Deepa; Bobb, Warren O; Donahue, Stephanie; Rennert, Hanna E; Tan, Adrian Y; Giambrone, Ashley E; Prince, Martin R

2016-09-01

Purpose To define the magnetic resonance (MR) imaging prevalence of pancreatic cysts in a cohort of patients with autosomal dominant polycystic kidney disease (ADPKD) compared with a control group without ADPKD that was matched for age, sex, and renal function. Materials and Methods In this HIPAA-compliant, institutional review board-approved study, all patients with ADPKD provided informed consent; for control subjects, informed consent was waived. Patients with ADPKD (n = 110) with mutations identified in PKD1 or PKD2 and control subjects without ADPKD or known pancreatic disease (n = 110) who were matched for age, sex, estimated glomerular filtration rate, and date of MR imaging examination were evaluated for pancreatic cysts by using axial and coronal single-shot fast spin-echo T2-weighted images obtained at 1.5 T. Total kidney volume and liver volume were measured. Univariate and multivariable logistic regression analyses were conducted to evaluate potential associations between collected variables and presence of pancreatic cysts among patients with ADPKD. The number, size, location, and imaging characteristics of the cysts were recorded. Results Patients with ADPKD were significantly more likely than control subjects to have at least one pancreatic cyst (40 of 110 patients [36%] vs 25 of 110 control subjects [23%]; P = .027). In a univariate analysis, pancreatic cysts were more prevalent in patients with ADPKD with mutations in PKD2 than in PKD1 (21 of 34 patients [62%] vs 19 of 76 patients [25%]; P = .0002). In a multivariable logistic regression model, PKD2 mutation locus was significantly associated with the presence of pancreatic cysts (P = .0004) and with liver volume (P = .038). Patients with ADPKD and a pancreatic cyst were 5.9 times more likely to have a PKD2 mutation than a PKD1 mutation after adjusting for age, race, sex, estimated glomerular filtration rate, liver volume, and total kidney volume. Conclusion Pancreatic cysts were more prevalent in patients with ADPKD with PKD2 mutation than in control subjects or patients with PKD1 mutation. (©) RSNA, 2016 Online supplemental material is available for this article.

Portal vein thrombosis is a potentially preventable complication in clinical islet transplantation

PubMed Central

Kawahara, Toshiyasu; Kin, Tatsuya; Kashkoush, Samy; Gala-Lopez, Boris; Bigam, David L.; Kneteman, Norman M.; Koh, Angela; Senior, Peter A.; Shapiro, A.M. James

2011-01-01

Percutaneous transhepatic portal access avoids surgery, but is rarely associated with bleeding or portal venous thrombosis. We herein report our large, single-center experience of percutaneous islet implantation, and evaluate risk factors of portal vein thrombosis and graft function. Prospective data was collected on 268 intraportal islet transplants (122 subjects). A portal venous Doppler ultrasound was obtained on Days 1 and 7 days posttransplant. Therapeutic heparinization, complete ablation of the portal catheter tract with Avitene paste, and limiting packed cell volume to < 5 ml completely prevented any portal thrombosis in the most recent 101 islet transplant procedures over the past 5 years. In the previous cumulative experience, partial thrombosis did not affect islet function. Standard liver volume correlated negatively (r=−0.257, P<0.001), and packed cell volume correlated positively with portal pressure rise (r=0.463, P<0.001). Overall, partial portal thrombosis occurred after 10 procedures (overall incidence 3.7%, most recent 101 patient incidence 0%). There were no cases of complete thrombosis, and no patient developed sequelae of portal hypertension. In conclusion, portal thrombosis is a preventable complication in clinical islet transplantation, provided therapeutic anticoagulation is maintained, and packed cell volume is limited to <5 ml. PMID:21883914

A clinically feasible treatment protocol for magnetic resonance-guided high-intensity focused ultrasound ablation in the liver.

PubMed

Wijlemans, Joost W; de Greef, Martijn; Schubert, Gerald; Bartels, Lambertus W; Moonen, Chrit T W; van den Bosch, Maurice A A J; Ries, Mario

2015-01-01

Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) allows for noninvasive thermal ablation under real-time temperature imaging guidance. The purpose of this study was to assess the feasibility and safety of MR-HIFU ablation of liver tissue in a clinically acceptable setting. The experimental protocol was designed with a clinical ablation procedure of a small malignant tumor in mind; the procedures were performed within a clinically feasible time frame and care was taken to avoid adverse events. The main outcome was the size and quality of the ablated liver tissue volume on imaging and histology. Secondary outcomes were safety and treatment time. Healthy pigs (n = 10) under general anesthesia were positioned on a clinical MR-HIFU system, which consisted of an HIFU tabletop with a skin cooling system integrated into a 1.5-T MR scanner. A liver tissue volume was ablated with multiple sonication cells (4 × 4 × 10 mm, 450 W). Both MR thermometry and sonication were respiratory-gated using a pencil beam navigator on the diaphragm. Contrast-enhanced T1-weighted (CE-T1w) imaging was performed for treatment evaluation. Targeted total treatment time was 3 hours. The abdominal wall, liver, and adjacent organs were inspected postmortem for thermal damage. Ablated tissue volumes were processed for cell viability staining. The ablated volumes were analyzed using MR imaging, MR thermometry, and cell viability histology. Eleven volume ablations were performed in 10 animals, resulting in a median nonperfused volume (NPV) on CE-T1w imaging of 1.6 mL (interquartile range [IQR], 0.8-2.3; range, 0.7-3.0). Cell viability histology showed a damaged volume of 1.5 mL (IQR, 1.1-1.8; range, 0.7-2.3). The NPV was confluent in 10 of the 11 cases. The ablated tissue volume on cell viability histology was confluent in all 9 available cases. In all cases, there was a good correspondence between the aspects of the NPV on CE-T1w and the ablated volume on cell viability histology. Two treatment-related adverse events occurred: 1 animal had a 7-mm skin burn and 1 animal showed evidence of thermal damage on the surface of the spleen. Median ablation time was 108 minutes (IQR, 101-120; range, 96-181 minutes) and median total treatment time was 180 minutes (IQR, 165-224; 130-250 minutes). Our results demonstrate the feasibility and safety of MR-HIFU ablation of liver tissue volumes. The imaging data and cell viability histology show, for the first time, that confluent ablation volumes can be achieved with motion-gated ablation and MR guidance. These results were obtained using a readily available MR-HIFU system with only minor modifications, within a clinically acceptable time frame, and with only minor adverse events. This shows that this technique is sufficiently reliable and safe to initiate a clinical trial.

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

Li, Guang, E-mail: lig2@mskcc.org; Schmidtlein, C. Ross; Humm, John L.

Purpose: To assess and account for the impact of respiratory motion on the variability of activity and volume determination of liver tumor in positron emission tomography (PET) through a comparison between free-breathing (FB) and respiration-suspended (RS) PET images. Methods: As part of a PET/computed tomography (CT) guided percutaneous liver ablation procedure performed on a PET/CT scanner, a patient's breathing is suspended on a ventilator, allowing the acquisition of a near-motionless PET and CT reference images of the liver. In this study, baseline RS and FB PET/CT images of 20 patients undergoing thermal ablation were acquired. The RS PET provides near-motionlessmore » reference in a human study, and thereby allows a quantitative evaluation of the effect of respiratory motion on PET images obtained under FB conditions. Two methods were applied to calculate tumor activity and volume: (1) threshold-based segmentation (TBS), estimating the total lesion glycolysis (TLG) and the segmented volume and (2) histogram-based estimation (HBE), yielding the background-subtracted lesion (BSL) activity and associated volume. The TBS method employs 50% of the maximum standardized uptake value (SUV{sub max}) as the threshold for tumors with SUV{sub max} ≥ 2× SUV{sub liver-bkg}, and tumor activity above this threshold yields TLG{sub 50%}. The HBE method determines local PET background based on a Gaussian fit of the low SUV peak in a SUV-volume histogram, which is generated within a user-defined and optimized volume of interest containing both local background and lesion uptakes. Voxels with PET intensity above the fitted background were considered to have originated from the tumor and used to calculate the BSL activity and its associated lesion volume. Results: Respiratory motion caused SUV{sub max} to decrease from RS to FB by −15% ± 11% (p = 0.01). Using TBS method, there was also a decrease in SUV{sub mean} (−18% ± 9%, p = 0.01), but an increase in TLG{sub 50%} (18% ± 36%) and in the segmented volume (47% ± 52%, p = 0.01) from RS to FB PET images. The background uptake in normal liver was stable, 1% ± 9%. In contrast, using the HBE method, the differences in both BSL activity and BSL volume from RS to FB were −8% ± 10% (p = 0.005) and 0% ± 16% (p = 0.94), respectively. Conclusions: This is the first time that almost motion-free PET images of the human liver were acquired and compared to free-breathing PET. The BSL method's results are more consistent, for the calculation of both tumor activity and volume in RS and FB PET images, than those using conventional TBS. This suggests that the BSL method might be less sensitive to motion blurring and provides an improved estimation of tumor activity and volume in the presence of respiratory motion.« less

Liver ultrastructural morphology and mitochondrial DNA levels in HIV/hepatitis C virus coinfection: no evidence of mitochondrial damage with highly active antiretroviral therapy.

PubMed

Matsukura, Motoi; Chu, Fanny F S; Au, May; Lu, Helen; Chen, Jennifer; Rietkerk, Sonja; Barrios, Rolando; Farley, John D; Montaner, Julio S; Montessori, Valentina C; Walker, David C; Côté, Hélène C F

2008-06-19

Liver mitochondrial toxicity is a concern, particularly in HIV/hepatitis C virus (HCV) coinfection. Liver biopsies from HIV/HCV co-infected patients, 14 ON-highly active antiretroviral therapy (HAART) and nine OFF-HAART, were assessed by electron microscopy quantitative morphometric analyses. Hepatocytes tended to be larger ON-HAART than OFF-HAART (P = 0.05), but mitochondrial volume, cristae density, lipid volume, mitochondrial DNA and RNA levels were similar. We found no evidence of increased mitochondrial toxicity in individuals currently on HAART, suggesting that concomitant HAART should not delay HCV therapy.

High salt intake reprioritizes osmolyte and energy metabolism for body fluid conservation.

PubMed

Kitada, Kento; Daub, Steffen; Zhang, Yahua; Klein, Janet D; Nakano, Daisuke; Pedchenko, Tetyana; Lantier, Louise; LaRocque, Lauren M; Marton, Adriana; Neubert, Patrick; Schröder, Agnes; Rakova, Natalia; Jantsch, Jonathan; Dikalova, Anna E; Dikalov, Sergey I; Harrison, David G; Müller, Dominik N; Nishiyama, Akira; Rauh, Manfred; Harris, Raymond C; Luft, Friedrich C; Wassermann, David H; Sands, Jeff M; Titze, Jens

2017-05-01

Natriuretic regulation of extracellular fluid volume homeostasis includes suppression of the renin-angiotensin-aldosterone system, pressure natriuresis, and reduced renal nerve activity, actions that concomitantly increase urinary Na+ excretion and lead to increased urine volume. The resulting natriuresis-driven diuretic water loss is assumed to control the extracellular volume. Here, we have demonstrated that urine concentration, and therefore regulation of water conservation, is an important control system for urine formation and extracellular volume homeostasis in mice and humans across various levels of salt intake. We observed that the renal concentration mechanism couples natriuresis with correspondent renal water reabsorption, limits natriuretic osmotic diuresis, and results in concurrent extracellular volume conservation and concentration of salt excreted into urine. This water-conserving mechanism of dietary salt excretion relies on urea transporter-driven urea recycling by the kidneys and on urea production by liver and skeletal muscle. The energy-intense nature of hepatic and extrahepatic urea osmolyte production for renal water conservation requires reprioritization of energy and substrate metabolism in liver and skeletal muscle, resulting in hepatic ketogenesis and glucocorticoid-driven muscle catabolism, which are prevented by increasing food intake. This natriuretic-ureotelic, water-conserving principle relies on metabolism-driven extracellular volume control and is regulated by concerted liver, muscle, and renal actions.

High salt intake reprioritizes osmolyte and energy metabolism for body fluid conservation

PubMed Central

Kitada, Kento; Daub, Steffen; Zhang, Yahua; Klein, Janet D.; Nakano, Daisuke; Pedchenko, Tetyana; Lantier, Louise; LaRocque, Lauren M.; Marton, Adriana; Neubert, Patrick; Schröder, Agnes; Rakova, Natalia; Jantsch, Jonathan; Dikalova, Anna E.; Dikalov, Sergey I.; Harrison, David G.; Müller, Dominik N.; Nishiyama, Akira; Rauh, Manfred; Harris, Raymond C.; Luft, Friedrich C.; Wasserman, David H.; Sands, Jeff M.

2017-01-01

Natriuretic regulation of extracellular fluid volume homeostasis includes suppression of the renin-angiotensin-aldosterone system, pressure natriuresis, and reduced renal nerve activity, actions that concomitantly increase urinary Na+ excretion and lead to increased urine volume. The resulting natriuresis-driven diuretic water loss is assumed to control the extracellular volume. Here, we have demonstrated that urine concentration, and therefore regulation of water conservation, is an important control system for urine formation and extracellular volume homeostasis in mice and humans across various levels of salt intake. We observed that the renal concentration mechanism couples natriuresis with correspondent renal water reabsorption, limits natriuretic osmotic diuresis, and results in concurrent extracellular volume conservation and concentration of salt excreted into urine. This water-conserving mechanism of dietary salt excretion relies on urea transporter–driven urea recycling by the kidneys and on urea production by liver and skeletal muscle. The energy-intense nature of hepatic and extrahepatic urea osmolyte production for renal water conservation requires reprioritization of energy and substrate metabolism in liver and skeletal muscle, resulting in hepatic ketogenesis and glucocorticoid-driven muscle catabolism, which are prevented by increasing food intake. This natriuretic-ureotelic, water-conserving principle relies on metabolism-driven extracellular volume control and is regulated by concerted liver, muscle, and renal actions. PMID:28414295

Clamp-crushing vs. radiofrequency-assisted liver resection:changes in liver function tests.

PubMed

Palibrk, Ivan; Milicic, Biljana; Stojiljkovic, Ljuba; Manojlovic, Nebojsa; Dugalic, Vladimir; Bumbasirevic, Vesna; Kalezic, Nevena; Zuvela, Marinko; Milicevic, Miroslav

2012-05-01

Liver resection is the gold standard in managing patients with metastatic or primary liver cancer. The aim of our study was to compare the traditional clamp-crushing technique to the radiofrequency- assisted liver resection technique in terms of postoperative liver function. Liver function was evaluated preoperatively and on postoperative days 3 and 7. Liver synthetic function parameters (serum albumin level, prothrombin time and international normalized ratio), markers of hepatic injury and necrosis (serum alanine aminotransferase, aspartate aminotransferase and total bilirubin level) and microsomal activity (quantitative lidocaine test) were compared. Forty three patients completed the study (14 had clamp-crushing and 29 had radiofrequency assisted liver resection). The groups did not differ in demographic characteristics, pre-operative liver function, operative time and perioperative transfusion rate. In postoperative period, there were similar changes in monitored parameters in both groups except albumin levels, that were higher in radiofrequency-assisted liver resection group (p=0.047). Both, traditional clamp-crushing technique and radiofrequency assisted liver resection technique, result in similar postoperative changes of most monitored liver function parameters.

Size mismatch in liver transplantation.

PubMed

Fukazawa, Kyota; Nishida, Seigo

2016-08-01

Size mismatch is an unique and inevitable but critical issue in live donor liver transplantation. Unmatched metabolic demand of recipient as well as physiologic mismatch aggravates the damage to liver graft, inevitably leading to graft failure on recipient. Also, an excessive resection of liver graft for better recipient outcome in live donor liver transplant may jeopardize the healthy donor well-being and even put donor life in danger. There is a fine balance between resected graft volume required to meet the recipient's metabolic demand and residual graft volume required for donor safety. The obvious clinical necessity of finding that balance has prompted a clinical need and promoted the improvement of knowledge and development of management strategies for size-mismatched transplants. The development of the size-matching methodology has significantly improved graft outcome and recipient survival in live donor liver transplants. On the other hand, the effect of size mismatch in cadaveric transplants has never been observed as being so pronounced. The importance of matching of the donor recipient size has been unrecognized in cadaveric liver transplant. In this review, we attempt to summarize the current most updated knowledge on the subject, particularly addressing the definition and complications of size-mismatched cadaveric liver transplant, as well as management strategies. © 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Efficacy of Preoperative Portal Vein Embolization Among Patients with Hepatocellular Carcinoma, Biliary Tract Cancer, and Colorectal Liver Metastases: A Comparative Study Based on Single-Center Experience of 319 Cases.

PubMed

Yamashita, Suguru; Sakamoto, Yoshihiro; Yamamoto, Satoshi; Takemura, Nobuyuki; Omichi, Kiyohiko; Shinkawa, Hiroji; Mori, Kazuhiro; Kaneko, Junichi; Akamatsu, Nobuhisa; Arita, Junichi; Hasegawa, Kiyoshi; Kokudo, Norihiro

2017-06-01

Efficacy of preoperative portal vein embolization (PVE) has been established; however, differences of outcomes among diseases, including hepatocellular carcinoma (HCC), biliary tract cancer (BTC), and colorectal liver metastases (CLM), are unclear. Subjects included patients in a prospectively collected database undergoing PVE (from 1995 to 2013). A future liver remnant (FLR) volume ≥40% is the minimal requirement for patients with an indocyanine green retention rate at 15 min (ICGR15) <10%, and stricter criteria (FLR volume ≥50%) have been applied for patients with 20% > ICGR15 ≥ 10%. Patient characteristics and survivals were compared among those three diseases, and predictors of dropout and better FLR hypertrophy were determined. In 319 consecutive patients undergoing PVE for HCC (n = 70), BTC (n = 172), and CLM (n = 77), the degree of hypertrophy did not significantly differ by cancer types (median 10, 9.6, and 10%, respectively). Eighty percent (256 of 319) of patients completed subsequent hepatectomy after a median waiting interval of 24 days (range 5-90), while dropout after PVE was more common in BTC or CLM (odds ratio 2.75, p = 0.018), mainly because of disease progression. Ninety-day liver-related mortality after hepatectomy was 0% in the entire cohort, and 5-year overall survival of patients with HCC, BTC, and CLM was 56, 50, and 51%, respectively (p = 0.948). No patients who dropped out survived more than 2.5 years after PVE. PVE produced equivalent FLR hypertrophy among the three diseases as long as liver function was fulfilling the preset criteria; however, the completion rate of subsequent hepatectomy was highest in HCC. PVE followed by hepatectomy was a safe and feasible strategy for otherwise unresectable disease irrespective of cancer types.

Functional restoration of cirrhotic liver after partial hepatectomy in the rat.

PubMed

Hashimoto, Masaji; Watanabe, Goro

2005-01-01

Although cirrhosis is the terminal stage of various liver diseases, thanks to recent advances one might eliminate some causes of liver damage. Liver has a potent regeneration capacity. It is important to evaluate the regenerating cirrhotic liver after partial hepatectomy, morphologically and functionally, in the long term. We evaluated the functional capacity of the rat liver rendered cirrhotic by orally administered thioacetamide, and examined the correlation between morphological and functional restoration after 2/3 hepatectomy in comparison with hepatectomized normal rats and sham-operated cirrhotic rats. Morphological restoration was evaluated by remnant liver weight, proliferating cell nuclear antigen labeling index, and fibrosis ratio. Functional restoration was evaluated by the indocyanine green disappearance rate and aminopyrine clearance. Cirrhotic rats were functionally deteriorated in comparison with the normal rats. Morphological restoration in cirrhotic rats was delayed in comparison with normal rats. Functional restoration after 2/3 hepatectomy was advanced in comparison with morphological restoration. In comparison with sham-operated cirrhotic rats, functional restoration of the cirrhotic liver was accelerated by partial hepatectomy. In cirrhotic rats, functional restoration of the liver after 2/3 hepatectomy was advanced in comparison with morphological restoration. Partial hepatectomy seemed to promote functional restoration of the cirrhotic liver.

Pituitary iron and volume predict hypogonadism in transfusional iron overload.

PubMed

Noetzli, Leila J; Panigrahy, Ashok; Mittelman, Steven D; Hyderi, Aleya; Dongelyan, Ani; Coates, Thomas D; Wood, John C

2012-02-01

Hypogonadism is the most common morbidity in patients with transfusion-dependent anemias such as thalassemia major. We used magnetic resonance imaging (MRI) to measure pituitary R2 (iron) and volume to determine at what age these patients develop pituitary iron overload and volume loss. We recruited 56 patients (47 with thalassemia major, five with chronically transfused thalassemia intermedia and four with Blackfan-Diamond syndrome) to have pituitary MRIs to measure pituitary R2 and volume. Hypogonadism was defined clinically based on the timing of secondary sexual characteristics or the need for sex hormone replacement therapy. Patients with transfusional iron overload begin to develop pituitary iron overload in the first decade of life; however, clinically significant volume loss was not observed until the second decade of life. Severe pituitary iron deposition (Z > 5) and volume loss (Z < -2.5) were independently predictive of hypogonadism. Pituitary R2 correlated significantly with serum ferritin as well as liver, pancreatic, and cardiac iron deposition by MRI. Log pancreas R2* was the best single predictor for pituitary iron, with an area under the receiving operator characteristic curve of 0.88, but log cardiac R2* and ferritin were retained on multivariate regression with a combined r(2) of 0.71. Pituitary iron overload and volume loss were independently predictive of hypogonadism. Many patients with moderate-to-severe pituitary iron overload retained normal gland volume and function, representing a potential therapeutic window. The subset of hypogonadal patients having preserved gland volumes may also explain improvements in pituitary function observed following intensive chelation therapy. Copyright © 2011 Wiley Periodicals, Inc.

Low Hepatic Toxicity in Primary and Metastatic Liver Cancers after Stereotactic Ablative Radiotherapy Using 3 Fractions.

PubMed

Bae, Sun Hyun; Kim, Mi-Sook; Jang, Won Il; Cho, Chul Koo; Yoo, Hyung Jun; Kim, Kum Bae; Han, Chul Ju; Park, Su Cheol; Lee, Dong Han

2015-08-01

This study evaluated the incidence of hepatic toxicity after stereotactic ablative radiotherapy (SABR) using 3 fractions to the liver, and identified the predictors for hepatic toxicity. We retrospectively reviewed 78 patients with primary and metastatic liver cancers, who underwent SABR using 3 fractions between 2003 and 2011. To examine the incidence of hepatic toxicity, we defined newly developed hepatic toxicity≥grade 2 according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 within 3 months after the end of SABR as a significant adverse event. To identify the predictors for hepatic toxicity, we analyzed several clinical and dosimetric parameters (rV5Gy-rV35Gy: normal liver volume receiving

Significance of functional hepatic resection rate calculated using 3D CT/(99m)Tc-galactosyl human serum albumin single-photon emission computed tomography fusion imaging.

PubMed

Tsuruga, Yosuke; Kamiyama, Toshiya; Kamachi, Hirofumi; Shimada, Shingo; Wakayama, Kenji; Orimo, Tatsuya; Kakisaka, Tatsuhiko; Yokoo, Hideki; Taketomi, Akinobu

2016-05-07

To evaluate the usefulness of the functional hepatic resection rate (FHRR) calculated using 3D computed tomography (CT)/(99m)Tc-galactosyl-human serum albumin (GSA) single-photon emission computed tomography (SPECT) fusion imaging for surgical decision making. We enrolled 57 patients who underwent bi- or trisectionectomy at our institution between October 2013 and March 2015. Of these, 26 patients presented with hepatocellular carcinoma, 12 with hilar cholangiocarcinoma, six with intrahepatic cholangiocarcinoma, four with liver metastasis, and nine with other diseases. All patients preoperatively underwent three-phase dynamic multidetector CT and (99m)Tc-GSA scintigraphy. We compared the parenchymal hepatic resection rate (PHRR) with the FHRR, which was defined as the resection volume counts per total liver volume counts on 3D CT/(99m)Tc-GSA SPECT fusion images. In total, 50 patients underwent bisectionectomy and seven underwent trisectionectomy. Biliary reconstruction was performed in 15 patients, including hepatopancreatoduodenectomy in two. FHRR and PHRR were 38.6 ± 19.9 and 44.5 ± 16.0, respectively; FHRR was strongly correlated with PHRR. The regression coefficient for FHRR on PHRR was 1.16 (P < 0.0001). The ratio of FHRR to PHRR for patients with preoperative therapies (transcatheter arterial chemoembolization, radiation, radiofrequency ablation, etc.), large tumors with a volume of > 1000 mL, and/or macroscopic vascular invasion was significantly smaller than that for patients without these factors (0.73 ± 0.19 vs 0.82 ± 0.18, P < 0.05). Postoperative hyperbilirubinemia was observed in six patients. Major morbidities (Clavien-Dindo grade ≥ 3) occurred in 17 patients (29.8%). There was no case of surgery-related death. Our results suggest that FHRR is an important deciding factor for major hepatectomy, because FHRR and PHRR may be discrepant owing to insufficient hepatic inflow and congestion in patients with preoperative therapies, macroscopic vascular invasion, and/or a tumor volume of > 1000 mL.

Automatic 3D liver location and segmentation via convolutional neural network and graph cut.

PubMed

Lu, Fang; Wu, Fa; Hu, Peijun; Peng, Zhiyi; Kong, Dexing

2017-02-01

Segmentation of the liver from abdominal computed tomography (CT) images is an essential step in some computer-assisted clinical interventions, such as surgery planning for living donor liver transplant, radiotherapy and volume measurement. In this work, we develop a deep learning algorithm with graph cut refinement to automatically segment the liver in CT scans. The proposed method consists of two main steps: (i) simultaneously liver detection and probabilistic segmentation using 3D convolutional neural network; (ii) accuracy refinement of the initial segmentation with graph cut and the previously learned probability map. The proposed approach was validated on forty CT volumes taken from two public databases MICCAI-Sliver07 and 3Dircadb1. For the MICCAI-Sliver07 test dataset, the calculated mean ratios of volumetric overlap error (VOE), relative volume difference (RVD), average symmetric surface distance (ASD), root-mean-square symmetric surface distance (RMSD) and maximum symmetric surface distance (MSD) are 5.9, 2.7 %, 0.91, 1.88 and 18.94 mm, respectively. For the 3Dircadb1 dataset, the calculated mean ratios of VOE, RVD, ASD, RMSD and MSD are 9.36, 0.97 %, 1.89, 4.15 and 33.14 mm, respectively. The proposed method is fully automatic without any user interaction. Quantitative results reveal that the proposed approach is efficient and accurate for hepatic volume estimation in a clinical setup. The high correlation between the automatic and manual references shows that the proposed method can be good enough to replace the time-consuming and nonreproducible manual segmentation method.

Human albumin: old, new, and emerging applications.

PubMed

Rozga, Jacek; Piątek, Tomasz; Małkowski, Piotr

2013-05-10

Human serum albumin has been widely used in an array of clinical settings for nearly 7 decades. Although there is no evidence to support the use of albumin rather than crystalloid in acute volume resuscitation, many clinicians continue to use albumin because it has other important physiologic effects besides the oncotic function. In keeping with the improved understanding of albumin physiology and pathophysiology of many acute and chronic diseases, use of albumin for medical applications has increased in recent years. This, along with increased costs of manufacturing and lower production volume of medical-grade albumin, has lead to an ongoing shortage and rapid increase in albumin prices. This review is based on the analysis of major publications, related to albumin chemistry, physiology, and medical uses including guidelines developed by professional and governmental organizations. Results reflect current knowledge about the role of albumin in health and disease and relevance of albumin therapy in specific clinical settings. Albumin therapy is currently recommended in spontaneous bacterial peritonitis with ascites, refractory ascites not responsive to diuretics, large-volume paracentesis, post-paracentesis syndrome, and the treatment of hepatorenal syndrome as an adjunct to vasoconstrictors. New indications for albumin therapy are linked to the antioxidant activity of albumin and its effects on capillary integrity. In recent years, large-pore hemofiltration and albumin exchange have emerged as promising liver support therapies for liver failure and other toxic syndromes. They are designed to remove a broad range of blood-borne toxins and to restore normal functions of the circulating albumin by replacing defective forms of albumin and albumin molecules saturated with toxins with normal albumin. In view of the ongoing worldwide shortage and high cost of human albumin (native and recombinant), new usage criteria, protocols, and guidelines for appropriate utilization of albumin are needed.

Liver Function Tests

MedlinePlus

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Accuracy of Estimation of Graft Size for Living-Related Liver Transplantation: First Results of a Semi-Automated Interactive Software for CT-Volumetry

PubMed Central

Mokry, Theresa; Bellemann, Nadine; Müller, Dirk; Lorenzo Bermejo, Justo; Klauß, Miriam; Stampfl, Ulrike; Radeleff, Boris; Schemmer, Peter; Kauczor, Hans-Ulrich; Sommer, Christof-Matthias

2014-01-01

Objectives To evaluate accuracy of estimated graft size for living-related liver transplantation using a semi-automated interactive software for CT-volumetry. Materials and Methods Sixteen donors for living-related liver transplantation (11 male; mean age: 38.2±9.6 years) underwent contrast-enhanced CT prior to graft removal. CT-volumetry was performed using a semi-automated interactive software (P), and compared with a manual commercial software (TR). For P, liver volumes were provided either with or without vessels. For TR, liver volumes were provided always with vessels. Intraoperative weight served as reference standard. Major study goals included analyses of volumes using absolute numbers, linear regression analyses and inter-observer agreements. Minor study goals included the description of the software workflow: degree of manual correction, speed for completion, and overall intuitiveness using five-point Likert scales: 1–markedly lower/faster/higher for P compared with TR, 2–slightly lower/faster/higher for P compared with TR, 3–identical for P and TR, 4–slightly lower/faster/higher for TR compared with P, and 5–markedly lower/faster/higher for TR compared with P. Results Liver segments II/III, II–IV and V–VIII served in 6, 3, and 7 donors as transplanted liver segments. Volumes were 642.9±368.8 ml for TR with vessels, 623.8±349.1 ml for P with vessels, and 605.2±345.8 ml for P without vessels (P<0.01). Regression equations between intraoperative weights and volumes were y = 0.94x+30.1 (R2 = 0.92; P<0.001) for TR with vessels, y = 1.00x+12.0 (R2 = 0.92; P<0.001) for P with vessels, and y = 1.01x+28.0 (R2 = 0.92; P<0.001) for P without vessels. Inter-observer agreement showed a bias of 1.8 ml for TR with vessels, 5.4 ml for P with vessels, and 4.6 ml for P without vessels. For the degree of manual correction, speed for completion and overall intuitiveness, scale values were 2.6±0.8, 2.4±0.5 and 2. Conclusions CT-volumetry performed with P can predict accurately graft size for living-related liver transplantation while improving workflow compared with TR. PMID:25330198

Comparison of pre/post-operative CT image volumes to preoperative digitization of partial hepatectomies: a feasibility study in surgical validation

NASA Astrophysics Data System (ADS)

Dumpuri, Prashanth; Clements, Logan W.; Li, Rui; Waite, Jonathan M.; Stefansic, James D.; Geller, David A.; Miga, Michael I.; Dawant, Benoit M.

2009-02-01

Preoperative planning combined with image-guidance has shown promise towards increasing the accuracy of liver resection procedures. The purpose of this study was to validate one such preoperative planning tool for four patients undergoing hepatic resection. Preoperative computed tomography (CT) images acquired before surgery were used to identify tumor margins and to plan the surgical approach for resection of these tumors. Surgery was then performed with intraoperative digitization data acquire by an FDA approved image-guided liver surgery system (Pathfinder Therapeutics, Inc., Nashville, TN). Within 5-7 days after surgery, post-operative CT image volumes were acquired. Registration of data within a common coordinate reference was achieved and preoperative plans were compared to the postoperative volumes. Semi-quantitative comparisons are presented in this work and preliminary results indicate that significant liver regeneration/hypertrophy in the postoperative CT images may be present post-operatively. This could challenge pre/post operative CT volume change comparisons as a means to evaluate the accuracy of preoperative surgical plans.

Enzymatic liver function capacity correlates with disease severity of patients with liver cirrhosis: a study with the LiMAx test.

PubMed

Malinowski, Maciej; Jara, Maximilian; Lüttgert, Katja; Orr, James; Lock, Johan Friso; Schott, Eckart; Stockmann, Martin

2014-12-01

Assessment and quantification of actual liver function is crucial in patients with chronic liver disease to monitor disease progression and predict individual prognosis. Mathematical models, such as model for end-stage liver disease, are used for risk stratification of patients with chronic liver disease but do not include parameters that reflect the actual functional state of the liver. We aimed to evaluate the potential of a (13)C-based liver function test as a stratification tool by comparison with other liver function tests and clinical parameters in a large sample of healthy controls and cirrhotic patients. We applied maximum liver function capacity (LiMAx) to evaluate actual liver function in 347 patients with cirrhosis and in 86 controls. LiMAx showed strong negative correlation with Child-Pugh Score (r = -0.707; p < 0.001), MELD (r = -0.686; p < 0.001) and liver function tests. LiMAx was lower in patients with liver cirrhosis compared to healthy controls [99 (57-160) µg/kg/h vs. 412 (365-479) µg/kg/h, p < 0.001] and differed among Child-Pugh classes [a: 181 (144-227) µg/kg/h, b: 96 (62-132) µg/kg/h and c: 52 (37-81) µg/kg/h; p < 0.001]. When stratified patients according to disease severity, LiMAx results were not different between cirrhotic patients and cirrhotic patients with transjugular intrahepatic portosystemic shunt. LiMAx appears to provide reliable information on remnant enzymatic liver function in chronic liver disease and allows graduation of disease severity.

Is biological aging accelerated in drug addiction?

PubMed

Bachi, Keren; Sierra, Salvador; Volkow, Nora D; Goldstein, Rita Z; Alia-Klein, Nelly

2017-02-01

Drug-addiction may trigger early onset of age-related disease, due to drug-induced multi-system toxicity and perilous lifestyle, which remains mostly undetected and untreated. We present the literature on pathophysiological processes that may hasten aging and its relevance to addiction, including: oxidative stress and cellular aging, inflammation in periphery and brain, decline in brain volume and function, and early onset of cardiac, cerebrovascular, kidney, and liver disease. Timely detection of accelerated aging in addiction is crucial for the prevention of premature morbidity and mortality.

Long-term Effects on the Histology and Function of Livers and Spleens in Rats after 33% Toploading of PEG-PLA-nano Artificial Red Blood Cells

PubMed Central

Liu, Zun Chang; Chang, Thomas M.S.

2012-01-01

This study is to investigate the long-term effects of nanodimension PEG-PLA artificial red blood cells containing hemoglobin and red blood cell enzymes on the liver and spleen after 1/3 blood volume top loading in rats. The experimental rats received one of the following infusions: Nano artificial red blood cells in Ringer lactate, Ringer lactate, stroma-free hemoglobin, polyhemoglobin, and autologous rat whole blood. Blood samples were taken before infusions and on days 1, 7, and 21 after infusions for analysis. Nano artificial red blood cells, polyhemoglobin, Ringer lactate and rat red blood cells did not have any significant adverse effects on alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatine kinase, amylase and creatine kinase. On the other hand, stroma-free hemoglobin induced significant adverse effects on liver as shown by elevation in alanine aminotransferase and aspartate aminotransferase throughout the 21 days. On day 21 after infusions rats were sacrificed and livers and spleens were excised for histological examination. Nano artificial red blood cells, polyhemoglobin, Ringer lactate and rat red blood cells did not cause any abnormalities in the microscopic histology of the livers and spleens. In the stroma-free hemoglobin group the livers showed accumulation of hemoglobin in central veins and sinusoids, and hepatic steatosis. In conclusion, injected nano artificial red blood cells can be efficiently metabolized and removed by the reticuloendothelial system, and do not have any biochemical or histological adverse effects on the livers or the spleens. PMID:19043818

Importance of primary indication and liver function between stages: results of a multicenter Italian audit of ALPPS 2012-2014.

PubMed

Serenari, Matteo; Zanello, Matteo; Schadde, Erik; Toschi, Elena; Ratti, Francesca; Gringeri, Enrico; Masetti, Michele; Cillo, Umberto; Aldrighetti, Luca; Jovine, Elio

2016-05-01

Posthepatectomy liver failure is one of the most feared complications in extended hepatic resections. In 2012, a novel two-stage liver resection was developed, able to induce rapid and extensive hypertrophy by portal vein ligation and in situ liver splitting - Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS). The technique became more widely employed but its use remained controversial due to reporting of high complication and mortality rates. A national audit was performed to gather information about the safety of the procedure and to better understand the complications. The audit was offered to all high-volume hepatobiliary centers in Italy. Of all Italian centers approached in January 2012, 12 centers with experience in ALPPS enrolled and participated in collection of data. Fifty patients underwent ALPPS between 2012 and 2014. In 48/50 patients completion of hepatectomy was performed successfully. Major morbidity occurred in 54% with a 20% 90-day mortality. Uni- and multivariate analysis showed that ALPPS for cholangiocarcinoma and a peak of bilirubin over 5 mg/dl between stages was associated with increase of 90-day mortality and worse survival. It is proposed that a moratorium be introduced for classic ALPPS in cholangiocarcinoma and to abort ALPPS in patients who develop an interstage increase in bilirubin, due to the high risk of liver failure and mortality. Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Comparative factor analysis of the effect of postoperative peripheral parenteral nutrition on recovery of right lobe liver donors.

PubMed

Hsieh, Chia-En; Lin, Kuo-Hua; Lin, Chia-Cheng; Hwu, Yueh-Juen; Lin, Ping-Yi; Lin, Hui-Chuan; Ko, Chih-Jan; Wang, Su-Han; Chen, Yao-Li

2015-04-01

Intensive nutritional support can reduce the catabolic response, improve protein synthesis, and promote liver regeneration. This study examined whether postoperative peripheral parenteral nutrition may improve recovery and reduce the length of hospital stay in right lobe liver donors. In this retrospective study, we enrolled liver donors with residual liver volume < 50%. Donors were classified into 2 groups: donors who received (n = 44) or did not receive (n = 40) postoperative peripheral parenteral nutrition. Liver function tests included alanine aminotransferase and total bilirubin levels, and postoperative complications included pleural effusion, atelectasis, and wound complications. Hospital length of stay was included as a potential risk factor for the evaluation of the effect of postoperative peripheral parenteral nutrition on recovery of right lobe liver donors. Male sex (β, 22.04; 95% confidence interval: 6.22 - 37.86) was a significant predictor of changes in postoperative alanine aminotransferase level. Male sex (β, 0.045; 95% confidence interval: 0.16 - 37.86) and receipt of peripheral parenteral nutrition (β, -0.045; 95% confidence interval: -0.72 - 0.17) were significant predictors of changes in total bilirubin level. Postoperative atelectasis (P < .001), pleural effusion (P < .011), and total complications (P = .015) had significantly lower incidence in the peripheral parenteral nutrition than control group. Multivariate logistic regression showed that recipients of peripheral parenteral nutrition (odds ratio, 0.161; 95% confidence interval: 0.043 - 0.598) and age (odds ratio, 0.870; 95% confidence interval: 0.782 - 0.968) were significant preoperative risk factors for postoperative complications. Postoperative peripheral parenteral nutrition is associated with a lower incidence of pleural effusion and atelectasis, a more rapid recovery of hyperbilirubinemia, and shorter length of stay in right lobe liver donors.

A fourth dimension in decision making in hepatology.

PubMed

Ilan, Yaron

2010-12-01

Today, the assessment of liver function in patients suffering from acute or chronic liver disease is based on liver biopsy and blood tests including synthetic function, liver enzymes and viral load, most of which provide only circumstantial evidence as to the degree of hepatic impairment. Most of these tests lack the degree of sensitivity to be useful for follow-up of these patients at the frequency that is needed for decision making in clinical hepatology. Accurate assessment of liver function is essential to determine both short- and long-term prognosis, and for making decisions about liver and non-liver surgery, TIPS, chemoembolization or radiofrequency ablation in patients with chronic liver disease. Liver function tests can serve as the basis for accurate decision-making regarding the need for liver transplantation in the setting of acute failure or in patients with chronic liver disease. The liver metabolic breath test relies on measuring exhaled (13) C tagged methacetin, which is metabolized only by the liver. Measuring this liver-specific substrate by means of molecular correlation spectroscopy is a rapid, non-invasive method for assessing liver function at the point-of-care. The (13) C methacetin breath test (MBT) is a powerful tool to aid clinical hepatologists in bedside decision-making. Our recent findings regarding the ability of point-of-care (13) C MBT to assess the hepatic functional reserve in patients with acute and chronic liver disease are reviewed along with suggested treatment algorithms for common liver disorders. © 2010 The Japan Society of Hepatology.

Liver function tests

MedlinePlus

Liver function tests are common tests that are used to see how well the liver is working. Tests include: ... E, Bowne WB, Bluth MH. Evaluation of liver function. In: McPherson RA, Pincus MR, eds. Henry's Clinical ...

Liver Function Tests

MedlinePlus

... food, store energy, and remove poisons. Liver function tests are blood tests that check to see how well your liver ... hepatitis and cirrhosis. You may have liver function tests as part of a regular checkup. Or you ...

Left-liver hypertrophy after therapeutic right-liver radioembolization is substantial but less than after portal vein embolization.

PubMed

Garlipp, Benjamin; de Baere, Thierry; Damm, Robert; Irmscher, Romy; van Buskirk, Mark; Stübs, Patrick; Deschamps, Frederic; Meyer, Frank; Seidensticker, Ricarda; Mohnike, Konrad; Pech, Maciej; Amthauer, Holger; Lippert, Hans; Ricke, Jens; Seidensticker, Max

2014-05-01

In patients with liver malignancies potentially amenable to curative extended right hepatectomy but insufficient size of the future liver remnant (FLR), portal vein embolization (PVE) of the tumor-bearing liver is used to induce contralateral liver hypertrophy but leaves the tumor untreated. Radioembolization (RE) treats the tumor in the embolized lobe along with contralateral hypertrophy induction. We performed a matched-pair analysis to compare the capacity for hypertrophy induction of these two modalities. Patients with right-hepatic secondary liver malignancies with no or negligible left-hepatic tumor involvement who were treated by right-lobar PVE (n = 141) or RE (n = 35) at two centers were matched for criteria known to influence liver regeneration following PVE: 1) baseline FLR/Total liver volume ratio (<25 versus ≥ 25%); 2) prior platinum-containing systemic chemotherapy; 3) embolization of segments 5-8 versus 4-8; and 4) baseline platelet count (<200 versus ≥ 200 Gpt/L).The primary endpoint was relative change in FLR volume from baseline to follow-up. Twenty-six matched pairs were identified. FLR volume increase from baseline to follow-up (median 33 [24-56] days after PVE or 46 [27-79] days after RE) was significant in both groups but PVE produced significantly more FLR hypertrophy than RE (61.5 versus 29%, P < 0.001). Time between treatment and follow-up was not correlated with the degree of contralateral hypertrophy achieved in both groups. Although group differences in patient history and treatment setting were present and some bias cannot be excluded, this was minimized by the matched-pair design, as remaining group differences after matching were found to have no significant influence on contralateral hypertrophy development. PVE induces significantly more contralateral hypertrophy than RE with therapeutic (nonlobectomy) doses. However, contralateral hypertrophy induced by RE is substantial and RE minimizes the risk of tumor progression in the treated lobe, possibly making it a suitable modality for selected patients. © 2014 by the American Association for the Study of Liver Diseases.

Heat sink phenomenon of bipolar and monopolar radiofrequency ablation observed using polypropylene tubes for vessel simulation.

PubMed

Al-Alem, Ihssan; Pillai, Krishna; Akhter, Javed; Chua, Terence C; Morris, David L

2014-06-01

Radiofrequency ablation (RFA) is widely used for treating liver tumors; recurrence is common owing to proximity to blood vessels possibly due to the heat sink effect. We seek to investigate this phenomenon using unipolar and bipolar RFA on an egg white tumor tissue model and an animal liver model. Temperature profiles during ablation (with and without vessel simulation) were studied, using both bipolar and unipolar RFA probes by 4 strategically placed temperature leads to monitor temperature profile during ablation. The volume of ablated tissue was also measured. The volume ablated during vessel simulation confirmed the impact of the heat sink phenomenon. The heat sink effect of unipolar RFA was greater compared with bipolar RFA (ratio of volume affected 2:1) in both tissue and liver models. The volume ablated using unipolar RFA was less than the bipolar RFA (ratio of volume ablated = 1:4). Unipolar RFA achieved higher ablation temperatures (122°C vs 98°C). Unipolar RFA resulted in tissue damage beyond the vessel, which was not observed using bipolar RFA. Bipolar RFA ablates a larger tumor volume compared with unipolar RFA, with a single ablation. The impact of heat sink phenomenon in tumor ablation is less so with bipolar than unipolar RFA with sparing of adjacent vessel damage. © The Author(s) 2013.

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

Voroney, Jon-Paul; Brock, Kristy K.; Eccles, Cynthia

Purpose: The aim of this study was to compare magnetic resonance imaging (MRI) with computed tomography (CT) for liver cancer tumor definition for high-precision radiotherapy planning. Methods and Materials: Diagnostic quality MRI scans and triphasic CT scans, with the liver immobilized in exhale, were obtained at the time of radiation planning for 26 patients with unresectable liver metastases (n = 8), hepatocellular carcinoma (n = 10), and cholangiocarcinoma (n = 8). On the CT and MRI series best demonstrating the tumor, the liver and gross tumor volumes (GTVs) were contoured, and intrahepatic anatomic reference points were identified. Deformable registration wasmore » used to register the liver from the CT with that from the MRI. Results: A difference in the number of tumor foci was seen on CT vs. MRI in 5 patients with hepatocellular carcinoma: MRI showed more foci in 3 patients, CT in 2. After deformable registration of the livers, the population median of the average distance between the CT tumor surface and MRI tumor surface was 3.7 mm (2.2-21.3 mm). The median percentage of tumor surface area that differed by {>=}5 mm was 26% (1-86%). Median percentage concordance volumes were 81% (77-86%) in metastases, 77% (60-88%) in hepatocellular carcinoma and 64% (25-85%) in cholangiocarcinoma. Conclusion: Differences between MRI-defined liver cancer GTVs and CT-defined GTVs can be substantial and are more common in primary liver cancer.« less

Radiotherapy for gastric lymphoma: a planning study of 3D conformal radiotherapy, the half-beam method, and intensity-modulated radiotherapy.

PubMed

Inaba, Koji; Okamoto, Hiroyuki; Wakita, Akihisa; Nakamura, Satoshi; Kobayashi, Kazuma; Harada, Ken; Kitaguchi, Mayuka; Sekii, Shuhei; Takahashi, Kana; Yoshio, Kotaro; Murakami, Naoya; Morota, Madoka; Ito, Yoshinori; Sumi, Minako; Uno, Takashi; Itami, Jun

2014-11-01

During radiotherapy for gastric lymphoma, it is difficult to protect the liver and kidneys in cases where there is considerable overlap between these organs and the target volume. This study was conducted to compare the three radiotherapy planning techniques of four-fields 3D conformal radiotherapy (3DCRT), half-field radiotherapy (the half-beam method) and intensity-modulated radiotherapy (IMRT) used to treat primary gastric lymphoma in which the planning target volume (PTV) had a large overlap with the left kidney. A total of 17 patients with gastric diffuse large B-cell lymphoma (DLBCL) were included. In DLBCL, immunochemotherapy (Rituximab + CHOP) was followed by radiotherapy of 40 Gy to the whole stomach and peri-gastric lymph nodes. 3DCRT, the half-field method, and IMRT were compared with respect to the dose-volume histogram (DVH) parameters and generalized equivalent uniform dose (gEUD) to the kidneys, liver and PTV. The mean dose and gEUD for 3DCRT was higher than for IMRT and the half-beam method in the left kidney and both kidneys. The mean dose and gEUD of the left kidney was 2117 cGy and 2224 cGy for 3DCRT, 1520 cGy and 1637 cGy for IMRT, and 1100 cGy and 1357 cGy for the half-beam method, respectively. The mean dose and gEUD of both kidneys was 1335 cGy and 1559 cGy for 3DCRT, 1184 cGy and 1311 cGy for IMRT, and 700 cGy and 937 cGy for the half-beam method, respectively. Dose-volume histograms (DVHs) of the liver revealed a larger volume was irradiated in the dose range <25 Gy with 3DCRT, while the half-beam method irradiated a larger volume of liver with the higher dose range (>25 Gy). IMRT and the half-beam method had the advantages of dose reduction for the kidneys and liver. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Extreme liver resections with preservation of segment 4 only

PubMed Central

Balzan, Silvio Marcio Pegoraro; Gava, Vinícius Grando; Magalhães, Marcelo Arbo; Dotto, Marcelo Luiz

2017-01-01

AIM To evaluate safety and outcomes of a new technique for extreme hepatic resections with preservation of segment 4 only. METHODS The new method of extreme liver resection consists of a two-stage hepatectomy. The first stage involves a right hepatectomy with middle hepatic vein preservation and induction of left lobe congestion; the second stage involves a left lobectomy. Thus, the remnant liver is represented by the segment 4 only (with or without segment 1, ± S1). Five patients underwent the new two-stage hepatectomy (congestion group). Data from volumetric assessment made before the second stage was compared with that of 10 matched patients (comparison group) that underwent a single-stage right hepatectomy with middle hepatic vein preservation. RESULTS The two stages of the procedure were successfully carried out on all 5 patients. For the congestion group, the overall volume of the left hemiliver had increased 103% (mean increase from 438 mL to 890 mL) at 4 wk after the first stage of the procedure. Hypertrophy of the future liver remnant (i.e., segment 4 ± S1) was higher than that of segments 2 and 3 (144% vs 54%, respectively, P < 0.05). The median remnant liver volume-to-body weight ratio was 0.3 (range, 0.28-0.40) before the first stage and 0.8 (range, 0.45-0.97) before the second stage. For the comparison group, the rate of hypertrophy of the left liver after right hepatectomy with middle hepatic vein preservation was 116% ± 34%. Hypertrophy rates of segments 2 and 3 (123% ± 47%) and of segment 4 (108% ± 60%, P > 0.05) were proportional. The mean preoperative volume of segments 2 and 3 was 256 ± 64 cc and increased to 572 ± 257 cc after right hepatectomy. Mean preoperative volume of segment 4 increased from 211 ± 75 cc to 439 ± 180 cc after surgery. CONCLUSION The proposed method for extreme hepatectomy with preservation of segment 4 only represents a technique that could allow complete resection of multiple bilateral liver metastases. PMID:28765703

Liver function testing with nuclear medicine techniques is coming of age.

PubMed

Bennink, Roelof J; Tulchinsky, Mark; de Graaf, Wilmar; Kadry, Zakiyah; van Gulik, Thomas M

2012-03-01

Liver function is a broad term, as the organ participates in a multitude of different physiological and biochemical processes, including metabolic, synthetic, and detoxifying functions. However, it is the function of the hepatocyte that is central to sustaining normal life and dealing with disease states. When the liver begins to fail in severely ill patients, it forecasts a terminal outcome. However, unlike the glomerular filtration rate which clearly quantifies the key renal function, at most practice sites, there is no clinically available quantitative test for liver function. Although it is commonplace to assess indirect evidence of that function (by measuring blood levels of its end products and by-products) and to detect an acute injury (by following rising transaminases), a widely available test that would directly measure hepatocellular function is lacking. This article reviews current knowledge on liver function studies and focuses on those nuclear medicine tests available to study the whole liver and regional liver function. The clinical application driving these tests, prediction of remnant liver function after partial hepatectomy for primary liver malignancy or metastatic disease, is addressed here in detail. The test was recently validated for this specific application and was shown to be better than the current standard of practice (computed tomography volumetry), particularly in patients with hepatic comorbidities like cirrhosis, steatosis, or cholestasis. Furthermore, early assessment of regional liver function increase after preoperative portal vein embolization becomes possible with this technology. The limiting factor to a wider acceptance of this test is based on the lack of clinical software that would allow calculation of liver function parameters. This article provides information that enables a clinical nuclear medicine facility to provide this test using readily available equipment. Furthermore, it addresses emerging clinical applications that are under investigation. Copyright © 2012 Elsevier Inc. All rights reserved.

Changes in the planning target volume and liver volume dose based on the selected respiratory phase in respiratory-gated radiation therapy for a hepatocellular carcinoma

NASA Astrophysics Data System (ADS)

Lee, Jae-Seung; Im, In-Chul; Kang, Su-Man; Goo, Eun-Hoe; Baek, Seong-Min

2013-11-01

The aim of this study was to quantitatively analyze the changes in the planning target volume (PTV) and liver volume dose based on the respiratory phase to identify the optimal respiratory phase for respiratory-gated radiation therapy for a hepatocellular carcinoma (HCC). Based on the standardized procedure for respiratory-gated radiation therapy, we performed a 4-dimensional computed tomography simulation for 0 ˜ 90%, 30 ˜ 70%, and 40 ˜ 60% respiratory phases to assess the respiratory stability (S R ) and the defined PTV i for each respiratory phase i. A treatment plan was established, and the changes in the PTV i and dose volume of the liver were quantitatively analyzed. Most patients (91.5%) passed the respiratory stability test (S R = 0.111 ± 0.015). With standardized respiration training exercises, we were able to minimize the overall systematic error caused by irregular respiration. Furthermore, a quantitative analysis to identify the optimal respiratory phase revealed that when a short respiratory phase (40 ˜ 60%) was used, the changes in the PTV were concentrated inside the center line; thus, we were able to obtain both a PTV margin accounting for respiration and a uniform radiation dose within the PTV.

Liver failure in total artificial heart therapy.

PubMed

Dimitriou, Alexandros Merkourios; Dapunt, Otto; Knez, Igor; Wasler, Andrae; Oberwalder, Peter; Koerfer, Reiner; Tenderich, Gero; Spiliopoulos, Sotirios

2016-07-01

Congestive hepatopathy (CH) and acute liver failure (ALF) are common among biventricular heart failure patients. We sought to evaluate the impact of total artificial heart (TAH) therapy on hepatic function and associated clinical outcomes. A total of 31 patients received a Syncardia Total Artificial Heart. Preoperatively 17 patients exhibited normal liver function or mild hepatic derangements that were clinically insignificant and did not qualify as acute or chronic liver failure, 5 patients exhibited ALF and 9 various hepatic derangements owing to CH. Liver associated mortality and postoperative course of liver values were prospectively documented and retrospectively analyzed. Liver associated mortality in normal liver function, ALF and CH cases was 0%, 20% (P=0.03) and 44.4% (P=0.0008) respectively. 1/17 (5.8%) patients with a normal liver function developed an ALF, 4/5 (80%) patients with an ALF experienced a markedly improvement of hepatic function and 6/9 (66.6%) patients with CH a significant deterioration. TAH therapy results in recovery of hepatic function in ALF cases. Patients with CH prior to surgery form a high risk group with increased liver associated mortality.

Abdominal Ultrasound With Scintigraphic and Clinical Correlates in Infants With Sickle Cell Anemia: Baseline Data From the BABY HUG Trial

PubMed Central

McCarville, M. Beth; Luo, Zhaoyu; Huang, Xiangke; Rees, Renee C.; Rogers, Zora R.; Miller, Scott T.; Thompson, Bruce; Kalpatthi, Ram; Wang, Winfred C.

2015-01-01

OBJECTIVE The purpose of this study is to perform and evaluate baseline abdominal ultrasound in infants with sickle cell anemia who participated in the BABY HUG multiinstitutional randomized placebo-controlled trial of hydroxyurea therapy and to examine the potential relationships among ultrasound results and clinical, nuclear medicine, and laboratory data. SUBJECTS AND METHODS After local institutional review board approval and with informed guardian consent, 116 girls and 87 boys (age range, 7.5–18 months) with sickle cell anemia underwent standardized abdominal sonography at 14 institutions. Imaging was centrally reviewed by one radiologist who assessed and measured the spleen, kidneys, gallbladder, and common bile duct. Baseline physical assessment of spleen size, serum alanine aminotransferase and bilirubin levels, 99mTc sulfur colloid liver-spleen scans, and 99mTc diethylenetriaminepentaacetic acid clearance glomerular filtration rates (GFRs) were obtained. Analysis of variance and the Student test were performed to compare sonographic findings to published results in healthy children and to clinical and laboratory findings. RESULTS The mean (± SD) spleen volume (108 ± 47 mL) was significantly greater than published normal control values (30 ± 14 mL; p < 0.0001). There was no correlation between spleen volume and function assessed by liver-spleen scan. The mean GFR (125 ± 34 mL/min/1.73 m2) was elevated compared with control GFRs (92 ± 18 mL/min/1.73 m2). Renal volumes (right kidney, 29 ± 8 mL; left kidney, 31 ± 9 mL) were significantly greater than control volumes (right kidney, 27 ± 3 mL; left kidney, 27 ± 3 mL; p < 0.0001) and were positively correlated with GFR (p = 0.0009). Five percent of patients had sonographic biliary abnormalities (sludge, n = 6; dilated common bile duct, n = 2; and cholelithiasis and thickened gallbladder wall, n = 1 each). There was no correlation between biliary sonographic findings and laboratory results. CONCLUSION In infants with sickle cell anemia, sonographic spleen volume does not reflect function, but increased renal volume correlates with GFR and is consistent with hyperfiltration. Sonographic biliary abnormalities can occur early in life, while remaining clinically silent. PMID:21606305

[Cholestatic icterus due to oral contraceptives].

PubMed

Pestel, M; Lambert, C; Jeanmougin, M

1973-03-01

A case report of cholestatic jaundice in a 25 year old woman, who had had jaundice at age 4 years, and had taken Stediril (a combined oral contraceptive) for 1 month, implicates either the pill or a possibly hereditary hyperlipidemia. The jaundice developed in 2 weeks with vomiting, epigastric pain, anorexia, then discolored urine and feces, and intense pruritus. On hospitalization the patient had moderate bilirubinemia (56 mg/1), low alkaline phosphatase (13 U.K.) and slightly high serum glutamate pyruvate transaminase (270 U.W.). There were elevated serum cholesterol (3 gm/1), triglycerides (2.05 gm/1), total lipids (10.6 gm/1), and a definitely increased pre-beta lipoprotein, suggesting hyperlipidemia type IV (Frederickson classification). Liver biopsy showed fibrosis of the portal spaces lymphocytic infiltration, canalicular and intrahepatocytic thrombi. On laparoscopy the liver had a regular lower border, normal volume color and surface. Albumin, prothrombin and flocculation tests were normal. The patient's jaundice lasted about 1 month, then liver function slowly improved, although pruritus remained intense. Probably this jaundice was due to oral contraceptives, in a patient predisposed either by jaundice in childhood or endogenous hyperlipidemia.

High-intensity focused ultrasound ablation: an effective and safe treatment for secondary hypersplenism.

PubMed

Zhu, J; Zhu, H; Mei, Z; Zhang, L; Jin, C; Ran, L; Zhou, K; Yang, W

2014-11-01

Hypersplenism is a common disease. The conventional treatment is splenectomy and partial splenic embolization; however, both of them have high complication rates and technical defects. Therefore, safer and more effective techniques should be considered for the treatment of hypersplenism. High-intensity focused ultrasound (HIFU) may provide an effective and safe way for treatment of hypersplenism. Therefore, we conducted this study to assess the safety and efficacy of HIFU in treatment of secondary hypersplenism. A total of 28 patients who suffered from secondary hypersplenism were treated with HIFU ablation. All patients who underwent HIFU were closely followed-up over a year. MRI scan was performed, and the spleens were observed. Blood counts and liver function tests were also carried out. In the follow-up process, the levels of white blood cells and platelets in the blood after HIFU were significantly higher than those before HIFU, liver function also improved after HIFU treatment. In addition, the symptoms were ameliorated significantly or even disappeared. The MRI showed that the ablation area had turned into a non-perfused volume, and after 12 months of HIFU ablation, the ablated area shrank evidently; the sunken spleen formed a lobulated shape and the splenic volume decreased. HIFU ablation is a safe, effective and non-invasive approach for secondary hypersplenism. For the first time we used HIFU ablation to treat secondary hypersplenism. It not only expands indications of HIFU but also provides better choice for the treatment of secondary hypersplenism.

Sarcopenia Impairs Prognosis of Patients with Hepatocellular Carcinoma: The Role of Liver Functional Reserve and Tumor-Related Factors in Loss of Skeletal Muscle Volume.

PubMed

Imai, Kenji; Takai, Koji; Watanabe, Satoshi; Hanai, Tatsunori; Suetsugu, Atsushi; Shiraki, Makoto; Shimizu, Masahito

2017-09-22

Sarcopenia impairs survival in patients with hepatocellular carcinoma (HCC). This study aimed to clarify the factors that contribute to decreased skeletal muscle volume in patients with HCC. The third lumbar vertebra skeletal muscle index (L3 SMI) in 351 consecutive patients with HCC was calculated to identify sarcopenia. Sarcopenia was defined as an L3 SMI value ≤ 29.0 cm²/m² for women and ≤ 36.0 cm²/m² for men. The factors affecting L3 SMI were analyzed by multiple linear regression analysis and tree-based models. Of the 351 HCC patients, 33 were diagnosed as having sarcopenia and showed poor prognosis compared with non-sarcopenia patients ( p = 0.007). However, this significant difference disappeared after the adjustments for age, sex, Child-Pugh score, maximum tumor size, tumor number, and the degree of portal vein invasion by propensity score matching analysis. Multiple linear regression analysis showed that age ( p = 0.015) and sex ( p < 0.0001) were significantly correlated with a decrease in L3 SMI. Tree-based models revealed that sex (female) is the most significant factor that affects L3 SMI. In male patients, L3 SMI was decreased by aging, increased Child-Pugh score (≥56 years), and enlarged tumor size (<56 years). Maintaining liver functional reserve and early diagnosis and therapy for HCC are vital to prevent skeletal muscle depletion and improve the prognosis of patients with HCC.

Abnormal liver function in common variable immunodeficiency disorders due to nodular regenerative hyperplasia.

PubMed

Ward, C; Lucas, M; Piris, J; Collier, J; Chapel, H

2008-09-01

Patients with common variable immunodeficiency disorders are monitored for liver function test abnormalities. A proportion of patients develop deranged liver function and some also develop hepatomegaly. We investigated the prevalence of abnormalities and types of liver disease, aiming to identify those at risk and determine outcomes. The local primary immunodeficiency database was searched for patients with a common variable immunodeficiency disorder and abnormal liver function and/or a liver biopsy. Patterns of liver dysfunction were determined and biopsies reviewed. A total of 47 of 108 patients had deranged liver function, most commonly raised alkaline phosphatase levels. Twenty-three patients had liver biopsies. Nodular regenerative hyperplasia was found in 13 of 16 with unexplained pathology. These patients were more likely to have other disease-related complications of common variable immunodeficiency disorders, in particular non-coeliac (gluten insensitive) lymphocytic enteropathy. However, five had no symptoms of liver disease and only one died of liver complications. Nodular regenerative hyperplasia is a common complication of common variable immunodeficiency disorders but was rarely complicated by portal hypertension.

Future remnant liver function as predictive factor for the hypertrophy response after portal vein embolization.

PubMed

Cieslak, Kasia P; Huisman, Floor; Bais, Thomas; Bennink, Roelof J; van Lienden, Krijn P; Verheij, Joanne; Besselink, Marc G; Busch, Olivier R C; van Gulik, Thomas M

2017-07-01

Preoperative portal vein embolization is widely used to increase the future remnant liver. Identification of nonresponders to portal vein embolization is essential because these patients may benefit from associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), which induces a more powerful hypertrophy response. 99m Tc-mebrofenin hepatobiliary scintigraphy is a quantitative method for assessment of future remnant liver function with a calculated cutoff value for the prediction of postoperative liver failure. The aim of this study was to analyze future remnant liver function before portal vein embolization to predict sufficient functional hypertrophy response after portal vein embolization. Sixty-three patients who underwent preoperative portal vein embolization and computed tomography imaging were included. Hepatobiliary scintigraphy was performed to determine pre-portal vein embolization and post-portal vein embolization future remnant liver function. Receiver operator characteristic analysis of pre-portal vein embolization future remnant liver function was performed to identify patients who would meet the post-portal vein embolization cutoff value for sufficient function (ie, 2.7%/min/m 2 ). Mean pre-portal vein embolization future remnant liver function was 1.80% ± 0.45%/min/m 2 and increased to 2.89% ± 0.97%/min/m 2 post-portal vein embolization. Receiver operator characteristic analysis in 33 patients who did not receive chemotherapy revealed that a pre-portal vein embolization future remnant liver function of ≥1.72%/min/m 2 was able to identify patients who would meet the safe future remnant liver function cutoff value 3 weeks after portal vein embolization (area under the curve = 0.820). The predictive value was less pronounced in 30 patients treated with neoadjuvant chemotherapy (area under the curve = 0.618). A total of 45 of 63 patients underwent liver resection, of whom 5 of 45 developed postoperative liver failure; 4 of 5 patients had a post-portal vein embolization future remnant liver function below the cutoff value for safe resection. When selecting patients for portal vein embolization, future remnant liver function assessed with hepatobiliary scintigraphy can be used as a predictor of insufficient functional hypertrophy after portal vein embolization, especially in nonchemotherapy patients. These patients are potential candidates for ALPPS. Copyright © 2017 Elsevier Inc. All rights reserved.

Threshold doses for focal liver reaction after stereotactic ablative body radiation therapy for small hepatocellular carcinoma depend on liver function: evaluation on magnetic resonance imaging with Gd-EOB-DTPA.

PubMed

Sanuki, Naoko; Takeda, Atsuya; Oku, Yohei; Eriguchi, Takahisa; Nishimura, Shuichi; Aoki, Yosuke; Mizuno, Tomikazu; Iwabuchi, Shogo; Kunieda, Etsuo

2014-02-01

Focal liver reaction (FLR) appears on radiographic images after stereotactic ablative body radiation therapy (SABR) in patients with hepatocellular carcinoma (HCC) and chronic liver disease. We investigated the threshold dose (TD) of FLR and possible factors affecting the TD on gadoxetate acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI). In 50 patients who were treated with SABR for small HCC and followed up by MRI for >6 months, FLR, seen as a hypointense area, was evaluated on the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI. The follow-up MRI with the largest extent of FLR was fused to the planning computed tomography (CT) image, and patients with good image fusion concordance were eligible. After delineating the border of the FLR manually, a dose-volume histogram was used to identify the TD for the FLR. Clinical and volumetric factors were analyzed for correlation with the TD. A total of 45 patients were eligible for analysis with a median image fusion concordance of 84.9% (range, 71.6-95.4%). The median duration between SABR and subsequent hepatobiliary phase MRI with the largest extent of FLR was 3 months (range, 1-6 months). The median TD for FLR was 28.0 Gy (range, 22.3-36.4 Gy). On univariate analysis, pre-treatment Child-Pugh (CP) score and platelet count were significantly correlated with the TD. On multiple linear regression analysis, CP score was the only parameter that predicted TD. Median TDs were 30.5 Gy (range, 26.2.3-36.4 Gy) and 25.2 Gy (range, 22.3-27.5 Gy) for patients with CP-A and CP-B disease, respectively. The TD was significantly correlated with baseline liver function. We propose 30 Gy for CP-A disease and 25 Gy for CP-B disease in 5 fractions as TDs for FLR after SABR for patients with HCC and chronic liver disease. Use of these TDs will help to predict potential loss of liver tissue after SABR. Copyright © 2014 Elsevier Inc. All rights reserved.

Current Management of Neonatal Liver Tumors.

PubMed

Langham, Max R; Furman, Wayne L; Fernandez-Pineda, Israel

2015-01-01

This review is focused on the special issues and challenges confronting physicians and surgeons caring for an unborn child, or a newborn with a liver tumor. Liver tumors at this age are very rare and they make it difficult for pediatric surgeons to gain experience necessary to obtain good results. On the other hand, adult hepatobiliary surgeons faced with a fetus or infant with a liver mass are ill equipped to care for the patient even if they have done a high volume of adult liver surgery and are expert in the field. Often a team approach is the best solution.

Random forest classification of large volume structures for visuo-haptic rendering in CT images

NASA Astrophysics Data System (ADS)

Mastmeyer, Andre; Fortmeier, Dirk; Handels, Heinz

2016-03-01

For patient-specific voxel-based visuo-haptic rendering of CT scans of the liver area, the fully automatic segmentation of large volume structures such as skin, soft tissue, lungs and intestine (risk structures) is important. Using a machine learning based approach, several existing segmentations from 10 segmented gold-standard patients are learned by random decision forests individually and collectively. The core of this paper is feature selection and the application of the learned classifiers to a new patient data set. In a leave-some-out cross-validation, the obtained full volume segmentations are compared to the gold-standard segmentations of the untrained patients. The proposed classifiers use a multi-dimensional feature space to estimate the hidden truth, instead of relying on clinical standard threshold and connectivity based methods. The result of our efficient whole-body section classification are multi-label maps with the considered tissues. For visuo-haptic simulation, other small volume structures would have to be segmented additionally. We also take a look into these structures (liver vessels). For an experimental leave-some-out study consisting of 10 patients, the proposed method performs much more efficiently compared to state of the art methods. In two variants of leave-some-out experiments we obtain best mean DICE ratios of 0.79, 0.97, 0.63 and 0.83 for skin, soft tissue, hard bone and risk structures. Liver structures are segmented with DICE 0.93 for the liver, 0.43 for blood vessels and 0.39 for bile vessels.

Association between liver transplant center performance evaluations and transplant volume.

PubMed

Buccini, L D; Segev, D L; Fung, J; Miller, C; Kelly, D; Quintini, C; Schold, J D

2014-09-01

There has been increased oversight of transplant centers and stagnation in liver transplantation nationally in recent years. We hypothesized that centers that received low performance (LP) evaluations were more likely to alter protocols, resulting in reduced rates of transplants and patients placed on the waiting list. We evaluated the association of LP evaluations and transplant activity among liver transplant centers in the United States using national Scientific Registry of Transplant Recipients data (January 2007 to July 2012). We compared the average change in recipient and candidate volume and donor and patient characteristics based on whether the centers received LP evaluations. Of 92 eligible centers, 27 (29%) received at least one LP evaluation. Centers without an LP evaluation (n = 65) had an average increase of 9.3 transplants and 14.9 candidates while LP centers had an average decrease of 39.9 transplants (p < 0.01) and 67.3 candidates (p < 0.01). LP centers reduced the use of older donors, donations with longer cold ischemia, and donations after cardiac death (p-values < 0.01). There was no association between the change in transplant volume and measured performance (R(2)  = 0.002, p = 0.91). Findings indicate a strong association between performance evaluations and changes in candidate listings and transplants among liver transplant centers, with no measurable improvement in outcomes associated with reduction in transplant volume. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

Radiation-induced Liver Injury after 3D-conformal Radiotherapy for Hepatocellular Carcinoma: Quantitative Assessment Using Gd-EOB-DTPA-enhanced MRI.

PubMed

Fukugawa, Yoshiyuki; Namimoto, Tomohiro; Toya, Ryo; Saito, Tetsuo; Yuki, Hideaki; Matsuyama, Tomohiko; Ikeda, Osamu; Yamashita, Yasuyuki; Oya, Natsuo

2017-02-01

Focal liver reaction (FLR) appears in the hepatobiliary-phase images of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-enhanced MRI) following radiotherapy (RT). We investigated the threshold dose (TD) for FLR development in 13 patients with hepatocellular carcinoma (HCC) who underwent three-dimensional conformal radiotherapy (3D-CRT) with 45 Gy in 15 fractions. FLR volumes (FLRVs) were calculated based on planning CT images by referring to fused hepatobiliary- phase images. We also calculated the TD and the irradiated volumes (IVs) of the liver parenchyma at a given dose of every 5 Gy (IVdose) based on a dose-volume histogram (DVH). The median TD was 35.2 Gy. The median IV20, IV25, IV30, IV35, IV40, and IV45 values were 371.1, 274.8, 233.4, 188.6, 145.8, and 31.0 ml, respectively. The median FLRV was 144.9 ml. There was a significant difference between the FLRV and IV20, IV25, and IV45 (p<0.05), but no significant differences between the FLRV and IV30, IV35, or IV40. These results suggest that the threshold dose of the FLR is approx. 35 Gy in HCC patients who undergo 3D-CRT in 15 fractions. The percentage of the whole liver volume receiving a dose of more than 30-40 Gy (V30-40) is a potential candidate optimal DVH parameter for this fractionation schedule.

Treatment of hepatic metastases of colorectal cancer by robotic stereotactic radiation (Cyberknife ®).

PubMed

Peiffert, D; Baumann, A-S; Marchesi, V

2014-04-01

Cyberknife(®) is a dedicated stereotactic radiotherapy device. This new technology permits precise delivery of high dose gradient radiation therapy while sparing the surrounding organs at risk. Hepatic metastases of colorectal cancer (HMCRC) are an example of a lesion where treatment with Cyberknife(®) is indicated because they are located in a radio-sensitive organ and curative treatment is based on focal eradication (resection, radiofrequency ablation,...). The local control rate at one year is reported to be 70 to 100% depending on the study. Tolerance is excellent with less than a 5% rate of acute grade 3 or 4 side effects (nausea, vomiting, gastro-duodenal ulcer). The specific hepatotoxicity of radiotherapy, so-called radiation-induced liver disease (RILD), was found in only one study. Candidates for stereotactic radiotherapy are patients in whom disease is controlled except for intrahepatic disease with 1-3 hepatic metastases ≤ 6 cm in size who have contraindications for surgery, a WHO stage ≤ 2, a volume of healthy liver ≥ 700 cm(3) and normal liver function. It is actually a very simple treatment that results in very good local control with few contraindications. Its place in the management strategy of liver metastases needs further clarification. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

The Role of Akt in Chronic Liver Disease and Liver Regeneration.

PubMed

Morales-Ruiz, Manuel; Santel, Ansgar; Ribera, Jordi; Jiménez, Wladimiro

2017-02-01

The liver is continuously exposed to diverse insults, which may culminate in pathological processes causing liver disease. An effective therapeutic strategy for chronic liver disease should control the causal factors of the disease and stimulate functional liver regeneration. Preclinical studies have shown that interventions aimed at maintaining Akt activity in a dysfunctional liver meet most of the criteria. Although the central function of Akt is cell survival, other cellular aspects such as glucose uptake, glycogen synthesis, cell-cycle progression, and lipid metabolism have been shown to be prominent functions of Akt in the context of hepatic physiology. In this review, the authors describe the benefits of the Akt signaling pathway, emphasizing its importance in coordinating proper cellular growth and differentiation during liver regeneration, hepatic function, and liver disease. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Chemical Shift MR Imaging Methods for the Quantification of Transcatheter Lipiodol Delivery to the Liver: Preclinical Feasibility Studies in a Rodent Model

PubMed Central

Yin, Xiaoming; Guo, Yang; Li, Weiguo; Huo, Eugene; Zhang, Zhuoli; Nicolai, Jodi; Kleps, Robert A.; Hernando, Diego; Katsaggelos, Aggelos K.; Omary, Reed A.

2012-01-01

Purpose: To demonstrate the feasibility of using chemical shift magnetic resonance (MR) imaging fat-water separation methods for quantitative estimation of transcatheter lipiodol delivery to liver tissues. Materials and Methods: Studies were performed in accordance with institutional Animal Care and Use Committee guidelines. Proton nuclear MR spectroscopy was first performed to identify lipiodol spectral peaks and relative amplitudes. Next, phantoms were constructed with increasing lipiodol-water volume fractions. A multiecho chemical shift–based fat-water separation method was used to quantify lipiodol concentration within each phantom. Six rats served as controls; 18 rats underwent catheterization with digital subtraction angiography guidance for intraportal infusion of a 15%, 30%, or 50% by volume lipiodol-saline mixture. MR imaging measurements were used to quantify lipiodol delivery to each rat liver. Lipiodol concentration maps were reconstructed by using both single-peak and multipeak chemical shift models. Intraclass and Spearman correlation coefficients were calculated for statistical comparison of MR imaging–based lipiodol concentration and volume measurements to reference standards (known lipiodol phantom compositions and the infused lipiodol dose during rat studies). Results: Both single-peak and multipeak measurements were well correlated to phantom lipiodol concentrations (r2 > 0.99). Lipiodol volume measurements were progressively and significantly higher when comparing between animals receiving different doses (P < .05 for each comparison). MR imaging–based lipiodol volume measurements strongly correlated with infused dose (intraclass correlation coefficients > 0.93, P < .001) with both single- and multipeak approaches. Conclusion: Chemical shift MR imaging fat-water separation methods can be used for quantitative measurements of lipiodol delivery to liver tissues. © RSNA, 2012 PMID:22623693

Traditional surgical planning of liver surgery is modified by 3D interactive quantitative surgical planning approach: a single-center experience with 305 patients.

PubMed

Wang, Xue-Dong; Wang, Hong-Guang; Shi, Jun; Duan, Wei-Dong; Luo, Ying; Ji, Wen-Bin; Zhang, Ning; Dong, Jia-Hong

2017-06-01

Decision making and surgical planning are to achieve the precise balance of maximal removal of target lesion, maximal sparing of functional liver remnant volume, and minimal surgical invasiveness and therefore, crucial in liver surgery. The aim of this prospective study was to validate the accuracy and predictability of 3D interactive quantitative surgical planning approach (IQSP), and to evaluate the impact of IQSP on traditional surgical plans based on 2D images. A total of 305 consecutive patients undergoing hepatectomy were included in this study. Surgical plans were created by traditional 2D approach using picture archiving and communication system (PACS) and 3D approach using IQSP respectively by two groups of physicians who did not know the surgical plans of the other group. The two surgical plans were submitted to the chief surgeon for selection before operation. The specimens were weighed. The two surgical plans were compared and analyzed retrospectively based on the operation results. The two surgical plans were successfully developed in all 305 patients and all the 3D IQSP surgical plans were selected as the final decision. Total 278 patients successfully underwent surgery, including 147 uncomplex hepatectomy and 131 complex hepatectomy. Twenty-seven patients were withdrawn from hepatectomy. In the uncomplex group, the two surgical plans were the same in all 147 patients and no statistically significant difference was found among 2D calculated resection volume (2D-RV), 3D IQSP calculated resection volume (IQSP-RV) and the specimen volume. In the complex group, the two surgical plans were different in 49 patients (49/131, 37.4%). According to the significance of differences, the 49 different patients were classified into three grades. No statistically significant difference was found between IQSP-RV and specimen volume. The coincidence rate of territory analysis of IQSP with operation was 92.1% (93/101) for 101 patients of anatomic hepatectomy. The accuracy and predictability of 3D IQSP were validated. Compared with traditional surgical planning, 3D IQSP can provide more quantitative information of anatomic structure. With the assistance of 3D IQSP, traditional surgical plans were modified to be more radical and safe.

Effects of edaravone, a radical scavenger, on hepatocyte transplantation.

PubMed

Hayashi, Chihiro; Ito, Masahiro; Ito, Ryoutaro; Murakumo, Akiko; Yamamoto, Naoki; Hiramatsu, Noriko; Fox, Ira J; Horiguchi, Akihiko

2014-12-01

Hepatocyte transplantation (HTx) has yielded significant improvements in liver function and survival in experimentally induced acute liver failure and liver-based metabolic disease. However, transplantation is inefficient, and it is thought that transplanted hepatocytes have a shortened lifespan because of inflammation involving excess nitric oxide (NO). The present study aimed to clarify whether edaravone, a free radical scavenger used to treat ischemic stroke, could reduce ischemic changes in hepatocyte-transplanted livers. Edaravone (3 mg/kg) was administered intravenously 24 h before HTx to Nagase analbuminemic rats (NARs). Hepatocytes were isolated, and 30 × 10(6) cells were injected in a 1.0-ml volume directly into the spleens of NARs. All experimental groups studied received FK506 to control rejection. Animals in Group A received medium-only; Group B received HTx only; and Group C received HTx and edaravone. Forty-eight hours after transplantation, the hepatocytes from animals were isolated and analyzed for staining with propidium iodide- and annexin-V using flow cytometry. Liver sections were also studied by immunostaining for albumin, and TUNEL. Peripheral blood serum albumin levels were measured on post-transplant days 0, 3, 5, 7, 10 and 14 using ELISA. The edaravone-treated animals demonstrated an increased number of engrafted donor hepatocytes in the liver. The edaravone-treated liver sections also contained fewer TUNEL-positive cells and animals that received edaravone had higher serum albumin levels post-transplantation. Hepatocytes were also found to have increased in numbers 2 weeks following treatment with edaravone. Edaravone administration during HTx can suppress apoptosis near the transplanted cells, increasing engraftment. These studies indicate its potential usefulness for future clinical application. © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Longitudinal study of cognitive and academic outcomes after pediatric liver transplantation.

PubMed

Sorensen, Lisa G; Neighbors, Katie; Martz, Karen; Zelko, Frank; Bucuvalas, John C; Alonso, Estella M

2014-07-01

To determine the evolution of cognitive and academic deficits and risk factors in children after liver transplantation. Patients ≥2 years after liver transplantation were recruited through Studies of Pediatric Liver Transplantation. Participants age 5-6 years at Time 1 completed the Wechsler Preschool and Primary Scale of Intelligence, 3rd edition, Wide Range Achievement Test, 4th edition, and Behavior Rating Inventory of Executive Function (BRIEF). Participants were retested at age 7-9 years, Time 2 (T2), by use of the Wechsler Intelligence Scales for Children, 4th edition, Wide Range Achievement Test, 4th edition, and BRIEF. Medical and demographic variables significant at P ≤ .10 in univariate analysis were fitted to repeated measures modeling predicting Full Scale IQ (FSIQ). Of 144 patients tested at time 1, 93 (65%) completed T2; returning patients did not differ on medical or demographic variables. At T2, more participants than expected had below-average FSIQ, Verbal Comprehension, Working Memory, and Math Computation, as well as increased executive deficits on teacher BRIEF. Processing Speed approached significance. At T2, 29% (14% expected) had FSIQ = 71-85, and 7% (2% expected) had FSIQ ≤70 (P = .0001). A total of 42% received special education. Paired comparisons revealed that, over time, cognitive and math deficits persisted; only reading improved. Modeling identified household status (P < .002), parent education (P < .01), weight z-score at liver transplantation (P < .03), and transfusion volume during liver transplantation (P < .0001) as predictors of FSIQ. More young liver transplantation recipients than expected are at increased risk for lasting cognitive and academic deficits. Pretransplant markers of nutritional status and operative complications predicted intellectual outcome. Copyright © 2014 Elsevier Inc. All rights reserved.

Optimizing global liver function in radiation therapy treatment planning

NASA Astrophysics Data System (ADS)

Wu, Victor W.; Epelman, Marina A.; Wang, Hesheng; Romeijn, H. Edwin; Feng, Mary; Cao, Yue; Ten Haken, Randall K.; Matuszak, Martha M.

2016-09-01

Liver stereotactic body radiation therapy (SBRT) patients differ in both pre-treatment liver function (e.g. due to degree of cirrhosis and/or prior treatment) and radiosensitivity, leading to high variability in potential liver toxicity with similar doses. This work investigates three treatment planning optimization models that minimize risk of toxicity: two consider both voxel-based pre-treatment liver function and local-function-based radiosensitivity with dose; one considers only dose. Each model optimizes different objective functions (varying in complexity of capturing the influence of dose on liver function) subject to the same dose constraints and are tested on 2D synthesized and 3D clinical cases. The normal-liver-based objective functions are the linearized equivalent uniform dose (\\ell \\text{EUD} ) (conventional ‘\\ell \\text{EUD} model’), the so-called perfusion-weighted \\ell \\text{EUD} (\\text{fEUD} ) (proposed ‘fEUD model’), and post-treatment global liver function (GLF) (proposed ‘GLF model’), predicted by a new liver-perfusion-based dose-response model. The resulting \\ell \\text{EUD} , fEUD, and GLF plans delivering the same target \\ell \\text{EUD} are compared with respect to their post-treatment function and various dose-based metrics. Voxel-based portal venous liver perfusion, used as a measure of local function, is computed using DCE-MRI. In cases used in our experiments, the GLF plan preserves up to 4.6 % ≤ft(7.5 % \\right) more liver function than the fEUD (\\ell \\text{EUD} ) plan does in 2D cases, and up to 4.5 % ≤ft(5.6 % \\right) in 3D cases. The GLF and fEUD plans worsen in \\ell \\text{EUD} of functional liver on average by 1.0 Gy and 0.5 Gy in 2D and 3D cases, respectively. Liver perfusion information can be used during treatment planning to minimize the risk of toxicity by improving expected GLF; the degree of benefit varies with perfusion pattern. Although fEUD model optimization is computationally inexpensive and often achieves better GLF than \\ell \\text{EUD} model optimization does, the GLF model directly optimizes a more clinically relevant metric and can further improve fEUD plan quality.

Cryopreservation and re-culture of a 2.3 litre biomass for use in a bioartificial liver device

PubMed Central

Kilbride, Peter; Lamb, Stephen; Gibbons, Stephanie; Bundy, James; Erro, Eloy; Selden, Clare; Fuller, Barry; Morris, John

2017-01-01

For large and complex tissue engineered constructs to be available on demand, long term storage using methods, such as cryopreservation, are essential. This study optimised parameters such as excess media concentration and warming rates and used the findings to enable the successful cryopreservation of 2.3 litres of alginate encapsulated liver cell spheroids. This volume of biomass is typical of those required for successful treatment of Acute Liver Failure using our Bioartificial Liver Device. Adding a buffer of medium above the biomass, as well as slow (0.6°C/min) warming rates was found to give the best results, so long as the warming through the equilibrium melting temperature was rapid. After 72 h post thaw-culture, viable cell number, glucose consumption, lactate production, and alpha-fetoprotein production had recovered to pre-freeze values in the 2.3 litre biomass (1.00 ± 0.05, 1.19 ± 0.10, 1.23 ± 0.18, 2.03 ± 0.04 per ml biomass of the pre-cryopreservation values respectively). It was also shown that further improvements in warming rates of the biomass could reduce recovery time to < 48 h. This is the first example of a biomass of this volume being successfully cryopreserved in a single cassette and re-cultured. It demonstrates that a bioartificial liver device can be cryopreserved, and has wider applications to scale-up large volume cryopreservation. PMID:28841674

Cryopreservation and re-culture of a 2.3 litre biomass for use in a bioartificial liver device.

PubMed

Kilbride, Peter; Lamb, Stephen; Gibbons, Stephanie; Bundy, James; Erro, Eloy; Selden, Clare; Fuller, Barry; Morris, John

2017-01-01

For large and complex tissue engineered constructs to be available on demand, long term storage using methods, such as cryopreservation, are essential. This study optimised parameters such as excess media concentration and warming rates and used the findings to enable the successful cryopreservation of 2.3 litres of alginate encapsulated liver cell spheroids. This volume of biomass is typical of those required for successful treatment of Acute Liver Failure using our Bioartificial Liver Device. Adding a buffer of medium above the biomass, as well as slow (0.6°C/min) warming rates was found to give the best results, so long as the warming through the equilibrium melting temperature was rapid. After 72 h post thaw-culture, viable cell number, glucose consumption, lactate production, and alpha-fetoprotein production had recovered to pre-freeze values in the 2.3 litre biomass (1.00 ± 0.05, 1.19 ± 0.10, 1.23 ± 0.18, 2.03 ± 0.04 per ml biomass of the pre-cryopreservation values respectively). It was also shown that further improvements in warming rates of the biomass could reduce recovery time to < 48 h. This is the first example of a biomass of this volume being successfully cryopreserved in a single cassette and re-cultured. It demonstrates that a bioartificial liver device can be cryopreserved, and has wider applications to scale-up large volume cryopreservation.

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

McCulloch, M; Polan, D; Feng, M

Purpose: Previous studies have shown that radiotherapy treatment for liver metastases causes marked liver hypertrophy in areas receiving low dose and atrophy/fibrosis in areas receiving high dose. The purpose of this work is to develop and evaluate a biomechanical model-based dose-response model to describe these liver responses to SBRT. Methods: In this retrospective study, a biomechanical model-based deformable registration algorithm, Morfeus, was expanded to include dose-based boundary conditions. Liver and tumor volumes were contoured on the planning images and CT/MR images three months post-RT and converted to finite element models. A thermal expansion-based relationship correlating the delivered dose and volumemore » response was generated from 22 patients previously treated. This coefficient, combined with the planned dose, was applied as an additional boundary condition to describe the volumetric response of the liver of an additional cohort of metastatic liver patients treated with SBRT. The accuracy of the model was evaluated based on overall volumetric liver comparisons and the target registration error (TRE) using the average deviations in positions of identified vascular bifurcations on each set of registered images, with a target accuracy of the 2.5mm isotropic dose grid (vector dimension 4.3mm). Results: The thermal expansion coefficient models the volumetric change of the liver to within 3%. The accuracy of Morfeus with dose-expansion boundary conditions a TRE of 5.7±2.8mm compared to 11.2±3.7mm using rigid registration and 8.9±0.28mm using Morfeus with only spatial boundary conditions. Conclusion: A biomechanical model has been developed to describe the volumetric and spatial response of the liver to SBRT. This work will enable the improvement of correlating functional imaging with delivered dose, the mapping of the delivered dose from one treatment onto the planning images for a subsequent treatment, and will further provide information to assist with the biological characterization of patients’ response to radiation.« less

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

Choi, Y.; Hawkins, R.A.; Huang, S.C.

The liver plays an important role in glucose homeostasis. PET studies with 2-[F-18]fluro-2-deoxy-D-glucose (FDG) of the liver (e.g., in neoplasms) require an understanding of the effects of dietary conditions on hepatic FDG uptake. Twenty studies were performed on 10 normal volunteers (ages 24 {+-} 4) after fasting 4 to 19 hr and again after oral consumption of 100 g of dextrose to investigate tracer kinetic model configurations of FDG in the normal liver and to evaluate the impact of oral glucose on liver in normal subjects. Dynamic PET images were acquired for about 1 hr using a Siemens/CTI 931 tomograph.more » A three-compartment model with an input function delay time parameter was the statistically preferred model configuration. The model estimated transport rate constant from plasma to liver, K{sub 1}, increased significantly (p < 0.05) from 0.864 {+-} 0.136 ml/min/g in fasting studies to 1.058 {+-} 0.269 ml/min/g in postglucose studies. Glucose loading also significantly increased (p < 0.01) the rate constant for FDG phosphorylation, k{sub 3}, from 0.005 {+-} 0.003 min{sup -1} in fasting studies to 0.013 {+-} 0.007 min{sup -1} in postglucose administration and, consequently, significantly increased both the phosphorylation fraction (k{sub 3}/(k{sub 2} + k{sub 3})) and the influx constant (K{sub 1}k{sub 3}/(k{sub 2} + k{sub 3})). No significant differences in the liver-to-plasma transport rate constant, k{sub 2}, dephosphorylation constant, k{sub 4}, or distribution volume of FDG (K{sub 1}/(k{sub 2} + k{sub 3})) were observed. Dynamic FDG-PET studies can be used to evaluate kinetics of liver glucose metabolism. The results indicate that dietary conditions have a significant effect on hepatic FDG kinetics. Because of the higher net FDG uptake by normal liver after glucose loading, fasting conditions are preferred for FDG liver tumor studies to increase the tumor-to-background contrast. 22 refs., 2 figs., 3 tabs.« less

Multi-layer cube sampling for liver boundary detection in PET-CT images.

PubMed

Liu, Xinxin; Yang, Jian; Song, Shuang; Song, Hong; Ai, Danni; Zhu, Jianjun; Jiang, Yurong; Wang, Yongtian

2018-06-01

Liver metabolic information is considered as a crucial diagnostic marker for the diagnosis of fever of unknown origin, and liver recognition is the basis of automatic diagnosis of metabolic information extraction. However, the poor quality of PET and CT images is a challenge for information extraction and target recognition in PET-CT images. The existing detection method cannot meet the requirement of liver recognition in PET-CT images, which is the key problem in the big data analysis of PET-CT images. A novel texture feature descriptor called multi-layer cube sampling (MLCS) is developed for liver boundary detection in low-dose CT and PET images. The cube sampling feature is proposed for extracting more texture information, which uses a bi-centric voxel strategy. Neighbour voxels are divided into three regions by the centre voxel and the reference voxel in the histogram, and the voxel distribution information is statistically classified as texture feature. Multi-layer texture features are also used to improve the ability and adaptability of target recognition in volume data. The proposed feature is tested on the PET and CT images for liver boundary detection. For the liver in the volume data, mean detection rate (DR) and mean error rate (ER) reached 95.15 and 7.81% in low-quality PET images, and 83.10 and 21.08% in low-contrast CT images. The experimental results demonstrated that the proposed method is effective and robust for liver boundary detection.

Liver haemostasis using microbubble-enhanced ultrasound at a low acoustic intensity.

PubMed

Zhao, Xiaochen; Li, Lu; Zhao, Hongzhi; Li, Tao; Wu, Shengzheng; Zhong, Yu; Zhao, Yang; Liu, Zheng

2012-02-01

To explore the haemostatic effects of microbubble-enhanced ultrasound (MEUS) at a very low acoustic intensity on the bleeding liver of rabbits. Liver incisions made on 20 rabbits were treated with a pulsed therapeutic ultrasound transducer. The transducer was operated at 831 KHz with an acoustic intensity of 0.4 W/cm(2). The treatment was coordinated with intravenous injection of microbubbles. Ultrasound only and sham treatment served as the controls. Visual bleeding score and 10-min bleeding volume were evaluated for haemostatic efficacy. Contrast-enhanced ultrasound (CEUS) was performed to assess the liver perfusion. Nine treated livers were harvested for acute histological examination. Regarding the bleeding incisions made on rabbit livers, the haemorrhage stopped immediately after 2 min of MEUS treatment but bleeding continued in the controls treated by ultrasound or microbubble injection alone. The bleeding scores and the 10-min haemorrhagic volumes dropped significantly in the MEUS group compared with those of the controls (p < 0.01). The mechanism of MEUS haemostasis appears to involve the extensive swelling of hepatocytes and the haemorrhage of the portal area, which formed a joint compression on the regional liver circulation. Low acoustic intensity MEUS might provide a novel method for liver haemostasis. • This animal experiment demonstrates a novel method of controlling hepatic haemorrhage • The treatment uses therapeutic ultrasound during enhancement with intravenous microbubbles • This combined therapy was more effective than ultrasound or intravenous microbubbles alone • More work is required with larger animals before potential human trials.

Is liver SUV stable over time in ¹⁸F-FDG PET imaging?

PubMed

Laffon, Eric; Adhoute, Xavier; de Clermont, Henri; Marthan, Roger

2011-12-01

This work investigated whether (18)F-FDG PET standardized uptake value (SUV) is stable over time in the normal human liver. The SUV-versus-time curve, SUV(t), of (18)F-FDG in the normal human liver was derived from a kinetic model analysis. This derivation involved mean values of (18)F-FDG liver metabolism that were obtained from a patient series (n = 11), and a noninvasive population-based input function was used in each individual. Mean values (±95% reliability limits) of the (18)F-FDG uptake and release rate constant and of the fraction of free tracer in blood and interstitial volume were as follows: K = 0.0119 mL·min(-1)·mL(-1) (±0.0012), k(R) = 0.0065·min(-1) (±0.0009), and F = 0.21 mL·mL(-1) (±0.11), respectively. SUV(t) (corrected for (18)F physical decay) was derived from these mean values, showing that it smoothly peaks at 75-80 min on average after injection and that it is within 5% of the peak value between 50 and 110 min after injection. In the normal human liver, decay-corrected SUV(t) remains nearly constant (with a reasonable ±2.5% relative measurement uncertainty) if the time delay between tracer injection and PET acquisition is in the range of 50-110 min. In current clinical practice, the findings suggest that SUV of the normal liver can be used for comparison with SUV of suspected malignant lesions, if comparison is made within this time range.

Extracorporeal Bioartificial Liver for Treating Acute Liver Diseases

PubMed Central

Kumar, Ashok; Tripathi, Anuj; Jain, Shivali

2011-01-01

Abstract: Liver is a vital organ of the human body performing myriad of essential functions. Liver-related ailments are often life-threatening and dramatically deteriorate the quality of life of patients. Management of acute liver diseases requires adequate support of various hepatic functions. Thus far, liver transplantation has been proven as the only effective solution for acute liver diseases. However, broader application of liver transplantation is limited by demand for lifelong immunosuppression, shortage of organ donors, relative high morbidity, and high cost. Therefore, research has been focused on attempting to develop alternative support systems to treat liver diseases. Earlier attempts have been made to use nonbiological therapies based on the use of conventional detoxification procedures such as filtration and dialysis. However, the absence of liver cells in such techniques reduced the overall survival rate of the patients and led to inadequate essential liver-specific functions. As a result, there has been growing interest in the development of biological therapy-based extracorporeal liver support systems as a bridge to liver transplantation or to support the ailing liver. A bioartificial liver support is an extracorporeal device through which plasma is circulated over living and functionally active hepatocytes packed in a bioreactor with the aim to aid the diseased liver until it regenerates or until a suitable graft for transplantation is available. This review article gives a brief overview of efficacy of various liver support systems that are currently available. Also, the development of advanced liver support systems, which has been analyzed for improving the important system component such as cell source and other culture and circulation conditions for the maintenance of the liver-specific functions, have been described. PMID:22416599

Long space missions, gene therapy, and the vital role of magnesium: a three-pronged plan for the next 50 years

PubMed Central

Rowe, William J

2010-01-01

Since pharmaceuticals cannot be used in space until liver and kidney dysfunctions are corrected, and with invariable malabsorption, it appears there is no alternative other than to use subcutaneous magnesium (Mg) replacements in the presence of deficiencies and use of gene therapy. I suggest beginning with the correction of as many as four gene deficiencies: atrial natriuretic peptide (ANP), nitric oxide (NO), vascular endothelial growth factor (VEGF), and erythropoietin (EPO), all as well as Mg related to perfusion and angiogenesis. There is no evidence of significant lunar radiation levels in the absence of a solar storm. It could then be determined whether this has resulted in correction of liver and kidney dysfunction. If this persists, serial additions of gene therapy will be required determining the effect of each individual gene trial on organ function. Microgravity and endothelial gaps with leaks trigger reduced plasma volume. Partial correction by use of a plasma volume substitute and development of a delivery device may reduce complexity of gene therapy. Research would be conducted both on Earth and in microgravity, with the development of subcutaneous pharmaceuticals and Mg, and a space walk-reliable subcutaneous silicon device, given that no replenishable subcutaneous device is presently available. A three-pronged approach provides a plan for the next 50 years: A. complete correction of a Mg deficit; B. partial replacement with plasma volume substitutes, and C. multiple gene factor strategy. PMID:21694938

Long space missions, gene therapy, and the vital role of magnesium: a three-pronged plan for the next 50 years.

PubMed

Rowe, William J

2010-01-01

Since pharmaceuticals cannot be used in space until liver and kidney dysfunctions are corrected, and with invariable malabsorption, it appears there is no alternative other than to use subcutaneous magnesium (Mg) replacements in the presence of deficiencies and use of gene therapy. I suggest beginning with the correction of as many as four gene deficiencies: atrial natriuretic peptide (ANP), nitric oxide (NO), vascular endothelial growth factor (VEGF), and erythropoietin (EPO), all as well as Mg related to perfusion and angiogenesis. There is no evidence of significant lunar radiation levels in the absence of a solar storm. It could then be determined whether this has resulted in correction of liver and kidney dysfunction. If this persists, serial additions of gene therapy will be required determining the effect of each individual gene trial on organ function. Microgravity and endothelial gaps with leaks trigger reduced plasma volume. Partial correction by use of a plasma volume substitute and development of a delivery device may reduce complexity of gene therapy. Research would be conducted both on Earth and in microgravity, with the development of subcutaneous pharmaceuticals and Mg, and a space walk-reliable subcutaneous silicon device, given that no replenishable subcutaneous device is presently available. A three-pronged approach provides a plan for the next 50 years: A. complete correction of a Mg deficit; B. partial replacement with plasma volume substitutes, and C. multiple gene factor strategy. 2010 Halvorson et al, publisher and licensee Dove Medical Press Ltd.

Evaluation of HIFU-induced lesion region using temperature threshold and equivalent thermal dose methods

NASA Astrophysics Data System (ADS)

Chang, Shihui; Xue, Fanfan; Zhou, Wenzheng; Zhang, Ji; Jian, Xiqi

2017-03-01

Usually, numerical simulation is used to predict the acoustic filed and temperature distribution of high intensity focused ultrasound (HIFU). In this paper, the simulated lesion volumes obtained by temperature threshold (TRT) 60 °C and equivalent thermal dose (ETD) 240 min were compared with the experimental results which were obtained by animal tissue experiment in vitro. In the simulation, the calculated model was established according to the vitro tissue experiment, and the Finite Difference Time Domain (FDTD) method was used to calculate the acoustic field and temperature distribution in bovine liver by the Westervelt formula and Pennes bio-heat transfer equation, and the non-linear characteristics of the ultrasound was considered. In the experiment, the fresh bovine liver was exposed for 8s, 10s, 12s under different power conditions (150W, 170W, 190W, 210W), and the exposure was repeated 6 times under the same dose. After the exposures, the liver was sliced and photographed every 0.2mm, and the area of the lesion region in every photo was calculated. Then, every value of the areas was multiplied by 0.2mm, and summed to get the approximation volume of the lesion region. The comparison result shows that the lesion volume of the region calculated by TRT 60 °C in simulation was much closer to the lesion volume obtained in experiment, and the volume of the region above 60 °C was larger than the experimental results, but the volume deviation was not exceed 10%. The volume of the lesion region calculated by ETD 240 min was larger than that calculated by TRT 60 °C in simulation, and the volume deviations were ranged from 4.9% to 23.7%.

Intraoperative laparoscope augmentation for port placement and resection planning in minimally invasive liver resection.

PubMed

Feuerstein, Marco; Mussack, Thomas; Heining, Sandro M; Navab, Nassir

2008-03-01

In recent years, an increasing number of liver tumor indications were treated by minimally invasive laparoscopic resection. Besides the restricted view, two major intraoperative issues in laparoscopic liver resection are the optimal planning of ports as well as the enhanced visualization of (hidden) vessels, which supply the tumorous liver segment and thus need to be divided (e.g., clipped) prior to the resection. We propose an intuitive and precise method to plan the placement of ports. Preoperatively, self-adhesive fiducials are affixed to the patient's skin and a computed tomography (CT) data set is acquired while contrasting the liver vessels. Immediately prior to the intervention, the laparoscope is moved around these fiducials, which are automatically reconstructed to register the patient to its preoperative imaging data set. This enables the simulation of a camera flight through the patient's interior along the laparoscope's or instruments' axes to easily validate potential ports. Intraoperatively, surgeons need to update their surgical planning based on actual patient data after organ deformations mainly caused by application of carbon dioxide pneumoperitoneum. Therefore, preoperative imaging data can hardly be used. Instead, we propose to use an optically tracked mobile C-arm providing cone-beam CT imaging capability intraoperatively. After patient positioning, port placement, and carbon dioxide insufflation, the liver vessels are contrasted and a 3-D volume is reconstructed during patient exhalation. Without any further need for patient registration, the reconstructed volume can be directly augmented on the live laparoscope video, since prior calibration enables both the volume and the laparoscope to be positioned and oriented in the tracking coordinate frame. The augmentation provides the surgeon with advanced visual aid for the localization of veins, arteries, and bile ducts to be divided or sealed.

TH-A-9A-04: Incorporating Liver Functionality in Radiation Therapy Treatment Planning

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

Wu, V; Epelman, M; Feng, M

2014-06-15

Purpose: Liver SBRT patients have both variable pretreatment liver function (e.g., due to degree of cirrhosis and/or prior treatments) and sensitivity to radiation, leading to high variability in potential liver toxicity with similar doses. This work aims to explicitly incorporate liver perfusion into treatment planning to redistribute dose to preserve well-functioning areas without compromising target coverage. Methods: Voxel-based liver perfusion, a measure of functionality, was computed from dynamic contrast-enhanced MRI. Two optimization models with different cost functions subject to the same dose constraints (e.g., minimum target EUD and maximum critical structure EUDs) were compared. The cost functions minimized were EUDmore » (standard model) and functionality-weighted EUD (functional model) to the liver. The resulting treatment plans delivering the same target EUD were compared with respect to their DVHs, their dose wash difference, the average dose delivered to voxels of a particular perfusion level, and change in number of high-/low-functioning voxels receiving a particular dose. Two-dimensional synthetic and three-dimensional clinical examples were studied. Results: The DVHs of all structures of plans from each model were comparable. In contrast, in plans obtained with the functional model, the average dose delivered to high-/low-functioning voxels was lower/higher than in plans obtained with its standard counterpart. The number of high-/low-functioning voxels receiving high/low dose was lower in the plans that considered perfusion in the cost function than in the plans that did not. Redistribution of dose can be observed in the dose wash differences. Conclusion: Liver perfusion can be used during treatment planning potentially to minimize the risk of toxicity during liver SBRT, resulting in better global liver function. The functional model redistributes dose in the standard model from higher to lower functioning voxels, while achieving the same target EUD and satisfying dose limits to critical structures. This project is funded by MCubed and grant R01-CA132834.« less

Intention of donors to re-donate livers after living donor liver transplantation in a liver transplant center in Asia.

PubMed

Chang, Yuan-Min; Chung, Kuo-Piao; Chen, Teng-Wei; Hsieh, Chung-Bao

2014-08-25

The aim of this study was to examine donor complications, satisfaction with the liver donation process, and factors associated with re-donation. To address these issues, we conducted a cross-sectional study to assess donor complications and used questionnaires (including the Likert scale for donation satisfaction and simple yes/no responses for willingness to re-donate) in 110 adults who underwent living donor liver transplantation (LDLT) at Tri-Service General Hospital. The following clinical characteristics were determined: donation volume; first-degree relative; education; duration of hospital stay; occupation (donor-associated); MELD score; Child classification; complications; outcome (recipient-associated); and graft/recipient weight ratio (donor-recipient-associated). Descriptive statistics and mean values were compared using t-tests and p values <0.05 were considered significant. Twelve donors among 110 participants experienced complications above Clavien grade II. No surgical mortalities were observed. There were no differences in age, gender, left/right liver graft, donation volume, length of hospital stay, or satisfaction in donor complications. Ninety-four donors had satisfaction (score=4 and 5) about the donation process and no dissatisfaction was reported (score=1). Based on multivariate analysis, the intention to re-donate among liver donors was related to first-degree relatives, donor satisfaction, and recipient complications (P<0.05). Factors associated with a willingness to re-donate included first-degree relatives of the recipient, donor satisfaction with the donation process, and recipient complications. This study not only showed the safety of liver donation, but also had a positive effect on the intention to re-donate to enhance motivation for liver donation and increase the recruitment of living liver donors.

The HALT Polycystic Kidney Disease Trials – Analysis of baseline parameters

PubMed Central

Torres, Vicente E.; Chapman, Arlene B.; Perrone, Ronald D.; Bae, K. Ty; Abebe, Kaleab Z.; Bost, James E.; Miskulin, Dana C.; Steinman, Theodore I.; Braun, William; Winklhofer, Franz T.; Hogan, Marie C.; Oskoui, Frederic Rahbari; Kelleher, Cass; Masoumi, Amirali; Glockner, James; Halin, Neil J; Martin, Diego; Remer, Erick; Patel, Nayana.; Pedrosa, Ivan; Wetzel, Louis H.; Thompson, Paul A.; Miller, J. Philip; Meyers, Catherine M.; Schrier, Robert W.

2013-01-01

HALT-PKD consists of two randomized trials comparing treatment with an angiotensin converting inhibitor (ACEI)-angiotensin receptor blocker (ARB) combination vs ACEI alone and standard vs low blood pressure target in Study A (eGFR >60 ml/min/1.73 m2) and ACEI-ARB vs ACEI alone in Study B (eGFR 25-60 ml/min/1.73 m2). It includes the largest cohort of systematically studied ADPKD patients (558 A and 486 B) to date. We used correlation and multiple regression cross-sectional analyses to ascertain associations of baseline parameters with total kidney (TKV) and liver (TLV) or liver cyst (LCV) volumes measured by MRI in Study A and with eGFR in both studies. Lower eGFR and higher natural log transformed urine albumin excretion are independently associated with larger natural log transformed TKV adjusted for height (HtTKV). Higher BSA is independently associated with higher ln(HtTKV) and lower eGFR. Men have larger HtTKV and smaller LCV than women. A weak correlation was found between ln(HtTKV) and ln(HtTLV) or ln(LCV) in women only. Women have higher urine aldosterone excretions and lower plasma potassium levels. In summary, this analysis 1) confirms a strong association between renal volume and functional parameters, 2) shows that gender and other factors differentially affect the development of polycystic disease in the kidney and liver, and 3) suggests an association between anthropomorphic measures reflecting preand/or post-natal growth and the severity of the disease. PMID:22205355

Multipolar radiofrequency ablation with internally cooled electrodes: experimental study in ex vivo bovine liver with mathematic modeling.

PubMed

Clasen, Stephan; Schmidt, Diethard; Boss, Andreas; Dietz, Klaus; Kröber, Stefan M; Claussen, Claus D; Pereira, Philippe L

2006-03-01

To evaluate the size and geometry of thermally induced coagulation by using multipolar radiofrequency (RF) ablation and to determine a mathematic model to predict coagulation volume. Multipolar RF ablations (n = 80) were performed in ex vivo bovine livers by using three internally cooled bipolar applicators with two electrodes on the same shaft. Applicators were placed in a triangular array (spacing, 2-5 cm) and were activated in multipolar mode (power output, 75-225 W). The size and geometry of the coagulation zone, together with ablation time, were assessed. Mathematic functions were fitted, and the goodness of fit was assessed by using r(2). Coagulation volume, short-axis diameter, and ablation time were dependent on power output and applicator distance. The maximum zone of coagulation (volume, 324 cm(3); short-axis diameter, 8.4 cm; ablation time, 193 min) was induced with a power output of 75 W at an applicator distance of 5 cm. Coagulation volume and ablation time decreased as power output increased. Power outputs of 100-125 W at applicator distances of 2-4 cm led to a reasonable compromise between coagulation volume and ablation time. At 2 cm (100 W), coagulation volume, short-axis diameter, and ablation time were 66 cm(3), 4.5 cm, and 19 min, respectively; at 3 cm (100 W), 90 cm(3), 5.2 cm, and 22 min, respectively; at 4 cm (100 W), 132 cm(3), 6.1 cm, and 27 min, respectively; at 2 cm (125 W), 56 cm(3), 4.2 cm, and 9 min, respectively; at 3 cm (125 W), 73 cm(3), 4.9 cm, and 12 min, respectively; and at 4 cm (125 W), 103 cm(3), 5.5 cm, and 16 min, respectively. At applicator distances of 4 cm (>125 W) and 5 cm (>100 W), the zones of coagulation were not confluent. Coagulation volume (r(2) = 0.80) and RF ablation time (r(2) = 0.93) were determined by using the mathematic model. Multipolar RF ablation with three bipolar applicators may produce large volumes of confluent coagulation ex vivo. A compromise is necessary between prolonged RF ablations at lower power outputs, which produce larger volumes of coagulation, and faster RF ablations at higher power outputs, which produce smaller volumes of coagulation. Copyright RSNA, 2006.

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.

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

Pokhrel, D; Sood, S; Badkul, R

Purpose: To evaluate the dosimetric performance of X-ray Voxel Monte Carlo(XVMC) algorithm in effort to clinically validate Monte Carlo-approach in heterogeneous liver phantom and liver SBRT plans. Methods: An anthropomorphic RPC liver phantom incorporating a liver structure with two cylindrical targets and organs-at-risk (OARs) was used in phantom validation. Subsequently, five patients with metastatic liver cancer were treated using heterogeneity-corrected pencil-beam(PB-hete)algorithm were analyzed following RTOG-1112 criteria .ITV was delineated on MinIP and OARs were contoured on MeanIP images of 4D-CT. PTV was generated from ITV with 5-10mm uniform margin. Mean PTV was 81.3±46.4cc. Prescription was 30–45Gy in 5 fractions, withmore » at least PTV(D95%)=100%. Hybrid SBRT plans were generated with noncoplanar/3D-conformal arcs plus static-beams at Novalis-TX consisting of HD-MLC and 6MV-SRS. SBRT plans were re-computed using XVMC algorithm utilizing identical beam-geometry, MLC-positions, and monitor units and subsequently compared to clinical PB-hete plans. Results: Our results using RPC liver motion phantom validation were all compliance with MD Anderson standards. However, compared to PB-hete, average target volume encompassed by the prescribed percent isodose (Vp) was 9.1% and 8.5% less for PTV1 and PTV2 with XVMC. For the clinical liver SBRT plans, PB-hete systematically overestimated PTV dose (D95, Dmean and D10) within ±2.0% (p<0.05) compared to XVMC. Mean value of Vp was about 3.8% less with XVMC compared to PB-hete (ranged 2.9–5.7% (p<0.003)). However, mean liver dose (MLD) was 3.2% higher (p<0.003), on average, with XVMC compared to clinical PB-hete (ranged −1.0to−3.9%). OARs doses were statistically insignificant. Conclusion: Results from our XVMC dose calculations and validation study for liver SBRT indicate small-to-moderate under-dosing of the tumor volume when compared to PB-hete. Results were consistent with phantom validation and patients plans. However, Vp was less by up to 5.7% for some liver SBRT patients with XVMC–suggesting under-dosing of the target volume and overdosing of MLD by up to 3.9% occurred with PB-hete plan. These differences between PB-hete and XVMC dose calculations may be of clinical interest.« less

Assessment of functional liver reserve: old and new in 99mTc-sulfur colloid scintigraphy.

PubMed

Matesan, Manuela M; Bowen, Stephen R; Chapman, Tobias R; Miyaoka, Robert S; Velez, James W; Wanner, Michele F; Nyflot, Matthew J; Apisarnthanarax, Smith; Vesselle, Hubert J

2017-07-01

A semiquantitative assessment of hepatic reticuloendothelial system function using colloidal particles scintigraphy has been proposed previously as a surrogate for liver function evaluation. In this article, we present an updated method for the overall assessment of technetium-99m (Tc)-sulfur colloid (SC) biodistribution that combines information from planar and attenuation-corrected Tc-SC single-photon emission computed tomography (SPECT) images. The imaging protocol described here was developed as an easy-to-implement method to assess overall and regional liver function changes associated with chronic liver disease. Thirty patients with chronic liver disease and primary liver cancers underwent Tc-SC whole-body planar imaging and upper-abdomen SPECT/computed tomography (CT) imaging before external beam radiation therapy. Liver plus spleen and bone marrow counts as a fraction of whole-body total counts were calculated from SC planar imaging. Attenuation correction Tc-SC images were rigidly coregistered with treatment planning CT images that contained liver and spleen regions-of-interest. Ratios of total liver counts to total spleen counts were obtained from the aligned Tc-SC SPECT and CT images, and were subsequently used to separate liver plus spleen counts obtained on the planar images. This hybrid SPECT/CT and planar scintigraphy approach yielded an updated estimation of whole-body SC distribution. These biodistribution estimates were compared with historical data for reference. Statistical associations of Tc-SC biodistribution to liver function parameters and liver disease scoring systems (Child-Pugh) were evaluated by Spearman rank correlation. Percentages of Tc-SC uptake ranged from 19.3 to 77.3% for the liver; 3.4 to 40.7% for the spleen; and 19.0 to 56.7% for the bone marrow. Spearman's correlation coefficient showed a significant statistical association between Child-Pugh score and bone marrow uptake at 0.55 (P≤0.05), liver uptake at 0.71 (P≤0.001), spleen uptake at 0.56 (P≤0.05), and spleen plus bone marrow uptake at 0.71 (P≤0.001). There was also a good correlation of SC uptake percentages with individual quantitative liver function components such as albumin and total bilirubin, and qualitative liver function components (varices, portal hypertension, ascites). For albumin: r=0.64 (P<0.001) compared with liver uptake percentage from the whole-body counts, r=0.49 (P<0.001) compared with splenic uptake percentage, and r=0.45 (P≤0.05) compared with bone marrow uptake percentage. We describe a novel liver function quantitative assessment method that combines whole-body planar images and SPECT/CT attenuation-corrected images of Tc-SC distribution. Attenuation-corrected SC images provide valuable regional liver function information, which is a unique feature compared with other imaging methods available. The results of our study indicate that the Tc-SC uptake by the liver, spleen, and bone marrow correlates with liver function parameters in patients with diffuse liver disease and the correlation with liver disease severity is slightly better for liver uptake percentages than for individual values of bone marrow and spleen uptake percentages.

Tolvaptan for the treatment of liver cirrhosis oedema.

PubMed

Sakaida, Isao

2014-07-01

No alternative therapeutic option exists if liver cirrhosis patients have insufficient response to conventional diuretics and/or experience conventional diuretic-related adverse events. In 2013, tolvaptan (7.5 mg/day), an arginine vasopressin V2 receptor antagonist, was approved in Japan for the treatment of liver cirrhosis with oedema. Short-term use of tolvaptan produced decreases in body weight, reduction in ascites volume and increases in urine volume when compared to placebo, despite the use of conventional diuretics. Additionally, approximately 60% of patients with oedema-related symptoms improved. Low-dose tolvaptan, 3.75 mg, was also efficacious. Even in patients with low serum albumin (<2.5 g/dL), decrease in body weight was greater with tolvaptan than with placebo. For future research, the efficacy and safety of lower tolvaptan doses for the treatment of liver cirrhosis patients with oedema should be confirmed in Japan. The results of this research could be used as an indicator or a guideline for physicians around the world.

GMP Cryopreservation of Large Volumes of Cells for Regenerative Medicine: Active Control of the Freezing Process

PubMed Central

Massie, Isobel; Selden, Clare; Hodgson, Humphrey; Gibbons, Stephanie; Morris, G. John

2014-01-01

Cryopreservation protocols are increasingly required in regenerative medicine applications but must deliver functional products at clinical scale and comply with Good Manufacturing Process (GMP). While GMP cryopreservation is achievable on a small scale using a Stirling cryocooler-based controlled rate freezer (CRF) (EF600), successful large-scale GMP cryopreservation is more challenging due to heat transfer issues and control of ice nucleation, both complex events that impact success. We have developed a large-scale cryocooler-based CRF (VIA Freeze) that can process larger volumes and have evaluated it using alginate-encapsulated liver cell (HepG2) spheroids (ELS). It is anticipated that ELS will comprise the cellular component of a bioartificial liver and will be required in volumes of ∼2 L for clinical use. Sample temperatures and Stirling cryocooler power consumption was recorded throughout cooling runs for both small (500 μL) and large (200 mL) volume samples. ELS recoveries were assessed using viability (FDA/PI staining with image analysis), cell number (nuclei count), and function (protein secretion), along with cryoscanning electron microscopy and freeze substitution techniques to identify possible injury mechanisms. Slow cooling profiles were successfully applied to samples in both the EF600 and the VIA Freeze, and a number of cooling and warming profiles were evaluated. An optimized cooling protocol with a nonlinear cooling profile from ice nucleation to −60°C was implemented in both the EF600 and VIA Freeze. In the VIA Freeze the nucleation of ice is detected by the control software, allowing both noninvasive detection of the nucleation event for quality control purposes and the potential to modify the cooling profile following ice nucleation in an active manner. When processing 200 mL of ELS in the VIA Freeze—viabilities at 93.4%±7.4%, viable cell numbers at 14.3±1.7 million nuclei/mL alginate, and protein secretion at 10.5±1.7 μg/mL/24 h were obtained which, compared well with control ELS (viability −98.1%±0.9%; viable cell numbers −18.3±1.0 million nuclei/mL alginate; and protein secretion −18.7±1.8 μg/mL/24 h). Large volume GMP cryopreservation of ELS is possible with good functional recovery using the VIA Freeze and may also be applied to other regenerative medicine applications. PMID:24410575

Computer-aided liver volumetry: performance of a fully-automated, prototype post-processing solution for whole-organ and lobar segmentation based on MDCT imaging.

PubMed

Fananapazir, Ghaneh; Bashir, Mustafa R; Marin, Daniele; Boll, Daniel T

2015-06-01

To evaluate the performance of a prototype, fully-automated post-processing solution for whole-liver and lobar segmentation based on MDCT datasets. A polymer liver phantom was used to assess accuracy of post-processing applications comparing phantom volumes determined via Archimedes' principle with MDCT segmented datasets. For the IRB-approved, HIPAA-compliant study, 25 patients were enrolled. Volumetry performance compared the manual approach with the automated prototype, assessing intraobserver variability, and interclass correlation for whole-organ and lobar segmentation using ANOVA comparison. Fidelity of segmentation was evaluated qualitatively. Phantom volume was 1581.0 ± 44.7 mL, manually segmented datasets estimated 1628.0 ± 47.8 mL, representing a mean overestimation of 3.0%, automatically segmented datasets estimated 1601.9 ± 0 mL, representing a mean overestimation of 1.3%. Whole-liver and segmental volumetry demonstrated no significant intraobserver variability for neither manual nor automated measurements. For whole-liver volumetry, automated measurement repetitions resulted in identical values; reproducible whole-organ volumetry was also achieved with manual segmentation, p(ANOVA) 0.98. For lobar volumetry, automated segmentation improved reproducibility over manual approach, without significant measurement differences for either methodology, p(ANOVA) 0.95-0.99. Whole-organ and lobar segmentation results from manual and automated segmentation showed no significant differences, p(ANOVA) 0.96-1.00. Assessment of segmentation fidelity found that segments I-IV/VI showed greater segmentation inaccuracies compared to the remaining right hepatic lobe segments. Automated whole-liver segmentation showed non-inferiority of fully-automated whole-liver segmentation compared to manual approaches with improved reproducibility and post-processing duration; automated dual-seed lobar segmentation showed slight tendencies for underestimating the right hepatic lobe volume and greater variability in edge detection for the left hepatic lobe compared to manual segmentation.

Liver transplant center performance profiling: 2005-2011 reports of the Scientific Registry for Transplant Recipients.

PubMed

Kettelhut, Valeriya V; Nayar, Preethy

2013-06-01

CONTEXT-Transplant center performance profiling provides important information for various concerned parties. Comparing a transplant center's performance against the performance of the best-in-class centers may help in understanding the performance thresholds for the underperforming centers. OBJECTIVES-(1) To identify and describe "Centers for Medicare and Medicaid Services (CMS)-red-flag" performers and the "best-in-class" performers and (2) to examine the relationships between a center's performance profile and outcomes such as 1-year observed mortality, 1-month observed mortality, 1-year risk-adjusted mortality, and volume. METHODS-The data for analysis was obtained from the published reports on the Scientific Registry for Transplant Recipients (SRTR) website for adult liver transplant programs compiled for the rolling 2 1/2-year cohorts of patients and included 7 cohorts of liver transplant recipients in the study from January through July 1, 2002, through December 31, 2010. We defined 4 performance profiles: CMS-red-flag, lower-than-expected, higher-than-expected, and best-in-class performers. RESULTS-The current SRTR methods classify approximately 7% of the adult liver centers as CMS-red-flag performers and 6% of the centers as best-in-class performers in every reported period. Neither of the low-volume centers (<30 liver transplants per 2 1/2-year cohort) was profiled as CMS-red-flag until the 2010 reporting period. The transplant center's profile was significantly associated with the 1-year and 1-month observed mortality rates in every reported cohort (P< .001). CONCLUSION-The CMS-red-flag profile can be characterized with the following: (1) the highest observed 1-year mortality, (2) the highest observed 1-month mortality, (3) a very large difference between the observed and adjusted mortality rates, and (4) the center volume greater than 30 liver transplants per 2 1/2-year cohort. The SRTR methods are not sensitive for performance profiling in the centers that perform fewer than 30 orthotopic liver transplants per 2 1/2-year cohort.

[Definition of surgical degree of freedom by functional anatomy in liver resection surgery].

PubMed

Kraus, T W; Golling, M; Klar, E

2001-07-01

Liver resections have developed to very complex and differentiated operations, clearly adapted to individual anatomical and physiological conditions. In parallel, perioperative morbidity has been dramatically reduced. Intraoperative strict consideration of various details of hepatic anatomy, particularly of functional liver anatomy, has proved to be of particular importance when liver surgery reaches indication and technical limits. The term "functional anatomy" stands for a form of hepatic substructurization, which is primarily based on the existence of hemodynamically independent regions of liver parenchyma. A selection of some of the most important details and facts of functional liver anatomy and secondary derived guidelines for surgical strategy and technique is presented in an overview, with special focus on liver resection.

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

Li, Dengwang; Wang, Jie; Kapp, Daniel S.

Purpose: The aim of this work is to develop a robust algorithm for accurate segmentation of liver with special attention paid to the problems with fuzzy edges and tumor. Methods: 200 CT images were collected from radiotherapy treatment planning system. 150 datasets are selected as the panel data for shape dictionary and parameters estimation. The remaining 50 datasets were used as test images. In our study liver segmentation was formulated as optimization process of implicit function. The liver region was optimized via local and global optimization during iterations. Our method consists five steps: 1)The livers from the panel data weremore » segmented manually by physicians, and then We estimated the parameters of GMM (Gaussian mixture model) and MRF (Markov random field). Shape dictionary was built by utilizing the 3D liver shapes. 2)The outlines of chest and abdomen were located according to rib structure in the input images, and the liver region was initialized based on GMM. 3)The liver shape for each 2D slice was adjusted using MRF within the neighborhood of liver edge for local optimization. 4)The 3D liver shape was corrected by employing SSR (sparse shape representation) based on liver shape dictionary for global optimization. Furthermore, H-PSO(Hybrid Particle Swarm Optimization) was employed to solve the SSR equation. 5)The corrected 3D liver was divided into 2D slices as input data of the third step. The iteration was repeated within the local optimization and global optimization until it satisfied the suspension conditions (maximum iterations and changing rate). Results: The experiments indicated that our method performed well even for the CT images with fuzzy edge and tumors. Comparing with physician delineated results, the segmentation accuracy with the 50 test datasets (VOE, volume overlap percentage) was on average 91%–95%. Conclusion: The proposed automatic segmentation method provides a sensible technique for segmentation of CT images. This work is supported by NIH/NIBIB (1R01-EB016777), National Natural Science Foundation of China (No.61471226 and No.61201441), Research funding from Shandong Province (No.BS2012DX038 and No.J12LN23), and Research funding from Jinan City (No.201401221 and No.20120109)« less

Non-invasive assessment of the liver using imaging

NASA Astrophysics Data System (ADS)

Thorling Thompson, Camilla; Wang, Haolu; Liu, Xin; Liang, Xiaowen; Crawford, Darrell H.; Roberts, Michael S.

2016-12-01

Chronic liver disease causes 2,000 deaths in Australia per year and early diagnosis is crucial to avoid progression to cirrhosis and end stage liver disease. There is no ideal method to evaluate liver function. Blood tests and liver biopsies provide spot examinations and are unable to track changes in function quickly. Therefore better techniques are needed. Non-invasive imaging has the potential to extract increased information over a large sampling area, continuously tracking dynamic changes in liver function. This project aimed to study the ability of three imaging techniques, multiphoton and fluorescence lifetime imaging microscopy, infrared thermography and photoacoustic imaging, in measuring liver function. Collagen deposition was obvious in multiphoton and fluorescence lifetime imaging in fibrosis and cirrhosis and comparable to conventional histology. Infrared thermography revealed a significantly increased liver temperature in hepatocellular carcinoma. In addition, multiphoton and fluorescence lifetime imaging and photoacoustic imaging could both track uptake and excretion of indocyanine green in rat liver. These results prove that non-invasive imaging can extract crucial information about the liver continuously over time and has the potential to be translated into clinic in the assessment of liver disease.

[Effect of fenicaberan on liver function in patients with chronic noncalculous cholecystitis].

PubMed

Skroban, N V

1989-06-01

The author studied the effect of fenicaberan on the functional state of the liver in 34 patients with chronic noncalculous cholecystitis. It was found that fenicaberan favours improvement of the functional state of the liver but complete normalization of all liver values indicates necessity continuation of treatment in outpatient conditions.

Portal Vein Embolization: State-of-the-Art Technique and Options to Improve Liver Hypertrophy.

PubMed

Huang, Steven Y; Aloia, Thomas A

2017-12-01

Portal vein embolization (PVE) is associated with a high technical and clinical success rate for induction of future liver remnant hypertrophy prior to surgical resection. The degree of hypertrophy is variable and depends on multiple factors, including technical aspects of the procedure and underlying chronic liver disease. For patients with insufficient liver volume following PVE, adjunctive techniques, such as intra-portal administration of stem cells, dietary supplementation, transarterial embolization, and hepatic vein embolization, are available. Our purpose is to review the state-of-the-art technique associated with high-quality PVE and to discuss options to improve hypertrophy of the future liver remnant.

Transarterial Embolization for Treatment of Symptomatic Polycystic Liver Disease: More than 2-year Follow-up

PubMed Central

Zhang, Jin-Long; Yuan, Kai; Wang, Mao-Qiang; Yan, Jie-Yu; Xin, Hai-Nan; Wang, Yan; Liu, Feng-Yong; Bai, Yan-Hua; Wang, Zhi-Jun; Duan, Feng; Fu, Jin-Xin

2017-01-01

Background: Currently, treatment of symptomatic polycystic liver disease (PLD) is still a challenging problem, especially for these patients who are not feasible for surgery. Minimally invasive options such as laparoscopic fenestration and percutaneous cyst aspiration with sclerotherapy demonstrated disappointing results due to multiple lesions. Because the cysts in PLD are mostly supplied from hepatic arteries but not from portal veins, transcatheter arterial embolization (TAE) of the hepatic artery branches that supply the major hepatic cysts can lead to shrinkage of the cyst and liver size, relieve symptoms, and improve nutritional status. This study aimed to evaluate the effectiveness of TAE with a mixture of N-butyl-2-cyanoacrylate (NBCA) and iodized oil for patients with severe symptomatic PLD during a more than 2-year follow-up. Methods: Institutional review board had approved this study. Written informed consent was obtained from all patients. From February 2007 to December 2014, twenty-three patients (20 women and 3 men; mean age, 49.0 ± 14.5 years) infeasible for surgical treatments underwent TAE. Changes in the abdominal circumferences, volumes of intrahepatic cysts, hepatic parenchyma volume, and whole liver, clinical symptoms, laboratory data, and complications were evaluated after TAE. Results: Technical success was achieved in all cases. No procedure-related major complications occurred. The median follow-up period after TAE was 48.5 months (interquartile range, 30.0–72.0 months). PLD-related severe symptoms were improved remarkably in 86% of the treated patients; TAE failed to benefit in four patients (four patients did not benefit from TAE). The mean maximum abdominal circumference decreased significantly from 106.0 ± 8.0 cm to 87.0 ± 15.0 cm (P = 0.021). The mean intrahepatic cystic volume reduction rates compared with pre-TAE were 36% at 12 months, 37% at 24 months, and 38% at 36 months after TAE (P < 0.05). The mean liver volume reduction rates were 32% at 12 months, 31% at 24 months, and 33% at 36 months (P < 0.05). Conclusions: TAE with the mixture of NBCA and iodized oil appears to be a safe and effective treatment method for patients with symptomatic PLD, especially for those who are not good candidates for surgical treatments, to improve both hepatic volume and hepatic cysts volume. PMID:28776546

The Effect of Trauma Center Designation and Trauma Volume on Outcome in Specific Severe Injuries

PubMed Central

Demetriades, Demetrios; Martin, Mathew; Salim, Ali; Rhee, Peter; Brown, Carlos; Chan, Linda

2005-01-01

Objective: The objective of this study was to investigate the effect of American College of Surgeons (ACS) trauma center designation and trauma volume on outcome in patients with specific severe injuries. Background: Trauma centers are designated by the ACS into different levels on the basis of resources, trauma volume, and educational and research commitment. The criteria for trauma center designation are arbitrary and have never been validated. Methods: The National Trauma Data Bank study, which included patients >14 years of age and had injury severity score (ISS) >15, were alive on admission and had at least one of the following severe injuries: aortic, vena cava, iliac vessels, cardiac, grade IV/V liver injuries, quadriplegia, or complex pelvic fractures. Outcomes (mortality, intensive care unit stay, and severe disability at discharge) were compared among level I and II trauma centers and between centers within the same level designation but different volumes of severe trauma (<240 vs ≥240 trauma admissions with ISS >15 per year). The outcomes were adjusted for age (<65 ≥65), gender, mechanism of injury, hypotension on admission, and ISS (≤25 and >25). Results: A total of 12,254 patients met the inclusion criteria. Overall, level I centers had significantly lower mortality (25.3% vs 29.3%; adjusted odds ratio [OR], 0.81; 95% confidence interval [CI], 0.71–0.94; P = 0.004) and significantly lower severe disability at discharge (20.3% vs 33.8%, adjusted OR, 0.55; 95% CI, 0.44–0.69; P < 0.001) than level II centers. Subgroup analysis showed that cardiovascular injuries (N = 2004) and grades IV–V liver injuries (N = 1415) had a significantly better survival in level I than level II trauma centers (adjusted P = 0.017 and 0.023, respectively). Overall, there was a significantly better functional outcome in level I centers (adjusted P < 0.001). Subgroup analysis showed level I centers had significantly better functional outcomes in complex pelvic fractures (P < 0.001) and a trend toward better outcomes in the rest of the subgroups. The volume of trauma admissions with ISS >15 (<240 vs ≥240 cases per year) had no effect on outcome in either level I or II centers. Conclusions: Level I trauma centers have better outcomes than lower-level centers in patients with specific injuries associated with high mortality and poor functional outcomes. The volume of major trauma admissions does not influence outcome in either level I or II centers. These findings may have significant implications in the planning of trauma systems and the billing of services according to level of accreditation. PMID:16192811

Nadolol for lithium tremor in the presence of liver damage.

PubMed

Dave, M; Langbart, M M

1994-03-01

Lithium-induced tremor classically responds to treatment with propranolol. Since it is metabolized in the liver, propranolol may not be the drug of choice in those patients who have compromised liver function or who are recovering from prior liver diseases. Another nonselective beta-adrenergic blocker, nadolol, has no hepatic biotransformation. We present here the first case report of successful treatment of lithium-induced tremor with nadolol, which was selected because the patient had compromised liver function. The patient's liver function tests remained stable with the therapy.

Liver function testing on the Abaxis Piccolo Xpress: Use in Ebola virus disease protocols.

PubMed

Owen, William E; Caron, Justin E; Genzen, Jonathan R

2015-06-15

Laboratories that choose a point-of-care approach for liver function testing in patients undergoing evaluation for Ebola virus disease (EVD) have few options to choose from. The primary objective of this study was to conduct a performance characterization of a Clinical Laboratory Improvement Amendments (CLIA)-waived liver function panel on the Abaxis Piccolo® Xpress chemistry analyzer. The secondary objectives were to evaluate multiple specimen types, characterize whole blood specimen stability, and validate disposable exact transfer pipettes. Our final objective was to assess instrument airflow from a biosafety perspective. An instrument performance characterization, including precision, linearity, accuracy, reference interval verification, and specimen type evaluation was conducted using Liver Panel Plus reagent discs on the Piccolo® Xpress. All assays demonstrated acceptable linearity (slopes, 0.938-1.061; observed error, 0.8-6.3%). Assay precision was 0.0-3.6% (%CV; within-day studies) and 0.9-5.6% (between-day studies). Method comparison experiments (versus Roche cobas c502/c702 chemistry analyzers) showed excellent correlation for most assays, although a few notable differences were observed (Piccolo versus Roche): alkaline phosphatase, -18.6%; amylase, -29.0%; total bilirubin, +0.3mg/dl. Pre-programmed reference intervals were verified except for the alkaline phosphatase (male and female) and alanine aminotransferase (female), which had greater than 10% of results fall below the programmed ranges. Piccolo instrument results were largely consistent across specimen types tested (lithium-heparin whole blood, lithium-heparin plasma, and serum), although some statistical differences were observed for aspartate aminotransferase, gamma glutamyltransferase, and total protein. Whole blood time course studies demonstrated that some analytes (albumin, amylase, and total protein) showed remarkable stability, while others (such as aspartate aminotransferase) showed a slight trend toward decreased activity over time. Exact volume transfer pipettes provided an effective disposable option for disc loading. Finally, airflow studies suggested that, in the context of EVD protocols, instrument placement in a biosafety level (BSL) 2 cabinet or greater is justified. Given its analytical performance and ease of operation, the Piccolo Xpress was transferred to a BSL-2 cabinet in our BSL-3 suite for use in our hospital's diagnostic protocol for providing liver function testing in patients undergoing evaluation for EVD. Copyright © 2015 Elsevier B.V. All rights reserved.

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

Dosimetric impact of different CT datasets for stereotactic treatment planning using 3D conformal radiotherapy or volumetric modulated arc therapy.

PubMed

Oechsner, Markus; Odersky, Leonhard; Berndt, Johannes; Combs, Stephanie Elisabeth; Wilkens, Jan Jakob; Duma, Marciana Nona

2015-12-01

The purpose of this study was to assess the impact on dose to the planning target volume (PTV) and organs at risk (OAR) by using four differently generated CT datasets for dose calculation in stereotactic body radiotherapy (SBRT) of lung and liver tumors. Additionally, dose differences between 3D conformal radiotherapy and volumetric modulated arc therapy (VMAT) plans calculated on these CT datasets were determined. Twenty SBRT patients, ten lung cases and ten liver cases, were retrospectively selected for this study. Treatment plans were optimized on average intensity projection (AIP) CTs using 3D conformal radiotherapy (3D-CRT) and volumetric modulated arc therapy (VMAT). Afterwards, the plans were copied to the planning CTs (PCT), maximum intensity projection (MIP) and mid-ventilation (MidV) CT datasets and dose was recalculated keeping all beam parameters and monitor units unchanged. Ipsilateral lung and liver volumes and dosimetric parameters for PTV (Dmean, D2, D98, D95), ipsilateral lung and liver (Dmean, V30, V20, V10) were determined and statistically analysed using Wilcoxon test. Significant but small mean differences were found for PTV dose between the CTs (lung SBRT: ≤2.5 %; liver SBRT: ≤1.6 %). MIPs achieved the smallest lung and the largest liver volumes. OAR mean doses in MIP plans were distinctly smaller than in the other CT datasets. Furthermore, overlapping of tumors with the diaphragm results in underestimated ipsilateral lung dose in MIP plans. Best agreement was found between AIP and MidV (lung SBRT). Overall, differences in liver SBRT were smaller than in lung SBRT and VMAT plans achieved slightly smaller differences than 3D-CRT plans. Only small differences were found for PTV parameters between the four CT datasets. Larger differences occurred for the doses to organs at risk (ipsilateral lung, liver) especially for MIP plans. No relevant differences were observed between 3D-CRT or VMAT plans. MIP CTs are not appropriate for OAR dose assessment. PCT, AIP and MidV resulted in similar doses. If a 4DCT is acquired PCT can be omitted using AIP or MidV for treatment planning.

Biochemical and morphological changes in the liver after hepatic artery ligation in the presence or absence of extrahepatic cholestasis.

PubMed Central

Soares, A. F.; Castro e Silva Júnior, O.; Ceneviva, R.; Roselino, J. E.; Zucoloto, S.

1993-01-01

The present study was carried out to investigate the biochemical and morphological changes in the liver after ligation of the hepatic artery (HA) in the presence and in the absence of extrahepatic cholestasis (EHC). The study was conducted on 100 rats divided into four groups of 25 animals each: group 1, sham operation; group 2, hepatic artery ligation (HAL); group 3, bile duct ligation (BDL); and group 4, HAL plus BDL. All animals were sacrificed 7 days after surgery when total bilirubin and fractions, alkaline phosphatase (AP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured in serum and on the inner hepatocyte mitochondrial membrane (IHMM); the incidence of necrosis and the volume fractions of vessels, bile ducts and hepatocytes in the liver were also determined. HAL reduces the relative volumes of bile ducts, with no changes in levels of bilirubin and fractions, AP, ALT, AST and IHMM, but HAL associated with EHC reduces duct proliferation and the liver becomes more vulnerable to necrosis. In conclusion, the normal liver depends on HA flow and this dependence is more evident in the presence of EHC. PMID:8398809

Liver Ischemic Preconditioning (IPC) Improves Intestinal Microbiota Following Liver Transplantation in Rats through 16s rDNA-Based Analysis of Microbial Structure Shift

PubMed Central

Lu, Haifeng; Chen, Xinhua; Jiang, Jianwen; Liu, Hui; He, Yong; Ding, Songming; Hu, Zhenhua; Wang, Weilin; Zheng, Shusen

2013-01-01

Background Ischemia-reperfusion (I/R) injury is associated with intestinal microbial dysbiosis. The “gut-liver axis” closely links gut function and liver function in health and disease. Ischemic preconditioning (IPC) has been proven to reduce I/R injury in the surgery. This study aims to explore the effect of IPC on intestinal microbiota and to analyze characteristics of microbial structure shift following liver transplantation (LT). Methods The LT animal models of liver and gut IPC were established. Hepatic graft function was assessed by histology and serum ALT/AST. Intestinal barrier function was evaluated by mucosal ultrastructure, serum endotoxin, bacterial translocation, fecal sIgA content and serum TNF-α. Intestinal bacterial populations were determined by quantitative PCR. Microbial composition was characterized by DGGE and specific bacterial species were determined by sequence analysis. Principal Findings Liver IPC improved hepatic graft function expressed as ameliorated graft structure and reduced ALT/AST levels. After administration of liver IPC, intestinal mucosal ultrastructure improved, serum endotoxin and bacterial translocation mildly decreased, fecal sIgA content increased, and serum TNF-α decreased. Moreover, liver IPC promoted microbial restorations mainly through restoring Bifidobacterium spp., Clostridium clusters XI and Clostridium cluster XIVab on bacterial genus level. DGGE profiles indicated that liver IPC increased microbial diversity and species richness, and cluster analysis demonstrated that microbial structures were similar and clustered together between the NC group and Liver-IPC group. Furthermore, the phylogenetic tree of band sequences showed key bacteria corresponding to 10 key band classes of microbial structure shift induced by liver IPC, most of which were assigned to Bacteroidetes phylum. Conclusion Liver IPC cannot only improve hepatic graft function and intestinal barrier function, but also promote restorations of intestinal microbiota following LT, which may further benefit hepatic graft by positive feedback of the “gut-liver axis”. PMID:24098410

Liver ischemic preconditioning (IPC) improves intestinal microbiota following liver transplantation in rats through 16s rDNA-based analysis of microbial structure shift.

PubMed

Ren, Zhigang; Cui, Guangying; Lu, Haifeng; Chen, Xinhua; Jiang, Jianwen; Liu, Hui; He, Yong; Ding, Songming; Hu, Zhenhua; Wang, Weilin; Zheng, Shusen

2013-01-01

Ischemia-reperfusion (I/R) injury is associated with intestinal microbial dysbiosis. The "gut-liver axis" closely links gut function and liver function in health and disease. Ischemic preconditioning (IPC) has been proven to reduce I/R injury in the surgery. This study aims to explore the effect of IPC on intestinal microbiota and to analyze characteristics of microbial structure shift following liver transplantation (LT). The LT animal models of liver and gut IPC were established. Hepatic graft function was assessed by histology and serum ALT/AST. Intestinal barrier function was evaluated by mucosal ultrastructure, serum endotoxin, bacterial translocation, fecal sIgA content and serum TNF-α. Intestinal bacterial populations were determined by quantitative PCR. Microbial composition was characterized by DGGE and specific bacterial species were determined by sequence analysis. Liver IPC improved hepatic graft function expressed as ameliorated graft structure and reduced ALT/AST levels. After administration of liver IPC, intestinal mucosal ultrastructure improved, serum endotoxin and bacterial translocation mildly decreased, fecal sIgA content increased, and serum TNF-α decreased. Moreover, liver IPC promoted microbial restorations mainly through restoring Bifidobacterium spp., Clostridium clusters XI and Clostridium cluster XIVab on bacterial genus level. DGGE profiles indicated that liver IPC increased microbial diversity and species richness, and cluster analysis demonstrated that microbial structures were similar and clustered together between the NC group and Liver-IPC group. Furthermore, the phylogenetic tree of band sequences showed key bacteria corresponding to 10 key band classes of microbial structure shift induced by liver IPC, most of which were assigned to Bacteroidetes phylum. Liver IPC cannot only improve hepatic graft function and intestinal barrier function, but also promote restorations of intestinal microbiota following LT, which may further benefit hepatic graft by positive feedback of the "gut-liver axis".

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.

One year of baclofen in 100 patients with or without cirrhosis: a French real-life experience.

PubMed

Barrault, Camille; Lison, Hortensia; Roudot-Thoraval, Françoise; Garioud, Armand; Costentin, Charlotte; Béhar, Véronique; Medmoun, Mourad; Pulwermacher, Georges; Hagège, Hervé; Cadranel, Jean-François

2017-10-01

Several studies have suggested the efficacy of baclofen in reducing alcohol consumption, leading to a temporary recommendation for use in France. Our aim was to report our experience in using baclofen in alcohol-dependant patients with or without liver cirrhosis. Consecutive patients from two liver and alcohol units were recruited over a 3-year period and received increasing doses of baclofen associated with social, psychological, and medical care. One hundred patients were treated, of whom 65 were cirrhotic. After 1 year, 86 patients were still being followed up. At a mean dosage of 40 mg/day (extremes: 30-210), the median daily alcohol consumption reduced from 80 to 0 g/day (P<0.001). Twenty patients drank a small amount of alcohol of up to 30 g/day and 44 patients were completely abstinent. These declarative results were associated with a significant improvement in alcohol-related biological markers in this 'low-consumption' group of 64 patients: the median γ-glutamyl transferase decreased from 3.9 to 2.0 UNL (P<0.001), the mean aspartate transaminase decreased from 2.6 to 1.2 UNL (P<0.001), and the mean corpuscular volume decreased from 101 to 93 µm (P<0.001). In cirrhotic patients, bilirubinemia decreased significantly from 22 to 11 µmol/l (P=0.026), prothrombin time increased from 68 to 77% (P<0.001), and albuminemia increased from 34.1 to 37.4 g/l (P<0.001). Twenty patients reported grades 1-2 adverse events. No liver or renal function deterioration occurred in cirrhotic patients. In our cohort, baclofen associated with a global care was very well tolerated even in cirrhotic patients. The marked reduction in alcohol consumption in 64 patients translated into a significant improvement in biological markers and in liver function tests. Baclofen could be very useful, especially in cases of severe alcoholic liver disease.

Estimation of contrast agent bolus arrival delays for improved reproducibility of liver DCE MRI

NASA Astrophysics Data System (ADS)

Chouhan, Manil D.; Bainbridge, Alan; Atkinson, David; Punwani, Shonit; Mookerjee, Rajeshwar P.; Lythgoe, Mark F.; Taylor, Stuart A.

2016-10-01

Delays between contrast agent (CA) arrival at the site of vascular input function (VIF) sampling and the tissue of interest affect dynamic contrast enhanced (DCE) MRI pharmacokinetic modelling. We investigate effects of altering VIF CA bolus arrival delays on liver DCE MRI perfusion parameters, propose an alternative approach to estimating delays and evaluate reproducibility. Thirteen healthy volunteers (28.7  ±  1.9 years, seven males) underwent liver DCE MRI using dual-input single compartment modelling, with reproducibility (n  =  9) measured at 7 days. Effects of VIF CA bolus arrival delays were assessed for arterial and portal venous input functions. Delays were pre-estimated using linear regression, with restricted free modelling around the pre-estimated delay. Perfusion parameters and 7 days reproducibility were compared using this method, freely modelled delays and no delays using one-way ANOVA. Reproducibility was assessed using Bland-Altman analysis of agreement. Maximum percent change relative to parameters obtained using zero delays, were  -31% for portal venous (PV) perfusion, +43% for total liver blood flow (TLBF), +3247% for hepatic arterial (HA) fraction, +150% for mean transit time and  -10% for distribution volume. Differences were demonstrated between the 3 methods for PV perfusion (p  =  0.0085) and HA fraction (p  <  0.0001), but not other parameters. Improved mean differences and Bland-Altman 95% Limits-of-Agreement for reproducibility of PV perfusion (9.3 ml/min/100 g, ±506.1 ml/min/100 g) and TLBF (43.8 ml/min/100 g, ±586.7 ml/min/100 g) were demonstrated using pre-estimated delays with constrained free modelling. CA bolus arrival delays cause profound differences in liver DCE MRI quantification. Pre-estimation of delays with constrained free modelling improved 7 days reproducibility of perfusion parameters in volunteers.

Preservation of nutritional-status in patients with refractory ascites due to hepatic cirrhosis who are undergoing repeated paracentesis.

PubMed

Sorrentino, Paolo; Castaldo, Giuseppe; Tarantino, Luciano; Bracigliano, Alessandra; Perrella, Alessandro; Perrella, Oreste; Fiorentino, Francesco; Vecchione, Raffaela; D' Angelo, Salvatore

2012-04-01

Refractory ascites in liver-cirrhosis is associated with a poor prognosis. We performed a prospective study to investigate whether aggressive nutritional-support could improve outcomes in cirrhotic patients. Cirrhotic patients undergoing serial large-volume paracentesis for refractory-ascites were enrolled and randomized into three groups. Group A received post-paracentesis intravenous nutritional-support in addition to a balanced oral diet and a late-evening protein snack, group B received the same oral nutritional-protocol as the first group but without parenteral support, and group C (the control group) received a low-sodium or sodium-free diet. Clinical, anthropometric and laboratory nutritional parameters and biochemical tests of liver and renal function were reported for 12 months of follow-up. We enrolled 120 patients, who were randomized into three groups of equal size. Patients on the nutritional-protocol showed better preservation of clinical, anthropometric and laboratory nutritional parameters that were associated with decreased deterioration of liver function compared with patients on the low-sodium or sodium-free diet (group C). Groups A and B had lower morbidity and mortality rates than the control group (C). Mortality rates were significantly better in patients who were treated with parenteral-nutritional-support than for the other two groups. In patients who were on the nutritional-protocol, there was a reduction in the requirement of taps for the treatment of refractory ascites. Post-paracentesis parenteral-nutritional-support with a balanced oral diet and an evening protein snack appears to be the best care protocol for patients with liver-cirrhosis that has been complicated by refractory-ascites. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Dexmedetomidine metabolic clearance is not affected by fat mass in obese patients.

PubMed

Rolle, A; Paredes, S; Cortínez, L I; Anderson, B J; Quezada, N; Solari, S; Allende, F; Torres, J; Cabrera, D; Contreras, V; Carmona, J; Ramírez, C; Oliveros, A M; Ibacache, M

2018-05-01

Obesity has been associated with reduced dexmedetomidine clearance, suggesting impaired hepatic function or reduced hepatic blood flow. The aim of this study was to clarify the effect of obesity in dexmedetomidine metabolic clearance. Forty patients, ASA I-III, 18-60 yr old, weighing 47-126 kg, scheduled for abdominal laparoscopic surgery, were enrolled. Anaesthetic agents (propofol, remifentanil, and dexmedetomidine) were dosed based on lean body weight measured by dual X-ray absorptiometry. Serial venous samples were drawn during and after dexmedetomidine infusion. A pharmacokinetic analysis was undertaken using non-linear mixed-effect models. In the modelling approach, the total body weight, lean body weight, and adjusted body weight were first tested as size descriptors for volumes and clearances. Hepatic blood flow, liver histopathology, liver enzymes, and gene expression of metabolic enzymes (UGT2B10 and UGT1A4) were tested as covariates of dexmedetomidine metabolic clearance. A decrease in NONMEM objective function value (ΔOFV) of 3.84 points, for an added parameter, was considered significant at the 0.05 level. A total of 637 dexmedetomidine serum samples were obtained. A two-compartmental model scaled to measured lean weight adequately described the dexmedetomidine pharmacokinetics. Liver blood flow was a covariate for dexmedetomidine clearance (ΔOFV=-5.878). Other factors, including fat mass, histopathological damage, and differential expression of enzymes, did not affect the dexmedetomidine clearance in the population studied (ΔOFV<3.84). We did not find a negative influence of obesity in dexmedetomidine clearance when doses were adjusted to lean body weight. Liver blood flow showed a significant effect on dexmedetomidine clearance. NCT02557867. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Portal Vein Embolization before Right Hepatectomy: Improved Results Using n-Butyl-Cyanoacrylate Compared to Microparticles Plus Coils

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

Guiu, Boris, E-mail: boris.guiu@chu-dijon.fr; Bize, Pierre; Gunthern, Daniel

Background: There is currently no consensus in the literature on which embolic agent induces the greatest degree of liver hypertrophy after portal vein embolization (PVE). Only experimental results in a pig model have demonstrated an advantage of n-butyl-cyanoacrylate (NBCA) over 3 other embolic materials (hydrophilic gel, small and large polyvinyl alcohol particles) for PVE. Therefore, the aim of this human study was to retrospectively compare the results of PVE using NBCA with those using spherical microparticles plus coils. Methods: A total of 34 patients underwent PVE using either NBCA (n = 20), or spherical microparticles plus coils (n = 14).more » PVE was decided according to preoperative volumetry on the basis of contrast-enhanced CT. Groups were compared for age, sex, volume of the left lobe before PVE and future remnant liver ratio (FRL) (volume of the left lobe/total liver volume - tumor volume). The primary end point was the increase in left lobe volume 1 month after PVE. Secondary end points were procedure complications and biological tolerance. Results: Both groups were similar in terms of age, sex ratio, left lobe volume, and FRL before PVE. NBCA induced a greater increase in volume after PVE than did microparticles plus coils (respectively, +74 {+-} 69 % and +23 {+-} 14 %, p < 0.05). The amount of contrast medium used for the procedure was significantly larger when microparticles and coils rather than NBCA were used (respectively, 264 {+-} 43 ml and 162 {+-} 34 ml, p < 0.01). The rate of PVE complications as well as the biological tolerance was similar in both groups. Conclusion: NBCA seems more effective than spherical microparticles plus coils to induce left-lobe hypertrophy.« less

Long live the liver: immunohistochemical and stereological study of hepatocytes, liver sinusoidal endothelial cells, Kupffer cells and hepatic stellate cells of male and female rats throughout ageing.

PubMed

Marcos, Ricardo; Correia-Gomes, Carla

2016-12-01

Male/female differences in enzyme activity and gene expression in the liver are known to be attenuated with ageing. Nevertheless, the effect of ageing on liver structure and quantitative cell morphology remains unknown. Male and female Wistar rats aged 2, 6, 12 and 18 months were examined by means of stereological techniques and immunohistochemical tagging of hepatocytes (HEP), liver sinusoidal endothelial cells (LSEC), Kupffer cells (KC) and hepatic stellate cells (HSC) in order to assess the total number and number per gram of these cells throughout life. The mean cell volume of HEP and HSC, the lobular position and the collagen content of the liver were also evaluated with stereological techniques. The number per gram of HSC was similar for both genders and was maintained throughout ageing. The mean volume of HSC was also conserved but differences in the cell body and lobular location were observed. Statistically significant gender differences in HEP were noted in young rats (females had smaller and more binucleated HEP) but were attenuated with ageing. The same occurred for KC and LSEC, since the higher number per gram in young females disappeared in older animals. Liver collagen increased with ageing but only in males. Thus, the numbers of these four cell types are related throughout ageing, with well-defined cell ratios. The shape and lobular position of HSC change with ageing in both males and females. Gender dimorphism in HEP, KC and LSEC of young rat liver disappears with ageing.

International trends in liver cancer incidence, overall and by histologic subtype, 1978-2007.

PubMed

Petrick, Jessica L; Braunlin, Megan; Laversanne, Mathieu; Valery, Patricia C; Bray, Freddie; McGlynn, Katherine A

2016-10-01

Primary liver cancer, the most common histologic types of which are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), is the second leading cause of cancer death worldwide. While rising incidence of liver cancer in low-risk areas and decreasing incidence in some high-risk areas has been reported, trends have not been thoroughly explored by country or by histologic type. We examined liver cancer incidence overall and by histology by calendar time and birth cohort for selected countries between 1978 and 2007. For each successive 5-year period, age-standardized incidence rates were calculated from volumes V-IX of the Cancer Incidence in Five Continents electronic database (CI5plus) and the newly released CI5X (volume X) database. Wide global variations persist in liver cancer incidence. Rates of liver cancer remain highest in Asian countries, specifically Eastern and South-Eastern Asian countries. While rates in most of these high-risk countries have been decreasing in recent years, rates in India and several low-risk countries of Africa, Europe, the Americas, and Oceania have been on the rise. Liver cancer rates by histologic type tend to convey a similar temporal profile. However, in Thailand, France, and Italy, ICC rates have increased while HCC rates have declined. We expect rates in high-risk countries to continue to decrease, as the population seroprevalence of hepatitis B virus (HBV) continues to decline. In low-risk countries, targeted screening and treatment of the hepatitis C virus (HCV), treatment of diabetes and primary prevention of obesity, will be key in reducing future liver cancer incidence. © 2016 UICC.

Metabolomics discloses donor liver biomarkers associated with early allograft dysfunction.

PubMed

Cortes, Miriam; Pareja, Eugenia; García-Cañaveras, Juan C; Donato, M Teresa; Montero, Sandra; Mir, Jose; Castell, José V; Lahoz, Agustín

2014-09-01

Early allograft dysfunction (EAD) dramatically influences graft and patient outcome after orthotopic liver transplantation and its incidence is strongly determined by donor liver quality. Nevertheless, objective biomarkers, which can assess graft quality and anticipate organ function, are still lacking. This study aims to investigate whether there is a preoperative donor liver metabolomic biosignature associated with EAD. A comprehensive metabolomic profiling of 124 donor liver biopsies collected before transplantation was performed by mass spectrometry coupled to liquid chromatography. Donor liver grafts were classified into two groups: showing EAD and immediate graft function (IGF). Multivariate data analysis was used to search for the relationship between the metabolomic profiles present in donor livers before transplantation and their function in recipients. A set of liver graft dysfunction-associated biomarkers was identified. Key changes include significantly increased levels of bile acids, lysophospholipids, phospholipids, sphingomyelins and histidine metabolism products, all suggestive of disrupted lipid homeostasis and altered histidine pathway. Based on these biomarkers, a predictive EAD model was built and further evaluated by assessing 24 independent donor livers, yielding 91% sensitivity and 82% specificity. The model was also successfully challenged by evaluating donor livers showing primary non-function (n=4). A metabolomic biosignature that accurately differentiates donor livers, which later showed EAD or IGF, has been deciphered. The remarkable metabolomic differences between donor livers before transplant can relate to their different quality. The proposed metabolomic approach may become a clinical tool for donor liver quality assessment and for anticipating graft function before transplant. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Successful introduction of Model for End-stage Liver Disease scoring in deceased donor liver transplantation in Korea: analysis of first 1 year experience at a high-volume transplantation center.

PubMed

Ha, Soo-Min; Hwang, Shin; Song, Gi-Won; Ahn, Chul-Soo; Moon, Deok-Bog; Ha, Tae-Yong; Jung, Dong-Hwan; Park, Gil-Chun; Kim, Ki-Hun; Kim, Dae-Yeon; Namgung, Jungman; Kang, Woo-Hyoung; Kim, Seok-Hwan; Jwa, Eunkyoung; Kwon, Jae-Hyeon; Cho, Hui-Dong; Jung, Yong-Kyu; Kang, Sang-Hyeon; Lee, Sung-Gyu

2017-11-01

Model for End-stage Liver Disease (MELD) score was adopted in June 2016 in Korea. We analyzed changes in volumes and outcomes of deceased donor liver transplantation (DDLT) for 1 year before and after introduction of MELD scoring at Asan Medical Center. There were 64 cases of DDLT in 1 year before MELD introduction and 106 in 1 year after MELD introduction, an increase of 65%. The volume of DDLTs abruptly increased during first 3 months, but then returned to its usual level before MELD introduction, which indicated 3-month depletion of accumulated recipient pool with high MELD scores. The number of pediatric DDLT cases increased from 3 before MELD introduction to 11 after it, making up 21.4% and 47.8% of all cases of pediatric liver transplantation, respectively. The number of cases of retransplanted DDLTs increased from 4 to 27, representing 6.3% and 25.5% of all DDLT cases, respectively. The number of status 1 DDLT cases increased from 5 to 12, being 7.8% and 11.3% of all cases. Patient survival outcomes were similar before and after MELD introduction. The number of DDLTs temporarily increased after adoption of MELD scoring due to accumulated recipient pool with high MELD scores. The numbers of retransplanted and pediatric DDLT cases significantly increased. Patient survival in adult and pediatric DDLT was comparable before and after adoption of MELD scoring. These results imply that Korean MELD score-based allocation system was successfully established within its first year.

Localization of liver tumors in freehand 3D laparoscopic ultrasound

NASA Astrophysics Data System (ADS)

Shahin, O.; Martens, V.; Besirevic, A.; Kleemann, M.; Schlaefer, A.

2012-02-01

The aim of minimally invasive laparoscopic liver interventions is to completely resect or ablate tumors while minimizing the trauma caused by the operation. However, restrictions such as limited field of view and reduced depth perception can hinder the surgeon's capabilities to precisely localize the tumor. Typically, preoperative data is acquired to find the tumor(s) and plan the surgery. Nevertheless, determining the precise position of the tumor is required, not only before but also during the operation. The standard use of ultrasound in hepatic surgery is to explore the liver and identify tumors. Meanwhile, the surgeon mentally builds a 3D context to localize tumors. This work aims to upgrade the use of ultrasound in laparoscopic liver surgery. We propose an approach to segment and localize tumors intra-operatively in 3D ultrasound. We reconstruct a 3D laparoscopic ultrasound volume containing a tumor. The 3D image is then preprocessed and semi-automatically segmented using a level set algorithm. During the surgery, for each subsequent reconstructed volume, a fast update of the tumor position is accomplished via registration using the previously segmented and localized tumor as a prior knowledge. The approach was tested on a liver phantom with artificial tumors. The tumors were localized in approximately two seconds with a mean error of less than 0.5 mm. The strengths of this technique are that it can be performed intra-operatively, it helps the surgeon to accurately determine the location, shape and volume of the tumor, and it is repeatable throughout the operation.

Registration-free laparoscope augmentation for intra-operative liver resection planning

NASA Astrophysics Data System (ADS)

Feuerstein, Marco; Mussack, Thomas; Heining, Sandro M.; Navab, Nassir

2007-03-01

In recent years, an increasing number of liver tumor indications were treated by minimally invasive laparoscopic resection. Besides the restricted view, a major issue in laparoscopic liver resection is the enhanced visualization of (hidden) vessels, which supply the tumorous liver segment and thus need to be divided prior to the resection. To navigate the surgeon to these vessels, pre-operative abdominal imaging data can hardly be used due to intraoperative organ deformations mainly caused by appliance of carbon dioxide pneumoperitoneum and respiratory motion. While regular respiratory motion can be gated and synchronized intra-operatively, motion caused by pneumoperitoneum is individual for every patient and difficult to estimate. Therefore, we propose to use an optically tracked mobile C-arm providing cone-beam CT imaging capability intraoperatively. The C-arm is able to visualize soft tissue by means of its new flat panel detector and is calibrated offline to relate its current position and orientation to the coordinate system of a reconstructed volume. Also the laparoscope is optically tracked and calibrated offline, so both laparoscope and C-arm are registered in the same tracking coordinate system. Intra-operatively, after patient positioning, port placement, and carbon dioxide insufflation, the liver vessels are contrasted and scanned during patient exhalation. Immediately, a three-dimensional volume is reconstructed. Without any further need for patient registration, the volume can be directly augmented on the live laparoscope video, visualizing the contrasted vessels. This augmentation provides the surgeon with advanced visual aid for the localization of veins, arteries, and bile ducts to be divided or sealed.

Characterization of HIFU ablation using DNA fragmentation labeling as apoptosis stain

NASA Astrophysics Data System (ADS)

Anquez, Jeremie; Corréas, Jean-Michel; Pau, Bernard; Lacoste, François; Yon, Sylvain

2012-11-01

The goal of this work was to compare modalities to precisely quantify the extent of thermally induced lesions: gross pathology vs. histopathology vs. devascularization. Liver areas of 14 rabbits were targeted with HIFU and RF ablations in an acute study. Contrast enhanced computorized tomography (CE-CT) scan images were acquired two hours after HIFU and RF treatment to obtain the devascularized volumes of the livers. The animals were then euthanized and deep frozen. The livers were sliced and each slice was photographed and stacked yielding a volume of gross pathology. The volume VGP of the HIFU lesions were derived. The area AGP of the lesions were computed on a particular slice. The lesions were segmented as hypo intense (devascularized) regions on CE-CT images and their volumes VC were computed. The ratios VC/VGP were computed for all the HIFU lesions on all the 14 subjects with a mean value of 1.2. Histology was performed on the livers using Hematoxyline Eosine Staining (HES) and DNA Fragmentation labeling (TUNEL® technology) which characterizes apoptosis. Apoptotic regions of area AT were segmented on the images stained by TUNEL®. No necrosis was identified on the HES data. While TUNEL® did not mark the cores of the RF lesions as apoptotic, the periphery of HIFU and RF lesions was always recognized with TUNEL® as apoptotic. The ratio AGP/AT was computed. The mean value was 0.95 and 0.25 for HIFU and RF lesions respectively. These findings show that the devascularized territory seen on CE-CT scan coincide with the coagulated territories seen with gross pathology. Those actually correspond to cells in apoptosis. It is confirmed that HES stain does not show necrosis 2 hours after thermal ablation. TUNEL® technology for DNA fragmentation labeling appears as a useful marker for thermally induced acute lesions in the liver.

Semiautomatic segmentation of liver metastases on volumetric CT images

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

Yan, Jiayong; Schwartz, Lawrence H.; Zhao, Binsheng, E-mail: bz2166@cumc.columbia.edu

2015-11-15

Purpose: Accurate segmentation and quantification of liver metastases on CT images are critical to surgery/radiation treatment planning and therapy response assessment. To date, there are no reliable methods to perform such segmentation automatically. In this work, the authors present a method for semiautomatic delineation of liver metastases on contrast-enhanced volumetric CT images. Methods: The first step is to manually place a seed region-of-interest (ROI) in the lesion on an image. This ROI will (1) serve as an internal marker and (2) assist in automatically identifying an external marker. With these two markers, lesion contour on the image can be accuratelymore » delineated using traditional watershed transformation. Density information will then be extracted from the segmented 2D lesion and help determine the 3D connected object that is a candidate of the lesion volume. The authors have developed a robust strategy to automatically determine internal and external markers for marker-controlled watershed segmentation. By manually placing a seed region-of-interest in the lesion to be delineated on a reference image, the method can automatically determine dual threshold values to approximately separate the lesion from its surrounding structures and refine the thresholds from the segmented lesion for the accurate segmentation of the lesion volume. This method was applied to 69 liver metastases (1.1–10.3 cm in diameter) from a total of 15 patients. An independent radiologist manually delineated all lesions and the resultant lesion volumes served as the “gold standard” for validation of the method’s accuracy. Results: The algorithm received a median overlap, overestimation ratio, and underestimation ratio of 82.3%, 6.0%, and 11.5%, respectively, and a median average boundary distance of 1.2 mm. Conclusions: Preliminary results have shown that volumes of liver metastases on contrast-enhanced CT images can be accurately estimated by a semiautomatic segmentation method.« less

Improved hepatic arterial fraction estimation using cardiac output correction of arterial input functions for liver DCE MRI

NASA Astrophysics Data System (ADS)

Chouhan, Manil D.; Bainbridge, Alan; Atkinson, David; Punwani, Shonit; Mookerjee, Rajeshwar P.; Lythgoe, Mark F.; Taylor, Stuart A.

2017-02-01

Liver dynamic contrast enhanced (DCE) MRI pharmacokinetic modelling could be useful in the assessment of diffuse liver disease and focal liver lesions, but is compromised by errors in arterial input function (AIF) sampling. In this study, we apply cardiac output correction to arterial input functions (AIFs) for liver DCE MRI and investigate the effect on dual-input single compartment hepatic perfusion parameter estimation and reproducibility. Thirteen healthy volunteers (28.7  ±  1.94 years, seven males) underwent liver DCE MRI and cardiac output measurement using aortic root phase contrast MRI (PCMRI), with reproducibility (n  =  9) measured at 7 d. Cardiac output AIF correction was undertaken by constraining the first pass AIF enhancement curve using the indicator-dilution principle. Hepatic perfusion parameters with and without cardiac output AIF correction were compared and 7 d reproducibility assessed. Differences between cardiac output corrected and uncorrected liver DCE MRI portal venous (PV) perfusion (p  =  0.066), total liver blood flow (TLBF) (p  =  0.101), hepatic arterial (HA) fraction (p  =  0.895), mean transit time (MTT) (p  =  0.646), distribution volume (DV) (p  =  0.890) were not significantly different. Seven day corrected HA fraction reproducibility was improved (mean difference 0.3%, Bland-Altman 95% limits-of-agreement (BA95%LoA)  ±27.9%, coefficient of variation (CoV) 61.4% versus 9.3%, ±35.5%, 81.7% respectively without correction). Seven day uncorrected PV perfusion was also improved (mean difference 9.3 ml min-1/100 g, BA95%LoA  ±506.1 ml min-1/100 g, CoV 64.1% versus 0.9 ml min-1/100 g, ±562.8 ml min-1/100 g, 65.1% respectively with correction) as was uncorrected TLBF (mean difference 43.8 ml min-1/100 g, BA95%LoA  ±586.7 ml min-1/ 100 g, CoV 58.3% versus 13.3 ml min-1/100 g, ±661.5 ml min-1/100 g, 60.9% respectively with correction). Reproducibility of uncorrected MTT was similar (uncorrected mean difference 2.4 s, BA95%LoA  ±26.7 s, CoV 60.8% uncorrected versus 3.7 s, ±27.8 s, 62.0% respectively with correction), as was and DV (uncorrected mean difference 14.1%, BA95%LoA  ±48.2%, CoV 24.7% versus 10.3%, ±46.0%, 23.9% respectively with correction). Cardiac output AIF correction does not significantly affect the estimation of hepatic perfusion parameters but demonstrates improvements in normal volunteer 7 d HA fraction reproducibility, but deterioration in PV perfusion and TLBF reproducibility. Improved HA fraction reproducibility maybe important as arterialisation of liver perfusion is increased in chronic liver disease and within malignant liver lesions.

Impact of Estimated Liver Volume and Liver Weight on Gender Disparity in Liver Transplantation

PubMed Central

Mindikoglu, Ayse L.; Emre, Sukru H.; Magder, Laurence S.

2012-01-01

OBJECTIVES While lower Model for End-Stage Liver Disease (MELD) scores due to lower levels of serum creatinine in women might account for some gender disparity in liver transplant (LT) rates, even within MELD scores, women are transplanted at lower rates than men. It is unclear what causes this disparity, but transplant candidate-donor liver size mismatch may be a factor. METHODS We analyzed Organ Procurement and Transplantation Network data for patients with end-stage liver disease on the waiting list. Pooled conditional logistic regression analysis was used to assess the association between gender and LT and determine the degree to which this association was explained by lower MELD scores or liver size. RESULTS A total of 28,866 patients and 424,001 person-months were included in the analysis. Median estimated liver volume (eLV) and liver weight (eLW) were significantly lower in women than in men on the LT waiting list (P<0.0001). Controlling for region and blood type, women were 25% less likely to receive LT in a given month compared to men (P<0.0001). When MELD was included in the model, the odds ratio (OR) for gender increased to 0.84 suggesting that 9 percentage points of the 25% gender disparity was due to MELD score. When eLV was added to the model, there was an additional 3% increase in OR of gender suggesting that transplant candidate-donor liver size mismatch is an underlying factor for lower LT rates in women compared to men (OR=0.87, P<0.0001). CONCLUSIONS Lower LT rates among women on the waiting list can be explained in part by lower MELD scores, eLV and eLW than those of men. However; at least half of the gender disparity still remains unexplained. PMID:23008117

Liver Resections in a High-Volume Center: Form Standard Procedures to Extreme Surgery and Ultrasound-guided Resections.

PubMed

Botea, Florin; Ionescu, Mihnea; Braşoveanu, Vladislav; Hrehoreţ, Doina; Alexandrescu, Sorin; Grigorie, Mihai; Stanciulea, Oana; Nicolaescu, Diana; Tomescu, Dana; Droc, Gabriela; Ungureanu, Daniela; Fota, Ruxandra; Croitoru, Adina; Gheorghe, Liana; Gheorghe, Cristian; Lupescu, Ioana; Grasu, Mugur; Boroş, Mirela; Dumitru, Radu; Toma, Mihai; Herlea, Vlad; Popescu, Irinel

2017-01-01

Background: Liver resection (LR) is the treatment of choice for most benign and malignant focal liver lesions, as well as in selected patients with liver trauma. Few other therapies can compete with LR in selected cases, such as liver transplantation in hepatocellular carcinoma (HCC) and ablative therapies in small HCCs or liver metastases. The present paper analyses a single center experience in LR, reviewing the indications of LR, the operative techniques and their short-term results. Between January 2000 and December 2016, in "œDan Setlacec" Center of General Surgery and Liver Transplantation were performed 3165 LRs in 3016 patients, for pathologic conditions of the liver. In the present series, liver resections for living-donor liver transplantation were excluded. The median age of the patients was 56 years (mean 58 years; range 1-88), with male/female ratio 1524/1492 and adult/pediatric patient ratio 2973/43. Results: Malignant lesions were the main indication for LR (2372 LRs; 74.9%). Among these, colorectal liver metastases were the most frequent indication (952 LRs; 30.1%), followed by hepatocellular carcinoma (575 patients, 18.2%). The highest number of resected tumors per patient was 21, and the median diameter of the largest tumor was 40 mm (mean 51 mm; range 3-250). Major resections rate was 18.6% (588 LRs) and anatomical LRs were performed in 789 patients (24.9%). The median operative time was 180 minutes (mean 204 minutes; range 45-920). The median blood loss was 500 ml (mean 850 ml; range 500-9500), with a transfusion rate of 41.6% (1316 LRs). The morbidity rate was 40.1% (1270 LRs) and the rate of major complications (Dindo-Clavien IIIa or more) was 13.2% (418 LRs). Mortality rate was 4.2% (127 pts). LRs should be performed in specialized high-volume centers to achieve the best results (low morbidity and mortality rates). Celsius.

Baseline Characteristics of the Autosomal Dominant Polycystic Kidney Disease Subcohort of the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD).

PubMed

Kim, Hyunsuk; Koh, Junga; Park, Sue K; Oh, Kook Hwan; Kim, Yeong Hoon; Kim, Yaeni; Ahn, Curie; Oh, Yun Kyu

2018-05-24

The aim of this study was to describe the baseline characteristics of autosomal dominant polycystic kidney disease (ADPKD) in a cohort of Korean patients with chronic kidney disease (CKD). From April 2011 to February 2016, patients with CKD stage 1 to 5 (pre-dialysis) were enrolled as an ADPKD subcohort of the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease. Baseline characteristics, the correlation of kidney and liver volume and kidney function, and the factors associated with kidney function were analyzed. A total of 364 ADPKD patients with a mean estimated glomerular filtration rate (eGFR) of 68.1 ± 33.3 mL/min/1.73 m 2 (50.5% male with a mean age of 47.0 ± 10.6 years) were enrolled from nine hospitals in Korea. Initially, 55.8% of the patients were asymptomatic, and pain was the most common symptom (12.9%); 87.6% and 77.5% of the patients had hypertension and hepatic cysts, respectively. The height-adjusted total kidney volumes (htTKV) were higher in male patients than in female patients. In contrast, the height-adjusted total liver volumes were higher in female patients than in male patients. The decrease rate of eGFR depending on Log(htTKV) was larger in the group aged between 41 and 50 than the other age groups. Older age, a higher 24-hour urine protein excretion, larger htTKV, and hyperuricemia were independently associated with lower eGFR, whereas using febuxostat was independently associated with higher eGFR. This subcohort will provide clinical characteristics and outcomes of Korean ADPKD patients and can compare with those of other previous cohorts. We have identified factors associated with advanced-stage CKD in Korean patients with ADPKD. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Cirrhotic cardiomyopathy

PubMed Central

Ruiz-del-Árbol, Luis; Serradilla, Regina

2015-01-01

During the course of cirrhosis, there is a progressive deterioration of cardiac function manifested by the disappearance of the hyperdynamic circulation due to a failure in heart function with decreased cardiac output. This is due to a deterioration in inotropic and chronotropic function which takes place in parallel with a diastolic dysfunction and cardiac hypertrophy in the absence of other known cardiac disease. Other findings of this specific cardiomyopathy include impaired contractile responsiveness to stress stimuli and electrophysiological abnormalities with prolonged QT interval. The pathogenic mechanisms of cirrhotic cardiomyopathy include impairment of the b-adrenergic receptor signalling, abnormal cardiomyocyte membrane lipid composition and biophysical properties, ion channel defects and overactivity of humoral cardiodepressant factors. Cirrhotic cardiomyopathy may be difficult to determine due to the lack of a specific diagnosis test. However, an echocardiogram allows the detection of the diastolic dysfunction and the E/e′ ratio may be used in the follow-up progression of the illness. Cirrhotic cardiomyopathy plays an important role in the pathogenesis of the impairment of effective arterial blood volume and correlates with the degree of liver failure. A clinical consequence of cardiac dysfunction is an inadequate cardiac response in the setting of vascular stress that may result in renal hypoperfusion leading to renal failure. The prognosis is difficult to establish but the severity of diastolic dysfunction may be a marker of mortality risk. Treatment is non-specific and liver transplantation may normalize the cardiac function. PMID:26556983

Impact of pretransplant renal function on survival after liver transplantation.

PubMed

Gonwa, T A; Klintmalm, G B; Levy, M; Jennings, L S; Goldstein, R M; Husberg, B S

1995-02-15

To determine the effect of pretransplant liver function on survival following orthotopic liver transplantation and to quantify the effects of cyclosporine administration on long-term renal function in patients undergoing liver transplant, we performed an analysis of a prospectively maintained database. Data from 569 consecutive patients undergoing liver transplantation alone who were treated with CsA for immunosuppression were used for this study. Actuarial graft and patient survival rates were calculated using Kaplan-Meier statistics. Glomerular filtration rates, serum creatinine, and the use of various immunosuppressives were analyzed for this study. The initial analysis demonstrated that patients presenting for liver transplant with hepatorenal syndrome have a significantly decreased acturial patient survival after liver transplant at 5 years compared with patients without hepatorenal syndrome (60% vs. 68%, P < 0.03). Patients with hepatorenal syndrome recovered their renal function after liver transplant. Patients who had hepatorenal syndrome were sicker and required longer stays in the intensive care unit, longer hospitalizations, and more dialysis treatments after transplantation compared with patients who did not have hepatorenal syndrome. The incidence of end-stage renal disease after liver transplantation in patients who had hepatorenal syndrome was 7%, compared with 2% in patients who did not have hepatorenal syndrome. To more fully examine the effect of pretransplant renal function on posttransplant survival, the non-hepatorenal syndrome patients were divided into quartiles depending upon their pretransplant renal function. The patients with the lowest pretransplant renal function had the same survival as the patients with the highest pretransplant renal function. In addition, there was no increased incidence of acute or chronic rejection in any of the groups. The patients with the lower pretransplant renal function were treated with more azathioprine to maintain renal function and had a negligible decrease in glomerular filtration rate following transplant. Conversely, patients with the highest level of renal function pretransplant had a 40% decline in renal function in the first year, but maintained stable renal function up to 4 years after transplant. We conclude that pretransplant renal function other than hepato-renal syndrome has no effect on patient survival after orthotopic liver transplant. Renal function after liver transplant is stable after an initial decline, despite continued administration of CsA.(ABSTRACT TRUNCATED AT 400 WORDS)

Evaluation of abnormal liver function tests.

PubMed

Agrawal, Swastik; Dhiman, Radha K; Limdi, Jimmy K

2016-04-01

Incidentally detected abnormality in liver function tests is a common situation encountered by physicians across all disciplines. Many of these patients do not have primary liver disease as most of the commonly performed markers are not specific for the liver and are affected by myriad factors unrelated to liver disease. Also, many of these tests like liver enzyme levels do not measure the function of the liver, but are markers of liver injury, which is broadly of two types: hepatocellular and cholestatic. A combination of a careful history and clinical examination along with interpretation of pattern of liver test abnormalities can often identify type and aetiology of liver disease, allowing for a targeted investigation approach. Severity of liver injury is best assessed by composite scores like the Model for End Stage Liver Disease rather than any single parameter. In this review, we discuss the interpretation of the routinely performed liver tests along with the indications and utility of quantitative tests. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

[The clinicopathological analysis of 88 patients with abnormal liver function test of unknown etiology].

PubMed

Pang, Shu-zhen; Ou, Xiao-juan; Shi, Xiao-yan; Wang, Tai-ling; Duan, Wei-jia; Jia, Ji-dong

2011-01-01

To evaluate the clinical and histological features of patients with abnormal liver tests of unknown etiology, and then to investigate the diagnosis and differential diagnosis. Patients with abnormal liver function test hospitalized and had liver biopsies during 2008 - 2009 constituted this retrospective study cohort. After excluding those patients diagnosed with hepatotropic viral hepatitis, space occupying lesions of the liver, alcoholic liver disease and obstruction of bile duct caused by stone or malignancy and AMA/AMA-M(2) positive of primary biliary cirrhosis (PBC), the clinical and histological characteristics were evaluated. Out of the 180 patients who underwent liver biopsy, 88 patients were included in the present analysis. The final diagnosis involved 15 categories of diseases, with drug-induced liver injury (DILI) [34.09% (30/88)], autoimmune liver diseases [22.73% (20/88)], and nonalcoholic fatty liver disease (NAFLD) [12.50% (11/88)] being the most common causes, following by genetic and other rare diseases. DILI, autoimmune liver disease and NAFLD were the most common causes of abnormal liver tests in these non-viral liver diseases. Some rare diseases such as hereditary metabolic liver disease also represent a considerable proportion in patients with abnormal liver function test.

In vivo quantification of chromophore concentration using fluorescence differential path length spectroscopy

NASA Astrophysics Data System (ADS)

Kruijt, Bastiaan; Kascakova, Slavka; de Bruijn, Henriette S.; van der Ploeg-van den Heuvel, Angelique; Sterenborg, Henricus J. C. M.; Robinson, Dominic J.; Amelink, Arjen

2009-05-01

We present an optical method based on fluorescence spectroscopy for measuring chromophore concentrations in vivo. Fluorescence differential path length spectroscopy (FPDS) determines chromophore concentration based on the fluorescence intensity corrected for absorption. The concentration of the photosensitizer m-THPC (Foscan®) was studied in vivo in normal rat liver, which is highly vascularized and therefore highly absorbing. Concentration estimates of m-THPC measured by FDPS on the liver are compared with chemical extraction. Twenty-five rats were injected with 0.3 mg/kg m-THPC. In vivo optical concentration measurements were performed on tissue 3, 24, 48, and 96 h after m-THPC administration to yield a 10-fold variation in tissue concentration. After the optical measurements, the liver was harvested for chemical extraction. FDPS showed good correlation with chemical extraction. FDPS also showed a correlation between m-THPC fluorescence and blood volume fraction at the two shortest drug-light intervals. This suggests different compartmental localization of m-THPC for different drug-light intervals that can be resolved using fluorescence spectroscopy. Differences in measured m-THPC concentration between FDPS and chemical extraction are related to the interrogation volume of each technique; ~0.2 mm3 and ~102 mm3, respectively. This indicates intra-animal variation in m-THPC distribution in the liver on the scale of the FDPS sampling volume.

Kupffer Cell Metabolism and Function

PubMed Central

Nguyen-Lefebvre, Anh Thu; Horuzsko, Anatolij

2015-01-01

Kupffer cells are resident liver macrophages and play a critical role in maintaining liver functions. Under physiological conditions, they are the first innate immune cells and protect the liver from bacterial infections. Under pathological conditions, they are activated by different components and can differentiate into M1-like (classical) or M2-like (alternative) macrophages. The metabolism of classical or alternative activated Kupffer cells will determine their functions in liver damage. Special functions and metabolism of Kupffer cells suggest that they are an attractive target for therapy of liver inflammation and related diseases, including cancer and infectious diseases. Here we review the different types of Kupffer cells and their metabolism and functions in physiological and pathological conditions. PMID:26937490

Physiological ranges of matrix rigidity modulate primary mouse hepatocyte function in part through hepatocyte nuclear factor 4 alpha.

PubMed

Desai, Seema S; Tung, Jason C; Zhou, Vivian X; Grenert, James P; Malato, Yann; Rezvani, Milad; Español-Suñer, Regina; Willenbring, Holger; Weaver, Valerie M; Chang, Tammy T

2016-07-01

Matrix rigidity has important effects on cell behavior and is increased during liver fibrosis; however, its effect on primary hepatocyte function is unknown. We hypothesized that increased matrix rigidity in fibrotic livers would activate mechanotransduction in hepatocytes and lead to inhibition of liver-specific functions. To determine the physiologically relevant ranges of matrix stiffness at the cellular level, we performed detailed atomic force microscopy analysis across liver lobules from normal and fibrotic livers. We determined that normal liver matrix stiffness was around 150 Pa and increased to 1-6 kPa in areas near fibrillar collagen deposition in fibrotic livers. In vitro culture of primary hepatocytes on collagen matrix of tunable rigidity demonstrated that fibrotic levels of matrix stiffness had profound effects on cytoskeletal tension and significantly inhibited hepatocyte-specific functions. Normal liver stiffness maintained functional gene regulation by hepatocyte nuclear factor 4 alpha (HNF4α), whereas fibrotic matrix stiffness inhibited the HNF4α transcriptional network. Fibrotic levels of matrix stiffness activated mechanotransduction in primary hepatocytes through focal adhesion kinase. In addition, blockade of the Rho/Rho-associated protein kinase pathway rescued HNF4α expression from hepatocytes cultured on stiff matrix. Fibrotic levels of matrix stiffness significantly inhibit hepatocyte-specific functions in part by inhibiting the HNF4α transcriptional network mediated through the Rho/Rho-associated protein kinase pathway. Increased appreciation of the role of matrix rigidity in modulating hepatocyte function will advance our understanding of the mechanisms of hepatocyte dysfunction in liver cirrhosis and spur development of novel treatments for chronic liver disease. (Hepatology 2016;64:261-275). © 2016 by the American Association for the Study of Liver Diseases.

Composite Configuration Interventional Therapy Robot for the Microwave Ablation of Liver Tumors

NASA Astrophysics Data System (ADS)

Cao, Ying-Yu; Xue, Long; Qi, Bo-Jin; Jiang, Li-Pei; Deng, Shuang-Cheng; Liang, Ping; Liu, Jia

2017-11-01

The existing interventional therapy robots for the microwave ablation of liver tumors have a poor clinical applicability with a large volume, low positioning speed and complex automatic navigation control. To solve above problems, a composite configuration interventional therapy robot with passive and active joints is developed. The design of composite configuration reduces the size of the robot under the premise of a wide range of movement, and the robot with composite configuration can realizes rapid positioning with operation safety. The cumulative error of positioning is eliminated and the control complexity is reduced by decoupling active parts. The navigation algorithms for the robot are proposed based on solution of the inverse kinematics and geometric analysis. A simulation clinical test method is designed for the robot, and the functions of the robot and the navigation algorithms are verified by the test method. The mean error of navigation is 1.488 mm and the maximum error is 2.056 mm, and the positioning time for the ablation needle is in 10 s. The experimental results show that the designed robot can meet the clinical requirements for the microwave ablation of liver tumors. The composite configuration is proposed in development of the interventional therapy robot for the microwave ablation of liver tumors, which provides a new idea for the structural design of medical robots.

Managing injuries of hepatic duct confluence variants after major hepatobiliary surgery: An algorithmic approach

PubMed Central

Fragulidis, Georgios; Marinis, Athanasios; Polydorou, Andreas; Konstantinidis, Christos; Anastasopoulos, Georgios; Contis, John; Voros, Dionysios; Smyrniotis, Vassilios

2008-01-01

AIM:To investigate injuries of anatomy variants of hepatic duct confluence during hepatobiliary surgery and their impact on morbidity and mortality of these procedures. An algorithmic approach for the management of these injuries is proposed. METHODS: During a 6-year period 234 patients who had undergone major hepatobiliary surgery were retrospectively reviewed in order to study postoperative bile leakage. Diagnostic workup included endoscopic and magnetic retrograde cholangiopancreatography (E/MRCP), scintigraphy and fistulography. RESULTS: Thirty (12.8%) patients who developed postoperative bile leaks were identified. Endoscopic stenting and percutaneous drainage were successful in 23 patients with bile leaks from the liver cut surface. In the rest seven patients with injuries of hepatic duct confluence, biliary variations were recognized and a stepwise therapeutic approach was considered. Conservative management was successful only in 2 patients. Volume of the liver remnant and functional liver reserve as well as local sepsis were used as criteria for either resection of the corresponding liver segment or construction of a biliary-enteric anastomosis. Two deaths occurred in this group of patients with hepatic duct confluence variants (mortality rate 28.5%). CONCLUSION: Management of major biliary fistulae that are disconnected from the mainstream of the biliary tree and related to injury of variants of the hepatic duct confluence is extremely challenging. These patients have a grave prognosis and an early surgical procedure has to be considered. PMID:18494057

Poster — Thur Eve — 16: 4DCT simulation with synchronized contrast injection of liver SBRT patients

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

Karotki, A.; Korol, R.; Milot, L.

2014-08-15

Stereotactic body radiation therapy (SBRT) has recently emerged as a valid option for treating liver metastases. SBRT delivers highly conformai dose over a small number of fractions. As such it is particularly sensitive to the accuracy of target volume delineation by the radiation oncologist. However, contouring liver metastases remains challenging for the following reasons. First, the liver usually undergoes significant motion due to respiration. Second, liver metastases are often nearly indistinguishable from the surrounding tissue when using computed tomography (CT) for imaging making it difficult to identify and delineate them. Both problems can be overcome by using four dimensional CTmore » (4DCT) synchronized with intravenous contrast injection. We describe a novel CT simulation process which involves two 4DCT scans. The first scan captures the tumor and immediately surrounding tissue which in turn reduces the 4DCT scan time so that it can be optimally timed with intravenous contrast injection. The second 4DCT scan covers a larger volume and is used as the primary CT dataset for dose calculation, as well as patient setup verification on the treatment unit. The combination of two 4DCT scans, short and long, allows visualization of the liver metastases over all phases of breathing cycle while simultaneously acquiring long enough 4DCT dataset suitable for planning and patient setup verification.« less

PREOPERATIVE COMPUTED TOMOGRAPHY VOLUMETRY AND GRAFT WEIGHT ESTIMATION IN ADULT LIVING DONOR LIVER TRANSPLANTATION.

PubMed

Pinheiro, Rafael S; Cruz, Ruy J; Andraus, Wellington; Ducatti, Liliana; Martino, Rodrigo B; Nacif, Lucas S; Rocha-Santos, Vinicius; Arantes, Rubens M; Lai, Quirino; Ibuki, Felicia S; Rocha, Manoel S; D Albuquerque, Luiz A C

2017-01-01

Computed tomography volumetry (CTV) is a useful tool for predicting graft weights (GW) for living donor liver transplantation (LDLT). Few studies have examined the correlation between CTV and GW in normal liver parenchyma. To analyze the correlation between CTV and GW in an adult LDLT population and provide a systematic review of the existing mathematical models to calculate partial liver graft weight. Between January 2009 and January 2013, 28 consecutive donors undergoing right hepatectomy for LDLT were retrospectively reviewed. All grafts were perfused with HTK solution. Estimated graft volume was estimated by CTV and these values were compared to the actual graft weight, which was measured after liver harvesting and perfusion. Median actual GW was 782.5 g, averaged 791.43±136 g and ranged from 520-1185 g. Median estimated graft volume was 927.5 ml, averaged 944.86±200.74 ml and ranged from 600-1477 ml. Linear regression of estimated graft volume and actual GW was significantly linear (GW=0.82 estimated graft volume, r2=0.98, slope=0.47, standard deviation of 0.024 and p<0.0001). Spearman Linear correlation was 0.65 with 95% CI of 0.45 - 0.99 (p<0.0001). The one-to-one rule did not applied in patients with normal liver parenchyma. A better estimation of graft weight could be reached by multiplying estimated graft volume by 0.82. A volumetria por tomografia computadorizada (VTC) é uma ferramenta útil para a previsão do peso do enxerto (PE) para o transplante hepático com doador vivo (TFDV). Poucos estudos examinaram a correlação entre o VTC e PE no parênquima hepático normal. Analisar a correlação entre VTC e PE em uma população adulta de doadores para o TFDV e realização de revisão sistemática dos modelos matemáticos existentes para calcular o peso de enxertos hepáticos parciais. Foram revisados retrospectivamente 28 doadores consecutivos submetidos à hepatectomia direita para o TFDV entre janeiro de 2009 a janeiro de 2013. Todos os doadores eram adultos saudáveis ​​com VTC pré-operatório. Os enxertos foram perfundidos com solução de preservação HTK. O volume estimado foi obtido por VTC e estes valores foram comparados com o peso real do enxerto, o qual foi aferido depois da hepatectomia e perfusão do enxerto. A mediana do PE real foi de 782,5 g, média de 791,43±136 g, variando de 520-1185 g. A mediana do volume estimado do enxerto foi de 927,5 ml, média de 944,86±200,74 ml e variou de 600-1477 ml. A regressão linear volume estimado do enxerto e PE real foi significativamente linear (PE=0.82 do volume estimado do enxerto, r2=0,98, declive=0,47, desvio-padrão de 0,024 e p<0,0001). Correlação linear de Spearman foi de 0,65, com IC de 95% do 0,45-0,99 (p<0,0001). A regra de "um-para-um" não deve ser empregada em pacientes com parênquima hepático normal. A melhor estimativa do peso do enxerto hepático de doador vivo pode ser alcançado através da multiplicação do VTC por 0,82.

Multi organ assessment of Compensated Cirrhosis Patients using quantitative Magnetic Resonance Imaging.

PubMed

Bradley, Christopher R; Cox, Eleanor F; Scott, Robert A; James, Martin W; Kaye, Phillip; Aithal, Guruprasad P; Francis, Susan T; Guha, Indra Neil

2018-06-07

Advancing liver disease results in deleterious changes in a number of critical organs. The ability to measure structure, blood flow and tissue perfusion within multiple organs in a single scan has implications for determining the balance of benefit versus harm for therapies. Our aim was to establish the feasibility of Magnetic Resonance Imaging to assess changes in compensated cirrhosis (CC), and relate this to disease severity and future liver related outcomes (LROs). 60 CC patients, 40 healthy volunteers and 7 decompensated cirrhotics were recruited. In a single scan session, MRI measures comprised phase-contrast MRI vessel blood flow, arterial spin labelling tissue perfusion, T 1 longitudinal relaxation time and volume assessment of liver, spleen and kidneys, heart rate and cardiac index. We explore MRI parameters with disease severity and differences in baseline MRI parameters in those 11 (18%) of CC patients who had future LROs. In the liver compositional changes were reflected by increased T 1 in progressive disease (p<0.001) and an increase in liver volume in CC (p=0.006), with associated progressive reduction in liver (p < 0.001) and splenic (p<0.001) perfusion. A significant reduction in renal cortex T 1 and increase in cardiac index and superior mesenteric arterial (SMA) blood flow was seen with increasing disease severity. Baseline liver T 1 (p=0.01) and perfusion (p< 0.01), and renal cortex T 1 (p<0.01) were significantly different in CC patients who subsequently developed negative LROs. MRI allows the contemporaneous assessment of organs in liver cirrhosis in a single scan without the requirement of contrast agent. MRI parameters of liver T 1, renal T 1, hepatic and splenic perfusion, and SMA blood flow were related to risk of LROs. This study assesses the changes to structure, blood flow and perfusion that occur in the key organs (liver, spleen and kidney) associated with severe liver disease (compensated cirrhosis). Those MRI measures which change with disease severity and are related to negative liver related clinical outcomes are described. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Scaffold-free 3D bio-printed human liver tissue stably maintains metabolic functions useful for drug discovery.

PubMed

Kizawa, Hideki; Nagao, Eri; Shimamura, Mitsuru; Zhang, Guangyuan; Torii, Hitoshi

2017-07-01

The liver plays a central role in metabolism. Although many studies have described in vitro liver models for drug discovery, to date, no model has been described that can stably maintain liver function. Here, we used a unique, scaffold-free 3D bio-printing technology to construct a small portion of liver tissue that could stably maintain drug, glucose, and lipid metabolism, in addition to bile acid secretion. This bio-printed normal human liver tissue maintained expression of several kinds of hepatic drug transporters and metabolic enzymes that functioned for several weeks. The bio-printed liver tissue displayed glucose production via cAMP/protein kinase A signaling, which could be suppressed with insulin. Bile acid secretion was also observed from the printed liver tissue, and it accumulated in the culture medium over time. We observed both bile duct and sinusoid-like structures in the bio-printed liver tissue, which suggested that bile acid secretion occurred via a sinusoid-hepatocyte-bile duct route. These results demonstrated that our bio-printed liver tissue was unique, because it exerted diverse liver metabolic functions for several weeks. In future, we expect our bio-printed liver tissue to be applied to developing new models that can be used to improve preclinical predictions of long-term toxicity in humans, generate novel targets for metabolic liver disease, and evaluate biliary excretion in drug development.

The bioimpedance analysis of a parenchyma of a liver in the conditions of its extensive resection in experiment

NASA Astrophysics Data System (ADS)

Agibalov, D. Y.; Panchenkov, D. N.; Chertyuk, V. B.; Leonov, S. D.; Astakhov, D. A.

2017-01-01

The liver failure which is result of disharmony of functionality of a liver to requirements of an organism is the main reason for unsatisfactory results of an extensive resection of a liver. However, uniform effective criterion of definition of degree of a liver failure it isn’t developed now. One of data acquisition methods about a morfo-functional condition of internals is the bioimpedance analysis (BIA) based on impedance assessment (full electric resistance) of a biological tissue. Measurements of an impedance are used in medicine and biology for the characteristic of physical properties of living tissue, studying of the changes bound to a functional state and its structural features. In experimental conditions we carried out an extensive resection of a liver on 27 white laboratory rats of the Vistar line. The comparative characteristic of data of a bioimpedansometriya in intraoperative and after the operational period with the main existing methods of assessment of a functional condition of a liver was carried out. By results of the work performed by us it is possible to claim that the bioimpedance analysis of a liver on the basis of an invasive bioimpedansometriya allows to estimate morphological features and functional activity of a liver before performance of an extensive resection of a liver. The data obtained during scientific work are experimental justification for use of an impedansometriya during complex assessment of functional reserves of a liver. Preliminary data of clinical approbation at a stage of introduction of a technique speak about rather high informational content of a bioimpedansometriya. The subsequent analysis of efficiency of the invasive bioimpedance analysis of a liver requires further accumulation of clinical data. However even at this stage the method showed the prospect for further use in clinical surgical hepathology.

Chronic DON exposure and acute LPS challenge: effects on porcine liver morphology and function.

PubMed

Renner, Lydia; Kahlert, Stefan; Tesch, Tanja; Bannert, Erik; Frahm, Jana; Barta-Böszörményi, Anikó; Kluess, Jeannette; Kersten, Susanne; Schönfeld, Peter; Rothkötter, Hermann-Josef; Dänicke, Sven

2017-08-01

The aim of the present study was to examine the role of chronic deoxynivalenol (DON) exposition on the liver morphology and function in combination with pre- and post-hepatic lipopolysaccharide (LPS) stress in young pigs fed for 4 weeks with a DON-contaminated diet (4.59 mg/kg feed). At the end of the experiment, LPS (7.5 μg/kg BW) was administered for 1 h pre-hepatically (Vena portae hepatis) or post-hepatically (Vena jugularis). Liver morphology was macroscopically checked and showed haemorrhage in all LPS groups, significantly higher relative liver weights, accompanied by marked oedema in the gallbladder wall. Histological changes were judged by a modified histology activity index (HAI). Liver HAI score was significantly increased in all LPS groups compared to placebo, primarily due to neutrophil infiltration and haemorrhage. DON feed alone was without effect on the liver HAI. Liver function was characterized by (i) hepatic biochemical markers, (ii) mitochondrial respiration and (iii) Ca 2+ accumulation capacity of isolated mitochondria. Clinical chemical parameters characterizing liver function were initially (<3 h) slightly influenced by LPS. After 3 h, bilirubin and alkaline phosphatase were increased significantly, in DON-fed, jugular-infused LPS group. Respiration and Ca 2+ accumulation capacity of isolated liver mitochondria was not impaired by chronic DON exposure, acute LPS challenge or combined treatments. DON-contaminated feed did not change macroscopy and histology of the liver, but modified the function under LPS stress. The different function was not linked to modifications of liver mitochondria.

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.

Kidney growth and renal functions under the growth hormone replacement therapy in children.

PubMed

Ece, Aydın; Çetinkaya, Semra; Ekşioğlu, Seçil; Şenel, Saliha; Özkasap, Serdar; Giniş, Tayfur; Sen, Velat; Şahin, Cahit

2014-05-01

The aim of this study was to investigate the kidney growth and renal functions in children receiving recombinant human growth hormone (rhGH) treatment. A total of 37 children who received rhGH for 1.5 years before the study was started and 48 healthy controls were included at first evaluation. Hormone levels were determined and kidney sizes were measured by ultrasound. Kidney functions were assessed by serum creatinine and estimated glomerular filtration rate (eGFR). After 3 years of first evaluation, 23 patients were re-assessed. Kidney sizes were found to be lower in rhGH received children compared with controls at first evaluation (p<0.05). Significant positive correlations were found between anthropometric measurements and kidney length and kidney volume (p<0.05). Height was the most significant predictor of kidney volume in rhGH received children (p<0.001). After 3-years of follow-up significantly increases were found in kidney length and volume compared with the first measurements (p<0.05). Increase percentage of body height was similar to increasing percent of kidney length and liver long axis (14.2%, 11.7.1% and 7.7%, respectively, p>0.05). Although no abnormal renal function test results were found at first and second evaluations; rhGH received children had significantly lower eGFR, at first evaluation, compared with controls; however, renal functions significantly increased after 3 years of follow-up (p<0.05). In conclusion, effect rhGH treatment on kidney growth is parallel to growth in body height and other visceral organs. A 3-years rhGH treatment resulted in significant increases in renal functions.

[MORPHOLOGICAL CHANGES OF THE LIVER IN OBTURATION JAUNDICE, CAUSED BY CHOLEDOCHOLITHIASIS, DEPENDING ON ITS DURATION].

PubMed

Sipliviy, V A; Yevtushenko, D V; Naumova, O V; Andreyeshchev, S A; Yevtushenko, A V

2016-02-01

Abstract The results of surgical treatment of 184 patients for obturation jaundice, caused by choledocholithiasis, were analyzed. Morphological changes of the liver were studied in 20 patients. There were three groups of patients delineated, depending on the obturation jaundice duration: up to 7 days, from 8 to 14 days, more than 15 days, and also a group of patients after the bile outflow restoration. The obturation jaundice occurrence in choledocholithiasis is accompanied by significant morphological changes in the liver, severity of which is enhancing while the obturation jaundice persistence increasing. While persistence of obturation jaundice through 8 days and more the connective tissue volume is enhancing, a relative volume of hepatocytes is reducing and a stromal-parenchymatous index is increasing. The bile outflow restoration secures significant reduction of intensity of alterative and inflammatory changes in hepatic parenchyma, as well as activation of reparative processes in the tissue. In cholangitis, caused by P. aeruginosa and E. coli, according to morphological investigations data, in the liver a diffuse purulent cholangitis on background of chronic changes in accordance to duration of the obturation jaundice persists.

Acoustic accessibility investigation for ultrasound mediated treatment of glycogen storage disease type Ia patients.

PubMed

Wang, Shutao; Raju, Balasundar I; Leyvi, Evgeniy; Weinstein, David A; Seip, Ralf

2011-09-01

Glycogen storage disease type Ia (GSDIa) is caused by an inherited defect in the glucose-6-phosphatase gene. The recent advent of targeted ultrasound-mediated delivery (USMD) of plasmid DNA (pDNA) to the liver in conjunction with microbubbles may provide an alternative treatment option. This study focuses on determining the acoustically accessible liver volume in GSDIa patients using transducer models of various geometries with an image-based geometry-driven approach. Results show that transducers with longer focal lengths and smaller apertures (up to an f/number of 2) are able to access larger liver volumes in GSDIa patients while still being capable of delivering the required ultrasound dose in situ (2.5 MPa peak negative pressure at the focus). With sufficiently large acoustic windows and the ability to use glucose to easily assess efficacy, GSD appears to be a good model for testing USMD as proof of principle as a potential therapy for liver applications in general. Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Causes of altered liver function tests - the role of alpha-1 antitrypsin.

PubMed

Stollenwerk, J; Schepke, M; Biecker, E

2016-09-01

Altered liver function tests are a common finding in clinical practice. Our retrospective study aimed to identify the diagnoses in a non-selected cohort of patients with altered liver tests and to investigate whether alpha-1 antitrypsin genotyping should be part of the diagnostic workup. 501 patients who were admitted to our outpatient clinic for further evaluation of altered liver function tests were included in the study. The patients underwent a standardized diagnostic program with history taking, physical examination, laboratory tests and ultrasonography. Liver biopsy was performed if appropriate. More than 50 % of the patients had nonalcoholic fatty liver disease. Alcoholic and drug-induced liver injury were found in 8.6 % and 7 % of patients, respectively. Chronic hepatitis B and C, autoimmune liver disease and inherited causes of liver disease made up for approximately 16 % of the diagnoses. The remaining patients were diagnosed with kryptogenic liver disease or had miscellaneous diagnoses. In 3.7 % of the genotyped patients, the alpha-1 antitrypsin genotype PiMZ was found. Nonalcoholic fatty liver disease is nowadays the most frequent cause of altered liver tests. Alcoholic liver disease might be underrepresented in our study since these patients less often seek medical attention or the diagnosis is already made by the primary care physician. Drug-induced liver injury was found in more patients than expected and might therefore be underdiagnosed in practice. The alpha-1 antitrypsin genotype PiMZ was found in absence of other possible causes of liver disease, indicating that the PiMZ genotype is itself a risk factor for liver disease. Genotyping for alpha-1 antitrypsin should therefore be done when other causes for altered liver function tests have been ruled out. © Georg Thieme Verlag KG Stuttgart · New York.

Interaction of the endocrine system with inflammation: a function of energy and volume regulation

PubMed Central

2014-01-01

During acute systemic infectious disease, precisely regulated release of energy-rich substrates (glucose, free fatty acids, and amino acids) and auxiliary elements such as calcium/phosphorus from storage sites (fat tissue, muscle, liver, and bone) are highly important because these factors are needed by an energy-consuming immune system in a situation with little or no food/water intake (sickness behavior). This positively selected program for short-lived infectious diseases is similarly applied during chronic inflammatory diseases. This review presents the interaction of hormones and inflammation by focusing on energy storage/expenditure and volume regulation. Energy storage hormones are represented by insulin (glucose/lipid storage and growth-related processes), insulin-like growth factor-1 (IGF-1) (muscle and bone growth), androgens (muscle and bone growth), vitamin D (bone growth), and osteocalcin (bone growth, support of insulin, and testosterone). Energy expenditure hormones are represented by cortisol (breakdown of liver glycogen/adipose tissue triglycerides/muscle protein, and gluconeogenesis; water retention), noradrenaline/adrenaline (breakdown of liver glycogen/adipose tissue triglycerides, and gluconeogenesis; water retention), growth hormone (glucogenic, lipolytic; has also growth-related aspects; water retention), thyroid gland hormones (increase metabolic effects of adrenaline/noradrenaline), and angiotensin II (induce insulin resistance and retain water). In chronic inflammatory diseases, a preponderance of energy expenditure pathways is switched on, leading to typical hormonal changes such as insulin/IGF-1 resistance, hypoandrogenemia, hypovitaminosis D, mild hypercortisolemia, and increased activity of the sympathetic nervous system and the renin-angiotensin-aldosterone system. Though necessary during acute inflammation in the context of systemic infection or trauma, these long-standing changes contribute to increased mortality in chronic inflammatory diseases. PMID:24524669

Interaction of the endocrine system with inflammation: a function of energy and volume regulation.

PubMed

Straub, Rainer H

2014-02-13

During acute systemic infectious disease, precisely regulated release of energy-rich substrates (glucose, free fatty acids, and amino acids) and auxiliary elements such as calcium/phosphorus from storage sites (fat tissue, muscle, liver, and bone) are highly important because these factors are needed by an energy-consuming immune system in a situation with little or no food/water intake (sickness behavior). This positively selected program for short-lived infectious diseases is similarly applied during chronic inflammatory diseases. This review presents the interaction of hormones and inflammation by focusing on energy storage/expenditure and volume regulation. Energy storage hormones are represented by insulin (glucose/lipid storage and growth-related processes), insulin-like growth factor-1 (IGF-1) (muscle and bone growth), androgens (muscle and bone growth), vitamin D (bone growth), and osteocalcin (bone growth, support of insulin, and testosterone). Energy expenditure hormones are represented by cortisol (breakdown of liver glycogen/adipose tissue triglycerides/muscle protein, and gluconeogenesis; water retention), noradrenaline/adrenaline (breakdown of liver glycogen/adipose tissue triglycerides, and gluconeogenesis; water retention), growth hormone (glucogenic, lipolytic; has also growth-related aspects; water retention), thyroid gland hormones (increase metabolic effects of adrenaline/noradrenaline), and angiotensin II (induce insulin resistance and retain water). In chronic inflammatory diseases, a preponderance of energy expenditure pathways is switched on, leading to typical hormonal changes such as insulin/IGF-1 resistance, hypoandrogenemia, hypovitaminosis D, mild hypercortisolemia, and increased activity of the sympathetic nervous system and the renin-angiotensin-aldosterone system. Though necessary during acute inflammation in the context of systemic infection or trauma, these long-standing changes contribute to increased mortality in chronic inflammatory diseases.

Portal inflow and pressure changes in right liver living donor liver transplantation including the middle hepatic vein.

PubMed

Chan, See Ching; Lo, Chung Mau; Ng, Kelvin K C; Ng, Irene O L; Yong, Boon Hun; Fan, Sheung Tat

2011-02-01

The middle hepatic vein may be included in right liver living donor liver transplantation (LDLT) to optimize hepatic venous outflow. We studied the graft's ability to relieve portal hypertension and accommodate portal hyperperfusion with portal manometry and ultrasonic flowmetry. Surgical outcomes with respect to portal hemodynamometry were also investigated. The ages of the recipients and donors for 46 consecutive LDLT procedures were 50 (range, 16-66 years) and 31 years (range, 18-54 years), respectively. The graft to standard liver volume ratio was 47.4% (range, 32.4%-69.0%). The hospital mortality rate was 4.4% as 2 recipients died from a subarachnoid hemorrhage and sepsis. The portal pressure dropped by 8 mm Hg (range, -7 to 19 mm Hg) from 23 (range, 8-37 mm Hg) to 14 mm Hg (range, 10-26 mm Hg) after graft implantation. The portal inflow positively correlated with the portal pressure before native liver hepatectomy (R(2) = 0.305, P = 0.001) and not with the graft size. The portal inflow increased from 81 mL/minute/100 g (range, 35-210 mL/minute/100 g) before donor right hepatectomy to 318 mL/minute/100 g (range, 102-754 mL/minute/100 g) after graft implantation. The graft portal inflow had a positive linear correlation with the recipient portal pressure before native liver total hepatectomy (R(2) = 0.261, P = 0.001) but not after graft implantation, and it had a negative correlation with the graft to standard liver volume ratio (R(2) = 0.247, P = 0.001). Only 1 of the graft biopsies showed moderate sinusoidal congestion. Twelve recipients had Clavien grade 2+ complications that were not related to the portal inflow and pressure or graft size. Right liver LDLT including the middle hepatic vein effectively lowered the recipient portal pressure by allowing unimpeded venous outflow. Copyright © 2011 American Association for the Study of Liver Diseases.

Effect of hepatic impairment on the pharmacokinetics of a single dose of cilostazol.

PubMed

Bramer, S L; Forbes, W P

1999-01-01

The pharmacokinetic profiles of cilostazol and its metabolites following a single oral dose of cilostazol 100 mg were compared between individuals with impaired and normal liver function. The study was conducted as a single-centre, open-label, single dose pharmacokinetic and tolerability trial. 12 patients with impaired and compensated liver function were compared with 12 volunteers with normal liver function. Participants in each group were matched for gender, age and weight. Of the 12 patients with hepatic impairment examined in this study, 10 had mild impairment (Child-Pugh class A) and 2 had moderate impairment (Child-Pugh class B). Blood and urine were collected up to 144 hours after drug administration. Pharmacokinetics were determined by noncompartmental methods. Protein binding did not differ between the groups (95.2% healthy volunteers, 94.6% hepatically impaired patients). Mean +/- SD unbound oral clearance of cilostazol decreased by 8.6% because of hepatic impairment (3380 +/- 1400 ml/min in healthy volunteers, 3260 +/- 2030 ml/min in hepatically impaired patients). Total urinary excretion of metabolites was significantly higher in healthy volunteers (26 vs 17% of dose). Overall, the pharmacokinetics of cilostazol and its metabolites, OPC-13213 and OPC-13015, were not substantially different in those with mild and moderate hepatic disease compared with values in healthy volunteers. Except for terminal-phase disposition half-life and apparent terminal-phase volume of distribution for cilostazol, the ratios of geometric means of pharmacokinetic parameters for plasma cilostazol, OPC-13213 and OPC-13015 in those with hepatic impairment versus healthy volunteers were close to 100%. Based on the results of the pharmacokinetic analysis, dose adjustment in patients with mild hepatic impairment is not necessary. However, caution should be exercised when cilostazol is administered to patients with moderate or severe hepatic impairment.

Intrahepatic Left to Right Portoportal Venous Collateral Vascular Formation in Patients Undergoing Right Portal Vein Ligation

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

Lienden, K. P. van, E-mail: k.p.vanlienden@amc.uva.nl; Hoekstra, L. T.; Bennink, R. J.

2013-12-15

Purpose: We investigated intrahepatic vascular changes in patients undergoing right portal vein ligation (PVL) or portal vein embolization (PVE) in conjunction with the ensuing hypertrophic response and function of the left liver lobe. Methods: Between December 2008 and October 2011, 7 patients underwent right PVL and 14 patients PVE. Computed tomographic (CT) volumetry to assess future remnant liver (FRL) and functional hepatobiliary scintigraphy were performed in all patients before and 3 weeks after portal vein occlusion. In 18 patients an intraoperative portography was performed to assess perfusion through the occluded portal branches. Results: In all patients after initially successful PVL,more » reperfused portal veins were observed on CT scan 3 weeks after portal occlusion. This was confirmed in all cases during intraoperative portography. Intrahepatic portoportal collaterals were identified in all patients in the PVL group and in one patient in the PVE group. In all other PVE patients, complete occlusion of the embolized portal branches was observed on CT scan and on intraoperative portography. The median increase of FRL volume after PVE was 41.6 % (range 10-305 %), and after PVL was only 8.1 % (range 0-102 %) (p = 0.179). There were no differences in FRL function between both groups. Conclusion: Preoperative PVE and PVL are both methods to induce hypertrophy of the FRL in anticipation of major liver resection. Compared to PVE, PVL seems less efficient in inducing hypertrophy of the nonoccluded left lobe. This could be caused by the formation of intrahepatic portoportal neocollateral vessels, through which the ligated portal branches are reperfused within 3 weeks.« less

Malnutrition induces gut atrophy and increases hepatic fat infiltration: studies in a pig model of childhood malnutrition.

PubMed

Lykke, Mikkel; Hother, Anne-Louise; Hansen, Christian F; Friis, Henrik; Mølgaard, Christian; Michaelsen, Kim F; Briend, André; Larsen, Torben; Sangild, Per T; Thymann, Thomas

2013-01-01

Childhood malnutrition is a problem in developing countries, and pathological changes in digestive organs such as the intestine and liver are poorly understood. An animal model to study the progression of severe acute malnutrition could elucidate pathological changes in the intestine and liver. We sought to characterize growth and clinical changes during malnutrition related to structural and functional indices in the intestine and liver. Newly weaned piglets were given ad libitum access to a maize flour diet (MAIZE, n=9) or a nutritionally optimized reference diet (REFERENCE, n=12) for 7 weeks. Growth, hematology and clinical biochemistry where recorded weekly. After 7 weeks, the MAIZE pigs had lower body weights than the REF pigs (8.3 kg vs. 32.4 kg, P < 0.001), indicating severe stunting and moderate to severe wasting. This was paralleled by lower values for hematocrit, hemoglobin and mean cell volume in MAIZE vs. REFERENCE (P < 0.01), indicating anemia. Although the observed temporal changes in MAIZE were associated with atrophy of the small intestinal mucosa (P < 0.001), digestive enzyme activity was only marginally reduced. Serum alanine aminotransferase, bilirubin and albumin were increased in the MAIZE pigs (P < 0.001), and the liver had a vacuolated appearance and tendency toward increased triglyceride content (P=0.054). We conclude that liver and intestinal indices are compromised during malnutrition and are associated with temporal changes in growth and hematological and biochemical endpoints. The pig model is relevant for malnourished infants and can act as a valuable tool for understanding the pathophysiology of malnutrition.

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

Unkelbach, J; Perko, Z; Wolfgang, J

Purpose: Stereotactic body radiotherapy (SBRT) has become an established treatment option for liver cancer. For patients with large tumors, the prescription dose is often limited by constraints on the mean liver dose, leading to tumor recurrence. In this work, we demonstrate that spatiotemporal fractionation schemes, ie delivering distinct dose distributions in different fractions, may allow for a 10% increase in biologically effective dose (BED) in the tumor compared to current practice where each fraction delivers the same dose distribution. Methods: We consider rotation therapy delivered with x-ray beams. Treatment plan optimization is performed using objective functions evaluated for the cumulativemore » BED delivered at the end of treatment. This allows for simultaneously optimizing multiple distinct treatment plans for different fractions. Results: The treatment that optimally exploits fractionation effects is designed such that each fraction delivers a similar dose bath to the uninvolved liver while delivering high single fraction doses to complementary parts of the target volume. Thereby, partial hypofractionation in the tumor is achieved along with near uniform fractionation in the surrounding liver - leading to an improvement in the therapeutic ratio. The benefit of such spatiotemporal fractionation schemes depends on tumor geometry and location as well as the number of fractions. For 5-fraction treatments (allowing for 5 distinct dose distributions) an improvement in the order of 10% is observed. Conclusion: Delivering distinct dose distributions in different fractions, purely motivated by fractionation effects rather than geometric changes, may improve the therapeutic ratio. For treatment sites where the prescriptions dose is limited by mean dose constraints in the surrounding organ, such as liver cancer, this approach may facilitate biological dose escalation and improved cure rates.« less

Malnutrition induces gut atrophy and increases hepatic fat infiltration: studies in a pig model of childhood malnutrition

PubMed Central

Lykke, Mikkel; Hother, Anne-Louise; Hansen, Christian F; Friis, Henrik; Mølgaard, Christian; Michaelsen, Kim F; Briend, André; Larsen, Torben; Sangild, Per T; Thymann, Thomas

2013-01-01

Childhood malnutrition is a problem in developing countries, and pathological changes in digestive organs such as the intestine and liver are poorly understood. An animal model to study the progression of severe acute malnutrition could elucidate pathological changes in the intestine and liver. We sought to characterize growth and clinical changes during malnutrition related to structural and functional indices in the intestine and liver. Newly weaned piglets were given ad libitum access to a maize flour diet (MAIZE, n=9) or a nutritionally optimized reference diet (REFERENCE, n=12) for 7 weeks. Growth, hematology and clinical biochemistry where recorded weekly. After 7 weeks, the MAIZE pigs had lower body weights than the REF pigs (8.3 kg vs. 32.4 kg, P < 0.001), indicating severe stunting and moderate to severe wasting. This was paralleled by lower values for hematocrit, hemoglobin and mean cell volume in MAIZE vs. REFERENCE (P < 0.01), indicating anemia. Although the observed temporal changes in MAIZE were associated with atrophy of the small intestinal mucosa (P < 0.001), digestive enzyme activity was only marginally reduced. Serum alanine aminotransferase, bilirubin and albumin were increased in the MAIZE pigs (P < 0.001), and the liver had a vacuolated appearance and tendency toward increased triglyceride content (P=0.054). We conclude that liver and intestinal indices are compromised during malnutrition and are associated with temporal changes in growth and hematological and biochemical endpoints. The pig model is relevant for malnourished infants and can act as a valuable tool for understanding the pathophysiology of malnutrition. PMID:23977413

Limitations of body surface area-based activity calculation for radioembolization of hepatic metastases in colorectal cancer.

PubMed

Lam, Marnix G E H; Louie, John D; Abdelmaksoud, Mohamed H K; Fisher, George A; Cho-Phan, Cheryl D; Sze, Daniel Y

2014-07-01

To calculate absorbed radiation doses in patients treated with resin microspheres prescribed by the body surface area (BSA) method and to analyze dose-response and toxicity relationships. A retrospective review was performed of 45 patients with colorectal carcinoma metastases who received single-session whole-liver resin microsphere radioembolization. Prescribed treatment activity was calculated using the BSA method. Liver volumes and whole-liver absorbed doses (D(WL)) were calculated. D(WL) was correlated with toxicity and radiographic and biochemical response. The standard BSA-based administered activity (range, 0.85-2.58 GBq) did not correlate with D(WL) (mean, 50.4 Gy; range, 29.8-74.7 Gy; r = -0.037; P = .809) because liver weight was highly variable (mean, 1.89 kg; range, 0.94-3.42 kg) and strongly correlated with D(WL) (r = -0.724; P < .001) but was not accounted for in the BSA method. Patients with larger livers were relatively underdosed, and patients with smaller livers were relatively overdosed. Patients who received D(WL) > 50 Gy experienced more toxicity and adverse events (> grade 2 liver toxicity, 46% vs 17%; P < .05) but also responded better to the treatment than patients who received D(WL)< 50 Gy (disease control, 88% vs 24%; P < .01). Using the standard BSA formula, the administered activity did not correlate with D(WL). Based on this short-term follow-up after salvage therapy in patients with late stage metastatic colorectal carcinoma, dose-response and dose-toxicity relationships support using a protocol based on liver volume rather than BSA to prescribe the administered activity. Copyright © 2014 SIR. Published by Elsevier Inc. All rights reserved.

Comparison of liver volumetry on contrast-enhanced CT images: one semiautomatic and two automatic approaches.

PubMed

Cai, Wei; He, Baochun; Fan, Yingfang; Fang, Chihua; Jia, Fucang

2016-11-08

This study was to evaluate the accuracy, consistency, and efficiency of three liver volumetry methods- one interactive method, an in-house-developed 3D medical Image Analysis (3DMIA) system, one automatic active shape model (ASM)-based segmentation, and one automatic probabilistic atlas (PA)-guided segmentation method on clinical contrast-enhanced CT images. Forty-two datasets, including 27 normal liver and 15 space-occupying liver lesion patients, were retrospectively included in this study. The three methods - one semiautomatic 3DMIA, one automatic ASM-based, and one automatic PA-based liver volumetry - achieved an accuracy with VD (volume difference) of -1.69%, -2.75%, and 3.06% in the normal group, respectively, and with VD of -3.20%, -3.35%, and 4.14% in the space-occupying lesion group, respectively. However, the three methods achieved an efficiency of 27.63 mins, 1.26 mins, 1.18 mins on average, respectively, compared with the manual volumetry, which took 43.98 mins. The high intraclass correlation coefficient between the three methods and the manual method indicated an excel-lent agreement on liver volumetry. Significant differences in segmentation time were observed between the three methods (3DMIA, ASM, and PA) and the manual volumetry (p < 0.001), as well as between the automatic volumetries (ASM and PA) and the semiautomatic volumetry (3DMIA) (p < 0.001). The semiautomatic interactive 3DMIA, automatic ASM-based, and automatic PA-based liver volum-etry agreed well with manual gold standard in both the normal liver group and the space-occupying lesion group. The ASM- and PA-based automatic segmentation have better efficiency in clinical use. © 2016 The Authors.

Correlations of Hepatic Hemodynamics, Liver Function, and Fibrosis Markers in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis Related to Hepatitis C Virus.

PubMed

Shigefuku, Ryuta; Takahashi, Hideaki; Nakano, Hiroyasu; Watanabe, Tsunamasa; Matsunaga, Kotaro; Matsumoto, Nobuyuki; Kato, Masaki; Morita, Ryo; Michikawa, Yousuke; Tamura, Tomohiro; Hiraishi, Tetsuya; Hattori, Nobuhiro; Noguchi, Yohei; Nakahara, Kazunari; Ikeda, Hiroki; Ishii, Toshiya; Okuse, Chiaki; Sase, Shigeru; Itoh, Fumio; Suzuki, Michihiro

2016-09-14

The progression of chronic liver disease differs by etiology. The aim of this study was to elucidate the difference in disease progression between chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) by means of fibrosis markers, liver function, and hepatic tissue blood flow (TBF). Xenon computed tomography (Xe-CT) was performed in 139 patients with NAFLD and 152 patients with CHC (including liver cirrhosis (LC)). The cutoff values for fibrosis markers were compared between NAFLD and CHC, and correlations between hepatic TBF and liver function tests were examined at each fibrosis stage. The cutoff values for detection of the advanced fibrosis stage were lower in NAFLD than in CHC. Although portal venous TBF (PVTBF) correlated with liver function tests, PVTBF in initial LC caused by nonalcoholic steatohepatitis (NASH-LC) was significantly lower than that in hepatitis C virus (C-LC) (p = 0.014). Conversely, the liver function tests in NASH-LC were higher than those in C-LC (p < 0.05). It is important to recognize the difference between NAFLD and CHC. We concluded that changes in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD; therefore, patients with NAFLD need to be followed carefully.

The effect of age and frailty upon acetanilide clearance in man.

PubMed

Wynne, H A; Cope, L H; James, O F; Rawlins, M D; Woodhouse, K W

1989-11-01

Six healthy young subjects (aged 23-32 years), six healthy elderly subjects (over 60 years) and six hospitalized long-stay geriatric subjects over 60 years received single oral doses of acetanilide. Acetanilide clearance was similar in the fit and frail elderly subjects at 26.4 +/- 2.5 and 26.3 +/- 3.6 l/h and significantly lower (p less than 0.05) than in the young subjects at 39.0 +/- 1.9 l/h. Liver volumes, measured by ultrasound, were significantly less in the elderly than in the young subjects, whether expressed in absolute terms or per unit body weight (p less than 0.05). When acetanilide clearance was expressed per unit volume of liver, no change occurred with age or frailty. These results suggest that a reduced liver size may be an important contributor to the reduced elimination of capacity limited drugs in elderly man.

Evaluation of liver function using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid enhanced magnetic resonance imaging based on a three-dimensional volumetric analysis system.

PubMed

Kudo, Masashi; Gotohda, Naoto; Sugimoto, Motokazu; Kobayashi, Tatsushi; Kojima, Motohiro; Takahashi, Shinichiro; Konishi, Masaru; Hayashi, Ryuichi

2018-06-02

Magnetic resonance imaging with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (EOB-MRI) is a diagnostic modality for liver tumors. Three-dimensional (3D) volumetric analysis systems using EOB-MRI data are used to simulate liver anatomy for surgery. This study was conducted to investigate clinical utility of a 3D volumetric analysis system on EOB-MRI to evaluate liver function. Between August 2014 and December 2015, 181 patients underwent laboratory and radiological exams as standardized preoperative evaluation for liver surgery. The liver-spleen contrast-enhanced ratio (LSR) was measured by a semi-automated 3D volumetric analysis system on EOB-MRI. First, the inter-evaluator variability of the calculated LSR was evaluated. Additionally, a subset of liver surgical specimens was evaluated histologically by using immunohistochemical staining. Finally, the correlations between the LSR and grading systems of liver function, laboratory data, or histological findings were analyzed. The inter-evaluator correlation coefficient of the measured LSR was 0.986. The mean LSR was significantly correlated with the Child-Pugh score (p = 0.014) and the ALBI score (p < 0.001). Significant correlations were also observed between the LSR and indocyanine green retention rate at 15 min (r = - 0.601, p < 0.001), between the LSR and liver fibrosis stage (r = - 0.556, p < 0.001), and between the LSR and liver steatosis grade (r = - 0.396, p < 0.001). The LSR calculated by a 3D volumetric analysis system on EOB-MRI was highly reproducible and was shown to be correlated with liver function parameters and liver histology. These data suggest that this imaging modality can be a reliable tool to evaluate liver function.

Laparoscopic splenectomy for patients with liver cirrhosis: Improvement of liver function in patients with Child-Pugh class B.

PubMed

Yamamoto, Naoki; Okano, Keiichi; Oshima, Minoru; Akamoto, Shitaro; Fujiwara, Masao; Tani, Joji; Miyoshi, Hisaaki; Yoneyama, Hirohito; Masaki, Tsutomu; Suzuki, Yasuyuki

2015-12-01

We aimed to assess the short-term outcomes of laparoscopic splenectomy (LS) and liver function at 1 year after splenectomy in the patients with liver cirrhosis. Forty-five patients with liver cirrhosis and hypersplenism underwent LS. We reviewed electronic medical records regarding the liver functional reserve, the etiology of liver cirrhosis, and the presence of hepatocellular carcinoma and esophago-gastric varices. Prospectively collected data of perioperative variables, postoperative complications, and long-term liver function were analyzed. Forty-five patients had a chronic liver disease classified into Child-Pugh classes (A/B/C: 23/20/2). The etiologies of disease were hepatitis C virus infection in 34 patients, hepatitis B virus infection in 4, and others in 7. Fourteen patients underwent procedures in addition to LS, including hepatectomy (n = 7) and devascularization for esophagogastric varices (n = 8). Postoperative complications occurred in 11 patients (24%). Neither postoperative liver failure nor in-hospital mortality occurred. White blood cell and platelet counts determined 7 days, 1 month, and 1 year after LS doubled or increased more than twice compared with the preoperative values (P < .001). One year after LS, patients who had been classified preoperatively into Child-Pugh class B had decreased total serum bilirubin levels (P = .03), and increased prothrombin activity (P = 003) and decreased Child-Pugh scores (P = .001). The Child-Pugh classifications improved in 14 of 18 patients (78%) who had Child-Pugh class B preoperatively. LS is a safe and feasible procedure for hypersplenism in patients with liver cirrhosis. In addition, LS most likely ameliorates liver function at 1 year after LS in patients with Child-Pugh class B liver cirrhosis. Copyright © 2015 Elsevier Inc. All rights reserved.

Medical Surveillance Monthly Report (MSMR). Volume 18, Number 08, August 2011

DTIC Science & Technology

2011-08-01

continue, and STI preven- tion eff orts should be reinforced. R E F E R E N C E S 1. Kuper H, Ye W, Broome U, et al. The risk of liver and bile duct ...hepatitis A virus (HAV) causes infl ammatory liver disease (hepatitis) in aff ected individu- als. Th e virus is spread through fecal-oral...ammatory liver disease (hepatitis B) in aff ected individ- uals. Th e virus is spread by percutaneous or mucous membrane exposure to infected blood or

Cyst infection in hospital-admitted autosomal dominant polycystic kidney disease patients is predominantly multifocal and associated with kidney and liver volume

PubMed Central

Balbo, B.E.P.; Sapienza, M.T.; Ono, C.R.; Jayanthi, S.K.; Dettoni, J.B.; Castro, I.; Onuchic, L.F.

2014-01-01

Positron-emission tomography/computed tomography (PET/CT) has improved cyst infection (CI) management in autosomal dominant polycystic kidney disease (ADPKD). The determinants of kidney and/or liver involvement, however, remain uncertain. In this study, we evaluated clinical and imaging factors associated with CI in kidney (KCI) and liver (LCI) in ADPKD. A retrospective cohort study was performed in hospital-admitted ADPKD patients with suspected CI. Clinical, imaging and surgical data were analyzed. Features of infected cysts were evaluated by PET/CT. Total kidney (TKV) and liver (TLV) volumes were measured by CT-derived multiplanar reconstruction. CI was detected in 18 patients who experienced 24 episodes during an interval of 30 months (LCI in 12, KCI in 10 and concomitant infection in 2). Sensitivities of CT, magnetic resonance imaging and PET/CT were 25.0, 71.4, and 95.0%. Dysuria (P<0.05), positive urine culture (P<0.01), and previous hematuria (P<0.05) were associated with KCI. Weight loss (P<0.01) and increased C-reactive protein levels (P<0.05) were associated with LCI. PET/CT revealed that three or more infected cysts were present in 70% of the episodes. TKV was higher in kidney-affected than in LCI patients (AUC=0.91, P<0.05), with a cut-off of 2502 mL (72.7% sensitivity, 100.0% specificity). TLV was higher in liver-affected than in KCI patients (AUC=0.89, P<0.01) with a cut-off of 2815 mL (80.0% sensitivity, 87.5% specificity). A greater need for invasive procedures was observed in LCI (P<0.01), and the overall mortality was 20.8%. This study supports PET/CT as the most sensitive imaging method for diagnosis of cyst infection, confirms the multifocal nature of most hospital-admitted episodes, and reveals an association of kidney and liver volumes with this complication. PMID:24919173

Left lobe living donor liver transplantation in adults: What is the safety limit?

PubMed

Ikegami, Toru; Yoshizumi, Tomoharu; Sakata, Kazuhito; Uchiyama, Hideaki; Harimoto, Norifumi; Harada, Noboru; Itoh, Shinji; Nagatsu, Akihisa; Soejima, Yuji; Maehara, Yoshihiko

2016-12-01

Small-for-size syndrome (SFSS) is the most significant cause of graft loss after living donor liver transplantation (LDLT), especially after left lobe (LL) LDLT in adults. The safety limit of applying LL-LDLT in adults without severe SFSS with a high rate of lethality needs to be determined. A total of 207 LL-LDLTs in adults since September 2005 were evaluated to analyze the risk factors for severe SFSS, defined as a serum total bilirubin concentration of ≥20.0 mg/dL after LDLT. Although there were no significant differences in cumulative graft survival after LDLT between medium grafts (graft volume [GV] to standard liver volume [SLV] ratio ≥ 40.0%), small grafts (35.0% ≤ GV/SLV < 40.0%), and extra small grafts (GV/SLV < 35.0%), patients with severe SFSS showed a significantly lower 5-year graft survival rate than those without (42.9% versus 94.3%, respectively; P < 0.001). Multivariate analysis for severe SFSS after LL-LDLT showed that donor age of ≥48 years (P = 0.01), Model for End-Stage Liver Disease (MELD) score of ≥ 19 (P < 0.01), and end portal venous pressure of ≥19 mm Hg (P = 0.04) were the significant and independent factors for severe SFSS after LL-LDLT. Within such high-risk subgroups of patients with a donor age of ≥48 years or MELD score of ≥ 19 before LDLT, operative blood loss volume of ≥8.0 L was a risk factor for severe SFSS. LL-LDLT in adults could be indicated and provide acceptable outcomes for the combinations of donors aged < 48 years and recipients with a MELD score of <19. Smaller grafts might yield acceptable outcomes in appropriately selected donor-recipient combinations. Liver Transplantation 22 1666-1675 2016 AASLD. © 2016 by the American Association for the Study of Liver Diseases.

Molecular regulation of urea cycle function by the liver glucocorticoid receptor.

PubMed

Okun, Jürgen G; Conway, Sean; Schmidt, Kathrin V; Schumacher, Jonas; Wang, Xiaoyue; de Guia, Roldan; Zota, Annika; Klement, Johanna; Seibert, Oksana; Peters, Achim; Maida, Adriano; Herzig, Stephan; Rose, Adam J

2015-10-01

One of the major side effects of glucocorticoid (GC) treatment is lean tissue wasting, indicating a prominent role in systemic amino acid metabolism. In order to uncover a novel aspect of GCs and their intracellular-receptor, the glucocorticoid receptor (GR), on metabolic control, we conducted amino acid and acylcarnitine profiling in human and mouse models of GC/GR gain- and loss-of-function. Blood serum and tissue metabolite levels were determined in Human Addison's disease (AD) patients as well as in mouse models of systemic and liver-specific GR loss-of-function (AAV-miR-GR) with or without dexamethasone (DEX) treatments. Body composition and neuromuscular and metabolic function tests were conducted in vivo and ex vivo, the latter using precision cut liver slices. A serum metabolite signature of impaired urea cycle function (i.e. higher [ARG]:[ORN + CIT]) was observed in human (CTRL: 0.45 ± 0.03, AD: 1.29 ± 0.04; p < 0.001) and mouse (AAV-miR-NC: 0.97 ± 0.13, AAV-miR-GR: 2.20 ± 0.19; p < 0.001) GC/GR loss-of-function, with similar patterns also observed in liver. Serum urea levels were consistently affected by GC/GR gain- (∼+32%) and loss (∼-30%) -of-function. Combined liver-specific GR loss-of-function with DEX treatment revealed a tissue-autonomous role for the GR to coordinate an upregulation of liver urea production rate in vivo and ex vivo, and prevent hyperammonaemia and associated neuromuscular dysfunction in vivo. Liver mRNA expression profiling and GR-cistrome mining identified Arginase I (ARG1) a urea cycle gene targeted by the liver GR. The liver GR controls systemic and liver urea cycle function by transcriptional regulation of ARG1 expression.

Portal Vein Embolization with Contralateral Application of Stem Cells Facilitates Increase of Future Liver Remnant Volume in Patients with Liver Metastases

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

Ludvík, Jaroslav, E-mail: ludvikj@fnplzen.cz; Duras, Petr; Třeška, Vladislav

ObjectivesThis study aimed to evaluate the progress of future liver remnant volume (FLRV) in patients with liver metastases after portal vein embolization (PVE) with the application of hematopoietic stem cells (HSCs) and compare it with a patients control group after PVE only.MethodsTwenty patients (group 1) underwent PVE with contralateral HSC application. Subsequently, CT volumetry with the determination of FLRV was performed at weekly intervals, in total three weeks. A sample of twenty patients (group 2) who underwent PVE without HSC application was used as a control group.ResultsThe mean of FLRV increased by 173.2 mL during three weeks after the PVE/HSC procedure,more » whereas by 98.9 mL after PVE only (p = 0.015). Furthermore, the mean daily growth of FLRV by 7.6 mL in group 1 was significantly higher in comparison with 4.1 mL in group 2 (p = 0.007).ConclusionsPVE with the application of HSC significantly facilitates growth of FLRV in comparison with PVE only. This method could be one of the new suitable approaches to increase the resectability of liver tumours.« less

Lovastatin decreases mortality and improves liver functions in fulminant hepatic failure from 90% partial hepatectomy in rats.

PubMed

Cai, S R; Motoyama, K; Shen, K J; Kennedy, S C; Flye, M W; Ponder, K P

2000-01-01

Liver insufficiency occurs when the liver cannot perform critical functions such as ammonia metabolism, gluconeogenesis, or production of coagulation factors The hypothesis of this study was that decreased function of existing hepatocytes may contribute to hepatic failure, and that the function of these cells might be increased pharmacologically. Lovastatin is a 3-hydroxy-3-methylglutaryl CoA reductase inhibitor that inhibits cholesterol biosynthesis and affects the activity of some signal transduction pathways and liver transcription factors. Changes in hepatic transcription factors during liver regeneration might result in decreased liver functions, and lovastatin might prevent these changes Rats received 90% partial hepatectomy (90% PH), and either lovastatin or vehicle alone daily. Survival and liver functions were assessed. Lovastatin increased survival to 58% (vs. 6% in controls that received 90% PH without drug), decreased the peak ammonia level to 427 microM (vs. 846 microM in controls), increased the nadir of glucose to 88 mg/dl (vs. 57 mg/dl in controls), decreased the peak prothrombin time to 23 s (vs 29 s in controls), and decreased the peak activated partial thromboplastin time to 29 s (vs. 39 s in controls). The full survival and metabolic benefits were observed when lovastatin was started at 30 min after 90% PH, but lovastatin was less efficacious when started at later times. Lovastatin increases the function of existing hepatocytes and might be used to improve liver function after extensive hepatic resection.

Inhibition of glycogen synthase kinase (GSK)-3-β improves liver microcirculation and hepatocellular function after hemorrhagic shock.

PubMed

Jellestad, Lena; Fink, Tobias; Pradarutti, Sascha; Kubulus, Darius; Wolf, Beate; Bauer, Inge; Thiemermann, Chris; Rensing, Hauke

2014-02-05

Ischemia and reperfusion may cause liver injury and are characterized by hepatic microperfusion failure and a decreased hepatocellular function. Inhibition of glycogen synthase kinase (GSK)-3β, a serine-threonine kinase that has recently emerged as a key regulator in the modulation of the inflammatory response after stress events, may be protective in conditions like sepsis, inflammation and shock. Therefore, aim of the study was to assess the role of GSK-3β in liver microcirculation and hepatocellular function after hemorrhagic shock and resuscitation (H/R). Anesthetized male Sprague-Dawley rats underwent pretreatment with Ringer´s solution, vehicle (DMSO) or TDZD-8 (1 mg/kg), a selective GSK-3β inhibitor, 30 min before induction of hemorrhagic shock (mean arterial pressure 35±5 mmHg for 90 min) and were resuscitated with shed blood and Ringer´s solution (2h). 5h after resuscitation hepatic microcirculation was assessed by intravital microscopy. Propidium iodide (PI) positive cells, liver enzymes and alpha-GST were measured as indicators of hepatic injury. Liver function was estimated by assessment of indocyanine green plasma disappearance rate. H/R led to a significant decrease in sinusoidal diameters and impairment of liver function compared to sham operation. Furthermore, the number of PI positive cells in the liver as well as serum activities of liver enzymes and alpha-GST increased significantly after H/R. Pretreatment with TDZD-8 prevented the changes in liver microcirculation, hepatocellular injury and liver function after H/R. A significant rise in the plasma level of IL-10 was observed. Thus, inhibition of GSK-3β before hemorrhagic shock modulates the inflammatory response and improves hepatic microcirculation and hepatocellular function. Copyright © 2013 Elsevier B.V. All rights reserved.

[Kidney function and liver transplantation].

PubMed

Gámán, György; Gelley, Fanni; Gerlei, Zsuzsa; Dabasi, Eszter; Görög, Dénes; Fehérvári, Imre; Kóbori, László; Lengyel, Gabriella; Zádori, Gergely; Fazakas, János; Doros, Attila; Sárváry, Enikő; Nemes, Balázs

2013-06-30

In liver cirrhosis renal function decreases as well. Hepatorenal syndrome is the most frequent cause of the decrease, but primary kidney failure, diabetes mellitus and some diseases underlying endstage liver failure (such as hepatitis C virus infection) can also play an important role. In liver transplantation several further factors (total cross-clamping of vena cava inferior, polytransfusion, immunosuppression) impair the renal function, too. The aim of this study was to analyse the changes in kidney function during the first postoperative year after liver transplantation. Retrospective data analysis was performed after primary liver transplantations (n = 319). impaired preoperative renal function increased the devepolment of postoperative complications and the first year cumulative patient survival was significantly worse (91,7% vs 69,9%; p<0,001) in this group. If renal function of the patients increased above 60 ml/min/1,73 m2 after the first year, patient survival was better. Independently of the preoperative kidney function, 76% of the patients had impaired kidney function at the first postoperative year. In this group, de novo diabetes mellitus was more frequently diagnosed (22,5% vs 9,5%; p = 0,023). Selection of personalized immunosuppressive medication has a positive effect on renal function.

Liver Transplant

MedlinePlus

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Assessment of liver ablation using cone beam computed tomography.

PubMed

Abdel-Rehim, Mohamed; Ronot, Maxime; Sibert, Annie; Vilgrain, Valérie

2015-01-14

To investigate the feasibility and accuracy of cone beam computed tomography (CBCT) in assessing the ablation zone after liver tumor ablation. Twenty-three patients (17 men and 6 women, range: 45-85 years old, mean age 65 years) with malignant liver tumors underwent ultrasound-guided percutaneous tumor ablation [radiofrequency (n = 14), microwave (n = 9)] followed by intravenous contrast-enhanced CBCT. Baseline multidetector computed tomography (MDCT) and peri-procedural CBCT images were compared. CBCT image quality was assessed as poor, good, or excellent. Image fusion was performed to assess tumor coverage, and quality of fusion was rated as bad, good, or excellent. Ablation zone volumes on peri-procedural CBCT and post-procedural MDCT were compared using the non-parametric paired Wilcoxon t-test. Rate of primary ablation effectiveness was 100%. There were no complications related to ablation. Local tumor recurrence and new liver tumors were found 3 mo after initial treatment in one patient (4%). The ablation zone was identified in 21/23 (91.3%) patients on CBCT. The fusion of baseline MDCT and peri-procedural CBCT images was feasible in all patients and showed satisfactory tumor coverage (at least 5-mm margin). CBCT image quality was poor, good, and excellent in 2 (9%), 8 (35%), and 13 (56%), patients respectively. Registration quality between peri-procedural CBCT and post-procedural MDCT images was good to excellent in 17/23 (74%) patients. The median ablation volume on peri-procedural CBCT and post-procedural MDCT was 30 cm(3) (range: 4-95 cm(3)) and 30 cm(3) (range: 4-124 cm(3)), respectively (P-value > 0.2). There was a good correlation (r = 0.79) between the volumes of the two techniques. Contrast-enhanced CBCT after tumor ablation of the liver allows early assessment of the ablation zone.

Function of GATA Factors in the Adult Mouse Liver

PubMed Central

Zheng, Rena; Rebolledo-Jaramillo, Boris; Zong, Yiwei; Wang, Liqing; Russo, Pierre; Hancock, Wayne; Stanger, Ben Z.; Hardison, Ross C.; Blobel, Gerd A.

2013-01-01

GATA transcription factors and their Friend of Gata (FOG) cofactors control the development of diverse tissues. GATA4 and GATA6 are essential for the expansion of the embryonic liver bud, but their expression patterns and functions in the adult liver are unclear. We characterized the expression of GATA and FOG factors in whole mouse liver and purified hepatocytes. GATA4, GATA6, and FOG1 are the most prominently expressed family members in whole liver and hepatocytes. GATA4 chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq) identified 4409 occupied sites, associated with genes enriched in ontologies related to liver function, including lipid and glucose metabolism. However, hepatocyte-specific excision of Gata4 had little impact on gross liver architecture and function, even under conditions of regenerative stress, and, despite the large number of GATA4 occupied genes, resulted in relatively few changes in gene expression. To address possible redundancy between GATA4 and GATA6, both factors were conditionally excised. Surprisingly, combined Gata4,6 loss did not exacerbate the phenotype resulting from Gata4 loss alone. This points to the presence of an unusually robust transcriptional network in adult hepatocytes that ensures the maintenance of liver function. PMID:24367609

Single-session alcohol sclerotherapy of symptomatic liver cysts using 10-20 min of ethanol exposure: no recurrence at 2-16 years of follow-up.

PubMed

Larssen, Trond Bjerke; Viste, Asgaut; Horn, Arild; Haldorsen, Ingfrid Salvesen; Espeland, Ansgar

2016-09-01

To assess long-term results after single-session alcohol sclerotherapy of symptomatic benign liver cysts performed with maximum 20 min of exposure to alcohol. We included 47 patients aged 32-88 years (42 women, 5 men) with 51 benign non-parasitic liver cysts that were exposed to ethanol for 7-20 min in a single sclerotherapy session and were followed for at least 24 months. Each cyst was emptied before injecting ethanol (10% of cyst volume, but maximum 100 mL) into it. The patient rotated from side to side to facilitate contact between ethanol and the whole cyst wall. Pre-treatment cyst volume was defined as the volume of aspirated cyst fluid after complete emptying of the cyst. Follow-up cyst volume was estimated based on computed tomography images. Cyst volumes were 30-4900 (median 520) mL at pre-treatment and 0-230 (median 1) mL at 24-193 (median 56) months follow-up, a reduction of 83-100% (median 99.7%). No cyst required repeated treatment during the follow-up. Median volume reduction was 99.7% at median 49 months of follow-up for 35 cysts exposed to ethanol for 7-10 min vs. 99.6% at median 75 months of follow-up for 16 cysts exposed for 20 min (p = 0.83, Mann-Whitney test). Ethanol intoxication occurred in one patient. There were no other complications except for pain. Long-term results of single-session alcohol sclerotherapy performed with maximum 20 min of exposure to ethanol were satisfactory with no sign of recurrence of cyst fluid.

Functional hepatocyte clusters on bioactive blend silk matrices towards generating bioartificial liver constructs.

PubMed

Janani, G; Nandi, Samit K; Mandal, Biman B

2018-02-01

The creation of in vitro functional hepatic tissue simulating micro-environmental niche of native liver is a keen area of research due to its demand in bioartificial liver (BAL) and cell-based tissue engineering. Here, we investigated the potential of novel blend (BA) silk scaffold fabricated by blending mulberry (Bombyx mori, BM) silk fibroin with cell adhesion motif (RGD) rich non-mulberry (Antheraea assamensis, AA) silk fibroin, in generating a functional liver construct. Three-dimensional (3D) porous silk scaffolds (BM, AA and BA) were physico-chemically characterized and functionally evaluated using human hepatocarcinoma cells (HepG2) and primary neonatal rat hepatocytes. The growth and distribution of hepatocytes within the scaffolds were tracked by FESEM, alamar blue proliferation assay and live/dead staining. Hemocompatible BA scaffolds supported the formation of high density hepatocyte clusters, facilitating cell-matrix and cell-cell interactions. Blend scaffolds evinced enhanced liver-specific functions of cultured hepatocytes in terms of albumin synthesis, urea synthesis and cytochrome P450 enzyme activity over 21 days. Subcutaneous implantation of scaffolds demonstrated minimal macrophage infiltration in blend scaffolds. These findings substantiate that the integral property of blend (BA) scaffold offers a befitting environment by influencing spheroidal growth of hepatocytes with enhanced biological activity. Collectively, the present study provides a new 3D bio-matrix niche for growing functional liver cells that would have future prospects in BAL as well as regenerative medicine. An end stage liver disease called cirrhosis perturbs the self-healing ability and physiological functions of liver. Due to the scarcity of healthy donors, a functional in vitro hepatic construct retaining the liver-specific functions is in great demand for its prospects in bioartificial liver (BAL) and cell-based tissue engineering. Physicochemical attributes of a matrix influence the behavior of cultured hepatocytes in terms of attachment, morphology and functionality. Mulberry and non-mulberry silk fibroin presents unique amino acid sequence with difference in hydrophobicity and crystallinity. Considering this, the present study focuses on the development of a suitable three-dimensional (3D) bioactive matrix incorporating both mulberry silk fibroin and cell adhesion motif (RGD) rich non-mulberry silk fibroin. Porous silk blend scaffolds facilitated the formation of hepatocyte clusters with enhanced liver-specific functions emphasizing both cell-cell and cell-matrix interactions. Hemocompatibility and integral property of blend scaffolds offers a biological niche for seeding functional liver cells that would have future prospects in biohybrid devices. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Benign Liver Tumors

MedlinePlus

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Risk of venous congestion in live donors of extended right liver graft

PubMed Central

Radtke, Arnold; Sgourakis, George; Molmenti, Ernesto P; Beckebaum, Susanne; Cicinnati, Vito R; Schmidt, Hartmut; Peitgen, Heinz-Otto; Broelsch, Christoph E; Malagó, Massimo; Schroeder, Tobias

2015-01-01

AIM: To investigate middle hepatic vein (MHV) management in adult living donor liver transplantation and safer remnant volumes (RV). METHODS: There were 59 grafts with and 12 grafts without MHV (including 4 with MHV-5/8 reconstructions). All donors underwent our five-step protocol evaluation containing a preoperative protocol liver biopsy Congestive vs non-congestive RV, remnant-volume-body-weight ratios (RVBWR) and postoperative outcomes were evaluated in 71 right graft living donors. Dominant vs non-dominant MHV anatomy in total liver volume (d-MHV/TLV vs nd-MHV/TLV) was constellated with large/small congestion volumes (CV-index). Small for size (SFS) and non-SFS remnant considerations were based on standard cut-off- RVBWR and RV/TLV. Non-congestive RVBWR was based on non-congestive RV. RESULTS: MHV and non-MHV remnants showed no significant differences in RV, RV/TLV, RVBWR, total bilirubin, or INR. SFS-remnants with RV/TLV < 30% and non-SFS-remnants with RV/TLV ≥ 30% showed no significant differences either. RV and RVBWR for non-MHV (n = 59) and MHV-containing (n = 12) remnants were 550 ± 95 mL and 0.79 ± 0.1 mL vs 568 ± 97 mL and 0.79 ± 0.13, respectively (P = 0.423 and P = 0.919. Mean left RV/TLV was 35.8% ± 3.9%. Non-MHV (n = 59) and MHV-containing (n = 12) remnants (34.1% ± 3% vs 36% ± 4% respectively, P = 0.148. Eight SFS-remnants with RVBWR < 0.65 had a significantly smaller RV/TLV than 63 non-SFS-remnants with RVBWR ≥ 0.65 [SFS: RV/TLV 32.4% (range: 28%-35.7%) vs non-SFS: RV/TLV 36.2% (range: 26.1%-45.5%), P < 0.009. Six SFS-remnants with RV/TLV < 30% had significantly smaller RVBWR than 65 non-SFS-remnants with RV/TLV ≥ 30% (0.65 (range: 0.6-0.7) vs 0.8 (range: 0.6-1.27), P < 0.01. Two (2.8%) donors developed reversible liver failure. RVBWR and RV/TLV were concordant in 25%-33% of SFS and in 92%-94% of non-SFS remnants. MHV management options including complete MHV vs MHV-4A selective retention were necessary in n = 12 vs n = 2 remnants based on particularly risky congestive and non-congestive volume constellations. CONCLUSION: MHV procurement should consider individual remnant congestive- and non-congestive volume components and anatomy characteristics, RVBWR-RV/TLV constellation enables the identification of marginally small remnants. PMID:26019467

Primary biliary cirrhosis

MedlinePlus

... stools Itching Poor appetite and weight loss As liver function worsens, symptoms may include: Fluid buildup in the ... your liver is working properly: Albumin blood test Liver function tests (serum alkaline phosphatase is most important) Prothrombin ...

Bioengineered transplantable porcine livers with re-endothelialized vasculature.

PubMed

Ko, In Kap; Peng, Li; Peloso, Andrea; Smith, Charesa J; Dhal, Abritee; Deegan, Daniel B; Zimmerman, Cindy; Clouse, Cara; Zhao, Weixin; Shupe, Thomas D; Soker, Shay; Yoo, James J; Atala, Anthony

2015-02-01

Donor shortage remains a continued challenge in liver transplantation. Recent advances in tissue engineering have provided the possibility of creating functional liver tissues as an alternative to donor organ transplantation. Small bioengineered liver constructs have been developed, however a major challenge in achieving functional bioengineered liver in vivo is the establishment of a functional vasculature within the scaffolds. Our overall goal is to bioengineer intact livers, suitable for transplantation, using acellular porcine liver scaffolds. We developed an effective method for reestablishing the vascular network within decellularized liver scaffolds by conjugating anti-endothelial cell antibodies to maximize coverage of the vessel walls with endothelial cells. This procedure resulted in uniform endothelial attachment throughout the liver vasculature extending to the capillary bed of the liver scaffold and greatly reduced platelet adhesion upon blood perfusion in vitro. The re-endothelialized livers, when transplanted to recipient pigs, were able to withstand physiological blood flow and maintained for up to 24 h. This study demonstrates, for the first time, that vascularized bioengineered livers, of clinically relevant size, can be transplanted and maintained in vivo, and represents the first step towards generating engineered livers for transplantation to patients with end-stage liver failure. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Correlation between red blood cell count and liver function status].

PubMed

Xie, Xiaomeng; Wang, Leijie; Yao, Mingjie; Wen, Xiajie; Chen, Xiangmei; You, Hong; Jia, Jidong; Zhao, Jingmin; Lu, Fengmin

2016-02-01

To investigate the changes in red blood cell count in patients with different liver diseases and the correlation between red blood cell count and degree of liver damage. The clinical data of 1427 patients with primary liver cancer, 172 patients with liver cirrhosis, and 185 patients with hepatitis were collected, and the Child-Pugh class was determined for all patients. The differences in red blood cell count between patients with different liver diseases were retrospectively analyzed, and the correlation between red blood cell count and liver function status was investigated. The Mann-Whitney U test, Kruskal-Wallis H test, rank sum test, Spearman rank sum correlation test, and chi-square test were performed for different types of data. Red blood cell count showed significant differences between patients with chronic hepatitis, liver cancer, and liver cirrhosis and was highest in patients with chronic hepatitis and lowest in patients with liver cirrhosis (P < 0.05). In the patients with liver cirrhosis, red blood cell count tended to decrease in patients with a higher Child-Pugh class (P < 0.05). For patients with liver cirrhosis, red blood cell count can reflect the degree of liver damage, which may contribute to an improved liver function prediction model for these patients.

Pathological characteristics of liver allografts from donation after brain death followed by cardiac death in pigs.

PubMed

Ye, Hui; Wang, Dong-Ping; Zhang, Chuan-Zhao; Zhang, Long-Juan; Wang, Hao-Chen; Li, Zhuo-Hui; Chen, Zhen; Zhang, Tao; Cai, Chang-Jie; Ju, Wei-Qiang; Ma, Yi; Guo, Zhi-Yong; He, Xiao-Shun

2014-10-01

Donation after brain death followed by circulatory death (DBCD) is a unique practice in China. The aim of this study was to define the pathologic characteristics of DBCD liver allografts in a porcine model. Fifteen male pigs (25-30 kg) were allocated randomly into donation after brain death (DBD), donation after circulatory death (DCD) and DBCD groups. Brain death was induced by augmenting intracranial pressure. Circulatory death was induced by withdrawal of life support in DBCD group and by venous injection of 40 mL 10% potassium chloride in DCD group. The donor livers were perfused in situ and kept in cold storage for 4 h. Liver tissue and common bile duct samples were collected for hematoxylin and eosin staining, TUNEL testing and electron microscopic examination. Spot necrosis was found in hepatic parenchyma of DBD and DBCD groups, while a large area of necrosis was shown in DCD group. The apoptosis rate of hepatocytes in DBD [(0.56±0.30)%] and DBCD [(0.50 ± 0.11)%] groups was much lower than that in DCD group [(3.78±0.33)%] (P<0.05). And there was no significant difference between DBD group and DBCD group (P>0.05)). The structures of bile duct were intact in both DBD and DBCD groups, while the biliary epithelium was totally damaged in DCD group. Under electron microscope, the DBD hepatocytes were characterized by intact cell membrane, well-organized endoplasmic reticulum, mild mitochondria edema and abundant glycogens. Broken cell membrane, mild inflammatory cell infiltration and sinusoidal epithelium edema, as well as reduced glycogen volume, were found in the DBCD hepatocytes. The DCD hepatocytes had more profound cell organelle injury and much less glycogen storage. In conclusion, the preservation injury of DBCD liver allografts is much less severe than that of un-controlled DCD, but more severe than that of DBD liver allografts under electron microscope, which might reflect post-transplant liver function to some extent.

Postoperative Decrease in Platelet Counts Is Associated with Delayed Liver Function Recovery and Complications after Partial Hepatectomy.

PubMed

Takahashi, Kazuhiro; Kurokawa, Tomohiro; Oshiro, Yukio; Fukunaga, Kiyoshi; Sakashita, Shingo; Ohkohchi, Nobuhiro

2016-05-01

Peripheral platelet counts decrease after partial hepatectomy; however, the implications of this phenomenon are unclear. We assessed if the observed decrease in platelet counts was associated with postoperative liver function and morbidity (complications grade ≤ II according to the Clavien-Dindo classification). We enrolled 216 consecutive patients who underwent partial hepatectomy for primary liver cancers, metastatic liver cancers, benign tumors, and donor hepatectomy. We classified patients as either low or high platelet percentage (postoperative platelet count/preoperative platelet count) using the optimal cutoff value calculated by a receiver operating characteristic (ROC) curve analysis, and analyzed risk factors for delayed liver functional recovery and morbidity after hepatectomy. Delayed liver function recovery and morbidity were significantly correlated with the lowest value of platelet percentage based on ROC analysis. Using a cutoff value of 60% acquired by ROC analysis, univariate and multivariate analysis determined that postoperative lowest platelet percentage ≤ 60% was identified as an independent risk factor of delayed liver function recovery (odds ratio (OR) 6.85; P < 0.01) and morbidity (OR, 4.90; P < 0.01). Furthermore, patients with the lowest platelet percentage ≤ 60% had decreased postoperative prothrombin time ratio and serum albumin level and increased serum bilirubin level when compared with patients with platelet percentage ≥ 61%. A greater than 40% decrease in platelet count after partial hepatectomy was an independent risk factor for delayed liver function recovery and postoperative morbidity. In conclusion, the decrease in platelet counts is an early marker to predict the liver function recovery and complications after hepatectomy.

Physiological Ranges of Matrix Rigidity Modulate Primary Mouse Hepatocyte Function In Part Through Hepatocyte Nuclear Factor 4 Alpha

PubMed Central

Desai, Seema S.; Tung, Jason C.; Zhou, Vivian X.; Grenert, James P.; Malato, Yann; Rezvani, Milad; Español-Suñer, Regina; Willenbring, Holger; Weaver, Valerie M.; Chang, Tammy T.

2016-01-01

Matrix rigidity has important effects on cell behavior and is increased during liver fibrosis; however, its effect on primary hepatocyte function is unknown. We hypothesized that increased matrix rigidity in fibrotic livers would activate mechanotransduction in hepatocytes and lead to inhibition of hepatic-specific functions. To determine the physiologically relevant ranges of matrix stiffness at the cellular level, we performed detailed atomic force microscopy analysis across liver lobules from normal and fibrotic livers. We determined that normal liver matrix stiffness was around 150Pa and increased to 1–6kPa in areas near fibrillar collagen deposition in fibrotic livers. In vitro culture of primary hepatocytes on collagen matrix of tunable rigidity demonstrated that fibrotic levels of matrix stiffness had profound effects on cytoskeletal tension and significantly inhibited hepatocyte-specific functions. Normal liver stiffness maintained functional gene regulation by hepatocyte nuclear factor 4 alpha (HNF4α) whereas fibrotic matrix stiffness inhibited the HNF4α transcriptional network. Fibrotic levels of matrix stiffness activated mechanotransduction in primary hepatocytes through focal adhesion kinase (FAK). In addition, blockade of the Rho/Rho-associated protein kinase (ROCK) pathway rescued HNF4α expression from hepatocytes cultured on stiff matrix. Conclusion Fibrotic levels of matrix stiffness significantly inhibit hepatocyte-specific functions in part by inhibiting the HNF4α transcriptional network mediated through the Rho/ROCK pathway. Increased appreciation of the role of matrix rigidity in modulating hepatocyte function will advance our understanding of the mechanisms of hepatocyte dysfunction in liver cirrhosis and spur development of novel treatments for chronic liver disease. PMID:26755329

Progression of Liver Disease

MedlinePlus

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Design of liver functional reserve monitor based on three-wavelength from IR to NIR.

PubMed

Ye, Fuli; Zhan, Huimiao; Shi, Guilian

2018-05-04

The preoperative evaluation of liver functional reserve is very important to determine the excision of liver lobe for the patients with liver cancer. There already exist many effective evaluation methods, but these ones have many disadvantages such as large trauma, complicated process and so on. Therefore, it is essential to develop a fast, accurate and simple detection method of liver functional reserve for the practical application in the clinical engineering field. According to the principle of spectrophotometry, this paper proposes a detection method of liver functional reserve based on three-wavelength from infrared light (IR) to near-infrared light (NIR), in which the artery pulse, the vein pulse and the move of tissue are taken into account. By using near-infrared photoelectric sensor technology and excreting experiment of indocyanine green, a minimally invasive, fast and simple testing equipment is designed in this paper. The testing result shows this equipment can greatly reduce the interference from human body and ambient, realize continuous and real-time detection of arterial degree of blood oxygen saturation and liver functional reserve.

Functions of autophagy in normal and diseased liver

PubMed Central

Czaja, Mark J.; Ding, Wen-Xing; Donohue, Terrence M.; Friedman, Scott L.; Kim, Jae-Sung; Komatsu, Masaaki; Lemasters, John J.; Lemoine, Antoinette; Lin, Jiandie D.; Ou, Jing-hsiung James; Perlmutter, David H.; Randall, Glenn; Ray, Ratna B.; Tsung, Allan; Yin, Xiao-Ming

2013-01-01

Autophagy has emerged as a critical lysosomal pathway that maintains cell function and survival through the degradation of cellular components such as organelles and proteins. Investigations specifically employing the liver or hepatocytes as experimental models have contributed significantly to our current knowledge of autophagic regulation and function. The diverse cellular functions of autophagy, along with unique features of the liver and its principal cell type the hepatocyte, suggest that the liver is highly dependent on autophagy for both normal function and to prevent the development of disease states. However, instances have also been identified in which autophagy promotes pathological changes such as the development of hepatic fibrosis. Considerable evidence has accumulated that alterations in autophagy are an underlying mechanism of a number of common hepatic diseases including toxin-, drug- and ischemia/reperfusion-induced liver injury, fatty liver, viral hepatitis and hepatocellular carcinoma. This review summarizes recent advances in understanding the roles that autophagy plays in normal hepatic physiology and pathophysiology with the intent of furthering the development of autophagy-based therapies for human liver diseases. PMID:23774882

Weight loss and severe jaundice in a patient with hyperthyroidism.

PubMed

Breidert, M; Offensperger, S; Blum, H E; Fischer, R

2011-09-01

Thyrotoxicosis may significantly alter hepatic function and is associated with autoimmune disorders of the liver. We report the case of a thyrotoxic patient with Graves' disease and histologically established cholestatic hepatitis. Medical treatment of hyperthyroidism normalized liver function tests. In patients with elevated liver function parameters and jaundice of unknown origin, thyroid function should generally be tested. Moreover, medical treatment of hyperthyroidism with thyrostatics may cause severe hepatitis whereas untreated hyperthyroid patients are at risk of developing chronic liver failure. © Georg Thieme Verlag KG Stuttgart · New York.

HEPATIC FUNCTION AFTER GENETICALLY-ENGINEERED PIG LIVER TRANSPLANTATION IN BABOONS

PubMed Central

Ekser, Burcin; Echeverri, Gabriel J.; Hassett, Andrea Cortese; Yazer, Mark H.; Long, Cassandra; Meyer, Michael; Ezzelarab, Mohamed; Lin, Chih Che; Hara, Hidetaka; van der Windt, Dirk J.; Dons, Eefje M.; Phelps, Carol; Ayares, David; Cooper, David K.C.; Gridelli, Bruno

2010-01-01

Background If ‘bridging’ to allotransplantation is to be achieved by a pig liver xenograft, adequate hepatic function needs to be assured. Methods We have studied hepatic function in baboons after transplantation of livers from α1,3-galactosyltransferase gene-knockout (GTKO,n=1) or GTKO pigs transgenic for CD46 (GTKO/CD46,n=5). Monitoring was by liver function tests and coagulation parameters. Pig-specific proteins in the baboon serum/plasma were identified by Western blot. In 4 baboons, coagulation factors were measured. The results were compared with values from healthy humans, baboons, and pigs. Results Recipient baboons died or were euthanized after 4-7 days following internal bleeding associated with profound thrombocytopenia. However, parameters of liver function, including coagulation, remained in the near-normal range, except for some cholestasis. Western blot demonstrated that pig proteins (albumin, fibrinogen, haptoglobin, plasminogen) were produced by the liver from day 1. Production of several pig coagulation factors was confirmed. Conclusions After the transplantation of genetically-engineered pig livers into baboons (1) many parameters of hepatic function, including coagulation, were normal or near-normal; (2) there was evidence for production of pig proteins, including coagulation factors, and (3) these appeared to function adequately in baboons, though inter-species compatibility of such proteins remains to be confirmed. PMID:20606605

Evaluation of Encapsulated Liver Cell Spheroids in a Fluidised-Bed Bioartificial Liver for Treatment of Ischaemic Acute Liver Failure in Pigs in a Translational Setting

PubMed Central

Selden, Clare; Spearman, Catherine Wendy; Kahn, Delawir; Miller, Malcolm; Figaji, Anthony; Erro, Eloy; Bundy, James; Massie, Isobel; Chalmers, Sherri-Ann; Arendse, Hiram; Gautier, Aude; Sharratt, Peter; Fuller, Barry; Hodgson, Humphrey

2013-01-01

Liver failure is an increasing problem. Donor-organ shortage results in patients dying before receiving a transplant. Since the liver can regenerate, alternative therapies providing temporary liver-support are sought. A bioartificial-liver would temporarily substitute function in liver failure buying time for liver regeneration/organ-procurement. Our aim: to develop a prototype bioartificial-liver-machine (BAL) comprising a human liver-derived cell-line, cultured to phenotypic competence and deliverable in a clinical setting to sites distant from its preparation. The objective of this study was to determine whether its use would improve functional parameters of liver failure in pigs with acute liver failure, to provide proof-of-principle. HepG2cells encapsulated in alginate-beads, proliferated in a fluidised-bed-bioreactor providing a biomass of 4–6×1010cells, were transported from preparation-laboratory to point-of-use operating theatre (6000miles) under perfluorodecalin at ambient temperature. Irreversible ischaemic liver failure was induced in anaesthetised pigs, after portal-systemic-shunt, by hepatic-artery-ligation. Biochemical parameters, intracranial pressure, and functional-clotting were measured in animals connected in an extracorporeal bioartificial-liver circuit. Efficacy was demonstrated comparing outcomes between animals connected to a circuit containing alginate-encapsulated cells (Cell-bead BAL), and those connected to circuit containing alginate capsules without cells (Empty-bead BAL). Cells of the biomass met regulatory standards for sterility and provenance. All animals developed progressive liver-failure after ischaemia induction. Efficacy of BAL was demonstrated since animals connected to a functional biomass (+ cells) had significantly smaller rises in intracranial pressure, lower ammonia levels, more bilirubin conjugation, improved acidosis and clotting restoration compared to animals connected to the circuit without cells. In the +cell group, human proteins accumulated in pigs' plasma. Delivery of biomass using a short-term cold-chain enabled transport and use without loss of function over 3days. Thus, a fluidised-bed bioreactor containing alginate-encapsulated HepG2cell-spheroids improved important parameters of acute liver failure in pigs. The system can readily be up-scaled and transported to point-of-use justifying development at clinical scale. PMID:24367515

Effect of ethanol on the retention of americium-241 in the baboon liver.

PubMed

Cohen, N; Antonelli, R; Lo Sasso, T; Wrenn, M E

1978-01-01

The oral administration of ethyl alcohol enhanced the excretion of 241Am from the liver of a baboon by 2.5 times that of a control animal. After ethanol administration, increases in the total content of 241Am excreted in feces were accompanied by corresponding increases in fecal volumes, although administration of nonalcoholic cathartics would not be expected to produce a similar effect. The effectiveness of ethanol as a decorporating agent may result from its ability to mobilize intracellularly bound 241Am from the liver, thereby making the nuclide more available for metabolic secretory mechanisms occurring via liver-bile-fecal route.

Prevalence and causes of abnormal liver function in patients with coeliac disease.

PubMed

Casella, Giovanni; Antonelli, Elisabetta; Di Bella, Camillo; Villanacci, Vincenzo; Fanini, Lucia; Baldini, Vittorio; Bassotti, Gabrio

2013-08-01

Coeliac disease patients frequently display mild elevation of liver enzymes and this abnormality usually normalizes after gluten-free diet. To investigate the cause and prevalence of altered liver function tests in coeliac patients, basally and after 1 year of gluten-free diet. Data from 245 untreated CD patients (196 women and 49 men, age range 15-80 years) were retrospectively analysed and the liver function tests before and after diet, as well as associated liver pathologies, were assessed. Overall, 43/245 (17.5%) patients had elevated values of one or both aminotransferases; the elevation was mild (<5 times the upper reference limit) in 41 (95%) and marked (>10 times the upper reference limit) in the remaining 2 (5%) patients. After 1 year of gluten-free diet, aminotransferase levels normalized in all but four patients with HCV infection or primary biliary cirrhosis. In coeliac patients, hypertransaminaseaemia at diagnosis and the lack of normalization of liver enzymes after 12 months of diet suggest coexisting liver disease. In such instance, further evaluation is recommended to exclude the liver disease. Early recognition and treatment of coeliac disease in patients affected by liver disease are important to improve the liver function and prevent complications. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Amiodarone-Induced Liver Injury and Cirrhosis

PubMed Central

Kappus, Matthew; Lagoo, Anand S.; Brady, Carla W.

2015-01-01

We present a case report of an 80-year-old woman with volume overload thought initially to be secondary to heart failure, but determined to be amiodarone-induced acute and chronic liver injury leading to submassive necrosis and bridging fibrosis consistent with early cirrhosis. Her histopathology was uniquely absent of steatosis and phospholipidosis, which are commonly seen in AIC. PMID:26157932

Amiodarone-Induced Liver Injury and Cirrhosis.

PubMed

Buggey, Jonathan; Kappus, Matthew; Lagoo, Anand S; Brady, Carla W

2015-01-01

We present a case report of an 80-year-old woman with volume overload thought initially to be secondary to heart failure, but determined to be amiodarone-induced acute and chronic liver injury leading to submassive necrosis and bridging fibrosis consistent with early cirrhosis. Her histopathology was uniquely absent of steatosis and phospholipidosis, which are commonly seen in AIC.

Visualizing surface area and volumes of lumens in 3 dimensions using images from histological sections

USDA-ARS?s Scientific Manuscript database

Visualizing areas of tissue that are occupied by air or liquid can provide a unique perspective on the relationships between various spaces within the tissue. The portal tracts of liver tissue are an example of such a space since the liver contains several vessels and ducts in various patterns of i...

Liver cell therapy and tissue engineering for transplantation.

PubMed

Vacanti, Joseph P; Kulig, Katherine M

2014-06-01

Liver transplantation remains the only definitive treatment for liver failure and is available to only a tiny fraction of patients with end-stage liver diseases. Major limitations for the procedure include donor organ shortage, high cost, high level of required expertise, and long-term consequences of immune suppression. Alternative cell-based liver therapies could potentially greatly expand the number of patients provided with effective treatment. Investigative research into augmenting or replacing liver function extends into three general strategies. Bioartificial livers (BALs) are extracorporeal devices that utilize cartridges of primary hepatocytes or cell lines to process patient plasma. Injection of liver cell suspensions aims to foster organ regeneration or provide a missing metabolic function arising from a genetic defect. Tissue engineering recreates the organ in vitro for subsequent implantation to augment or replace patient liver function. Translational models and clinical trials have highlighted both the immense challenges involved and some striking examples of success. Copyright © 2014. Published by Elsevier Inc.

Volume comparison of radiofrequency ablation at 3- and 5-cm target volumes for four different radiofrequency generators: MR volumetry in an open 1-T MRI system versus macroscopic measurement.

PubMed

Rathke, Hendrik; Hamm, Bernd; Guettler, Felix; Lohneis, Philipp; Stroux, Andrea; Suttmeyer, Britta; Jonczyk, Martin; Teichgräber, Ulf; de Bucourt, Maximilian

2015-12-01

In a patient, it is usually not macroscopically possible to estimate the non-viable volume induced by radiofrequency ablation (RFA) after the procedure. The purpose of this study was to use an ex vivo bovine liver model to perform magnetic resonance (MR) volumetry of the visible tissue signal change induced by RFA and to correlate the MR measurement with the actual macroscopic volume measured in the dissected specimens. Sixty-four liver specimens cut from 16 bovine livers were ablated under constant simulated, close physiological conditions with target volumes set to 14.14 ml (3-cm lesion) and 65.45 ml (5-cm lesion). Four commercially available radiofrequency (RF) systems were tested (n=16 for each system; n=8 for 3 cm and n=8 for 5 cm). A T1-weighted turbo spin echo (TSE) sequence with inversion recovery and a proton-density (PD)-weighted TSE sequence were acquired in a 1.0-T open magnetic resonance imaging (MRI) system. After manual dissection, actual macroscopic ablation diameters were measured and volumes calculated. MR volumetry was performed using a semiautomatic software tool. To validate the correctness and feasibility of the volume formula in macroscopic measurements, MR multiplanar reformation diameter measurements with subsequent volume calculation and semiautomatic MR volumes were correlated. Semiautomatic MR volumetry yielded smaller volumes than manual measurement after dissection, irrespective of RF system used, target lesion size, and MR sequence. For the 3-cm lesion, only 43.3% (T1) and 41.5% (PD) of the entire necrosis are detectable. For the 5-cm lesion, only 40.8% (T1) and 37.2% (PD) are visualized in MRI directly after intervention. The correlation between semiautomatic MR volumes and calculated MR volumes was 0.888 for the T1-weighted sequence and 0.875 for the PD sequence. After correlation of semiautomatic MR volumes and calculated MR volumes, it seems reasonable to use the respective volume formula for macroscopic volume calculation. Hyperacute MRI after ex vivo intervention may result in the underestimation of the real expansion of the produced necrosis zone. This must be kept in mind when using MRI for validating ablation success directly after RFA. One reason for the discrepancy between macroscopic and MRI appearance immediately after RFA may be that the transitional zone shows no or only partially visible MR signal change.

Stereology shows that damaged liver recovers after protein refeeding.

PubMed

Gomes, Silvio Pires; da Silva, Andréa Almeida Pinto; Crisma, Amanda Rabello; Borelli, Primavera; Hernandez-Blazquez, Francisco Javier; de Melo, Mariana P; Bacci, Barbara; Loesch, Andrzej; Coppi, A Augusto

2017-06-01

The aim of the present study was to investigate the putative effects of a low-protein diet on the three-dimensional structure of hepatocytes and determine whether this scenario could be reversed by restoring the adequate levels of protein to the diet. Using design-based stereology, the total number and volume of hepatocytes were estimated in the liver of mice in healthy and altered (by protein malnutrition) conditions and after protein renutrition. This study demonstrated a 65% decrease in the liver volume (3302 mm 3 for the control for undernourished versus 1141 mm 3 for the undernourished group) accompanied by a 46% reduction in the hepatocyte volume (8223 μm 3 for the control for undernourished versus 4475 μm 3 for the undernourished group) and a 90% increase in the total number of binucleate hepatocytes (1 549 393 for the control for undernourished versus 2 941 353 for the undernourished group). Reinstating a normoproteinic diet (12% casein) proved to be effective in restoring the size of hepatocytes, leading to an 85% increase in the total number of uninucleate hepatocytes (15 988 560 for the undernourished versus 29 600 520 for the renourished group), and partially reversed the liver atrophy. Awareness of these data will add to a better morphologic understanding of malnutrition-induced hepatopathies and will help clinicians improve the diagnosis and treatment of this condition in humans and in veterinary practice. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Cavitation enhances coagulated size during pulsed high-intensity focussed ultrasound ablation in an isolated liver perfusion system.

PubMed

Zhao, Lu-Yan; Liu, Shan; Chen, Zong-Gui; Zou, Jian-Zhong; Wu, Feng

2016-11-24

To investigate whether cavitation enhances the degree of coagulation during pulsed high-intensity focussed ultrasound (HIFU) in an isolated liver perfusion system. Isolated liver was treated by pulsed HIFU or continuous-wave HIFU with different portal vein flow rates. The cavitation emission during exposure was recorded, and real-time ultrasound images were used to observe changes in the grey scale. The coagulation size was measured and calculated. HIFU treatment led to complete coagulation necrosis and total cell destruction in the target regions. Compared to exposure at a duty cycle (DC) of 100%, the mean volumes of lesions induced by 6 s exposure at DCs of 50% and 10% were significantly larger (P < .01) but were smaller at a DC of 5%. The necrosis volume was negatively related to the perfusion rate in the pulsed HIFU at a DC of 50% for exposure durations of 4 and 6 s, while the perfusion flow rate did not affect the necrosis volume for exposure durations of 1, 2 and 3 s. For increased perfusion flow rates, there was no significant decrease in the cavitation activity for the pulsed-HIFU (P > .05). For continuous-wave HIFU exposure, there was a significant decrease in the necrosis volume and cavitation activity for exposure times of 1, 2, 3, 4, and 6 s with increasing portal perfusion rates. Perfusion flow rates negatively influence cavitation activity and coagulation volume. Ablation is significantly enhanced during pulsed HIFU exposure compared with continuous-wave HIFU.

Prognostic value of enzymatic liver function for the estimation of short-term survival of liver transplant candidates: a prospective study with the LiMAx test.

PubMed

Jara, Maximilian; Malinowski, Maciej; Lüttgert, Katja; Schott, Eckart; Neuhaus, Peter; Stockmann, Martin

2015-01-01

LiMAx has been recently proposed as a new quantitative liver function test. Thus, we aimed to evaluate the diagnostic ability of LiMAx to assess short-term survival in liver transplant candidates and compare its performance to the model for end-stage liver disease (MELD) and indocyanine green plasma disappearance rate (ICG-PDR). Liver function of 167 chronic liver failure patients without hepatocellular carcinoma was prospectively investigated when they were evaluated for liver transplantation. Primary study endpoints were liver-related death within 6 months of follow-up. Within 6 months of follow-up, 18 patients died and 36 underwent liver transplantation. Median LiMAx results on evaluation day were significantly lower in patients who died (99 μg/kg/h vs. 55 μg/kg/h; P = 0.024), while median ICG-PDR results did not differ within both groups (4.4%/min vs. 3.5%/min; P = 0.159). LiMAx showed a higher negative predictive value (NPV: 0.93) as compared with ICG-PDR (NPV: 0.90) and the MELD (NPV: 0.91) in predicting risk of death within 6 months. In conclusion, LiMAx provides good prognostic information of liver transplant candidates. In particular, patients who are not at risk of death can be identified reliably by measuring actual enzymatic liver function capacity. © 2014 Steunstichting ESOT.

Prevalence and factors associated with the presence of abnormal function liver tests in patients with ulcerative colitis.

PubMed

Yamamoto-Furusho, Jesús K; Sánchez-Osorio, Magdalena; Uribe, Misael

2010-01-01

To investigate the prevalence of abnormal function liver tests and risk factors associated with their development in Mexican patients with UC. A total of 200 patients with confirmed diagnosis of UC were evaluated prospectively during a one year period from January 1, 2007 to December 31, 2008. A total of 94 females and 106 males patients with UC were analyzed. The age at diagnosis was 31.4 ± 13.2 years and the mean of disease duration was 6.7 ± 5.2 years. We found a high prevalence of abnormal function livers tests in 40% of UC patients. The pattern of abnormal function liver test was hepatitis in 70%, cholestatic (20%) and mixed (10%). The most common cause of abnormal function liver test was transient elevation in 50 patients (63%) followed by fatty liver disease (11.2%), primary sclerosing cholangitis (6.3%), drug-toxicity (6%) and others (13.5%) including chronic hepatitis C, total parenteral nutrition, granulomatous and ischemic hepatitis. In the multivariate logistic regression model, active disease, colectomy and abdominal sepsis were factors that persisted associated with the development of abnormal liver tests in UC patients. A high prevalence of abnormal function liver tests (40%) was found in Mexican UC patients is likely to be related to active disease, colectomy and the presence of sepsis.

Ratio of mean platelet volume to platelet count is a potential surrogate marker predicting liver cirrhosis.

PubMed

Iida, Hiroya; Kaibori, Masaki; Matsui, Kosuke; Ishizaki, Morihiko; Kon, Masanori

2018-01-27

To provide a simple surrogate marker predictive of liver cirrhosis (LC). Specimens from 302 patients who underwent resection for hepatocellular carcinoma between January 2006 and December 2012 were retrospectively analyzed. Based on pathologic findings, patients were divided into groups based on whether or not they had LC. Parameters associated with hepatic functional reserve were compared in these two groups using Mann-Whitney U -test for univariate analysis. Factors differing significantly in univariate analyses were entered into multivariate logistic regression analysis. There were significant differences between the LC group ( n = 100) and non-LC group ( n = 202) in prothrombin activity, concentrations of alanine aminotransferase, aspartate aminotransferase, total bilirubin, albumin, cholinesterase, type IV collagen, hyaluronic acid, indocyanine green retention rate at 15 min, maximal removal rate of technitium-99m diethylene triamine penta-acetic acid-galactosyl human serum albumin and ratio of mean platelet volume to platelet count (MPV/PLT). Multivariate analysis showed that prothrombin activity, concentrations of alanine aminotransferase, aspartate aminotransferase, total bilirubin and hyaluronic acid, and MPV/PLT ratio were factors independently predictive of LC. The area under the curve value for MPV/PLT was 0.78, with a 0.8 cutoff value having a sensitivity of 65% and a specificity of 78%. The MPV/PLT ratio, which can be determined simply from the complete blood count, may be a simple surrogate marker predicting LC.

A predictive scoring system for insufficient liver hypertrophy after preoperative portal vein embolization.

PubMed

Watanabe, Nobuyuki; Yamamoto, Yusuke; Sugiura, Teiichi; Okamura, Yukiyasu; Ito, Takaaki; Ashida, Ryo; Aramaki, Takeshi; Uesaka, Katsuhiko

2018-05-01

The factors which affect hypertrophy of the future liver remnant after portal vein embolization remain unclear. The aim of this study was to clarify the clinical factors affecting the hypertrophy rate after portal vein embolization and to develop a scoring system predicting insufficient liver hypertrophy. The cases of a total of 152 patients who underwent portal vein embolization of the right portal branch between 2006 and 2016 were reviewed retrospectively. The score to predict insufficient (<25%) hypertrophy was established based on logistic regression analyses of the clinical parameters before portal vein embolization. After portal vein embolization, the future liver remnant volume, expressed as the median (range), significantly increased from 364 (151-801) mL, 33% (18%-54%), to 451 (242-866) mL, 42% (26%-65%). The median hypertrophy rate was 24% (-5% to 96%). A preoperative predictive scoring system for insufficient liver hypertrophy was constructed using the following 3 factors: an initial future liver remnant volume ≥35% (2 points), alkaline phosphatase ≥450 IU/dL (1 point), and cholinesterase <220 mg/dL (1 point). The constructed scoring system indicated the proportion of patients with insufficient liver hypertrophy (<25%) to be 6 out of 42 (14%) in the low-score group (0 points), 44 out of 77 (57%) in the medium-score group (1-2 points), and 30 out of 33 (91%) in the high-score group (3-4 points). The hypertrophy rate of future liver remnant was different among the 3 groups (low-score group, 38.9% [-2.4% to 81.4%]; medium-score group, 22.7% [-5.1% to 95.5%]; high-score group, 18.2% [2.4%-30.7%]) (P < .001). The constructed scoring system was able to stratify patients before portal vein embolization according to the possibility of developing insufficient liver hypertrophy. Copyright © 2017 Elsevier Inc. All rights reserved.

[Liver diseases in the elderly].

PubMed

Bruguera, Miguel

2014-11-01

Liver diseases in the elderly have aroused less interest than diseases of other organs, since the liver plays a limited role in aging. There are no specific liver diseases of old age, but age-related anatomical and functional modifications of the liver cause changes in the frequency and clinical behavior of some liver diseases compared with those in younger patients. This review discusses the most important features of liver function in the healthy elderly population, as well as the features of the most prevalent liver diseases in this age group, especially the diagnostic approach to the most common liver problems in the elderly: asymptomatic elevation of serum transaminases and jaundice. Copyright © 2014 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

Ectopic fat depots and left ventricular function in nondiabetic men with nonalcoholic fatty liver disease.

PubMed

Granér, Marit; Nyman, Kristofer; Siren, Reijo; Pentikäinen, Markku O; Lundbom, Jesper; Hakkarainen, Antti; Lauerma, Kirsi; Lundbom, Nina; Nieminen, Markku S; Taskinen, Marja-Riitta

2015-01-01

Nonalcoholic fatty liver disease has emerged as a novel cardiovascular risk factor. The aim of the study was to assess the effect of different ectopic fat depots on left ventricular (LV) function in subjects with nonalcoholic fatty liver disease. Myocardial and hepatic triglyceride contents were measured with 1.5 T magnetic resonance spectroscopy and LV function, visceral adipose tissue (VAT) and subcutaneous adipose tissue, epicardial and pericardial fat by MRI in 75 nondiabetic men. Subjects were stratified by hepatic triglyceride content into low, moderate, and high liver fat groups. Myocardial triglyceride, epicardial and pericardial fat, VAT, and subcutaneous adipose tissue increased stepwise from low to high liver fat group. Parameters of LV diastolic function showed a stepwise decrease over tertiles of liver fat and VAT, and they were inversely correlated with hepatic triglyceride, VAT, and VAT/subcutaneous adipose tissue ratio. In multivariable analyses, hepatic triglyceride and VAT were independent predictors of LV diastolic function, whereas myocardial triglyceride was not associated with measures of diastolic function. Myocardial triglyceride, epicardial and pericardial fat increased with increasing amount of liver fat and VAT. Hepatic steatosis and VAT associated with significant changes in LV structure and function. The association of LV diastolic function with hepatic triglyceride and VAT may be because of toxic systemic effects. The effects of myocardial triglyceride on LV structure and function seem to be more complex than previously thought and merit further study. © 2014 American Heart Association, Inc.

Growth hormone and drug metabolism. Acute effects on microsomal mixed-function oxidase activities in rat liver.

PubMed Central

Wilson, J T; Spelsberg, T C

1976-01-01

Adult male rats were subjected either to sham operation or to hypophysectomy and adrenalectomy and maintained for a total of 10 days before treatment with growth hormone. Results of the early effects of growth hormone on the activities of the mixed-function oxidases in rat liver over a 96h period after growth-hormone treatment are presented. 2. Hypophysectomy and adrenalectomy result in decreased body and liver weight and decreased drug metabolism (mixed-function oxidases). Concentrations of electron-transport-system components are also decreased. 3. In the hypophysectomized/adrenalectomized rats, growth hormone decreases the activities of the liver mixed-function oxidases and the cytochrome P-450 and cytochrome c reductases, as well as decreasing the concentration of cytochrome P-450 compared with that of control rats. Similar but less dramatic results are obtained with sham-operated rats. 4. It is concluded that whereas growth hormone enhances liver growth, including induction of many enzyme activities, it results in a decrease in mixed-function oxidase activity. Apparently, mixed-function oxidase activity decreases in liver when growth (mitogenesis) increases. PMID:938458

Steatotic livers are susceptible to normothermic ischemia-reperfusion injury from mitochondrial Complex-I dysfunction

PubMed Central

Chu, Michael JJ; Premkumar, Rakesh; Hickey, Anthony JR; Jiang, Yannan; Delahunt, Brett; Phillips, Anthony RJ; Bartlett, Adam SJR

2016-01-01

AIM: To assess the effects of ischemic preconditioning (IPC, 10-min ischemia/10-min reperfusion) on steatotic liver mitochondrial function after normothermic ischemia-reperfusion injury (IRI). METHODS: Sixty male Sprague-Dawley rats were fed 8-wk with either control chow or high-fat/high-sucrose diet inducing > 60% mixed steatosis. Three groups (n = 10/group) for each dietary state were tested: (1) the IRI group underwent 60 min partial hepatic ischemia and 4 h reperfusion; (2) the IPC group underwent IPC prior to same standard IRI; and (3) sham underwent the same surgery without IRI or IPC. Hepatic mitochondrial function was analyzed by oxygraphs. Mitochondrial Complex-I, Complex-II enzyme activity, serum alanine aminotransferase (ALT), and histological injury were measured. RESULTS: Steatotic-IRI livers had a greater increase in ALT (2476 ± 166 vs 1457 ± 103 IU/L, P < 0.01) and histological injury following IRI compared to the lean liver group. Steatotic-IRI demonstrated lower Complex-I activity at baseline [78.4 ± 2.5 vs 116.4 ± 6.0 nmol/(min.mg protein), P < 0.001] and following IRI [28.0 ± 6.2 vs 104.3 ± 12.6 nmol/(min.mg protein), P < 0.001]. Steatotic-IRI also demonstrated impaired Complex-I function post-IRI compared to the lean liver IRI group. Complex-II activity was unaffected by hepatic steatosis or IRI. Lean liver mitochondrial function was unchanged following IRI. IPC normalized ALT and histological injury in steatotic livers but had no effect on overall steatotic liver mitochondrial function or individual mitochondrial complex enzyme activities. CONCLUSION: Warm IRI impairs steatotic liver Complex-I activity and function. The protective effects of IPC in steatotic livers may not be mediated through mitochondria. PMID:27217699

Hemochromatosis

MedlinePlus

... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

Galactosemia

MedlinePlus

... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

Culture of C3A cells in alginate beads for fluidized bed bioartificial liver.

PubMed

Kinasiewicz, A; Gautier, A; Lewinska, D; Bukowski, J; Legallais, C; Weryński, A

2007-11-01

Extracorporeal bioartificial liver has been designed to sustain the detoxification and synthetic function of the failed liver in patients suffering from acute liver failure until the time of liver allotransplantation or regeneration of their own. A fluidized bed, bioartificial liver improves the mass transfer velocity between the medium and the hepatocytes. Detoxification functions of the liver could be replaced by completely artificial systems, but the synthetic functions of hepatocytes may be obtained only by metabolically active cells. The aim of our study was to investigate the influence of C3A cell culture in alginate beads on synthetic function in a fluidized bed, bioartificial liver. Cells in alginate beads were prepared using an electrostatic droplet generator of our own design using low-viscosity alginate. Beads were cultured for 24 hours then 7 days in static conditions and then 24 hours of fluidization in the bioreactor to assess albumin production. We observed significantly increased albumin production by C3A cells entrapped in alginate beads during static culture. Fluidization increased albumin production compared with static culture. Fluidization performed after 7 days of static culture resulted in a significant increase in albumin synthesis. In conclusion, static culture of alginate beads hosting hepatic cells facilitates restoration of cell function.

Effect of Liver Disease on Hepatic Transporter Expression and Function.

PubMed

Thakkar, Nilay; Slizgi, Jason R; Brouwer, Kim L R

2017-09-01

Liver disease can alter the disposition of xenobiotics and endogenous substances. Regulatory agencies such as the Food and Drug Administration and the European Medicines Evaluation Agency recommend, if possible, studying the effect of liver disease on drugs under development to guide specific dose recommendations in these patients. Although extensive research has been conducted to characterize the effect of liver disease on drug-metabolizing enzymes, emerging data have implicated that the expression and function of hepatobiliary transport proteins also are altered in liver disease. This review summarizes recent developments in the field, which may have implications for understanding altered disposition, safety, and efficacy of new and existing drugs. A brief review of liver physiology and hepatic transporter localization/function is provided. Then, the expression and function of hepatic transporters in cholestasis, hepatitis C infection, hepatocellular carcinoma, human immunodeficiency virus infection, nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, and primary biliary cirrhosis are reviewed. In the absence of clinical data, nonclinical information in animal models is presented. This review aims to advance the understanding of altered expression and function of hepatic transporters in liver disease and the implications of such changes on drug disposition. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Measurement of hepatic functional mass by means of 13C-methacetin and 13C-phenylalanine breath tests in chronic liver disease: Comparison with Child-Pugh score and serum bile acid levels

PubMed Central

Festi, D.; Capodicasa, S.; Sandri, L.; Colaiocco-Ferrante, L.; Staniscia, T.; Vitacolonna, E.; Vestito, A.; Simoni, P.; Mazzella, G.; Portincasa, P.; Roda, E.; Colecchia, A.

2005-01-01

AIM: To evaluate and compare the clinical usefulness of 13C-phenylalanine and 13C-methacetin breath tests in quantitating functional hepatic mass in patients with chronic liver disease and to further compare these results with those of conventional tests, Child-Pugh score and serum bile acid levels. METHODS: One hundred and forty patients (50 HCV- related chronic hepatitis, 90 liver cirrhosis patients) and 40 matched healthy controls were studied. Both breath test and routine liver test, serum levels of cholic and chenodeoxycholic acid conjugates were evaluated. RESULTS: Methacetin breath test, expressed as 60 min cumulative percent of oxidation, discriminated the hepatic functional capacity not only between controls and liver disease patients, but also between different categories of chronic liver disease patients. Methacetin breath test was correlated with liver function tests and serum bile acids. Furthermore, methacetin breath test, as well as serum bile acids, were highly predictive of Child-Pugh scores. The diagnostic power of phenylalanine breath test was always less than that of methacetin breath test. CONCLUSION: Methacetin breath test represents a safe and accurate diagnostic tool in the evaluation of hepatic functional mass in chronic liver disease patients. PMID:15609414

Ob/ob Mouse Livers Show Decreased Oxidative Phosphorylation Efficiencies and Anaerobic Capacities after Cold Ischemia

PubMed Central

Tagaloa, Sherry; Zhang, Linda; Dare, Anna J.; MacDonald, Julia R.; Yeong, Mee-Ling; Bartlett, Adam S. J. R.; Phillips, Anthony R. J.

2014-01-01

Background Hepatic steatosis is a major risk factor for graft failure in liver transplantation. Hepatic steatosis shows a greater negative influence on graft function following prolonged cold ischaemia. As the impact of steatosis on hepatocyte metabolism during extended cold ischaemia is not well-described, we compared markers of metabolic capacity and mitochondrial function in steatotic and lean livers following clinically relevant durations of cold preservation. Methods Livers from 10-week old leptin-deficient obese (ob/ob, n = 9) and lean C57 mice (n = 9) were preserved in ice-cold University of Wisconsin solution. Liver mitochondrial function was then assessed using high resolution respirometry after 1.5, 3, 5, 8, 12, 16 and 24 hours of storage. Metabolic marker enzymes for anaerobiosis and mitochondrial mass were also measured in conjunction with non-bicarbonate tissue pH buffering capacity. Results Ob/ob and lean mice livers showed severe (>60%) macrovesicular and mild (<30%) microvesicular steatosis on Oil Red O staining, respectively. Ob/ob livers had lower baseline enzymatic complex I activity but similar adenosine triphosphate (ATP) levels compared to lean livers. During cold storage, the respiratory control ratio and complex I-fueled phosphorylation deteriorated approximately twice as fast in ob/ob livers compared to lean livers. Ob/ob livers also demonstrated decreased ATP production capacities at all time-points analyzed compared to lean livers. Ob/ob liver baseline lactate dehydrogenase activities and intrinsic non-bicarbonate buffering capacities were depressed by 60% and 40%, respectively compared to lean livers. Conclusions Steatotic livers have impaired baseline aerobic and anaerobic capacities compared to lean livers, and mitochondrial function indices decrease particularly from after 5 hours of cold preservation. These data provide a mechanistic basis for the clinical recommendation of shorter cold storage durations in steatotic donor livers. PMID:24956382

Neutrophil gelatinase‐associated lipocalin level is a prognostic factor for survival in rat and human chronic liver diseases

PubMed Central

Yoshikawa, Kyoko; Iwasa, Motoh; Kojima, Shinichi; Yoshizawa, Naohiko; Tempaku, Mina; Sugimoto, Ryosuke; Yamamoto, Norihiko; Sugimoto, Kazushi; Kobayashi, Yoshinao; Hasegawa, Hiroshi; Takei, Yoshiyuki

2017-01-01

Chronic liver disease patients often have complications, such as hepatocellular carcinoma (HCC) and acute bacterial infection. Model for end‐stage liver disease and Child‐Pugh scores are useful prognostic factors for chronic liver diseases but not for all chronic conditions, such as HCC. Our investigative aim targeted the prognostic abilities of neutrophil gelatinase‐associated lipocalin (NGAL) in rat and human chronic liver diseases. Blood NGAL levels were measured by enzyme‐linked immunosorbent assay in rats with cirrhosis and 96 patients with chronic liver disease and HCC. We examined the correlation between blood NGAL levels and liver functions as well as survival. In our rat model, liver NGAL expression was assessed by immunostaining, real‐time quantitative polymerase chain reaction, and immunoblot. In rats with cirrhosis, blood NGAL levels were continuously and significantly elevated in the deceased group and were significantly correlated with liver functions. Liver NGAL, toll‐like receptor 4, and interleukin‐6 levels were increased in the deceased group compared to the survival group. Blood NGAL levels were significantly correlated with liver NGAL levels, indicating blood NGAL was derived from the liver. In patients with chronic liver disease, blood NGAL levels were associated with liver function and renal function. Blood NGAL levels were significantly increased in patients with chronic liver disease with HCC compared to without HCC. For the survival group, 38 out of 96 patients were dead in the average follow‐up period of 9.9 months. The patients with blood NGAL ≤119 ng/mL had significantly longer rates of survival compared to patients with blood NGAL >119 ng/mL. Conclusion: Blood NGAL predicts the survival rate in rat and human chronic liver diseases. Our findings suggest blood NGAL may be prognostic of survival in chronic liver diseases complicated by HCC. (Hepatology Communications 2017;1:946–956) PMID:29404502

Initial 12-h operative fluid volume is an independent risk factor for pleural effusion after hepatectomy.

PubMed

Cheng, Xiang; Wu, Jia-Wei; Sun, Ping; Song, Zi-Fang; Zheng, Qi-Chang

2016-12-01

Pleural effusion after hepatectomy is associated with significant morbidity and prolonged hospital stays. Several studies have addressed the risk factors for postoperative pleural effusion. However, there are no researches concerning the role of the initial 12-h operative fluid volume. The aim of this study was to evaluate whether the initial 12-h operative fluid volume during liver resection is an independent risk factor for pleural effusion after hepatectomy. In this study, we retrospectively analyzed clinical data of 470 patients consecutively undergoing elective hepatectomy between January 2011 and December 2012. We prospectively collected and retrospectively analyzed baseline and clinical data, including preoperative, intraoperative, and postoperative variables. Univariate and multivariate analyses were carried out to identify whether the initial 12-h operative fluid volume was an independent risk factor for pleural effusion after hepatectomy. The multivariate analysis identified 2 independent risk factors for pleural effusion: operative time [odds ratio (OR)=10.2] and initial 12-h operative fluid volume (OR=1.0003). Threshold effect analyses revealed that the initial 12 h operative fluid volume was positively correlated with the incidence of pleural effusion when the initial 12-h operative fluid volume exceeded 4636 mL. We conclude that the initial 12-h operative fluid volume during liver resection and operative time are independent risk factors for pleural effusion after hepatectomy. Perioperative intravenous fluids should be restricted properly.

Hepatobiliary magnetic resonance imaging in patients with liver disease: correlation of liver enhancement with biochemical liver function tests.

PubMed

Kukuk, Guido M; Schaefer, Stephanie G; Fimmers, Rolf; Hadizadeh, Dariusch R; Ezziddin, Samer; Spengler, Ulrich; Schild, Hans H; Willinek, Winfried A

2014-10-01

To evaluate hepatobiliary magnetic resonance imaging (MRI) using Gd-EOB-DTPA in relation to various liver function tests in patients with liver disorders. Fifty-one patients with liver disease underwent Gd-EOB-DTPA-enhanced liver MRI. Based on region-of-interest (ROI) analysis, liver signal intensity was calculated using the spleen as reference tissue. Liver-spleen contrast ratio (LSCR) and relative liver enhancement (RLE) were calculated. Serum levels of total bilirubin, gamma glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH), lactate dehydrogenase (LDH), serum albumin level (AL), prothrombin time (PT), creatinine (CR) as well as international normalised ratio (INR) and model for end-stage liver disease (MELD) score were tested for correlation with LSCR and RLE. Pre-contrast LSCR values correlated with total bilirubin (r = -0.39; p = 0.005), GGT (r = -0.37; p = 0.009), AST (r = -0.38; p = 0.013), ALT (r = -0.29; p = 0.046), PT (r = 0.52; p < 0.001), GLDH (r = -0.55; p = 0.044), INR (r = -0.42; p = 0.003), and MELD Score (r = -0.53; p < 0.001). After administration of Gd-EOB-DTPA bilirubin (r = -0.45; p = 0.001), GGT (r = -0.40; p = 0.004), PT (r = 0.54; p < 0.001), AST (r = -0.46; p = 0.002), ALT (r = -0.31; p = 0.030), INR (r = -0.45; p = 0.001) and MELD Score (r = -0.56; p < 0.001) significantly correlated with LSCR. RLE correlated with bilirubin (r = -0.40; p = 0.004), AST (r = -0.38; p = 0.013), PT (r = 0.42; p = 0.003), GGT (r = -0.33; p = 0.020), INR (r = -0.36; p = 0.011) and MELD Score (r = -0.43; p = 0.003). Liver-spleen contrast ratio and relative liver enhancement using Gd-EOB-DTPA correlate with a number of routinely used biochemical liver function tests, suggesting that hepatobiliary MRI may serve as a valuable biomarker for liver function. The strongest correlation with liver enhancement was found for the MELD Score. • Relative enhancement (RLE) of Gd-EOB-DTPA is related to biochemical liver function tests. • Correlation of RLE with bilirubin, ALT, AST, GGT, INR and MELD Score is reverse. • The correlation of relative liver enhancement with prothrombin time is positive. • AST, ALT, GLDH, prothrombin time, INR and MELD Score correlate with pre-contrast liver-spleen contrast ratio. • Such biomarkers may help to evaluate liver function.

Cognitive and Adaptive Functioning after Liver Transplantation for Maple Syrup Urine Disease: A Case Series

PubMed Central

Shellmer, D. A.; Dabbs, A. DeVito; Dew, M. A.; Noll, R. B.; Feldman, H.; Strauss, K.; Morton, D. H.; Vockley, G.; Mazariegos, G. V.

2011-01-01

MSUD is a complex metabolic disorder that has been associated with central nervous system damage, developmental delays, and neurocognitive deficits. Although liver transplantation provides a metabolic cure for MSUD, changes in cognitive and adaptive functioning following transplantation have not been investigated. In this report we present data from 14 patients who completed cognitive and adaptive functioning testing pre- and one year and/or three years post-liver transplantation. Findings show either no significant change or improvement in IQ scores pre- to post-liver transplantation. Greater variability was observed in adaptive functioning scores, but the majority of patients evidenced either no significant change or improvement in adaptive scores. In general, findings may indicate that liver transplantation curtails additional central nervous system damage and neurocognitive decline providing an opportunity for stabilization or improvement in functioning. PMID:20946191

A Prospective, Cross-Sectional Survey Study of the Natural History of Niemann-Pick B Disease

PubMed Central

McGovern, Margaret M.; Wasserstein, Melissa P.; Giugliani, Roberto; Bembi, Bruno; Vanier, Marie; Mengel, Eugen; Brodie, Scott E.; Mendelson, David; Skloot, Gwen; Desnick, Robert J.; Kuriyama, Noriko; Cox, Gerald F.

2009-01-01

Objective The objective of this study was to characterize the clinical features of patients with Niemann-Pick disease Type B and to identify efficacy endpoints for future clinical trials of enzyme replacement therapy. Patients and Methods Fifty-nine patients who had Niemann-Pick disease Type B, were at least 6 years of age, and manifested at least 2 disease symptoms participated in this multicenter, multinational, cross-sectional survey study. Medical histories; physical examinations; and assessments of cardiorespiratory function, clinical laboratory data, and liver and spleen volumes; radiographic evaluation of the lungs and bone age; and quality-of-life were obtained during a 2 to 3 day period. Results Fifty-three percent of the patients were male, 92% white, and the median age was 17.6 years. The R508del mutation accounted for 25% of all disease alleles. Most patients initially presented with splenomegaly (78%) or hepatomegaly (73%). Frequent symptoms included bleeding (49%), pulmonary infections and shortness of breath (42% each), and joint/limb pain (39%). Growth was markedly delayed during adolescence. Patients commonly had low levels of platelets and high-density lipoprotein, elevated levels of LDL, VLDL, triglycerides, leukocyte sphingomyelin, and serum chitotriosidase, and abnormal liver function tests. Nearly all patients had documented splenomegaly and hepatomegaly and interstitial lung disease. Patients commonly showed restrictive lung disease physiology with impaired pulmonary gas exchange and decreased maximal exercise tolerance. Quality of life was only mildly decreased by standardized questionnaires. The degree of splenomegaly correlated with most aspects of disease, including hepatomegaly, growth, lipid profile, hematologic parameters, and pulmonary function. Conclusions This study documents the multisystem involvement and clinical variability of Niemann-Pick B disease. Several efficacy endpoints were identified for future clinical treatment studies. Because of its correlation with disease severity, spleen volume may be a useful surrogate endpoint in treatment trials, whereas biomarkers such as chitotriosidase also may play a role in monitoring treatment responses. PMID:18625664

SU-F-T-121: Abdominal Compression Effectively Reduces the Interplay Effect and Enables Pencil Beam Scanning Proton Therapy of Liver Tumors

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

Souris, K; University of Pennsylvania, Philadelphia, PA; Glick, A

Purpose: To study if abdominal compression can reduce breathing motion and mitigate interplay effect in pencil beam scanning proton therapy (PBSPT) treatment of liver tumors in order to better spare healthy liver volumes compared with photon therapy. Methods: Ten patients, six having large tumors initially treated with IMRT and four having small tumors treated with SBRT, were replanned for PBSPT. ITV and beam-specific PTVs based on 4D-CT were used to ensure target coverage in PBSPT. The use of an abdominal compression belt and volumetric repainting was investigated to mitigate the interplay effect between breathing motion and PBSPT dynamic delivery. Anmore » in-house Matlab script has been developed to simulate this interplay effect. The dose is computed on each phase individually by sorting all spots according to their simulated delivery timing. The final dose distribution is then obtained by accumulating all dose maps to a reference phase. Results: For equivalent target coverage PBSPT reduced average healthy liver dose by 9.5% of the prescription dose compared with IMRT/SBRT. Abdominal compression of 113.2±42.2 mmHg was effective for all 10 patients and reduced average motion by 2.25 mm. As a result, the average ITV volume decreased from 128.2% to 123.1% of CTV volume. Similarly, the average beam-specific PTV volume decreased from 193.2% to 183.3%. For 8 of the 10 patients, the average motion was reduced below 5 mm, and up to 3 repainting were sufficient to mitigate interplay. For the other two patients with larger residual motion, 4–5 repainting were needed. Conclusion: We recommend evaluation of the 4DCT motion histogram following simulation and the interplay effect following treatment planning in order to personalize the use of compression and volumetric repainting for each patient. Abdominal compression enables safe and more effective PBS treatment of liver tumors by reduction of motion and interplay effect. Kevin Souris is supported by IBA and Televie Grant from F.R.S.-FNRS. Liyong Lin is partially supported by Varian.« less

Expression of Enzymes that Metabolize Medications

NASA Technical Reports Server (NTRS)

Wotring, Virginia E.; Peters, C. P.

2012-01-01

Most pharmaceuticals are metabolized by the liver. Clinically-used medication doses are given with normal liver function in mind. A drug overdose can result if the liver is damaged and removing pharmaceuticals from the circulation at a rate slower than normal. Alternatively, if liver function is elevated and removing drugs from the system more quickly than usual, it would be as if too little drug had been given for effective treatment. Because of the importance of the liver in drug metabolism we want to understand the effects of spaceflight on the enzymes of the liver.

Liver function assessment using 99mTc-GSA single-photon emission computed tomography (SPECT)/CT fusion imaging in hilar bile duct cancer: A retrospective study.

PubMed

Sumiyoshi, Tatsuaki; Shima, Yasuo; Okabayashi, Takehiro; Kozuki, Akihito; Hata, Yasuhiro; Noda, Yoshihiro; Kouno, Michihiko; Miyagawa, Kazuyuki; Tokorodani, Ryotaro; Saisaka, Yuichi; Tokumaru, Teppei; Nakamura, Toshio; Morita, Sojiro

2016-07-01

The objective of this study was to determine the utility of Tc-99m-diethylenetriamine-penta-acetic acid-galactosyl human serum albumin ((99m)Tc-GSA) single-photon emission computed tomography (SPECT)/CT fusion imaging for posthepatectomy remnant liver function assessment in hilar bile duct cancer patients. Thirty hilar bile duct cancer patients who underwent major hepatectomy with extrahepatic bile duct resection were retrospectively analyzed. Indocyanine green plasma clearance rate (KICG) value and estimated KICG by (99m)Tc-GSA scintigraphy (KGSA) and volumetric and functional rates of future remnant liver by (99m)Tc-GSA SPECT/CT fusion imaging were used to evaluate preoperative whole liver function and posthepatectomy remnant liver function, respectively. Remnant (rem) KICG (= KICG × volumetric rate) and remKGSA (= KGSA × functional rate) were used to predict future remnant liver function; major hepatectomy was considered unsafe for values <0.05. The correlation of remKICG and remKGSA with posthepatectomy mortality and morbidity was determined. Although remKICG and remKGSA were not significantly different (median value: 0.071 vs 0.075), functional rates of future remnant liver were significantly higher than volumetric rates (median: 0.54 vs 0.46; P < .001). Hepatectomy was considered unsafe in 17% and 0% of patients using remKICG and remKGSA, respectively. Postoperative liver failure and mortality did not occur in the patients for whom hepatectomy was considered unsafe based on remKICG. remKGSA showed a stronger correlation with postoperative prothrombin time activity than remKICG. (99m)Tc-GSA SPECT/CT fusion imaging enables accurate assessment of future remnant liver function and suitability for hepatectomy in hilar bile duct cancer patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Alagille Syndrome

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Newborn Jaundice

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Reye Syndrome

MedlinePlus

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A knowledge-based approach to automated planning for hepatocellular carcinoma.

PubMed

Zhang, Yujie; Li, Tingting; Xiao, Han; Ji, Weixing; Guo, Ming; Zeng, Zhaochong; Zhang, Jianying

2018-01-01

To build a knowledge-based model of liver cancer for Auto-Planning, a function in Pinnacle, which is used as an automated inverse intensity modulated radiation therapy (IMRT) planning system. Fifty Tomotherapy patients were enrolled to extract the dose-volume histograms (DVHs) information and construct the protocol for Auto-Planning model. Twenty more patients were chosen additionally to test the model. Manual planning and automatic planning were performed blindly for all twenty test patients with the same machine and treatment planning system. The dose distributions of target and organs at risks (OARs), along with the working time for planning, were evaluated. Statistically significant results showed that automated plans performed better in target conformity index (CI) while mean target dose was 0.5 Gy higher than manual plans. The differences between target homogeneity indexes (HI) of the two methods were not statistically significant. Additionally, the doses of normal liver, left kidney, and small bowel were significantly reduced with automated plan. Particularly, mean dose and V15 of normal liver were 1.4 Gy and 40.5 cc lower with automated plans respectively. Mean doses of left kidney and small bowel were reduced with automated plans by 1.2 Gy and 2.1 Gy respectively. In contrast, working time was also significantly reduced with automated planning. Auto-Planning shows availability and effectiveness in our knowledge-based model for liver cancer. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Analysis of the Liver Soluble Proteome from Bull Terriers Affected with Inherited Lethal Acrodermatitis

PubMed Central

Mouat, Michael F.; Mauldin, Elizabeth A.; Casal, Margret L.

2012-01-01

Lethal acrodermatitis (LAD) is a genetic disease affecting bull terrier dogs. The phenotype is similar to that for acrodermatitis enteropathica in humans, but is currently without treatment. The purpose of the research presented here is to determine the biochemical defects associated with LAD using proteomic methodologies. Two affected (male and female) and one unaffected (male) bull terrier pups were euthanized at 14 weeks of age, their livers dissected and prepared for two-dimensional gel electrophoresis (2DE) and densitometry. Approximately 200 protein spots were observed. The density of the spots within each gel was normalized to the total spot volume of the gel; only those soluble liver protein spots that were consistently different in both of the livers of the affected pups compared to the unaffected pup were excised manually and submitted for MALDI mass spectrometry. Thirteen proteins were identified as differentially expressed in the affected, compared to the unaffected, pups. The proteins were involved in numerous cellular physiological functions, including chaperones, calcium binding, and energy metabolism, as well as being associated with the inflammatory response. Of note were haptoglobin, glutamine synthetase, prohibitin and keratin 10 which exhibited at least a 4-fold level of differential expression. These data represent the first proteomic analysis of this mutation. The differentially expressed proteins that were identified may be key in understanding the etiology of LAD, and may lead to diagnostic tools for its identification within the bull terrier population. PMID:17693109

Elasticity-based development of functionally enhanced multicellular 3D liver encapsulated in hybrid hydrogel.

PubMed

Lee, Ho-Joon; Son, Myung Jin; Ahn, Jiwon; Oh, Soo Jin; Lee, Mihee; Kim, Ansoon; Jeung, Yun-Ji; Kim, Han-Gyeul; Won, Misun; Lim, Jung Hwa; Kim, Nam-Soon; Jung, Cho-Rock; Chung, Kyung-Sook

2017-12-01

Current in vitro liver models provide three-dimensional (3-D) microenvironments in combination with tissue engineering technology and can perform more accurate in vivo mimicry than two-dimensional models. However, a human cell-based, functionally mature liver model is still desired, which would provide an alternative to animal experiments and resolve low-prediction issues on species differences. Here, we prepared hybrid hydrogels of varying elasticity and compared them with a normal liver, to develop a more mature liver model that preserves liver properties in vitro. We encapsulated HepaRG cells, either alone or with supporting cells, in a biodegradable hybrid hydrogel. The elastic modulus of the 3D liver dynamically changed during culture due to the combined effects of prolonged degradation of hydrogel and extracellular matrix formation provided by the supporting cells. As a result, when the elastic modulus of the 3D liver model converges close to that of the in vivo liver (≅ 2.3 to 5.9 kPa), both phenotypic and functional maturation of the 3D liver were realized, while hepatic gene expression, albumin secretion, cytochrome p450-3A4 activity, and drug metabolism were enhanced. Finally, the 3D liver model was expanded to applications with embryonic stem cell-derived hepatocytes and primary human hepatocytes, and it supported prolonged hepatocyte survival and functionality in long-term culture. Our model represents critical progress in developing a biomimetic liver system to simulate liver tissue remodeling, and provides a versatile platform in drug development and disease modeling, ranging from physiology to pathology. We provide a functionally improved 3D liver model that recapitulates in vivo liver stiffness. We have experimentally addressed the issues of orchestrated effects of mechanical compliance, controlled matrix formation by stromal cells in conjunction with hepatic differentiation, and functional maturation of hepatocytes in a dynamic 3D microenvironment. Our model represents critical progress in developing a biomimetic liver system to simulate liver tissue remodeling, and provides a versatile platform in drug development and disease modeling, ranging from physiology to pathology. Additionally, recent advances in the stem-cell technologies have made the development of 3D organoid possible, and thus, our study also provides further contribution to the development of physiologically relevant stem-cell-based 3D tissues that provide an elasticity-based predefined biomimetic 3D microenvironment. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

All-In-One: Advanced preparation of Human Parenchymal and Non-Parenchymal Liver Cells.

PubMed

Werner, Melanie; Driftmann, Sabrina; Kleinehr, Kathrin; Kaiser, Gernot M; Mathé, Zotlan; Treckmann, Juergen-Walter; Paul, Andreas; Skibbe, Kathrin; Timm, Joerg; Canbay, Ali; Gerken, Guido; Schlaak, Joerg F; Broering, Ruth

2015-01-01

Liver cells are key players in innate immunity. Thus, studying primary isolated liver cells is necessary for determining their role in liver physiology and pathophysiology. In particular, the quantity and quality of isolated cells are crucial to their function. Our aim was to isolate a large quantity of high-quality human parenchymal and non-parenchymal cells from a single liver specimen. Hepatocytes, Kupffer cells, liver sinusoidal endothelial cells, and stellate cells were isolated from liver tissues by collagenase perfusion in combination with low-speed centrifugation, density gradient centrifugation, and magnetic-activated cell sorting. The purity and functionality of cultured cell populations were controlled by determining their morphology, discriminative cell marker expression, and functional activity. Cell preparation yielded the following cell counts per gram of liver tissue: 2.0 ± 0.4 × 10(7) hepatocytes, 1.8 ± 0.5 × 10(6 )Kupffer cells, 4.3 ± 1.9 × 10(5) liver sinusoidal endothelial cells, and 3.2 ± 0.5 × 10(5) stellate cells. Hepatocytes were identified by albumin (95.5 ± 1.7%) and exhibited time-dependent activity of cytochrome P450 enzymes. Kupffer cells expressed CD68 (94.5 ± 1.2%) and exhibited phagocytic activity, as determined with 1 μm latex beads. Endothelial cells were CD146(+) (97.8 ± 1.1%) and exhibited efficient uptake of acetylated low-density lipoprotein. Hepatic stellate cells were identified by the expression of α-smooth muscle actin (97.1 ± 1.5%). These cells further exhibited retinol (vitamin A)-mediated autofluorescence. Our isolation procedure for primary parenchymal and non-parenchymal liver cells resulted in cell populations of high purity and quality, with retained physiological functionality in vitro. Thus, this system may provide a valuable tool for determining liver function and disease.

A bio-impedance probe to assess liver steatosis during transplant surgery.

PubMed

Smith, Penny Probert; You, Fusheng; Vogel, Thomas; Silva, Michael

2011-01-01

This work addresses the design of a bioimpedance probe to assess steatosis on the exposed liver in the donor during liver transplant surgery. Whereas typically bioimpedance uses needle probes to avoid surface effects, for clinical reasons a non-penetrative probe is required. In addition the need to ensure that the measurement is representative of the bulk tissue suggests a larger probe than is normally used to ensure a sufficiently large measurement volume. Using a simple model, simulations and tests on bovine liver, this paper investigates the relationship between probe dimensions and depth of measurement penetration and investigates the accuracy which might be expected in a configuration suitable for use in the operating theatre on intact but exposed livers. A probe using ECG electrodes is proposed and investigated.

Poor allostimulatory function of liver plasmacytoid DC is associated with pro-apoptotic activity, dependent on regulatory T cells

PubMed Central

Tokita, Daisuke; Sumpter, Tina L.; Raimondi, Giorgio; Zahorchak, Alan F.; Wang, Zhiliang; Nakao, Atsunori; Mazariegos, George V.; Abe, Masanori; Thomson, Angus W.

2008-01-01

Background/Aims The liver is comparatively rich in plasmacytoid (p) dendritic cells (DC),- innate immune effector cells that are also thought to play key roles in the induction and regulation of adaptive immunity. Methods Liver and spleen pDC were purified from fms-like tyrosine kinase ligand-reated control or lipopolysaccharide-injected C57BL/10 mice. Flow cytometric and molecular biologic assays were used to characterize their function and interaction with naturally-occurring regulatory T cells (Treg). Results While IL-10 production was greater for freshly-isolated liver compared with splenic pDC, the former produced less bioactive IL-12p70. Moreover, liver pDC expressed a low Delta4/Jagged1 Notch ligand ratio, skewed towards T helper 2 cell differentiation/cytokine production, and promoted allogeneic CD4+ T cell apoptosis. T cell proliferation in response to liver pDC was, however, enhanced by blocking IL-10 function at the initiation of cultures. In the absence of naturally occurring CD4+CD25+ regulatory T cells, similar levels of T cell proliferation were induced by liver and spleen pDC and the pro-apoptotic activity of liver pDC was reversed. Conclusion The inferior T cell allostimulatory activity of in vivo-stimulated liver pDC may depend on the presence and function of Treg, a property that may contribute to inherent liver tolerogenicity. PMID:18926588

Correlation of four potential biomarkers of liver fibrosis with liver function and grade of hepatic fibrosis in a neonatal cholestatic rat model.

PubMed

Tang, Ning; Zhang, Yaping; Liu, Zeyu; Ai, Xuemei; Liang, Qinghong

2017-07-01

The present study investigated the correlation between four serum biomarkers of liver fibrosis, liver function and pathological hepatic fibrosis grade in neonatal cholestatic rats. A total of 38 Sprague‑Dawley rats, aged 3 weeks, were randomly assigned to the experimental group (EG), control group (CG) and the blank control group (BCG). EG received intragastric administration of 1% α‑naphthylisothiocyanate, 75 mg/kg, to induce acute cholestasis liver injury, CG and BCG were set as control groups. Blood samples from all groups were collected 48 h following the procedure. The levels of liver function markers, and four biomarkers of liver fibrosis in serum, were measured and sections of liver tissue were stained for pathological analysis. The results of the present study demonstrated that the degree of hepatic fibrosis in EG, in the serum levels or by pathological analysis, was markedly more evident compared with the CG. Several indices of four biomarkers for liver fibrosis in serum were identified and correlated with the levels of liver function markers. The pathological hepatic fibrosis grade was correlated with γ‑glutamyl transferase (γ‑GT) and Hyaluronic acid (HA). Therefore, HA and γ‑GT were positively correlated with the grade of hepatic fibrosis, indicating their efficacy as biomarkers of infantile cholestatic hepatic fibrosis.

Evaluation of liver function using gadoxetate disodium (Gd-EOB-DTPA) enhanced MR imaging

NASA Astrophysics Data System (ADS)

Yamada, Akira; Hara, Takeshi; Li, Feng; Doi, Kunio

2010-03-01

Indocyanine green (ICG) is widely used for its clearance test in the evaluation of liver function. Gadoxetate disodium (Gd-EOB-DTPA) is a targeted MR contrast agent partially taken up by hepatocytes. The objective of this study was to evaluate the feasibility of an estimation of the liver function corresponding to plasma disappearance rate of indocyanine green (ICG-PDR) by use of the signal intensity of the liver alone in Gd-EOB-DTPA enhanced MR imaging (EOB-MRI). We evaluated fourteen patients who had EOB-MRI and ICG clearance test within 1 month. 2D-GRE T1 weighted images were obtained at pre contrast, 3 min (equilibrium phase) and 20 min (hepatobiliary phase) after the intravenous administration of Gd-EOB-DTPA, and the mean signal intensity of the liver was measured. The correlation between ICG-PDR and many parameters derived from the signal intensity of the liver in EOB-MRI was evaluated. The correlation coefficient between ICG-PDR and many parameters derived from the signal intensity of the liver in EOBMRI was low and not significant. The estimation of the liver function corresponding to ICG-PDR by use of the signal intensity of the liver alone in EOB-MRI would not be reliable.

Native kidney function following liver transplantation using calcineurin inhibitors: single-center analysis with 20 years of follow-up.

PubMed

LaMattina, John C; Mezrich, Joshua D; Fernandez, Luis A; D'Alessandro, Anthony M; Djamali, Arjang; Musat, Alexandru I; Pirsch, John D; Foley, David P

2013-01-01

The incidence of chronic kidney disease (CKD) in liver transplant recipients has been estimated to be from 18% to 28% at 10 yr after transplantation. As outcomes from liver transplantation continue to improve, long-term native kidney function in these recipients becomes more critical to patient survival. We analyzed 1151 adult, deceased-donor, single-organ primary liver transplantations performed at our center between 7/17/84 and 12/31/07. Analysis of renal function was performed on 972 patients with liver allograft survival >1 yr. Kaplan-Meier analysis revealed that 3%, 7%, and 18% of liver transplant recipients with allograft survival >1 yr developed end-stage renal disease (ESRD) at five, 10, and 20 yr, respectively. Significant independent risk factors for ESRD included dialysis during the transplant hospitalization, the stage of CKD at one yr, hypercholesterolemia, non-Caucasian race, and hepatitis C as the primary indication for liver transplantation. The initial immunosuppression of essentially all recipients was a calcineurin inhibitor-based regimen. Close, long-term follow-up of liver transplant recipients permits optimal management of liver allograft and native renal function and can lead to excellent long-term outcomes despite a calcineurin inhibitor-based immunosuppressive regimen. © 2013 John Wiley & Sons A/S.

Generation, characterization and potential therapeutic applications of mature and functional hepatocytes from stem cells.

PubMed

Zhang, Zhenzhen; Liu, Jianfang; Liu, Yang; Li, Zheng; Gao, Wei-Qiang; He, Zuping

2013-02-01

Liver cancer is the sixth most common tumor in the world and the majority of patients with this disease usually die within 1 year. The effective treatment for end-stage liver disease (also known as liver failure), including liver cancer or cirrhosis, is liver transplantation. However, there is a severe shortage of liver donors worldwide, which is the major handicap for the treatment of patients with liver failure. Scarcity of liver donors underscores the urgent need of using stem cell therapy to the end-stage liver disease. Notably, hepatocytes have recently been generated from hepatic and extra-hepatic stem cells. We have obtained mature and functional hepatocytes from rat hepatic stem cells. Here, we review the advancements on hepatic differentiation from various stem cells, including hepatic stem cells, embryonic stem cells, the induced pluripotent stem cells, hematopoietic stem cells, mesenchymal stem cells, and probably spermatogonial stem cells. The advantages, disadvantages, and concerns on differentiation of these stem cells into hepatic cells are highlighted. We further address the methodologies, phenotypes, and functional characterization on the differentiation of numerous stem cells into hepatic cells. Differentiation of stem cells into mature and functional hepatocytes, especially from an extra-hepatic stem cell source, would circumvent the scarcity of liver donors and human hepatocytes, and most importantly it would offer an ideal and promising source of hepatocytes for cell therapy and tissue engineering in treating liver disease. Copyright © 2012 Wiley Periodicals, Inc.

Primary Sclerosing Cholangitis (PSC)

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Type I Glycogen Storage Disease

MedlinePlus

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Relative tumour promoting activity of three polychlorinated biphenyls in rat liver.

PubMed

Hemming, H; Flodström, S; Wärngård, L; Bergman, A; Kronevi, T; Nordgren, I; Ahlborg, U G

1993-08-02

The relative tumour promoting activity of three structurally and toxicologically diverse polychlorinated biphenyls (3,4,5,3',4'-penta- 2,3,4,3',4'-penta- and 2,4,5,2',4',5'-hexachlorobiphenyl) was measured in an initiation/promotion assay in nitrosodiethylamine-initiated female Sprague-Dawley rats. The congeners under study were administered by once-weekly subcutaneous injections for 20 weeks. Evaluation of the development of gamma-glutamyl transpeptidase (GGT)- and glutation transferase P (GST-P)-positive hepatic foci showed that all congeners promoted altered hepatic foci, although 3,4,5,3',4'-pentachlorobiphenyl was far more potent. The volume fraction of the liver occupied by GGT-positive tissue in the 3,4,5,3',4'-pentachlorobiphenyl-treated animals (100 micrograms/kg per week) was 23%, while the volume fractions of altered liver tissue in the rats treated with 2,3,4,3',4'-pentachlorobiphenyl (5000 micrograms/kg per week) and 2,4,5,2',4',5'-hexaCB (20,000 micrograms/kg per week) were 1.2 and 2.3, respectively. The enhancement of GGT- and GST-P-positive foci was accompanied by an increased incidence of histological changes in the livers.

Direct peritoneal resuscitation improves obesity-induced hepatic dysfunction after trauma.

PubMed

Matheson, Paul J; Franklin, Glen A; Hurt, Ryan T; Downard, Cynthia D; Smith, Jason W; Garrison, Richard N

2012-04-01

The metabolic syndrome and associated fatty liver disease are thought to contribute to poor outcomes in trauma patients. Experimentally, obesity compromises liver blood flow. We sought to correlate the effect of obesity, injury severity, and liver dysfunction with trauma outcomes. We hypothesized that obesity-related liver dysfunction could be mitigated with the novel technique of adjunctive direct peritoneal resuscitation (DPR). This study has clinical and experimental arms. The clinical study was a case-controlled retrospective analysis of ICU trauma patients (n = 72 obese, n = 187 nonobese). The experimental study was a hemorrhagic shock model in obese rats to assess the effect of DPR on liver blood flow, liver function, and inflammatory mediators. In trauma patients, univariate and multivariate analyses demonstrated increasing mortality (p < 0.05), septic complications (p < 0.05), liver dysfunction (p < 0.001), and renal impairment (p < 0.05) with increasing body mass index and injury severity score. Obesity in rats impairs liver blood flow, liver function, renal function, and inflammation (interleukin [IL]-1β, IL-6, high mobility group protein B1[HMGB-1]). The addition of DPR to shock resuscitation restores liver blood flow, improves organ function, and reverses the systemic proinflammatory response. Our clinical review substantiates that obesity worsens trauma outcomes regardless of injury severity. Obesity-related liver and renal dysfunction is aggravated by injury severity. In an obese rat model of resuscitated hemorrhagic shock, the addition of DPR abrogates trauma-induced liver, renal, and inflammatory responses. We conclude that the addition of DPR to the clinical resuscitation regimen will benefit the obese trauma patient. Published by Elsevier Inc.

Increased mean platelet volume in patients with idiopathic subjective tinnitus.

PubMed

Sarıkaya, Yasin; Bayraktar, Cem; Karataş, Mehmet; Doğan, Sedat; Olt, Serdar; Kaskalan, Emin; Türkbeyler, İbrahim Halil

2016-11-01

Tinnitus is the perception of sound with no external stimulus and idiopathic subjective tinnitus is the most common type in adults. Mean platelet volume (MPV) alterations were shown in some inflammatory diseases and were evaluated as a clinically useful marker. Our aim was to investigate MPV alterations in idiopathic subjective tinnitus patients. A total of 101 patients and 54 age- and sex-matched healthy control subjects were enrolled in the study. Patients included in the study had complaints of tinnitus for at least 3 months. All patients underwent detailed otolaryngologic examination, blood sampling, pure tone audiometry, magnetic resonance imaging of ear, and vertebrobasilar artery Doppler ultrasonography to make the differential diagnosis of tinnitus. Blood sampling consisted of renal-liver-thyroid function tests, lipid profile, and complete blood count. All tests and examinations except the imaging modalities were also performed for the control group. There were no differences in age and sex distribution of groups. Mean platelet volume values were significantly increased in tinnitus patients when compared with controls (p = 0.001). We think that MPV can be qualified as a useful marker in tinnitus patients.

13C Methacetin Breath Test for Assessment of Microsomal Liver Function: Methodology and Clinical Application.

PubMed

Gorowska-Kowolik, Katarzyna; Chobot, Agata; Kwiecien, Jaroslaw

2017-01-01

Assessment of the liver function, and the need of constant monitoring of the organ's capacity, concerns not only patients with primary liver diseases, but also those at risk of hepatopathies secondary to other chronic diseases. Most commonly, the diagnostics is based on measurements of static biochemical parameters, which allow us to draw conclusions only indirectly about the function and the degree of damage of the organ. On the other hand, liver biopsy is an invasive procedure and therefore it is associated with a considerable risk of complications. Dynamic tests enable us to assess quantitatively the organ's functional reserve by analyzing the kinetics of the metabolization of the substrate by the liver. In practice applied are breath tests using substances such as aminopyrine, caffeine, methacetin, erythromycin (for assessment of the microsomal function); phenylalanine, galactose (for assessment of the cytosolic function); methionine, octanoate, ketoisocaproic acid (for assessment of the mitochondrial function). The test with 13 C methacetin belongs to the best described and most widely applied methods in noninvasive liver function assessment. Due to the rising availability of this method, knowledge concerning its limitations and controversies regarding the methodology, as well as its usefulness in chosen groups of patients, seems to be vital.

Regional metabolic liver function measured in patients with cirrhosis by 2-[¹⁸F]fluoro-2-deoxy-D-galactose PET/CT.

PubMed

Sørensen, Michael; Mikkelsen, Kasper S; Frisch, Kim; Villadsen, Gerda E; Keiding, Susanne

2013-06-01

There is a clinical need for methods that can quantify regional hepatic function non-invasively in patients with cirrhosis. Here we validate the use of 2-[(18)F]fluoro-2-deoxy-d-galactose (FDGal) PET/CT for measuring regional metabolic function to this purpose, and apply the method to test the hypothesis of increased intrahepatic metabolic heterogeneity in cirrhosis. Nine cirrhotic patients underwent dynamic liver FDGal PET/CT with blood samples from a radial artery and a liver vein. Hepatic blood flow was measured by indocyanine green infusion/Fick's principle. From blood measurements, hepatic systemic clearance (Ksyst, Lblood/min) and hepatic intrinsic clearance (Vmax/Km, Lblood/min) of FDGal were calculated. From PET data, hepatic systemic clearance of FDGal in liver parenchyma (Kmet, mL blood/mL liver tissue/min) was calculated. Intrahepatic metabolic heterogeneity was evaluated in terms of coefficient-of-variation (CoV, %) using parametric images of Kmet. Mean approximation of Ksyst to Vmax/Km was 86% which validates the use of FDGal as PET tracer of hepatic metabolic function. Mean Kmet was 0.157 mL blood/mL liver tissue/min, which was lower than 0.274 mL blood/mL liver tissue/min, previously found in healthy subjects (p<0.001), in accordance with decreased metabolic function in cirrhotic livers. Mean CoV for Kmet in liver tissue was 24.4% in patients and 14.4% in healthy subjects (p<0.0001). The degree of intrahepatic metabolic heterogeneity correlated positively with HVPG (p<0.05). A 20-min dynamic FDGal PET/CT with arterial sampling provides an accurate measure of regional hepatic metabolic function in patients with cirrhosis. This is likely to have clinical implications for the assessment of patients with liver disease as well as treatment planning and monitoring. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Study of Abnormal Liver Function Test during Pregnancy in a Tertiary Care Hospital in Chhattisgarh.

PubMed

Mishra, Nalini; Mishra, V N; Thakur, Parineeta

2016-10-01

Abnormal liver function tests (LFTs) in pregnancy require proper interpretation in order to avoid pitfalls in the diagnosis. The underlying disorder can have a significant effect on the outcome of both mother and foetus. The present study was done with the objective to study the clinical profile, incidence and possible causes of derangements of liver function tests. Eighty pregnant women with abnormal liver dysfunction were studied prospectively. Women with chronic liver disease and drug-induced abnormal liver function test were excluded. All available LFTs including LDH were studied along with some more definitive tests to aid identification of underlying cause. Foetomaternal outcome was noted in all. The incidence of abnormal LFT was 0.9 %. 13/80 (16.75 %) women had liver disorder not specific to pregnancy, whereas 67/80 (83.25 %) women had pregnancy-specific liver dysfunction. Of these, 65(81.25 %) women with liver dysfunction had pre-eclampsia including 11 (13.75 %) with HELLP and six women with eclampsia. 48/65 (60 %) women had pre-eclampsia in the absence of HELLP syndrome or eclampsia. The mean value for bilirubin (mg %) in hypertensive disorders of pregnancy ranged from 1.64 to 3.8, between 5 and 10 for ICP and AFLP and >10 in infective hepatitis. Transaminases were highest in infective hepatitis, whereas alkaline phosphate was highest in ICP. Total 27 (33.75 %) women suffered from adverse outcome with four (5 %) maternal deaths and 23 (28.75 %) major maternal morbidities. 33/80 (41.25 %) women had intrauterine death. 26.25 % babies were small for date. Pregnancy-specific disorders are the leading cause of abnormal liver function test during pregnant state particularly in the third trimester. Pre-eclampsia-related disorder is the commonest. Gestational age of pregnancy and relative values of various liver function tests in different pregnancy-specific and pregnancy nonspecific disorders appear to be the best guide to clinch the diagnosis.

Sexual dysfunction in chronic liver disease: is liver transplantation an effective cure?

PubMed

Burra, Patrizia; Germani, Giacomo; Masier, Annalisa; De Martin, Eleonora; Gambato, Martina; Salonia, Andrea; Bo, Patrizio; Vitale, Alessandro; Cillo, Umberto; Russo, Francesco Paolo; Senzolo, Marco

2010-06-27

The goal of liver transplantation is not only to ensure patient long-term survival but also to offer the opportunity to achieve psychologic and physical integrity. Quality of life after liver transplantation may be affected by unsatisfactory sexual function. Before liver transplantation, sexual dysfunction and sex hormone disturbances are reported in men and women mainly due to abnormality of physiology of the hypothalamic-pituitary-gonadal axis and, in some cases, origin of liver disease. Successful liver transplantation should theoretically restore hormonal balance and improve sexual function both in men and women, thus improving the reproductive performance. However, after transplantation, up to 25% of patients report persistent sexual dysfunction, and approximately one third of patients describe the appearance of de novo sexual dysfunction. Despite the described high prevalence of this condition, epidemiologic data are relatively scant. Further studies on pathophysiology and risk factors in the field of sexual function after liver transplantation along with new strategies to support and inform patients on the waiting list and after surgery are needed.

[Pilot study of levosimendan : Effect on liver blood flow and liver function in acute decompensated heart failure].

PubMed

Lenz, K; Gegenhuber, A; Firlinger, F; Lohr, G; Piringer, P

2014-05-01

In a pilot study, 9 patients (39-48 years) with acute decompensated heart failure and a cardiac index (CI) of 1.9 ± 0.3 l/min/m(2) were included after exclusion of an underlying hepatic disease. The effect of levosimendan on liver blood flow and liver function was measured with the LiMON(®) system using the indocyane green plasma disappearance rate (ICG PDR). Levosimendan (Simdax(®)) infusion resulted in a significant increase of the CI, thus, achieving normal ranges of 2.9 ± 0.9 l/min/m(2) after 4 h and 3.3 ± 1 l/min/m(2) (p = 0.003) after 24 h. ICG PDR increased from 8.2 ± 0.8 % to 10.2 + 1.8 % after 4 h and to 11.9 ± 2.9 % after 24 h (p = 0.04). The reason for the early increase in systemic blood flow with no concomitant change in ICG PDR is not clear. A primary increase in liver blood flow with sustained low liver function might be one explanation; a low flow-mediated increased release of cytokines from liver cells with consequent deterioration of liver function is another possible explanation.

Assessment of gadoxetate DCE-MRI as a biomarker of hepatobiliary transporter inhibition

PubMed Central

Ulloa, Jose L; Stahl, Simone; Yates, James; Woodhouse, Neil; Kenna, J Gerry; Jones, Huw B; Waterton, John C; Hockings, Paul D

2013-01-01

Drug-induced liver injury (DILI) is a clinically important adverse drug reaction, which prevents the development of many otherwise safe and effective new drugs. Currently, there is a lack of sensitive and specific biomarkers that can be used to predict, assess and manage this toxicity. The aim of this work was to evaluate gadoxetate-enhanced MRI as a potential novel biomarker of hepatobiliary transporter inhibition in the rat. Initially, the volume fraction of extracellular space in the liver was determined using gadopentetate to enable an estimation of the gadoxetate concentration in hepatocytes. Using this information, a compartmental model was developed to characterise the pharmacokinetics of hepatic uptake and biliary excretion of gadoxetate. Subsequently, we explored the impact of an investigational hepatobiliary transporter inhibitor on the parameters of the model in vivo in rats. The investigational hepatobiliary transporter inhibitor reduced both the rate of uptake of gadoxetate into the hepatocyte, k1, and the Michaelis–Menten constant, Vmax, characterising its excretion into bile, whereas KM values for biliary efflux were increased. These effects were dose dependent and correlated with effects on plasma chemistry markers of liver dysfunction, in particular bilirubin and bile acids. These results indicate that gadoxetate-enhanced MRI provides a novel functional biomarker of inhibition of transporter-mediated hepatic uptake and clearance in the rat. Since gadoxetate is used clinically, the technology has the potential to provide a translatable biomarker of drug-induced perturbation of hepatic transporters that may also be useful in humans to explore deleterious functional alterations caused by transporter inhibition. Copyright © 2013 John Wiley & Sons, Ltd. PMID:23564602

Dietary Omega-3 Fatty Acid Deficiency and High Fructose intake in the Development of Metabolic Syndrome Brain, Metabolic Abnormalities, and Non-Alcoholic Fatty Liver Disease

PubMed Central

Simopoulos, Artemis P.

2013-01-01

Western diets are characterized by both dietary omega-3 fatty acid deficiency and increased fructose intake. The latter found in high amounts in added sugars such as sucrose and high fructose corn syrup (HFCS). Both a low intake of omega-3 fatty acids or a high fructose intake contribute to metabolic syndrome, liver steatosis or non-alcoholic fatty liver disease (NAFLD), promote brain insulin resistance, and increase the vulnerability to cognitive dysfunction. Insulin resistance is the core perturbation of metabolic syndrome. Multiple cognitive domains are affected by metabolic syndrome in adults and in obese adolescents, with volume losses in the hippocampus and frontal lobe, affecting executive function. Fish oil supplementation maintains proper insulin signaling in the brain, ameliorates NAFLD and decreases the risk to metabolic syndrome suggesting that adequate levels of omega-3 fatty acids in the diet can cope with the metabolic challenges imposed by high fructose intake in Western diets which is of major public health importance. This review presents the current status of the mechanisms involved in the development of the metabolic syndrome, brain insulin resistance, and NAFLD a most promising area of research in Nutrition for the prevention of these conditions, chronic diseases, and improvement of Public Health. PMID:23896654

Stomach position versus liver-to-thoracic volume ratio in left-sided congenital diaphragmatic hernia.

PubMed

Cordier, Anne-Gaël; Cannie, Mieke M; Guilbaud, Lucie; De Laveaucoupet, Jocelyne; Martinovic, Jéléna; Nowakowska, Dorota; Milejska-Lewandowska, Malgorzata; Rodó, Carlota; Viaris de Lesegno, Benjamin; Votino, Carmela; Senat, Marie-Victoire; Jani, Jacques C; Benachi, Alexandra

2015-01-01

To describe a new grading method for stomach position (SP) in fetuses with left-sided congenital diaphragmatic hernia (L-CDH) using ultrasound and to correlate SP to liver position and to liver-to-thoracic cavity volume ratio (LiTR) using magnetic resonance imaging. SP were graded at the level of the 4-chamber view as following: grade 1-to-4 for stomach not visualised, visualised anteriorly at the apex of the heart, stomach showing abdominal structures anteriorly and stomach with its larger part posterior to the level of the atrial-ventricular heart valves, respectively. The LiTR was calculated and correlated to SP using the Mann-Whitney U test. Seventy-four fetuses were included. Median LiTR for grade 1 SP was 0% and was not different from median LiTR for grade 2 SP (0%, p=NS). Median LiTR for grade 3 SP was 14.9% and was significantly higher than for grade 2 SP (p<0.001). Similarly, median LiTR for grade 4 SP was 20.7% and was significantly higher than for grade 3 SP (p<0.05). When SP was grade 1 or 2, liver was intra-abdominal in 21 (84%) out of 25 fetuses while it was always intrathoracic for SP 3 or 4. In L-CDH, SP as described represents a simple indirect measurement of intrathoracic position and quantification of liver.

Optimal future liver remnant in patients treated with extensive preoperative chemotherapy for colorectal liver metastases.

PubMed

Shindoh, Junichi; Tzeng, Ching-Wei D; Aloia, Thomas A; Curley, Steven A; Zimmitti, Giuseppe; Wei, Steven H; Huang, Steven Y; Mahvash, Armeen; Gupta, Sanjay; Wallace, Michael J; Vauthey, Jean-Nicolas

2013-08-01

Patients with colorectal liver metastases (CLM) are increasingly treated with preoperative chemotherapy. Chemotherapy associated liver injury is associated with postoperative hepatic insufficiency (PHI) and mortality. The adequate minimum future liver remnant (FLR) volume in patients treated with extensive chemotherapy remains unknown. All patients with standardized FLR > 20 %, who underwent extended right hepatectomy for CLM from 1993-2011, were divided into three cohorts by chemotherapy duration: no chemotherapy (NC, n = 30), short duration (SD, ≤12 weeks, n = 78), long duration (LD, >12 weeks, n = 86). PHI and mortality were compared by using uni-/multivariate analyses. Optimal FLR for LD chemotherapy was determined using a minimum p-value approach. A total of 194 patients met inclusion criteria. LD chemotherapy was significantly associated with PHI (NC + SD 3.7 vs. LD 16.3%, p = 0.006). Ninety-day mortality rates were 0 % in NC, 1.3 % in SD, and 2.3% in LD patients, respectively (p = 0.95). In patients with FLR > 30 %, PHI occurred in only two patients (both LD, 2/20, 10 %), but all patients with FLR > 30 % survived. The best cutoff of FLR for preventing PHI after chemotherapy >12 weeks was estimated as >30 %. Both LD chemotherapy (odds ratio [OR] 5.4, p = 0.004) and FLR ≤ 30 % (OR 6.3, p = 0.019) were independent predictors of PHI. Preoperative chemotherapy >12 weeks increases the risk of PHI after extended right hepatectomy. In patients treated with long-duration chemotherapy, FLR > 30 % reduces the rate of PHI and may provide enough functional reserve for clinical rescue if PHI develops.

The Hepatic Response to Thermal Injury: Is the Liver Important for Postburn Outcomes?

PubMed Central

Jeschke, Marc G

2009-01-01

Thermal injury produces a profound hypermetabolic and hypercatabolic stress response characterized by increased endogenous glucose production via gluconeogenesis and glycogenolysis, lipolysis, and proteolysis. The liver is the central body organ involved in these metabolic responses. It is suggested that the liver, with its metabolic, inflammatory, immune, and acute phase functions, plays a pivotal role in patient survival and recovery by modulating multiple pathways following thermal injury. Studies have evaluated the role and function of the liver during the postburn response and showed that liver integrity and function are essential for survival, and that hepatic acute phase proteins are strong predictors for postburn survival. This review discusses these studies and delineates the pivotal role of the liver in patients following severe thermal injury. PMID:19603107

Impact of Liver Indicators on Clinical Outcome in Patients Undergoing Transcatheter Aortic Valve Implantation.

PubMed

Wendt, Daniel; Kahlert, Philipp; Canbay, Ali; Knipp, Stephan; Thoenes, Martin; Cremer, Gordina; Al-Rashid, Fadi; Jánosi, Rolf-Alexander; El-Chilali, Karim; Kamler, Markus; El Gabry, Mohamed; Marx, Philipp; Dohle, Daniel Sebastian; Tsagakis, Konstantinos; Benedik, Jaroslav; Gerken, Guido; Rassaf, Tienush; Jakob, Heinz; Thielmann, Matthias

2017-10-01

Liver dysfunction increases death and morbidity after cardiac operations. There are currently no data evaluating liver function in patients undergoing transcatheter aortic valve replacement (TAVR). We aimed therefore to evaluate our TAVR results in regard to liver function. A total of 640 consecutive TAVR patients were evaluated. Of those, 11 patients presented with chronic liver disease before TAVR. The Model for End-Stage Liver Disease score was used to measure liver function in these patients. The primary study end point was 30-day mortality in patients presenting with liver dysfunction. Secondary study end point was liver enzymes after TAVR. The mean Model for End-Stage Liver Disease score in patients with chronic liver disease was 16.8 ± 6.2 (median, 18; range, 7 to 26). The 30-day mortality was 9.1% (57 of 629) in patients presenting without liver disease and 9.1% (1 of 11) in patients with liver disease (p = 1.00). Patients with chronic liver disease showed significantly higher preoperative levels of γ-glutamyl transpeptidase (p < 0.001). After TAVR, we observed a significant increase in alanine aminotransferase on postoperative day 3 compared with preoperative values (p < 0.001), accompanied by a decrease in albumin (p < 0.001). Liver cirrhosis per se is not considered as a contraindication for cardiac operations. In the present study, we did not observe a higher 30-day mortality rate in liver cirrhotic patients undergoing TAVR, suggesting TAVR as a feasible alternative with acceptable outcomes in patients with chronic liver disease. Moreover, the present study is the first to evaluate liver variables in patients undergoing TAVR. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Therapeutic effect comparison of hepatocyte-like cells and bone marrow mesenchymal stem cells in acute liver failure of rats.

PubMed

Li, Dongliang; Fan, Jingjing; He, Xiuhua; Zhang, Xia; Zhang, Zhiqiang; Zeng, Zhiyu; Ruan, Mei; Cai, Lirong

2015-01-01

To evaluate the therapeutic efficacy of rat bone marrow mesenchymal stem cells (BMSCs) induced into hepatocyte-like cells and of un-induced BMSCs in acute liver failure rats. BMSCs in highly homogenous passage 3 were cultured using the whole bone marrow adherent culture method. Hepatic-related characters were confirmed with morphology, RT-PCR analysis, glycogen staining and albumin (ALB) immunofluorescence assay. Carbon tetrachloride (CCl4) was injected intraperitoneally to establish an acute rat liver failure model. Hepatocyte-like cells or un-induced BMSCs were respectively injected into the models to examine rats' appearance, liver function assay and liver tissue pathology. Hepatocyte-like morphology, higher expression of cytokeratin 18 (CK18) mRNA and ALB protein, and glycogen accumulation were confirmed in the induced BMSCs. The transplanted DAPI-labeled BMSCs were localized in the liver tissue 3-14 days after transplantation. The levels of liver function indicators (AST, ALT, ALP, and TBIL) from transplanted rats were significant decreased and pathology was improved, indicating the recovery of liver function. However, the differences were statistically insignificant. Both hepatocyte-like cells and un-induced BMSCs had a similarly positively therapeutic efficacy on liver regeneration in rat liver failure model.

[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.

Automated geometric optimization for robotic HIFU treatment of liver tumors.

PubMed

Williamson, Tom; Everitt, Scott; Chauhan, Sunita

2018-05-01

High intensity focused ultrasound (HIFU) represents a non-invasive method for the destruction of cancerous tissue within the body. Heating of targeted tissue by focused ultrasound transducers results in the creation of ellipsoidal lesions at the target site, the locations of which can have a significant impact on treatment outcomes. Towards this end, this work describes a method for the optimization of lesion positions within arbitrary tumors, with specific anatomical constraints. A force-based optimization framework was extended to the case of arbitrary tumor position and constrained orientation. Analysis of the approximate reachable treatment volume for the specific case of treatment of liver tumors was performed based on four transducer configurations and constraint conditions derived. Evaluation was completed utilizing simplified spherical and ellipsoidal tumor models and randomly generated tumor volumes. The total volume treated, lesion overlap and healthy tissue ablated was evaluated. Two evaluation scenarios were defined and optimized treatment plans assessed. The optimization framework resulted in improvements of up to 10% in tumor volume treated, and reductions of up to 20% in healthy tissue ablated as compared to the standard lesion rastering approach. Generation of optimized plans proved feasible for both sub- and intercostally located tumors. This work describes an optimized method for the planning of lesion positions during HIFU treatment of liver tumors. The approach allows the determination of optimal lesion locations and orientations, and can be applied to arbitrary tumor shapes and sizes. Copyright © 2018 Elsevier Ltd. All rights reserved.

Paradoxical impact of the remnant pancreatic volume and infectious complications on the development of nonalcoholic fatty liver disease after pancreaticoduodenectomy.

PubMed

Sato, Rie; Kishiwada, Masashi; Kuriyama, Naohisa; Azumi, Yoshinori; Mizuno, Shugo; Usui, Masanobu; Sakurai, Hiroyuki; Tabata, Masami; Yamada, Tomomi; Isaji, Shuji

2014-08-01

The aim of the present study was to evaluate perioperative risk factors for development of nonalcoholic fatty liver disease (NAFLD) after pancreaticoduodenectomy (PD), paying special attention to remnant pancreatic volume (RPV) and postoperative infection. We reviewed the charts of 110 patients who had been followed more than 6 months after PD. These patients were classified into the two groups according to RPV measured by CT volumetry at one month: large-volume group (LVG) (10 ml or more, n = 75) and small-volume group (SVG) (less than 10 ml, n = 35). Nonalcoholic fatty liver disease developed in 44 (40.0%), being significantly higher in SVG than in LVG: 54.2% vs. 33.3% (P = 0.037). SVG was characterized as significantly higher incidence of pancreatic adenocarcinoma, while LVG was characterized as significantly higher incidences of soft pancreas, postoperative infection and pancreatic fistula. In LVG, the incidence of NAFLD was significantly higher in patients with suspicion of infection than in those without it: 45.2% vs. 18.1% (P = 0.014), while not different in SVG. By multivariate analysis, independent risk factor was determined as RPV and suspicion of infection in the whole patients, and in LVG it was suspicion of infection, while in SVG it was not identified. After PD, RPV and status of postoperative infection paradoxically influenced the development of NAFLD. © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Reproducible MRI Measurement of Adipose Tissue Volumes in Genetic and Dietary Rodent Obesity Models

PubMed Central

Johnson, David H.; Flask, Chris A.; Ernsberger, Paul R.; Wong, Wilbur C. K.; Wilson, David L.

2010-01-01

Purpose To develop ratio MRI [lipid/(lipid+water)] methods for assessing lipid depots and compare measurement variability to biological differences in lean controls (spontaneously hypertensive rats, SHRs), dietary obese (SHR-DO), and genetic/dietary obese (SHROBs) animals. Materials and Methods Images with and without CHESS water-suppression were processed using a semi-automatic method accounting for relaxometry, chemical shift, receive coil sensitivity, and partial volume. Results Partial volume correction improved results by 10–15%. Over six operators, volume variation was reduced to 1.9 ml from 30.6 ml for single-image-analysis with intensity inhomogeneity. For three acquisitions on the same animal, volume reproducibility was <1%. SHROBs had 6X visceral and 8X subcutaneous adipose tissue than SHRs. SHR-DOs had enlarged visceral depots (3X SHRs). SHROB had significantly more subcutaneous adipose tissue, indicating a strong genetic component to this fat depot. Liver ratios in SHR-DO and SHROB were higher than SHR, indicating elevated fat content. Among SHROBs, evidence suggested a phenotype SHROB* having elevated liver ratios and visceral adipose tissue volumes. Conclusion Effects of diet and genetics on obesity were significantly larger than variations due to image acquisition and analysis, indicating that these methods can be used to assess accumulation/depletion of lipid depots in animal models of obesity. PMID:18821617

SU-E-J-246: A Deformation-Field Map Based Liver 4D CBCT Reconstruction Method Using Gold Nanoparticles as Constraints

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

Harris, W; Zhang, Y; Ren, L

2014-06-01

Purpose: To investigate the feasibility of using nanoparticle markers to validate liver tumor motion together with a deformation field map-based four dimensional (4D) cone-beam computed tomography (CBCT) reconstruction method. Methods: A technique for lung 4D-CBCT reconstruction has been previously developed using a deformation field map (DFM)-based strategy. In this method, each phase of the 4D-CBCT is considered as a deformation of a prior CT volume. The DFM is solved by a motion modeling and free-form deformation (MM-FD) technique, using a data fidelity constraint and the deformation energy minimization. For liver imaging, there is low contrast of a liver tumor inmore » on-board projections. A validation of liver tumor motion using implanted gold nanoparticles, along with the MM-FD deformation technique is implemented to reconstruct onboard 4D CBCT liver radiotherapy images. These nanoparticles were placed around the liver tumor to reflect the tumor positions in both CT simulation and on-board image acquisition. When reconstructing each phase of the 4D-CBCT, the migrations of the gold nanoparticles act as a constraint to regularize the deformation field, along with the data fidelity and the energy minimization constraints. In this study, multiple tumor diameters and positions were simulated within the liver for on-board 4D-CBCT imaging. The on-board 4D-CBCT reconstructed by the proposed method was compared with the “ground truth” image. Results: The preliminary data, which uses reconstruction for lung radiotherapy suggests that the advanced reconstruction algorithm including the gold nanoparticle constraint will Resultin volume percentage differences (VPD) between lesions in reconstructed images by MM-FD and “ground truth” on-board images of 11.5% (± 9.4%) and a center of mass shift of 1.3 mm (± 1.3 mm) for liver radiotherapy. Conclusion: The advanced MM-FD technique enforcing the additional constraints from gold nanoparticles, results in improved accuracy for reconstructing on-board 4D-CBCT of liver tumor. Varian medical systems research grant.« less

Wnt/β-Catenin Signaling in Liver Development, Homeostasis, and Pathobiology

PubMed Central

Russell, Jacquelyn O.; Monga, Satdarshan P.

2018-01-01

The liver is an organ that performs a multitude of functions, and its health is pertinent and indispensable to survival. Thus, the cellular and molecular machinery driving hepatic functions is of utmost relevance. The Wnt signaling pathway is one such signaling cascade that enables hepatic homeostasis and contributes to unique hepatic attributes such as metabolic zonation and regeneration. The Wnt/β-catenin pathway plays a role in almost every facet of liver biology. Furthermore, its aberrant activation is also a hallmark of various hepatic pathologies. In addition to its signaling function, β-catenin also plays a role at adherens junctions. Wnt/β-catenin signaling also influences the function of many different cell types. Due to this myriad of functions, Wnt/β-catenin signaling is complex, context-dependent, and highly regulated. In this review, we discuss the Wnt/β-catenin signaling pathway, its role in cell-cell adhesion and liver function, and the cell type–specific roles of Wnt/β-catenin signaling as it relates to liver physiology and pathobiology. PMID:29125798

Association between liver function and metabolic syndrome in Chinese men and women

PubMed Central

Wang, Sen; Zhang, Jie; Zhu, Li; Song, Linlin; Meng, Zhaowei; Jia, Qiang; Li, Xue; Liu, Na; Hu, Tianpeng; Zhou, Pingping; Zhang, Qing; Liu, Li; Song, Kun; Jia, Qiyu

2017-01-01

Metabolic syndrome (MS) could be associated with liver function. Our study aimed to investigate the association between liver function and MS in a large cohort of Chinese men and women. We enrolled 32,768 ostensibly healthy participants. The associations between liver function and MS of both genders were analyzed separately after dividing total bilirubin (TBIL), gamma glutamyltransferase (GGT), alanine aminotransferase (ALT) into quartiles. Young males had significantly higher MS prevalence than females, yet after menopause, females had higher MS prevalence. We used TBIL, GGT and ALT quartiles as categorical variables in binary logistic regression models. Significantly decreased MS risks were demonstrated in TBIL quartiles 2 to 4 for males, and quartiles 3 to 4 for females. As to GGT and ALT, significantly increased MS risks were shown in high quartiles for both genders. Aging also resulted in significantly higher MS risks in both genders except for young females. This study displayed close associations between liver function and MS, which were influenced by gender and age. A high TBIL level had protective effect against MS, while high GGT and ALT levels were risk factors for MS. It is meaningful that liver function is used as clinical risk predictors for MS. PMID:28317840

Risk factors for deterioration of long-term liver function after radiofrequency ablation therapy

PubMed Central

Honda, Koichi; Seike, Masataka; Oribe, Junya; Endo, Mizuki; Arakawa, Mie; Syo, Hiroki; Iwao, Masao; Tokoro, Masanori; Nishimura, Junko; Mori, Tetsu; Yamashita, Tsutomu; Fukuchi, Satoshi; Muro, Toyokichi; Murakami, Kazunari

2016-01-01

AIM: To identify factors that influence long-term liver function following radiofrequency ablation (RFA) in patients with viral hepatitis-related hepatocellular carcinoma. METHODS: A total of 123 patients with hepatitis B virus- or hepatitis C virus-related hepatocellular car-cinoma (HCC) (n = 12 and n = 111, respectively) were enrolled. Cumulative rates of worsening Child-Pugh (CP) scores (defined as a 2-point increase) were examined. RESULTS: CP score worsening was confirmed in 22 patients over a mean follow-up period of 43.8 ± 26.3 mo. Multivariate analysis identified CP class, platelet count, and aspartate aminotransferase levels as signi-ficant predictors of a worsening CP score (P = 0.000, P = 0.011 and P = 0.024, respectively). In contrast, repeated RFA was not identified as a risk factor for liver function deterioration. CONCLUSION: Long-term liver function following RFA was dependent on liver functional reserve, the degree of fibrosis present, and the activity of the hepatitis condition for this cohort. Therefore, in order to maintain liver function for an extended period following RFA, suppression of viral hepatitis activity is important even after the treatment of HCC. PMID:27168872

Use of fibrinogen and thrombin sponge in pediatric split liver transplantation.

PubMed

Vicentine, Fernando Pompeu Piza; Gonzalez, Adriano Miziara; Beninni, Barbara Burza; Azevedo, Ramiro Anthero de; Linhares, Marcelo Moura; Goldenberg, Alberto; Lopes, Gaspar de Jesus; Martins, Jose Luiz; Salzedas, Alcides Augusto

2017-08-01

To analyze the use of this sponge in pediatric patients undergoing split-liver transplantation. Retrospective study, including 35 pediatric patients undergoing split-liver transplantation, divided into two groups according to the use of the sponge: 18 patients in Group A (no sponge) and 17 in Group B (with sponge). The characteristics of recipients and donors were similar. We observed greater number of reoperation due to bleeding in the wound area in Group A (10 patients - 55.5%) than in Group B (3 patients - 17.6%); p = 0.035. The median volume of red blood cells transfused in Group A was significantly higher (73.4 ± 102.38 mL/kg) than that in Group B (35.1 ± 41.67 mL/kg); p = 0.048. Regarding bile leak there was no statistical difference. The use of the human fibrinogen and thrombin sponge, required lower volume of red blood cell transfusion and presented lower reoperation rates due to bleeding in the wound area.

Management of Respiration-Induced Motion With 4-Dimensional Computed Tomography (4DCT) for Pancreas Irradiation

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

Tai, An, E-mail: atai@mcw.edu; Liang, Zhiwen; Radiation Oncology Center, Wuhan Union Hospital, Huazhong University of Science and Technology, Wuhan

2013-08-01

Purpose: The purposes of this study were to quantify respiration-induced organ motions for pancreatic cancer patients and to explore strategies to account for these motions. Methods and Materials: Both 3-dimensional computed tomography (3DCT) and 4-dimensional computed tomography (4DCT) scans were acquired sequentially for 15 pancreatic cancer patients, including 10 randomly selected patients and 5 patients selected from a subgroup of patients with large tumor respiratory motions. 3DCTs were fused with 2 sets of 4DCT data at the end of exhale phase (50%) and the end of inhale phase (0%). The target was delineated on the 50% and 0% phase CTmore » sets, and the organs at risk were drawn on the 3DCT. These contours were populated to the CT sets at other respiratory phases based on deformable image registration. Internal target volumes (ITV) were generated by tracing the target contours of all phases (ITV{sub 10}), 3 phases of 0%, 20% and 50% (ITV{sub 3}), and 2 phases of 0% and 50% (ITV{sub 2}). ITVs generated from phase images were compared using percentage of volume overlap, Dice coefficient, geometric centers, and average surface distance. Results: Volume variations of pancreas, kidneys, and liver as a function of respiratory phases were small (<5%) during respiration. For the 10 randomly selected patients, peak-to-peak amplitudes of liver, left kidney, right kidney, and the target along the superior-inferior (SI) direction were 7.9 ± 3.2 mm, 7.1 ± 3.1 mm, 5.7 ± 3.2 mm, and 5.9 ± 2.8 mm, respectively. The percentage of volume overlap and Dice coefficient were 92% ± 1% and 96% ± 1% between ITV{sub 10} and ITV{sub 2} and 96% ± 1% and 98% ± 1% between ITV{sub 10} and ITV{sub 3}, respectively. The percentage of volume overlap between ITV{sub 10} and ITV{sub 3} was 93.6 ± 1.1 for patients with tumor motion >8 mm. Conclusions: Appropriate motion management strategies are proposed for radiation treatment planning of pancreatic tumors based on magnitudes of tumor respiratory motions.« less

Assessment of Liver Function in Patients With Hepatocellular Carcinoma: A New Evidence-Based Approach—The ALBI Grade

PubMed Central

Johnson, Philip J.; Berhane, Sarah; Kagebayashi, Chiaki; Satomura, Shinji; Teng, Mabel; Reeves, Helen L.; O'Beirne, James; Fox, Richard; Skowronska, Anna; Palmer, Daniel; Yeo, Winnie; Mo, Frankie; Lai, Paul; Iñarrairaegui, Mercedes; Chan, Stephen L.; Sangro, Bruno; Miksad, Rebecca; Tada, Toshifumi; Kumada, Takashi; Toyoda, Hidenori

2015-01-01

Purpose Most patients with hepatocellular carcinoma (HCC) have associated chronic liver disease, the severity of which is currently assessed by the Child-Pugh (C-P) grade. In this international collaboration, we identify objective measures of liver function/dysfunction that independently influence survival in patients with HCC and then combine these into a model that could be compared with the conventional C-P grade. Patients and Methods We developed a simple model to assess liver function, based on 1,313 patients with HCC of all stages from Japan, that involved only serum bilirubin and albumin levels. We then tested the model using similar cohorts from other geographical regions (n = 5,097) and other clinical situations (patients undergoing resection [n = 525] or sorafenib treatment for advanced HCC [n = 1,132]). The specificity of the model for liver (dys)function was tested in patients with chronic liver disease but without HCC (n = 501). Results The model, the Albumin-Bilirubin (ALBI) grade, performed at least as well as the C-P grade in all geographic regions. The majority of patients with HCC had C-P grade A disease at presentation, and within this C-P grade, ALBI revealed two classes with clearly different prognoses. Its utility in patients with chronic liver disease alone supported the contention that the ALBI grade was indeed an index of liver (dys)function. Conclusion The ALBI grade offers a simple, evidence-based, objective, and discriminatory method of assessing liver function in HCC that has been extensively tested in an international setting. This new model eliminates the need for subjective variables such as ascites and encephalopathy, a requirement in the conventional C-P grade. PMID:25512453

Functional gadoxetate disodium-enhanced MRI in patients with primary sclerosing cholangitis (PSC).

PubMed

Hinrichs, Heiko; Hinrichs, Jan B; Gutberlet, Marcel; Lenzen, Henrike; Raatschen, Hans-Juergen; Wacker, Frank; Ringe, Kristina I

2016-04-01

To assess the value of variable flip angle-based T1 liver mapping on gadoxetate disodium-enhanced MRI in patients with primary sclerosing cholangitis (PSC) for evaluation of global and segmental liver function, and determine a possible correlation with disease severity. Sixty-one patients (19 female, 42 male; mean age 41 years) with PSC were included in this prospective study. T1 mapping was performed using a 3D-spoiled GRE sequence (flip angles 5°, 15°, 20°, 30°) before, 16 (HP1) and 132 min (HP2) after contrast injection. T1 values were measured and compared (Wilcoxon-Test) by placing ROIs in each liver segment. The mean reduction of T1 relaxation time at HP1 and HP2 was calculated and correlated with liver function tests (LFTs), MELD, Mayo Risk and Amsterdam Scores (Spearman correlation). Significant changes of T1 relaxation times between non-enhanced and gadoxetate disodium-enhanced MRI at HP1 and HP2 could be observed in all liver segments (p < 0.0001). A significant correlation of T1 reduction could be observed with LFTs, MELD and Mayo Risk Score (p < 0.05). T1 mapping of the liver using a variable flip angle-based sequence is a feasible technique to evaluate liver function on a global level, and may be extrapolated on a segmental level in patients with PSC. • T1 mapping enables evaluation of global liver function in PSC. • T1 relaxation time reduction correlates with the MELD and MayoRisk Score. • Extrapolated, T1 mapping may allow for segmental evaluation of liver function.

Safety of high volume lipid emulsion infusion: a first approximation of LD50 in rats.

PubMed

Hiller, David B; Di Gregorio, Guido; Kelly, Kemba; Ripper, Richard; Edelman, Lucas; Boumendjel, Redouane; Drasner, Kenneth; Weinberg, Guy L

2010-01-01

Lipid infusion reverses systemic local anesthetic toxicity. The acceptable upper limit for lipid administration is unknown and has direct bearing on clinical management. We hypothesize that high volumes of lipid could have undesirable effects and sought to identify the dose required to kill 50% of the animals (LD(50)) of large volume lipid administration. Intravenous lines and electrocardiogram electrodes were placed in anesthetized, male Sprague-Dawley rats. Twenty percent lipid emulsion (20, 40, 60, or 80 mL/kg) or saline (60 or 80 mL/kg), were administered over 30 mins; lipid dosing was assigned by the Dixon "up-and-down" method. Rats were recovered and observed for 48 hrs then euthanized for histologic analysis of major organs. Three additional rats were administered 60 mL/kg lipid emulsion and euthanized at 1, 4, and 24 hrs to identify progression of organ damage. The maximum likelihood estimate for LD(50) was 67.72 (SE, 10.69) mL/kg. Triglycerides were elevated immediately after infusion but returned to baseline by 48 hrs when laboratory abnormalities included elevated amylase, aspartate aminotransferase, and serum urea nitrogen for all lipid doses. Histologic diagnosis of myocardium, brain, pancreas, and kidneys was normal at all doses. Microscopic abnormalities in lung and liver were observed at 60 and 80 mL/kg; histopathology in the lung and liver was worse at 1 hr than at 4 and 24 hrs. The LD(50) of rapid, high volume lipid infusion is an order of magnitude greater than doses typically used for lipid rescue in humans and supports the safety of lipid infusion at currently recommended doses for toxin-induced cardiac arrest. Lung and liver histopathology was observed at the highest infused volumes.

Orchestrating liver development.

PubMed

Gordillo, Miriam; Evans, Todd; Gouon-Evans, Valerie

2015-06-15

The liver is a central regulator of metabolism, and liver failure thus constitutes a major health burden. Understanding how this complex organ develops during embryogenesis will yield insights into how liver regeneration can be promoted and how functional liver replacement tissue can be engineered. Recent studies of animal models have identified key signaling pathways and complex tissue interactions that progressively generate liver progenitor cells, differentiated lineages and functional tissues. In addition, progress in understanding how these cells interact, and how transcriptional and signaling programs precisely coordinate liver development, has begun to elucidate the molecular mechanisms underlying this complexity. Here, we review the lineage relationships, signaling pathways and transcriptional programs that orchestrate hepatogenesis. © 2015. Published by The Company of Biologists Ltd.

A scanning transmission electron microscopy approach to analyzing large volumes of tissue to detect nanoparticles.

PubMed

Kempen, Paul J; Thakor, Avnesh S; Zavaleta, Cristina; Gambhir, Sanjiv S; Sinclair, Robert

2013-10-01

The use of nanoparticles for the diagnosis and treatment of cancer requires the complete characterization of their toxicity, including accurately locating them within biological tissues. Owing to their size, traditional light microscopy techniques are unable to resolve them. Transmission electron microscopy provides the necessary spatial resolution to image individual nanoparticles in tissue, but is severely limited by the very small analysis volume, usually on the order of tens of cubic microns. In this work, we developed a scanning transmission electron microscopy (STEM) approach to analyze large volumes of tissue for the presence of polyethylene glycol-coated Raman-active-silica-gold-nanoparticles (PEG-R-Si-Au-NPs). This approach utilizes the simultaneous bright and dark field imaging capabilities of STEM along with careful control of the image contrast settings to readily identify PEG-R-Si-Au-NPs in mouse liver tissue without the need for additional time-consuming analytical characterization. We utilized this technique to analyze 243,000 mm³ of mouse liver tissue for the presence of PEG-R-Si-Au-NPs. Nanoparticles injected into the mice intravenously via the tail vein accumulated in the liver, whereas those injected intrarectally did not, indicating that they remain in the colon and do not pass through the colon wall into the systemic circulation.

A Scanning Transmission Electron Microscopy (STEM) Approach to Analyzing Large Volumes of Tissue to Detect Nanoparticles

PubMed Central

Kempen, Paul J.; Thakor, Avnesh S.; Zavaleta, Cristina; Gambhir, Sanjiv S.; Sinclair, Robert

2013-01-01

The use of nanoparticles for the diagnosis and treatment of cancer requires the complete characterization of their toxicity, including accurately locating them within biological tissues. Owing to their size, traditional light microscopy techniques are unable to resolve them. Transmission electron microscopy provides the necessary spatial resolution to image individual nanoparticles in tissue but is severely limited by the very small analysis volume, usually on the order of tens of cubic microns. In this work we developed a scanning transmission electron microscopy (STEM) approach to analyze large volumes of tissue for the presence of polyethylene glycol coated Raman-active-silica-gold-nanoparticles (PEG-R-Si-Au-NPs). This approach utilizes the simultaneous bright and dark field imaging capabilities of STEM along with careful control of the image contrast settings to readily identify PEG-R-Si-Au-NPs in mouse liver tissue without the need for additional time consuming analytical characterization. We utilized this technique to analyze 243,000 µm3 of mouse liver tissue for the presence of PEG-R-Si-Au-NPs. Nanoparticles injected into the mice intravenously via the tail-vein accumulated in the liver while those injected intrarectally did not, indicating that they remain in the colon and do not pass through the colon wall into the systemic circulation. PMID:23803218

Computed Tomography Perfusion Imaging for the Diagnosis of Hepatic Alveolar Echinococcosis

PubMed Central

Sade, Recep; Kantarci, Mecit; Genc, Berhan; Ogul, Hayri; Gundogdu, Betul; Yilmaz, Omer

2018-01-01

Objective: Alveolar echinococcosis (AE) is a rare life-threatening parasitic infection. Computed tomography perfusion (CTP) imaging has the potential to provide both quantitative and qualitative information about the tissue perfusion characteristics. The purpose of this study was the examination of the characteristic features and feasibility of CTP in AE liver lesions. Material and Methods: CTP scanning was performed in 25 patients who had a total of 35 lesions identified as AE of the liver. Blood flow (BF), blood volume (BV), portal venous perfusion (PVP), arterial liver perfusion (ALP), and hepatic perfusion indexes (HPI) were computed for background liver parenchyma and each AE lesion. Results: Significant differences were detected between perfusion values of the AE lesions and background liver tissue. The BV, BF, ALP, and PVP values for all components of the AE liver lesions were significantly lower than the normal liver parenchyma (p<0.01). Conclusions: We suggest that perfusion imaging can be used in AE of the liver. Thus, the quantitative knowledge of perfusion parameters are obtained via CT perfusion imaging. PMID:29531482

Molecular changes in hepatic metabolism and transport in cirrhosis and their functional importance

PubMed Central

Dietrich, Christoph G; Götze, Oliver; Geier, Andreas

2016-01-01

Liver cirrhosis is the common endpoint of many hepatic diseases and represents a relevant risk for liver failure and hepatocellular carcinoma. The progress of liver fibrosis and cirrhosis is accompanied by deteriorating liver function. This review summarizes the regulatory and functional changes in phase I and phase II metabolic enzymes as well as transport proteins and provides an overview regarding lipid and glucose metabolism in cirrhotic patients. Interestingly, phase I enzymes are generally downregulated transcriptionally, while phase II enzymes are mostly preserved transcriptionally but are reduced in their function. Transport proteins are regulated in a specific way that resembles the molecular changes observed in obstructive cholestasis. Lipid and glucose metabolism are characterized by insulin resistance and catabolism, leading to the disturbance of energy expenditure and wasting. Possible non-invasive tests, especially breath tests, for components of liver metabolism are discussed. The heterogeneity and complexity of changes in hepatic metabolism complicate the assessment of liver function in individual patients. Additionally, studies in humans are rare, and species differences preclude the transferability of data from rodents to humans. In clinical practice, some established global scores or criteria form the basis for the functional evaluation of patients with liver cirrhosis, but difficult treatment decisions such as selection for transplantation or resection require further research regarding the application of existing non-invasive tests and the development of more specific tests. PMID:26755861

Efficient and Controlled Generation of 2D and 3D Bile Duct Tissue from Human Pluripotent Stem Cell-Derived Spheroids.

PubMed

Tian, Lipeng; Deshmukh, Abhijeet; Ye, Zhaohui; Jang, Yoon-Young

2016-08-01

While in vitro liver tissue engineering has been increasingly studied during the last several years, presently engineered liver tissues lack the bile duct system. The lack of bile drainage not only hinders essential digestive functions of the liver, but also leads to accumulation of bile that is toxic to hepatocytes and known to cause liver cirrhosis. Clearly, generation of bile duct tissue is essential for engineering functional and healthy liver. Differentiation of human induced pluripotent stem cells (iPSCs) to bile duct tissue requires long and/or complex culture conditions, and has been inefficient so far. Towards generating a fully functional liver containing biliary system, we have developed defined and controlled conditions for efficient 2D and 3D bile duct epithelial tissue generation. A marker for multipotent liver progenitor in both adult human liver and ductal plate in human fetal liver, EpCAM, is highly expressed in hepatic spheroids generated from human iPSCs. The EpCAM high hepatic spheroids can, not only efficiently generate a monolayer of biliary epithelial cells (cholangiocytes), in a 2D differentiation condition, but also form functional ductal structures in a 3D condition. Importantly, this EpCAM high spheroid based biliary tissue generation is significantly faster than other existing methods and does not require cell sorting. In addition, we show that a knock-in CK7 reporter human iPSC line generated by CRISPR/Cas9 genome editing technology greatly facilitates the analysis of biliary differentiation. This new ductal differentiation method will provide a more efficient method of obtaining bile duct cells and tissues, which may facilitate engineering of complete and functional liver tissue in the future.

Non-Invasive Assessment of Liver Function

PubMed Central

Helmke, Steve; Colmenero, Jordi; Everson, Gregory T.

2015-01-01

Purpose of review It is our opinion that there is an unmet need in Hepatology for a minimally- or noninvasive test of liver function and physiology. Quantitative liver function tests (QLFTs) define the severity and prognosis of liver disease by measuring the clearance of substrates whose uptake or metabolism is dependent upon liver perfusion or hepatocyte function. Substrates with high affinity hepatic transporters exhibit high “first-pass” hepatic extraction and their clearance measures hepatic perfusion. In contrast, substrates metabolized by the liver have low first-pass extraction and their clearance measures specific drug metabolizing pathways. Recent Findings We highlight one QLFT, the dual cholate test, and introduce the concept of a disease severity index (DSI) linked to clinical outcome that quantifies the simultaneous processes of hepatocyte uptake, clearance from the systemic circulation, clearance from the portal circulation, and portal-systemic shunting. Summary It is our opinion that dual cholate is a relevant test for defining disease severity, monitoring the natural course of disease progression, and quantifying the response to therapy. PMID:25714706

Chronic liver injury in mice promotes impairment of skin barrier function via tumor necrosis factor-alpha.

PubMed

Yokoyama, Satoshi; Hiramoto, Keiichi; Koyama, Mayu; Ooi, Kazuya

2016-09-01

Alcohol is frequently used to induce chronic liver injury in laboratory animals. Alcohol causes oxidative stress in the liver and increases the expression of inflammatory mediators that cause hepatocellular damage. However, during chronic liver injury, it is unclear if/how these liver-derived factors affect distal tissues, such as the skin. The purpose of this study was to evaluate skin barrier function during chronic liver injury. Hairless mice were administered 5% or 10% ethanol for 8 weeks, and damages to the liver and skin were assessed using histological and protein-analysis methods, as well as by detecting inflammatory mediators in the plasma. After alcohol administration, the plasma concentration of the aspartate and alanine aminotransferases increased, while albumin levels decreased. In mice with alcohol-induced liver injury, transepidermal water loss was significantly increased, and skin hydration decreased concurrent with ceramide and type I collagen degradation. The plasma concentrations of [Formula: see text]/[Formula: see text] and tumor necrosis factor-alpha (TNF-α) were significantly increased in mice with induced liver injury. TNF receptor (TNFR) 2 expression was upregulated in the skin of alcohol-administered mice, while TNFR1 levels remained constant. Interestingly, the impairment of skin barrier function in mice administered with 10% ethanol was ameliorated by administering an anti-TNF-α antibody. We propose a novel mechanism whereby plasma TNF-α, via TNFR2 alone or with TNFR1, plays an important role in skin barrier function during chronic liver disease in these mouse models.

Adipokines in Liver Cirrhosis.

PubMed

Buechler, Christa; Haberl, Elisabeth M; Rein-Fischboeck, Lisa; Aslanidis, Charalampos

2017-06-29

Liver fibrosis can progress to cirrhosis, which is considered a serious disease. The Child-Pugh score and the model of end-stage liver disease score have been established to assess residual liver function in patients with liver cirrhosis. The development of portal hypertension contributes to ascites, variceal bleeding and further complications in these patients. A transjugular intrahepatic portosystemic shunt (TIPS) is used to lower portal pressure, which represents a major improvement in the treatment of patients. Adipokines are proteins released from adipose tissue and modulate hepatic fibrogenesis. These proteins affect various biological processes that are involved in liver function, including angiogenesis, vasodilation, inflammation and deposition of extracellular matrix proteins. The best studied adipokines are adiponectin and leptin. Adiponectin protects against hepatic inflammation and fibrogenesis, and leptin functions as a profibrogenic factor. These and other adipokines are supposed to modulate disease severity in patients with liver cirrhosis. Consequently, circulating levels of these proteins have been analyzed to identify associations with parameters of hepatic function, portal hypertension and its associated complications in patients with liver cirrhosis. This review article briefly addresses the role of adipokines in hepatitis and liver fibrosis. Here, studies having analyzed these proteins in systemic blood in cirrhotic patients are listed to identify adipokines that are comparably changed in the different cohorts of patients with liver cirrhosis. Some studies measured these proteins in systemic, hepatic and portal vein blood or after TIPS to specify the tissues contributing to circulating levels of these proteins and the effect of portal hypertension, respectively.

Adipokines in Liver Cirrhosis

PubMed Central

Haberl, Elisabeth M.; Rein-Fischboeck, Lisa; Aslanidis, Charalampos

2017-01-01

Liver fibrosis can progress to cirrhosis, which is considered a serious disease. The Child-Pugh score and the model of end-stage liver disease score have been established to assess residual liver function in patients with liver cirrhosis. The development of portal hypertension contributes to ascites, variceal bleeding and further complications in these patients. A transjugular intrahepatic portosystemic shunt (TIPS) is used to lower portal pressure, which represents a major improvement in the treatment of patients. Adipokines are proteins released from adipose tissue and modulate hepatic fibrogenesis. These proteins affect various biological processes that are involved in liver function, including angiogenesis, vasodilation, inflammation and deposition of extracellular matrix proteins. The best studied adipokines are adiponectin and leptin. Adiponectin protects against hepatic inflammation and fibrogenesis, and leptin functions as a profibrogenic factor. These and other adipokines are supposed to modulate disease severity in patients with liver cirrhosis. Consequently, circulating levels of these proteins have been analyzed to identify associations with parameters of hepatic function, portal hypertension and its associated complications in patients with liver cirrhosis. This review article briefly addresses the role of adipokines in hepatitis and liver fibrosis. Here, studies having analyzed these proteins in systemic blood in cirrhotic patients are listed to identify adipokines that are comparably changed in the different cohorts of patients with liver cirrhosis. Some studies measured these proteins in systemic, hepatic and portal vein blood or after TIPS to specify the tissues contributing to circulating levels of these proteins and the effect of portal hypertension, respectively. PMID:28661458

Sucrose ingestion after exhaustive exercise accelerates liver, but not muscle glycogen repletion compared with glucose ingestion in trained athletes.

PubMed

Fuchs, Cas J; Gonzalez, Javier T; Beelen, Milou; Cermak, Naomi M; Smith, Fiona E; Thelwall, Pete E; Taylor, Roy; Trenell, Michael I; Stevenson, Emma J; van Loon, Luc J C

2016-06-01

The purpose of this study was to assess the effects of sucrose vs. glucose ingestion on postexercise liver and muscle glycogen repletion. Fifteen well-trained male cyclists completed two test days. Each test day started with glycogen-depleting exercise, followed by 5 h of recovery, during which subjects ingested 1.5 g·kg(-1)·h(-1) sucrose or glucose. Blood was sampled frequently and (13)C magnetic resonance spectroscopy and imaging were employed 0, 120, and 300 min postexercise to determine liver and muscle glycogen concentrations and liver volume. Results were as follows: Postexercise muscle glycogen concentrations increased significantly from 85 ± 27 (SD) vs. 86 ± 35 mmol/l to 140 ± 23 vs. 136 ± 26 mmol/l following sucrose and glucose ingestion, respectively (no differences between treatments: P = 0.673). Postexercise liver glycogen concentrations increased significantly from 183 ± 47 vs. 167 ± 65 mmol/l to 280 ± 72 vs. 234 ± 81 mmol/l following sucrose and glucose ingestion, respectively (time × treatment, P = 0.051). Liver volume increased significantly over the 300-min period after sucrose ingestion only (time × treatment, P = 0.001). As a result, total liver glycogen content increased during postexercise recovery to a greater extent in the sucrose treatment (from 53.6 ± 16.2 to 86.8 ± 29.0 g) compared with the glucose treatment (49.3 ± 25.5 to 65.7 ± 27.1 g; time × treatment, P < 0.001), equating to a 3.4 g/h (95% confidence interval: 1.6-5.1 g/h) greater repletion rate with sucrose vs. glucose ingestion. In conclusion, sucrose ingestion (1.5 g·kg(-1)·h(-1)) further accelerates postexercise liver, but not muscle glycogen repletion compared with glucose ingestion in trained athletes. Copyright © 2016 the American Physiological Society.

Quantitative PET of liver functions

PubMed Central

Keiding, Susanne; Sørensen, Michael; Frisch, Kim; Gormsen, Lars C; Munk, Ole Lajord

2018-01-01

Improved understanding of liver physiology and pathophysiology is urgently needed to assist the choice of new and upcoming therapeutic modalities for patients with liver diseases. In this review, we focus on functional PET of the liver: 1) Dynamic PET with 2-deoxy-2-[18F]fluoro-D-galactose (18F-FDGal) provides quantitative images of the hepatic metabolic clearance K met (mL blood/min/mL liver tissue) of regional and whole-liver hepatic metabolic function. Standard-uptake-value (SUV) from a static liver 18F-FDGal PET/CT scan can replace K met and is currently used clinically. 2) Dynamic liver PET/CT in humans with 11C-palmitate and with the conjugated bile acid tracer [N-methyl-11C]cholylsarcosine (11C-CSar) can distinguish between individual intrahepatic transport steps in hepatic lipid metabolism and in hepatic transport of bile acid from blood to bile, respectively, showing diagnostic potential for individual patients. 3) Standard compartment analysis of dynamic PET data can lead to physiological inconsistencies, such as a unidirectional hepatic clearance of tracer from blood (K 1; mL blood/min/mL liver tissue) greater than the hepatic blood perfusion. We developed a new microvascular compartment model with more physiology, by including tracer uptake into the hepatocytes from the blood flowing through the sinusoids, backflux from hepatocytes into the sinusoidal blood, and re-uptake along the sinusoidal path. Dynamic PET data include information on liver physiology which cannot be extracted using a standard compartment model. In conclusion, SUV of non-invasive static PET with 18F-FDGal provides a clinically useful measurement of regional and whole-liver hepatic metabolic function. Secondly, assessment of individual intrahepatic transport steps is a notable feature of dynamic liver PET. PMID:29755841

Quantitative PET of liver functions.

PubMed

Keiding, Susanne; Sørensen, Michael; Frisch, Kim; Gormsen, Lars C; Munk, Ole Lajord

2018-01-01

Improved understanding of liver physiology and pathophysiology is urgently needed to assist the choice of new and upcoming therapeutic modalities for patients with liver diseases. In this review, we focus on functional PET of the liver: 1) Dynamic PET with 2-deoxy-2-[ 18 F]fluoro- D -galactose ( 18 F-FDGal) provides quantitative images of the hepatic metabolic clearance K met (mL blood/min/mL liver tissue) of regional and whole-liver hepatic metabolic function. Standard-uptake-value ( SUV ) from a static liver 18 F-FDGal PET/CT scan can replace K met and is currently used clinically. 2) Dynamic liver PET/CT in humans with 11 C-palmitate and with the conjugated bile acid tracer [ N -methyl- 11 C]cholylsarcosine ( 11 C-CSar) can distinguish between individual intrahepatic transport steps in hepatic lipid metabolism and in hepatic transport of bile acid from blood to bile, respectively, showing diagnostic potential for individual patients. 3) Standard compartment analysis of dynamic PET data can lead to physiological inconsistencies, such as a unidirectional hepatic clearance of tracer from blood ( K 1 ; mL blood/min/mL liver tissue) greater than the hepatic blood perfusion. We developed a new microvascular compartment model with more physiology, by including tracer uptake into the hepatocytes from the blood flowing through the sinusoids, backflux from hepatocytes into the sinusoidal blood, and re-uptake along the sinusoidal path. Dynamic PET data include information on liver physiology which cannot be extracted using a standard compartment model. In conclusion , SUV of non-invasive static PET with 18 F-FDGal provides a clinically useful measurement of regional and whole-liver hepatic metabolic function. Secondly, assessment of individual intrahepatic transport steps is a notable feature of dynamic liver PET.

Robotic intrafractional US guidance for liver SABR: System design, beam avoidance, and clinical imaging.

PubMed

Schlosser, Jeffrey; Gong, Ren Hui; Bruder, Ralf; Schweikard, Achim; Jang, Sungjune; Henrie, John; Kamaya, Aya; Koong, Albert; Chang, Daniel T; Hristov, Dimitre

2016-11-01

To present a system for robotic 4D ultrasound (US) imaging concurrent with radiotherapy beam delivery and estimate the proportion of liver stereotactic ablative body radiotherapy (SABR) cases in which robotic US image guidance can be deployed without interfering with clinically used VMAT beam configurations. The image guidance hardware comprises a 4D US machine, an optical tracking system for measuring US probe pose, and a custom-designed robot for acquiring hands-free US volumes. In software, a simulation environment incorporating the LINAC, couch, planning CT, and robotic US guidance hardware was developed. Placement of the robotic US hardware was guided by a target visibility map rendered on the CT surface by using the planning CT to simulate US propagation. The visibility map was validated in a prostate phantom and evaluated in patients by capturing live US from imaging positions suggested by the visibility map. In 20 liver SABR patients treated with VMAT, the simulation environment was used to virtually place the robotic hardware and US probe. Imaging targets were either planning target volumes (PTVs, range 5.9-679.5 ml) or gross tumor volumes (GTVs, range 0.9-343.4 ml). Presence or absence of mechanical interference with LINAC, couch, and patient body as well as interferences with treated beams was recorded. For PTV targets, robotic US guidance without mechanical interference was possible in 80% of the cases and guidance without beam interference was possible in 60% of the cases. For the smaller GTV targets, these proportions were 95% and 85%, respectively. GTV size (1/20), elongated shape (1/20), and depth (1/20) were the main factors limiting the availability of noninterfering imaging positions. The robotic US imaging system was deployed in two liver SABR patients during CT simulation with successful acquisition of 4D US sequences in different imaging positions. This study indicates that for VMAT liver SABR, robotic US imaging of a relevant internal target may be possible in 85% of the cases while using treatment plans currently deployed in the clinic. With beam replanning to account for the presence of robotic US guidance, intrafractional US may be an option for 95% of the liver SABR cases.

Entrapment of hepatocyte spheroids in a hollow fiber bioreactor as a potential bioartificial liver.

PubMed

Wu, F J; Peshwa, M V; Cerra, F B; Hu, W S

1995-01-01

A bioartificial liver (BAL) employing xenogeneic hepatocytes has been developed as a potential interim support for patients in hepatic failure. For application in human therapy, the BAL requires a substantial increase in liver-specific functions. Cultivation of hepatocytes as spheroids leads to enhanced liver specific functions. We explored the possibility of entrapping spheroids into the BAL in order to improve device performance. Rat hepatocyte spheroids were entrapped in collagen gel within the lumen fibers of the BAL. The morphology and ultrastructure of collagen-entrapped spheroids resembled those of suspended spheroids formed on petri dishes. Albumin synthesis and P-450 enzyme activity were measured as markers of liver specific functions of spheroids entrapped in the BAL. At least a 4-fold improvement in these functions was observed compared to BAL devices entrapped with dispersed hepatocytes in collagen gels.

Characterization of genetically engineered mouse hepatoma cells with inducible liver functions by overexpression of liver-enriched transcription factors.

PubMed

Yamamoto, Hideaki; Tonello, Jane Marie; Sambuichi, Takanori; Kawabe, Yoshinori; Ito, Akira; Kamihira, Masamichi

2018-01-01

New cell sources for the research and therapy of organ failure could significantly alleviate the shortage of donor livers that are available to patients who suffer from liver disease. Liver carcinoma derived cells, or hepatoma cells, are the ideal cells for developing bioartificial liver systems. Such cancerous liver cells are easy to prepare in large quantities and can be maintained over long periods under standard culture conditions, unlike primary hepatocytes. However, hepatoma cells possess only a fraction of the functions of primary hepatocytes. In a previous study, by transducing cells with liver-enriched transcription factors that could be inducibly overexpressed-hepatocyte nuclear factor (HNF)1α, HNF1β, HNF3β [FOXA2], HNF4α, HNF6, CCAAT/enhancer binding protein (C/EBP)α, C/EBPβ and C/EBPγ-we created mouse hepatoma cells with high liver-specific gene expression called the Hepa/8F5 cell line. In the present study, we performed functional and genetic analyses to characterize the Hepa/8F5 cell line. Further, in three-dimensional cultures, the function of these cells improved significantly compared to parental cells. Ultimately, these cells might become a new resource that can be used in basic and applied hepatic research. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Characterization of primary human hepatocyte spheroids as a model system for drug-induced liver injury, liver function and disease.

PubMed

Bell, Catherine C; Hendriks, Delilah F G; Moro, Sabrina M L; Ellis, Ewa; Walsh, Joanne; Renblom, Anna; Fredriksson Puigvert, Lisa; Dankers, Anita C A; Jacobs, Frank; Snoeys, Jan; Sison-Young, Rowena L; Jenkins, Rosalind E; Nordling, Åsa; Mkrtchian, Souren; Park, B Kevin; Kitteringham, Neil R; Goldring, Christopher E P; Lauschke, Volker M; Ingelman-Sundberg, Magnus

2016-05-04

Liver biology and function, drug-induced liver injury (DILI) and liver diseases are difficult to study using current in vitro models such as primary human hepatocyte (PHH) monolayer cultures, as their rapid de-differentiation restricts their usefulness substantially. Thus, we have developed and extensively characterized an easily scalable 3D PHH spheroid system in chemically-defined, serum-free conditions. Using whole proteome analyses, we found that PHH spheroids cultured this way were similar to the liver in vivo and even retained their inter-individual variability. Furthermore, PHH spheroids remained phenotypically stable and retained morphology, viability, and hepatocyte-specific functions for culture periods of at least 5 weeks. We show that under chronic exposure, the sensitivity of the hepatocytes drastically increased and toxicity of a set of hepatotoxins was detected at clinically relevant concentrations. An interesting example was the chronic toxicity of fialuridine for which hepatotoxicity was mimicked after repeated-dosing in the PHH spheroid model, not possible to detect using previous in vitro systems. Additionally, we provide proof-of-principle that PHH spheroids can reflect liver pathologies such as cholestasis, steatosis and viral hepatitis. Combined, our results demonstrate that the PHH spheroid system presented here constitutes a versatile and promising in vitro system to study liver function, liver diseases, drug targets and long-term DILI.

Characterization of primary human hepatocyte spheroids as a model system for drug-induced liver injury, liver function and disease

PubMed Central

Bell, Catherine C.; Hendriks, Delilah F. G.; Moro, Sabrina M. L.; Ellis, Ewa; Walsh, Joanne; Renblom, Anna; Fredriksson Puigvert, Lisa; Dankers, Anita C. A.; Jacobs, Frank; Snoeys, Jan; Sison-Young, Rowena L.; Jenkins, Rosalind E.; Nordling, Åsa; Mkrtchian, Souren; Park, B. Kevin; Kitteringham, Neil R.; Goldring, Christopher E. P.; Lauschke, Volker M.; Ingelman-Sundberg, Magnus

2016-01-01

Liver biology and function, drug-induced liver injury (DILI) and liver diseases are difficult to study using current in vitro models such as primary human hepatocyte (PHH) monolayer cultures, as their rapid de-differentiation restricts their usefulness substantially. Thus, we have developed and extensively characterized an easily scalable 3D PHH spheroid system in chemically-defined, serum-free conditions. Using whole proteome analyses, we found that PHH spheroids cultured this way were similar to the liver in vivo and even retained their inter-individual variability. Furthermore, PHH spheroids remained phenotypically stable and retained morphology, viability, and hepatocyte-specific functions for culture periods of at least 5 weeks. We show that under chronic exposure, the sensitivity of the hepatocytes drastically increased and toxicity of a set of hepatotoxins was detected at clinically relevant concentrations. An interesting example was the chronic toxicity of fialuridine for which hepatotoxicity was mimicked after repeated-dosing in the PHH spheroid model, not possible to detect using previous in vitro systems. Additionally, we provide proof-of-principle that PHH spheroids can reflect liver pathologies such as cholestasis, steatosis and viral hepatitis. Combined, our results demonstrate that the PHH spheroid system presented here constitutes a versatile and promising in vitro system to study liver function, liver diseases, drug targets and long-term DILI. PMID:27143246

Modeling liver physiology: combining fractals, imaging and animation.

PubMed

Lin, Debbie W; Johnson, Scott; Hunt, C Anthony

2004-01-01

Physiological modeling of vascular and microvascular networks in several key human organ systems is critical for a deeper understanding of pharmacology and the effect of pharmacotherapies on disease. Like the lung and the kidney, the morphology of its vascular and microvascular system plays a major role in its functional capability. To understand liver function in absorption and metabolism of food and drugs, one must examine the morphology and physiology at both higher and lower level liver function. We have developed validated virtualized dynamic three dimensional (3D) models of liver secondary units and primary units by combining a number of different methods: three-dimensional rendering, fractals, and animation. We have simulated particle dynamics in the liver secondary unit. The resulting models are suitable for use in helping researchers easily visualize and gain intuition on results of in silico liver experiments.

Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice

PubMed Central

Avraham, Y; Grigoriadis, NC; Poutahidis, T; Vorobiev, L; Magen, I; Ilan, Y; Mechoulam, R; Berry, EM

2011-01-01

BACKGROUND AND PURPOSE Hepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor 5-HT1A, on brain and liver functions in a model of hepatic encephalopathy associated with fulminant hepatic failure induced in mice by thioacetamide. EXPERIMENTAL APPROACH Female Sabra mice were injected with either saline or thioacetamide and were treated with either vehicle or cannabidiol. Neurological and motor functions were evaluated 2 and 3 days, respectively, after induction of hepatic failure, after which brains and livers were removed for histopathological analysis and blood was drawn for analysis of plasma liver enzymes. In a separate group of animals, cognitive function was tested after 8 days and brain 5-HT levels were measured 12 days after induction of hepatic failure. KEY RESULTS Neurological and cognitive functions were severely impaired in thioacetamide-treated mice and were restored by cannabidiol. Similarly, decreased motor activity in thioacetamide-treated mice was partially restored by cannabidiol. Increased plasma levels of ammonia, bilirubin and liver enzymes, as well as enhanced 5-HT levels in thioacetamide-treated mice were normalized following cannabidiol administration. Likewise, astrogliosis in the brains of thioacetamide-treated mice was moderated after cannabidiol treatment. CONCLUSIONS AND IMPLICATIONS Cannabidiol restores liver function, normalizes 5-HT levels and improves brain pathology in accordance with normalization of brain function. Therefore, the effects of cannabidiol may result from a combination of its actions in the liver and brain. PMID:21182490

Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice.

PubMed

Avraham, Y; Grigoriadis, Nc; Poutahidis, T; Vorobiev, L; Magen, I; Ilan, Y; Mechoulam, R; Berry, Em

2011-04-01

Hepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor 5-HT(1A) , on brain and liver functions in a model of hepatic encephalopathy associated with fulminant hepatic failure induced in mice by thioacetamide. Female Sabra mice were injected with either saline or thioacetamide and were treated with either vehicle or cannabidiol. Neurological and motor functions were evaluated 2 and 3 days, respectively, after induction of hepatic failure, after which brains and livers were removed for histopathological analysis and blood was drawn for analysis of plasma liver enzymes. In a separate group of animals, cognitive function was tested after 8 days and brain 5-HT levels were measured 12 days after induction of hepatic failure. Neurological and cognitive functions were severely impaired in thioacetamide-treated mice and were restored by cannabidiol. Similarly, decreased motor activity in thioacetamide-treated mice was partially restored by cannabidiol. Increased plasma levels of ammonia, bilirubin and liver enzymes, as well as enhanced 5-HT levels in thioacetamide-treated mice were normalized following cannabidiol administration. Likewise, astrogliosis in the brains of thioacetamide-treated mice was moderated after cannabidiol treatment. Cannabidiol restores liver function, normalizes 5-HT levels and improves brain pathology in accordance with normalization of brain function. Therefore, the effects of cannabidiol may result from a combination of its actions in the liver and brain. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Moderate doses of commercial preparations of Ginkgo biloba do not alter markers of liver function but moderate alcohol intake does: A new approach to identify and quantify biomarkers of 'adverse effects' of dietary supplements.

PubMed

Lieberman, Harris R; Kellogg, Mark D; Fulgoni, Victor L; Agarwal, Sanjiv

2017-03-01

It is difficult to determine if certain dietary supplements are safe for human consumption. Extracts of leaves of Ginkgo biloba trees are dietary supplements used for various purported therapeutic benefits. However, recent studies reported they increased risk of liver cancer in rodents. Therefore, this study assessed the association between ginkgo consumption and liver function using NHANES 2001-2012 data (N = 29,684). Since alcohol is known to adversely affect liver function, association of its consumption with liver function was also assessed. Alcohol and ginkgo extract intake of adult consumers and clinical markers of liver function (alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, lactate dehydrogenase, bilirubin) were examined. Moderate consumers of alcohol (0.80 ± 0.02 drinks/day) had higher levels of aspartate aminotransferase and gamma glutamyl transferase than non-consumers (P < 0.001). There was no difference (P > 0.01) in levels of markers of liver function in 616 ginkgo consumers (65.1 ± 4.4 mg/day intake) compared to non-consumers. While moderate alcohol consumption was associated with changes in markers of liver function, ginkgo intake as typically consumed by U.S. adults was not associated with these markers. Biomarkers measured by NHANES may be useful to examine potential adverse effects of dietary supplements for which insufficient human adverse event and toxicity data are available. Not applicable, as this is secondary analysis of publicly released observational data (NHANES 2001-2012). Published by Elsevier Inc.

Automatic liver segmentation on Computed Tomography using random walkers for treatment planning

PubMed Central

Moghbel, Mehrdad; Mashohor, Syamsiah; Mahmud, Rozi; Saripan, M. Iqbal Bin

2016-01-01

Segmentation of the liver from Computed Tomography (CT) volumes plays an important role during the choice of treatment strategies for liver diseases. Despite lots of attention, liver segmentation remains a challenging task due to the lack of visible edges on most boundaries of the liver coupled with high variability of both intensity patterns and anatomical appearances with all these difficulties becoming more prominent in pathological livers. To achieve a more accurate segmentation, a random walker based framework is proposed that can segment contrast-enhanced livers CT images with great accuracy and speed. Based on the location of the right lung lobe, the liver dome is automatically detected thus eliminating the need for manual initialization. The computational requirements are further minimized utilizing rib-caged area segmentation, the liver is then extracted by utilizing random walker method. The proposed method was able to achieve one of the highest accuracies reported in the literature against a mixed healthy and pathological liver dataset compared to other segmentation methods with an overlap error of 4.47 % and dice similarity coefficient of 0.94 while it showed exceptional accuracy on segmenting the pathological livers with an overlap error of 5.95 % and dice similarity coefficient of 0.91. PMID:28096782

The functional interrelationship between gap junctions and fenestrae in endothelial cells of the liver organoid.

PubMed

Saito, Masaya; Matsuura, Tomokazu; Nagatsuma, Keisuke; Tanaka, Ken; Maehashi, Haruka; Shimizu, Keiko; Hataba, Yoshiaki; Kato, Fumitaka; Kashimori, Isao; Tajiri, Hisao; Braet, Filip

2007-06-01

Functional intact liver organoid can be reconstructed in a radial-flow bioreactor when human hepatocellular carcinoma (FLC-5), mouse immortalized sinusoidal endothelial M1 (SEC) and A7 (HSC) hepatic stellate cell lines are cocultured. The structural and functional characteristics of the reconstructed organoid closely resemble the in vivo liver situation. Previous liver organoid studies indicated that cell-to-cell communications might be an important factor for the functional and structural integrity of the reconstructed organoid, including the expression of fenestrae. Therefore, we examined the possible relationship between functional intact gap junctional intercellular communication (GJIC) and fenestrae dynamics in M1-SEC cells. The fine morphology of liver organoid was studied in the presence of (1) irsogladine maleate (IM), (2) oleamide and (3) oleamide followed by IM treatment. Fine ultrastructural changes were studied by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) and compared with control liver organoid data. TEM revealed that oleamide affected the integrity of cell-to-cell contacts predominantly in FLC-5 hepatocytes. SEM observation showed the presence of fenestrae on M1-SEC cells; however, oleamide inhibited fenestrae expression on the surface of endothelial cells. Interestingly, fenestrae reappeared when IM was added after initial oleamide exposure. GJIC mediates the number of fenestrae in endothelial cells of the liver organoid.

Long-term culture of human liver tissue with advanced hepatic functions.

PubMed

Ng, Soon Seng; Xiong, Anming; Nguyen, Khanh; Masek, Marilyn; No, Da Yoon; Elazar, Menashe; Shteyer, Eyal; Winters, Mark A; Voedisch, Amy; Shaw, Kate; Rashid, Sheikh Tamir; Frank, Curtis W; Cho, Nam Joon; Glenn, Jeffrey S

2017-06-02

A major challenge for studying authentic liver cell function and cell replacement therapies is that primary human hepatocytes rapidly lose their advanced function in conventional, 2-dimensional culture platforms. Here, we describe the fabrication of 3-dimensional hexagonally arrayed lobular human liver tissues inspired by the liver's natural architecture. The engineered liver tissues exhibit key features of advanced differentiation, such as human-specific cytochrome P450-mediated drug metabolism and the ability to support efficient infection with patient-derived inoculums of hepatitis C virus. The tissues permit the assessment of antiviral agents and maintain their advanced functions for over 5 months in culture. This extended functionality enabled the prediction of a fatal human-specific hepatotoxicity caused by fialuridine (FIAU), which had escaped detection by preclinical models and short-term clinical studies. The results obtained with the engineered human liver tissue in this study provide proof-of-concept determination of human-specific drug metabolism, demonstrate the ability to support infection with human hepatitis virus derived from an infected patient and subsequent antiviral drug testing against said infection, and facilitate detection of human-specific drug hepatotoxicity associated with late-onset liver failure. Looking forward, the scalability and biocompatibility of the scaffold are also ideal for future cell replacement therapeutic strategies.

Morphometric investigations on the portal tracts of the liver, the differentiation of variable progression in chronic persistent hepatitis.

PubMed

Volmer, J; Lüders, C J

1981-01-01

Morphometric investigations were carried out on the portal tracts of the liver in different forms of chronic hepatitis. The investigation groups each contained 25 liver biopsies, which were subdivided into cases with normal liver, a subsiding acute virus hepatitis, three different forms of chronic persistent hepatitis (CPH) and chronic aggressive hepatitis type IIa (CAH IIa). Determinations of the volume and surface of the portal tracts and their components enabled three forms of COH (type Ia, Ib, Ic) to be characterised. Preliminary clinical and semiquantitative histological investigations were correlated with a significant difference in the histological characteristics and prognosis. HBsAg-positive and HBsAg-negative cases showed no significant morphologically detectable differences in all grups investigated. Morphometry is suitable for investigation of pathological changes in liver tissue, especially the portal tracts.

FXR and liver carcinogenesis

PubMed Central

Huang, Xiong-fei; Zhao, Wei-yu; Huang, Wen-dong

2015-01-01

Farnesoid X receptor (FXR) is a member of the nuclear receptor family and a ligand-modulated transcription factor. In the liver, FXR has been considered a multi-functional cell protector and a tumor suppressor. FXR can suppress liver carcinogenesis via different mechanisms: 1) FXR maintains the normal liver metabolism of bile acids, glucose and lipids; 2) FXR promotes liver regeneration and repair after injury; 3) FXR protects liver cells from death and enhances cell survival; 4) FXR suppresses hepatic inflammation, thereby preventing inflammatory damage; and 5) FXR can directly increase the expression of some tumor-suppressor genes and repress the transcription of several oncogenes. However, inflammation and epigenetic silencing are known to decrease FXR expression during tumorigenesis. The reactivation of FXR function in the liver may be a potential therapeutic approach for patients with liver cancer. PMID:25500874

Inhibition of Experimental Liver Cirrhosis in Mice by Telomerase Gene Delivery

NASA Astrophysics Data System (ADS)

Rudolph, Karl Lenhard; Chang, Sandy; Millard, Melissa; Schreiber-Agus, Nicole; DePinho, Ronald A.

2000-02-01

Accelerated telomere loss has been proposed to be a factor leading to end-stage organ failure in chronic diseases of high cellular turnover such as liver cirrhosis. To test this hypothesis directly, telomerase-deficient mice, null for the essential telomerase RNA (mTR) gene, were subjected to genetic, surgical, and chemical ablation of the liver. Telomere dysfunction was associated with defects in liver regeneration and accelerated the development of liver cirrhosis in response to chronic liver injury. Adenoviral delivery of mTR into the livers of mTR-/- mice with short dysfunctional telomeres restored telomerase activity and telomere function, alleviated cirrhotic pathology, and improved liver function. These studies indicate that telomere dysfunction contributes to chronic diseases of continual cellular loss-replacement and encourage the evaluation of ``telomerase therapy'' for such diseases.

Augmenter of Liver Regeneration (alr) Promotes Liver Outgrowth during Zebrafish Hepatogenesis

PubMed Central

Li, Yan; Farooq, Muhammad; Sheng, Donglai; Chandramouli, Chanchal; Lan, Tian; Mahajan, Nilesh K.; Kini, R. Manjunatha; Hong, Yunhan; Lisowsky, Thomas; Ge, Ruowen

2012-01-01

Augmenter of Liver Regeneration (ALR) is a sulfhydryl oxidase carrying out fundamental functions facilitating protein disulfide bond formation. In mammals, it also functions as a hepatotrophic growth factor that specifically stimulates hepatocyte proliferation and promotes liver regeneration after liver damage or partial hepatectomy. Whether ALR also plays a role during vertebrate hepatogenesis is unknown. In this work, we investigated the function of alr in liver organogenesis in zebrafish model. We showed that alr is expressed in liver throughout hepatogenesis. Knockdown of alr through morpholino antisense oligonucleotide (MO) leads to suppression of liver outgrowth while overexpression of alr promotes liver growth. The small-liver phenotype in alr morphants results from a reduction of hepatocyte proliferation without affecting apoptosis. When expressed in cultured cells, zebrafish Alr exists as dimer and is localized in mitochondria as well as cytosol but not in nucleus or secreted outside of the cell. Similar to mammalian ALR, zebrafish Alr is a flavin-linked sulfhydryl oxidase and mutation of the conserved cysteine in the CxxC motif abolishes its enzymatic activity. Interestingly, overexpression of either wild type Alr or enzyme-inactive AlrC131S mutant promoted liver growth and rescued the liver growth defect of alr morphants. Nevertheless, alr C131S is less efficacious in both functions. Meantime, high doses of alr MOs lead to widespread developmental defects and early embryonic death in an alr sequence-dependent manner. These results suggest that alr promotes zebrafish liver outgrowth using mechanisms that are dependent as well as independent of its sulfhydryl oxidase activity. This is the first demonstration of a developmental role of alr in vertebrate. It exemplifies that a low-level sulfhydryl oxidase activity of Alr is essential for embryonic development and cellular survival. The dose-dependent and partial suppression of alr expression through MO-mediated knockdown allows the identification of its late developmental role in vertebrate liver organogenesis. PMID:22292055

Well Preserved Renal Function in Children With Untreated Chronic Liver Disease.

PubMed

Berg, Ulla B; Németh, Antal

2018-04-01

On the basis of studies with hepatorenal syndrome, it is widely regarded that renal function is impacted in chronic liver disease (CLD). Therefore, we investigated renal function in children with CLD. In a retrospective study of 277 children with CLD, renal function was investigated as glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), measured as clearance of inulin and para-amino hippuric acid or clearance of iohexol. The data were analyzed with regard to different subgroups of liver disease and to the grade of damage. Hyperfiltration (>+2 SD of controls) was found in the subgroups of progressive familial intrahepatic cholestasis (44%), glycogenosis (75%), and acute fulminant liver failure (60%). Patients with biliary atresia, most other patients with metabolic disease and intrahepatic cholestasis, and those with vascular anomalies and cryptogenic cirrhosis had normal renal function. Decreased renal function was found in patients with Alagille's syndrome (64% < -2 SD). Increased GFR and ERPF was found in patients with elevated transaminases, low prothrombin level, high bile acid concentration, and high aspartate-aminotransferase-to-platelet ratio. Most children with CLD had surprisingly well preserved renal function and certain groups had even hyperfiltration. The finding that children with decompensated liver disease and ongoing liver failure had stable kidney function suggests that no prognostic markers of threatening hepatorenal syndrome were at hand. Moreover, estimation of GFR based on serum creatinine fails to reveal hyperfiltration.

Improvement of liver injury and survival by JNK2 and iNOS deficiency in liver transplants from cardiac death mice.

PubMed

Liu, Qinlong; Rehman, Hasibur; Krishnasamy, Yasodha; Schnellmann, Rick G; Lemasters, John J; Zhong, Zhi

2015-07-01

Inclusion of liver grafts from cardiac death donors (CDD) would increase the availability of donor livers but is hampered by a higher risk of primary non-function. Here, we seek to determine mechanisms that contribute to primary non-function of liver grafts from CDD with the goal to develop strategies for improved function and outcome, focusing on c-Jun-N-terminal kinase (JNK) activation and mitochondrial depolarization, two known mediators of graft failure. Livers explanted from wild-type, inducible nitric oxide synthase knockout (iNOS(-/-)), JNK1(-/-) or JNK2(-/-) mice after 45-min aorta clamping were implanted into wild-type recipients. Mitochondrial depolarization was detected by intravital confocal microscopy in living recipients. After transplantation of wild-type CDD livers, graft iNOS expression and 3-nitrotyrosine adducts increased, but hepatic endothelial NOS expression was unchanged. Graft injury and dysfunction were substantially higher in CDD grafts than in non-CDD grafts. iNOS deficiency and inhibition attenuated injury and improved function and survival of CDD grafts. JNK1/2 and apoptosis signal-regulating kinase-1 activation increased markedly in wild-type CDD grafts, which was blunted by iNOS deficiency. JNK inhibition and JNK2 deficiency, but not JNK1 deficiency, decreased injury and improved function and survival of CDD grafts. Mitochondrial depolarization and binding of phospho-JNK2 to Sab, a mitochondrial protein linked to the mitochondrial permeability transition, were higher in CDD than in non-CDD grafts. iNOS deficiency, JNK inhibition and JNK2 deficiency all decreased mitochondrial depolarization and blunted ATP depletion in CDD grafts. JNK inhibition and deficiency did not decrease 3-nitrotyrosine adducts in CDD grafts. The iNOS-JNK2-Sab pathway promotes CDD graft failure via increased mitochondrial depolarization, and is an attractive target to improve liver function and survival in CDD liver transplantation recipients. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Extended normothermic extracorporeal perfusion of isolated human liver after warm ischaemia: a preliminary report.

PubMed

Bellomo, Rinaldo; Marino, Bruno; Starkey, Graeme; Fink, Michael; Wang, Bao Zhong; Eastwood, Glenn M; Peck, Leah; Young, Helen; Houston, Shane; Skene, Alison; Opdam, Helen; Jones, Robert

2014-09-01

Donation after circulatory death (DCD) livers are at markedly increased risk of primary graft dysfunction and biliary tract ischaemia. Normothermic extracorporeal liver perfusion (NELP) may increase the ability to transplant DCD livers and may allow their use for artificial extracorporeal liver support of patients with fulminant liver failure. We conducted two proof-of-concept experiments using human livers after DCD to assess the feasibility and functional efficacy of NELP over an extended period. We applied extracorporeal membrane oxygenation, parenteral nutrition, separate hepatic artery and portal vein perfusion and physiological perfusion pressures to two livers obtained after DCD. We achieved NELP and evidence of liver function (bile production, paracetamol removal and maintenance of normal lactate levels) in both livers; one for 24 hours and the other for 43 hours. Histological examination showed areas of patchy ischaemia but preserved biliary ducts and canaliculi. Our experiments justify further investigations of the feasibility and efficacy of extended DCD liver preservation by ex-vivo perfusion.

Circulating lipocalin 2 is neither related to liver steatosis in patients with non-alcoholic fatty liver disease nor to residual liver function in cirrhosis.

PubMed

Meier, Elisabeth M; Pohl, Rebekka; Rein-Fischboeck, Lisa; Schacherer, Doris; Eisinger, Kristina; Wiest, Reiner; Krautbauer, Sabrina; Buechler, Christa

2016-09-01

Lipocalin 2 (LCN2) is induced in the injured liver and associated with inflammation. Aim of the present study was to evaluate whether serum LCN2 is a non-invasive marker to assess hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD) or residual liver function in patients with liver cirrhosis. Therefore, LCN2 was measured by ELISA in serum of 32 randomly selected patients without fatty liver (controls), 24 patients with ultrasound diagnosed NAFLD and 42 patients with liver cirrhosis mainly due to alcohol. Systemic LCN2 was comparable in patients with liver steatosis, those with liver cirrhosis and controls. LCN2 negatively correlated with bilirubin in both cohorts. In cirrhosis, LCN2 was not associated with more advanced liver injury defined by the CHILD-PUGH score and model for end-stage liver disease score. Resistin but not C-reactive protein or chemerin positively correlated with LCN2. LCN2 levels were not increased in patients with ascites or patients with esophageal varices. Consequently, reduction of portal pressure by transjugular intrahepatic portosystemic shunt did not affect LCN2 levels. Hepatic venous blood (HVS), portal venous blood and systemic venous blood levels of LCN2 were similar. HVS LCN2 was unchanged in patients with end-stage liver cirrhosis compared to those with well-compensated disease arguing against increased hepatic release. Current data exclude that serum LCN2 is of any value as steatosis marker in patients with NAFLD and indicator of liver function in patients with alcoholic liver cirrhosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Molecular and functional characterization of CD133+ stem/progenitor cells infused in patients with end-stage liver disease reveals their interplay with stromal liver cells.

PubMed

Catani, Lucia; Sollazzo, Daria; Bianchi, Elisa; Ciciarello, Marilena; Antoniani, Chiara; Foscoli, Licia; Caraceni, Paolo; Giannone, Ferdinando Antonino; Baldassarre, Maurizio; Giordano, Rosaria; Montemurro, Tiziana; Montelatici, Elisa; D'Errico, Antonia; Andreone, Pietro; Giudice, Valeria; Curti, Antonio; Manfredini, Rossella; Lemoli, Roberto Massimo

2017-12-01

Growing evidence supports the therapeutic potential of bone marrow (BM)-derived stem/progenitor cells for end-stage liver disease (ESLD). We recently demonstrated that CD133 + stem/progenitor cell (SPC) reinfusion in patients with ESLD is feasible and safe and improve, albeit transiently, liver function. However, the mechanism(s) through which BM-derived SPCs may improve liver function are not fully elucidated. Here, we characterized the circulating SPCs compartment of patients with ESLD undergoing CD133 + cell therapy. Next, we set up an in vitro model mimicking SPCs/liver microenvironment interaction by culturing granulocyte colony-stimulating factor (G-CSF)-mobilized CD133 + and LX-2 hepatic stellate cells. We found that patients with ESLD show normal basal levels of circulating hematopoietic and endothelial progenitors with impaired clonogenic ability. After G-CSF treatment, patients with ESLD were capable to mobilize significant numbers of functional multipotent SPCs, and interestingly, this was associated with increased levels of selected cytokines potentially facilitating SPC function. Co-culture experiments showed, at the molecular and functional levels, the bi-directional cross-talk between CD133 + SPCs and human hepatic stellate cells LX-2. Human hepatic stellate cells LX-2 showed reduced activation and fibrotic potential. In turn, hepatic stellate cells enhanced the proliferation and survival of CD133 + SPCs as well as their endothelial and hematopoietic function while promoting an anti-inflammatory profile. We demonstrated that the interaction between CD133 + SPCs from patients with ESLD and hepatic stellate cells induces significant functional changes in both cellular types that may be instrumental for the improvement of liver function in cirrhotic patients undergoing cell therapy. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Predictive factors of short term outcome after liver transplantation: A review

PubMed Central

Bolondi, Giuliano; Mocchegiani, Federico; Montalti, Roberto; Nicolini, Daniele; Vivarelli, Marco; De Pietri, Lesley

2016-01-01

Liver transplantation represents a fundamental therapeutic solution to end-stage liver disease. The need for liver allografts has extended the set of criteria for organ acceptability, increasing the risk of adverse outcomes. Little is known about the early postoperative parameters that can be used as valid predictive indices for early graft function, retransplantation or surgical reintervention, secondary complications, long intensive care unit stay or death. In this review, we present state-of-the-art knowledge regarding the early post-transplantation tests and scores that can be applied during the first postoperative week to predict liver allograft function and patient outcome, thereby guiding the therapeutic and surgical decisions of the medical staff. Post-transplant clinical and biochemical assessment of patients through laboratory tests (platelet count, transaminase and bilirubin levels, INR, factor V, lactates, and Insulin Growth Factor 1) and scores (model for end-stage liver disease, acute physiology and chronic health evaluation, sequential organ failure assessment and model of early allograft function) have been reported to have good performance, but they only allow late evaluation of patient status and graft function, requiring days to be quantified. The indocyanine green plasma disappearance rate has long been used as a liver function assessment technique and has produced interesting, although not univocal, results when performed between the 1th and the 5th day after transplantation. The liver maximal function capacity test is a promising method of metabolic liver activity assessment, but its use is limited by economic cost and extrahepatic factors. To date, a consensual definition of early allograft dysfunction and the integration and validation of the above-mentioned techniques, through the development of numerically consistent multicentric prospective randomised trials, are necessary. The medical and surgical management of transplanted patients could be greatly improved by using clinically reliable tools to predict early graft function. PMID:27468188

Predictive factors of short term outcome after liver transplantation: A review.

PubMed

Bolondi, Giuliano; Mocchegiani, Federico; Montalti, Roberto; Nicolini, Daniele; Vivarelli, Marco; De Pietri, Lesley

2016-07-14

Liver transplantation represents a fundamental therapeutic solution to end-stage liver disease. The need for liver allografts has extended the set of criteria for organ acceptability, increasing the risk of adverse outcomes. Little is known about the early postoperative parameters that can be used as valid predictive indices for early graft function, retransplantation or surgical reintervention, secondary complications, long intensive care unit stay or death. In this review, we present state-of-the-art knowledge regarding the early post-transplantation tests and scores that can be applied during the first postoperative week to predict liver allograft function and patient outcome, thereby guiding the therapeutic and surgical decisions of the medical staff. Post-transplant clinical and biochemical assessment of patients through laboratory tests (platelet count, transaminase and bilirubin levels, INR, factor V, lactates, and Insulin Growth Factor 1) and scores (model for end-stage liver disease, acute physiology and chronic health evaluation, sequential organ failure assessment and model of early allograft function) have been reported to have good performance, but they only allow late evaluation of patient status and graft function, requiring days to be quantified. The indocyanine green plasma disappearance rate has long been used as a liver function assessment technique and has produced interesting, although not univocal, results when performed between the 1(th) and the 5(th) day after transplantation. The liver maximal function capacity test is a promising method of metabolic liver activity assessment, but its use is limited by economic cost and extrahepatic factors. To date, a consensual definition of early allograft dysfunction and the integration and validation of the above-mentioned techniques, through the development of numerically consistent multicentric prospective randomised trials, are necessary. The medical and surgical management of transplanted patients could be greatly improved by using clinically reliable tools to predict early graft function.

Evaluation of Liver Biomarkers as Prognostic Factors for Outcomes to Yttrium-90 Radioembolization of Primary and Secondary Liver Malignancies.

PubMed

Henrie, Adam M; Wittstrom, Kristina; Delu, Adam; Deming, Paulina

2015-09-01

The objective of this study was to examine indicators of liver function and inflammation for prognostic value in predicting outcomes to yttrium-90 radioembolization (RE). In a retrospective analysis, markers of liver function and inflammation, biomarkers required to stage liver function and inflammation, and data regarding survival, tumor response, and progression after RE were recorded. Univariate regression models were used to investigate the prognostic value of liver biomarkers in predicting outcome to RE as measured by survival, tumor progression, and radiographic and biochemical tumor response. Markers from all malignancy types were analyzed together. A subgroup analysis was performed on markers from patients with metastatic colorectal cancer. A total of 31 patients received RE from 2004 to 2014. Median survival after RE for all malignancies combined was 13.6 months (95% CI: 6.7-17.6 months). Results from an exploratory analysis of patient data suggest that liver biomarkers, including albumin concentrations, international normalized ratio, bilirubin concentrations, and the model for end-stage liver disease score, possess prognostic value in predicting outcomes to RE.