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Find video protocols related to scientific articles indexed in Pubmed.
Survival analysis of proposed BCLC-B subgroups in hepatocellular carcinoma patients.
Liver Int.
PUBLISHED: 09-15-2014
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The BCLC-staging system is used to facilitate treatment decisions in patients with hepatocellular carcinoma (HCC). Owing to the observed clinical heterogeneity of the intermediate stage BCLC-B, a subclassification was proposed taking Child-Pugh score and extended criteria for transplantation into account. Analysis of the prognostic significance of a proposed subclassification of the BCLC-B score in a European cohort of HCC patients.
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Selective internal radiotherapy (SIRT) versus transarterial chemoembolization (TACE) for the treatment of intrahepatic cholangiocellular carcinoma (CCC): study protocol for a randomized controlled trial.
Trials
PUBLISHED: 03-24-2014
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Cholangiocellular carcinoma is the second most common primary liver cancer after hepatocellular carcinoma. Over the last 30 years, the incidence of intrahepatic cholangiocellular carcinoma has risen continuously worldwide. Meanwhile, the intrahepatic cholangiocellular carcinoma has become more common than the extrahepatic growth type and currently accounts for 10-15% of all primary hepatic malignancies. Intrahepatic cholangiocellular carcinoma is typically diagnosed in advanced stages due to late clinical symptoms and an absence of classic risk factors. A late diagnosis precludes curative surgical resection. There is evidence that transarterial chemoembolization leads to better local tumor control and prolongs survival compared to systemic chemotherapy. New data indicates that selective internal radiotherapy, also referred to as radioembolization, provides promising results for treating intrahepatic cholangiocellular carcinoma.
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Development of multiple focal nodular hyperplasia lesions after portocaval shunting. A case report.
J Gastrointestin Liver Dis
PUBLISHED: 12-27-2013
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It has been postulated that altered hepatic blood flow, particularly reduced portal flow, is responsible for the induction of hyperplasia of liver cells and nodule formation. This report describes the case of a 31-year old female patient developing multiple focal nodular hyperplasia (FNH) lesions two years after portocaval shunting and extended right hemihepatectomy due to the suspicion of a malignant liver tumor. Portocaval shunting became necessary due to iatrogenic thrombosis of the entire portal vein after preoperative embolization of the right portal vein. This observation provides for the first time direct evidence for the pathogenesis of FNH in humans.
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Hepatocellular carcinoma in Childs A cirrhosis: a retrospective analysis of matched pairs following liver transplantation vs. liver resection according to the intention-to-treat principle.
Clin Transplant
PUBLISHED: 09-30-2013
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This is the first matched pair analysis on the puzzling clinical problem of whether to perform liver transplantation (LT) or liver resection (LR) for Childs A hepatocellular carcinoma (HCC) patients. A total of 201 patients diagnosed with HCC and Childs A liver cirrhosis were treated with LT transarterial chemoembolization (TACE) or LR between 1998 and 2012. To achieve the most accurate study design, two groups of 57 patients were matched retrospectively according to their tumor characteristics detected by the initial computerized tomography (CT) scan. Sixteen of 57 LT candidates were not transplanted due to tumor progress during pre-treatment (TACE). Nevertheless, the retrospective analysis of the matched pairs according to the intention-to-treat principle resulted in a better five-yr overall survival (OS) rate of 54.3% for the group of LT candidates compared with 35.7% for those receiving LR (p = 0.19). In patients meeting the University of California, San Francisco (UCSF) criteria, five-yr OS reached 58.4% after LT and 45.1% after LR (p = 0.56). For Milan criteria (MC) patients, LT resulted in 57.9% and LR in 42% five-yr OS rate (p = 0.29). In conclusion, the finding of a better OS rate in LT was not statistically significant. There was also a selection bias in favor of LT, which may have influenced the OS. Therefore, particularly in regard to organ scarcity, LR remains a viable treatment option for respectable HCC in Childs A cirrhosis.
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Familial amyloid polyneuropathy.
Dig Dis
PUBLISHED: 06-17-2013
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Familial amyloid polyneuropathy (FAP; also known as familiar amyloidosis and hereditary amyloidosis) is an autosomal dominant inherited disease due to mutations of the transthyretin (TTR) gene coding for the corresponding protein, consisting of 127 amino acids. The gene is located on chromosome 18q. More than 100 different mutations are known. Other mutant precursor proteins produced in the liver, such as apolipoprotein I and II, lysozyme and fibrinogen A?, may be of etiological importance as well. Amyloidogenic mutations of the TTR gene lead to decreased stability of the corresponding protein and subsequently to extracellular deposition of amyloid in several tissues (peripheral and autonomic nerves, walls of the gastrointestinal tract, heart, etc.). The Val30Met mutation is the most prevalent cause of FAP worldwide. There are endemic regions in Portugal, Sweden and Japan. The onset of symptoms is usually between 25 and 35 years of age, but late-onset families are also known. The most common clinical symptoms are polyneuropathy of the lower limbs, rhythmological disturbances and diarrhea/obstipation. TTR amyloid is predominantly produced in the liver; only as few as 5% are synthesized in the retina and choroid plexus. Therefore, liver transplantation has become widely accepted as the ultimate curative treatment of this disease in order to prevent the ultimately fatal outcome and ameliorate disabling symptoms. Because of shortage of donor grafts, livers of FAP patients are used for domino liver transplantation. Last year, a new therapeutic option was approved by the European Medical Authority (EMA) for therapy of early-stage FAP. The first results of a multicenter-controlled trial have been published and show a benefit in patients with an early stage of disease regarding neurological symptoms as well as modified BMI. There are several other pharmacologic approaches that have been reported in the last years which may lead to stabilization of the TTR tetramer. Therefore, this might be the beginning of new therapeutic options with pharmacological therapies in patients with FAP.
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Liver transplantation: an appraisal of the present situation.
Dig Dis
PUBLISHED: 06-17-2013
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Liver transplantation (LT) is an established approach to treatment of end-stage liver diseases, metabolic diseases and early hepatocellular carcinoma, and the results of this procedure have improved considerably. MELD allocation and the great number of transplant centers had a negative influence on outcome in Germany. Typical surgical issues following transplantation are vascular thrombosis and the development of biliary lesions. Nonanastomotic strictures impact graft survival and cause considerable posttransplant morbidity. Nonsurgical issues in LT are hepatitis C reinfection, selection of appropriate patients with hepatocellular carcinoma and individualized immunosuppression. In hepatitis C the new antiviral drugs (protease and polymerase inhibitors) are promising tools to prevent reinfection. Nephrotoxicity caused by calcineurin inhibitors - which remain the mainstay of immunosuppression - can only partially be avoided. So far, alternative forms of treatment using mycophenolic acid and mTOR inhibitors cannot totally replace calcineurin inhibitors. In view of graft scarcity, we need to think about a benefit-based model of liver allocation which focuses on the optimal use of this resource. Deciding on this form of organ allocation requires an ethical consensus: not the most urgent patient is the first candidate to receive a graft, but rather the patient who is supposed to have the greatest benefit.
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How to decide about liver transplantation in patients with hepatocellular carcinoma: size and number of lesions or response to TACE?
J. Hepatol.
PUBLISHED: 04-03-2013
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Liver transplantation is a curative treatment option for patients with hepatocellular carcinoma (HCC) and liver cirrhosis. To date, patient selection for transplantation is based on size and number of nodules as assessed by imaging before listing. We hypothesized that changes in tumour features resulting from pre-transplant transarterial chemoembolisation (TACE) is a superior criterion to predict tumour recurrence.
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Alpha-fetoprotein and modified response evaluation criteria in solid tumors progression after locoregional therapy as predictors of hepatocellular cancer recurrence and death after transplantation.
Liver Transpl.
PUBLISHED: 02-28-2013
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Locoregional therapy (LRT) is being increasingly used for the management of hepatocellular cancer (HCC) in patients listed for liver transplantation (LT). Although several selection criteria have been developed, stratifications of survival according to the pathology of explanted livers and pre-LT LRT are lacking. Radiological progression according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and alpha-fetoprotein (AFP) behavior was reviewed for 306 patients within the Milan criteria (MC-IN) and 116 patients outside the Milan criteria (MC-OUT) who underwent LRT and LT between January 1999 and March 2010. A prospectively collected database originating from 6 collaborating European centers was used for the study. Sixty-one patients (14.5%) developed HCC recurrence. For both MC-IN and MC-OUT patients, an AFP slope > 15 ng/mL/month and mRECIST progression were unique independent risk factors for HCC recurrence and patient death. When the radiological Milan criteria (MC) status was combined with radiological and biological progression, MC-IN and MC-OUT patients without risk factors had similarly excellent 5-year tumor-free and patient survival rates. MC-IN patients with at least 1 risk factor had worse outcomes, and MC-OUT patients with at least 1 risk factor had the poorest survival (P < 0.001). In conclusion, both radiological and biological modifications permit documentation of the response to LRT in patients waiting for LT. According to these 2 parameters, tumor progression significantly increases the risk of recurrence and patient death not only for MC-OUT patients but also for MC-IN patients. The monitoring of both parameters in combination with the initial radiological MC status is an essential element for further refining the selection criteria for potential liver recipients with HCC.
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Evaluation of domino liver transplantations in Germany.
Transpl. Int.
PUBLISHED: 02-11-2013
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A retrospective multicenter study has been conducted to evaluate domino liver transplantations (DLTs) in Germany. The study provides insight into survival and features having an impact on the assessment of neuropathy after DLT. In addition, a neurologic follow-up program with a scheme to estimate the likelihood of de novo amyloidosis is presented. A series of 61 DLTs at seven transplant centers in Germany was enrolled. The mean age of domino recipients at the time of transplantation was 58 years, 46 of them being men, and 15 being women. The median follow-up was 46 months. The overall 1-, 3-, and 5-year survival of domino recipients was 81.6%, 70.8% and 68.8%, respectively. Causes of death were primarily not related to familial amyloidosis. The main indication of DLT was hepatocellular carcinoma. Two of the reported domino recipients developed symptoms and signs of de novo amyloidosis within 10 years after transplantation. A total of 30 domino graft recipients (49.18%) presented with diabetes post transplantation. In conclusion, an advanced follow-up program is crucial to evaluate the risk of transmitting familial amyloidosis by DLT and to establish more strict selection criteria for domino recipients.
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Reperfusion of liver graft during transplantation: techniques used in transplant centres within Eurotransplant and meta-analysis of the literature.
Transpl. Int.
PUBLISHED: 02-11-2013
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It remains unclear which liver graft reperfusion technique leads to the best outcome following transplantation. An online survey was sent to all transplant centres (n = 37) within Eurotransplant (ET) to collect information on their technique used for reperfusion of liver grafts. Furthermore, a systematic review of all literature was performed and a meta-analysis was conducted based on patients mortality, number of retransplantations and incidence of biliary complications, depending on the technique used. Of the 28 evaluated centres, 11 (39%) reported performing simultaneous reperfusion (SIMR), 13 (46%) perform initial portal vein reperfusion (IPR), 1 (4%) performs an initial hepatic artery reperfusion (IAR) and 3 (11%) perform retrograde reperfusion (RETR). In 21 centres (75%), one reperfusion technique is used as a standard, but in only one centre is this decision based on available literature. Twenty centres (71%) said they would agree to participate in randomized controlled trials (RCT) if required. For meta-analysis, IAR vs. IPR, SIMR vs. IPR and RETR vs. IPR were compared. There was no difference between any of the techniques compared. There is no consensus on a preferable reperfusion technique. Available evidence does not help in the decision-making process. There is thus an urgent need for multicentric RCTs.
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Downregulation of organic cation transporter 1 (SLC22A1) is associated with tumor progression and reduced patient survival in human cholangiocellular carcinoma.
Int. J. Oncol.
PUBLISHED: 01-11-2013
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Cholangiocellular carcinoma (CCA) is a primary hepatic malignancy derived from cholangiocytes. The prognosis for CCA patients is very poor and conventional chemotherapy has been proven ineffective in improving long?term patient survival rates. Organic cation transporters (OCTs) mediate the transport of a broad spectrum of endogenous substrates and the detoxification of xenobiotics. Moreover, OCTs are considered responsible for the responsiveness towards platinum?based chemotherapies. Currently, there are no data available regarding the role of OCTs in CCA. Therefore, the aim of this study was to investigate the expression of OCT1 and OCT3 in CCA and the corresponding non-neoplastic tumor?surrounding tissue (TST). OCT1 (SLC22A1) and OCT3 (SLC22A3) mRNA expression was measured in primary human CCA by real-time PCR (n=27). Protein expression was determined by western blot analysis and immunohistochemistry. Data were correlated with the clinicopathological parameters of CCA. Real-time PCR demonstrated a downregulation of the expression of SLC22A1 and SLC22A3 in CCA, compared to that in TST (p<0.001). A low SLC22A1 expression was associated with a worse patient survival (p<0.05). The downregulation of SLC22A1 was significantly associated with advanced CCA stages, since tumors with a low SLC22A1 mRNA expression presented with larger tumor diameters (p=0.02). There were no significant differences in tumor characteristics or patient survival in relation to the level of SLC22A3 expression. Western blot analysis and immunohistochemistry confirmed the downregulation of OCT1 and OCT3 protein levels in cancerous tissue compared to those in TST. In conclusion, the downregulation of OCT1 is associated with tumor progression and worse overall patient survival rates.
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Sorafenib perpetuates cellular anticancer effector functions by modulating the crosstalk between macrophages and natural killer cells.
Hepatology
PUBLISHED: 01-10-2013
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Alternatively polarized macrophages (M?) shape the microenvironment of hepatocellular carcinoma (HCC) and temper anticancer immune responses. We investigated if sorafenib alters the HCC microenvironment by restoring classical macrophage polarization and triggering tumor-directed natural killer (NK) cell responses. In vivo experiments were conducted with sorafenib (25 mg/kg)-treated C57BL/6 wildtype as well as hepatitis B virus (HBV) and lymphotoxin transgenic mice with and without HCC. Monocyte-derived M? or tumor-associated macrophages (TAM) isolated from HCC tissue were treated with sorafenib (0.07-5.0 ?g/mL) and cocultured with autologous NK cells. M? and NK cell activation was analyzed by flow cytometry and killing assays, respectively. Cytokine and growth factor release was measured by enzyme-linked immunosorbent assay. Short-term administration of sorafenib triggered activation of hepatic NK cells in wildtype and tumor-bearing mice. In vitro, sorafenib sensitized M? to lipopolysaccharide, reverted alternative M? polarization and enhanced IL12 secretion (P = 0.0133). NK cells activated by sorafenib-treated M? showed increased degranulation (15.3 ± 0.2% versus 32.0 ± 0.9%, P < 0.0001) and interferon-gamma (IFN-?) secretion (2.1 ± 0.2% versus 8.0 ± 0.2%, P < 0.0001) upon target cell contact. Sorafenib-triggered NK cell activation was verified by coculture experiments using TAM. Sorafenib-treated M? increased cytolytic NK cell function against K562, Raji, and HepG2 target cells in a dose-dependent manner. Neutralization of interleukin (IL)12 or IL18 as well as inhibition of the nuclear factor kappa B (NF-?B) pathway reversed NK cell activation in M?/NK cocultures. Conclusion: Sorafenib triggers proinflammatory activity of TAM and subsequently induces antitumor NK cell responses in a cytokine- and NF-?B-dependent fashion. This observation is relevant for HCC therapy, as sorafenib is a compound in clinical use that reverts alternative polarization of TAM in HCC. (HEPATOLOGY 2013;57:2358-2368).
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The recipient CYP2D6 allele 4-associated poor metabolizer status correlates with an early fibrosis development after liver transplantation.
Transpl. Int.
PUBLISHED: 07-28-2011
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CYP2D6 is part of the cytochrome P450 system, which catalyzes biotransformation of endogenous substrates and xenobiotics. Approximately 10% of the Caucasian population has two null alleles, resulting in a poor metabolizer (PM) status. Mostly, allele four (CYP2D6*4) is responsible for the PM status, which is suspected to be associated with an accelerated fibrosis progression (FP). The aim of the present study was to analyze the role of the CYP2D6*4 genotype for FP after liver transplantation (LT). Genotypes were determined in liver biopsies (donor) and peripheral blood (recipient) by fluorescence resonance energy transfer. Data were correlated with clinical variables and risk factors for fibrosis. We analyzed 517 LTs performed between 1997 and 2009. Overall donor and recipient allele frequencies were comparable (18.0%, 20.5%; P = 0.43). The donor genotype did not correlate with FP. In contrast, recipients carrying CYP2D6*4, showed a significant higher risk for an accelerated FP (P = 0.011) in HCV positive (P = 0.038) and HCV negative patients (P = 0.033). Results were confirmed by multivariate analysis (Hazard ratio 1.65; P = 0.001). The CYP2D6*4-associated PM status of the donor liver seems to have no influence on FP after LT. Recipients, carrying the allele, have an elevated risk for an accelerated FP.
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Dose determination using alanine detectors in a mixed neutron and gamma field for boron neutron capture therapy of liver malignancies.
Acta Oncol
PUBLISHED: 07-20-2011
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Boron Neutron Capture Therapy for liver malignancies is being investigated at the University of Mainz. One important aim is the set-up of a reliable dosimetry system. Alanine dosimeters have previously been applied for dosimetry of mixed radiation fields in antiproton therapy, and may be suitable for measurements in mixed neutron and gamma fields.
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Down-regulation of CYLD as a trigger for NF-?B activation and a mechanism of apoptotic resistance in hepatocellular carcinoma cells.
Int. J. Oncol.
PUBLISHED: 05-25-2011
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The cylindromatosis gene (CYLD) was identified as a tumor suppressor gene, which is mutated in familial cylindromatosis (Brooke-Spiegler syndrome), an autosomal-dominant predisposition to multiple tumors of the skin appendages. CYLD is a deubiquitinating enzyme acting as a negative regulator of the nuclear factor ?B (NF-?B) signaling pathway by removing lysine-63-linked polyubiquitin chains from NF-?B activating proteins. In order to investigate the role of CYLD in apoptotic signaling in human hepatocellular carcinoma (HCC) cells, we first studied the expression levels of CYLD in HCC tissues. CYLD expression was lower in HCC both at protein and mRNA levels compared to the surrounding non-malignant tissue. In order to further study the role of CYLD in the apoptotic sensitivity of HCC cells, CYLD was specifically down-regulated in HCC cell lines via RNA interference. The specific down-regulation of CYLD resulted in increased resistance towards treatment with doxorubicin, 5-fluorouracil and cisplatin. In addition, the down-regulation of CYLD in HCC cells decreased the sensitivity towards tumor necrosis factor-?-induced apoptosis. The CYLD knockdown also led to the degradation of the NF-?B inhibitor, I?B-?, resulting in enhanced NF-?B activity in HCC cells. Finally, we found that CYLD expression was triggered by the multikinase inhibitor, sorafenib, by the inhibition of Raf-1, as well as by the blockage of the pro-survival kinases, MEK (U0126) and the epidermal growth factor receptor (AG1478). In summary, we show that CYLD is down-regulated in human HCC and is involved in the apoptotic resistance of HCC cells. Our data identify the reconstitution of CYLD expression as an attractive approach for overcoming resistance to treatment in HCC.
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Early steroid-free immunosuppression with FK506 after liver transplantation: long-term results of a prospectively randomized double-blinded trial.
Transplantation
PUBLISHED: 11-05-2010
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The aim of this prospective, randomized, double-blinded, placebo-controlled single center study was to evaluate an early steroid-free immunosuppression in liver transplant patients.
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Dose calculation in biological samples in a mixed neutron-gamma field at the TRIGA reactor of the University of Mainz.
Acta Oncol
PUBLISHED: 09-14-2010
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To establish Boron Neutron Capture Therapy (BNCT) for non-resectable liver metastases and for in vitro experiments at the TRIGA Mark II reactor at the University of Mainz, Germany, it is necessary to have a reliable dose monitoring system. The in vitro experiments are used to determine the relative biological effectiveness (RBE) of liver and cancer cells in our mixed neutron and gamma field. We work with alanine detectors in combination with Monte Carlo simulations, where we can measure and characterize the dose. To verify our calculations we perform neutron flux measurements using gold foil activation and pin-diodes. Material and methods. When L-?-alanine is irradiated with ionizing radiation, it forms a stable radical which can be detected by electron spin resonance (ESR) spectroscopy. The value of the ESR signal correlates to the amount of absorbed dose. The dose for each pellet is calculated using FLUKA, a multipurpose Monte Carlo transport code. The pin-diode is augmented by a lithium fluoride foil. This foil converts the neutrons into alpha and tritium particles which are products of the (7)Li(n,?)(3)H-reaction. These particles are detected by the diode and their amount correlates to the neutron fluence directly. Results and discussion. Gold foil activation and the pin-diode are reliable fluence measurement systems for the TRIGA reactor, Mainz. Alanine dosimetry of the photon field and charged particle field from secondary reactions can in principle be carried out in combination with MC-calculations for mixed radiation fields and the Hansen & Olsen alanine detector response model. With the acquired data about the background dose and charged particle spectrum, and with the acquired information of the neutron flux, we are capable of calculating the dose to the tissue. Conclusion. Monte Carlo simulation of the mixed neutron and gamma field of the TRIGA Mainz is possible in order to characterize the neutron behavior in the thermal column. Currently we also speculate on sensitizing alanine to thermal neutrons by adding boron compounds.
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Multicentric evaluation of model for end-stage liver disease-based allocation and survival after liver transplantation in Germany--limitations of the sickest first-concept.
Transpl. Int.
PUBLISHED: 09-03-2010
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Since the introduction of model for end-stage liver disease (MELD) in 2006, post-orthotopic liver transplantation (OLT) survival in Germany has declined. The aim of this study was to evaluate risk factors and prognostic scores for outcome. All adult OLT recipients in seven German transplant centers after MELD implementation (December 2006-December 2007) were included. Recipient data were analyzed for their influence on 1-year outcome. A total of 462 patients (mean calculated MELD = 20.5, follow-up: 1 year) were transplanted for alcoholic cirrhosis (33.1%), hepatocellular carcinoma (26.6%), Hepatitis-C (17.1%), Hepatitis-B (9.5%), primary sclerosing cholangitis (5.6%) and late graft-failure after first OLT before December 2006 (8.7%). 1-year patient survival was 75.8% (graft survival 71.2%) correlating with MELD parameters and serum choline esterase. MELD score >30 [odds ratio (OR) = 4.17, confidence interval: 2.57-6.78, 12-month survival = 52.6%, c-statistic = 0.669], hyponatremia (OR = 2.07), and pre-OLT hemodialysis (OR = 2.35) were the main death risk factors. In alcoholic cirrhosis (n = 153, mean MELD = 21.1) and hepatocellular carcinoma (n = 123, mean MELD = 13.5), serum bilirubin and the survival after liver transplantation score were independent outcome parameters, respectively. MELD >30 currently represents a major risk factor for outcome. Risk factors differ in individual patient subgroups. In the current German practice of organ allocation to sicker patients, outcome prediction should be considered to prevent results below acceptable standards.
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A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma.
BMC Cancer
PUBLISHED: 05-11-2010
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The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC.
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Sunitinib in patients with advanced hepatocellular carcinoma after progression under sorafenib treatment.
Oncology
PUBLISHED: 05-10-2010
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To evaluate the safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma (HCC) after progression under sorafenib treatment.
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Liver transplantation and combined liver-heart transplantation in patients with familial amyloid polyneuropathy: a single-center experience.
Liver Transpl.
PUBLISHED: 03-09-2010
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Liver transplantation (LT) is the only curative option for patients with familial amyloid polyneuropathy (FAP) at present. Twenty patients with FAP underwent LT between May 1998 and June 2007. Transthyretin mutations included predominantly the Val30Met mutation but also 10 other mutations. Seven patients received a pacemaker prior to LT, and because of impairment of mechanical cardiac function, 4 combined heart-liver transplants were performed, 1 simultaneously and 3 sequentially. The first patient, who underwent simultaneous transplantation, died. Seven patients died after LT, with 5 dying within the first year after transplantation. The causes of death were cardiac complications (4 patients), infections (2 patients), and malnutrition (1 patient). One-year survival was 75.0%, and 5-year survival was 64.2%. Gly47Glu and Leu12Pro mutations showed an aggressive clinical manifestation: 2 patients with the Gly47Glu mutation, the youngest patients of all the non-Val30Met patients, suffered from severe cardiac symptoms leading to death despite LT. Two siblings with the Leu12Pro mutation, who presented only with grand mal seizures, died after LT because of sepsis. In conclusion, the clinical course in patients with FAP is very variable. Cardiac symptoms occurred predominantly in patients with non-Val30Met mutations and prompted combined heart-liver transplantation in 4 patients. Although early LT in Val30Met is indicated in order to halt the typical symptoms of polyneuropathy, additional complications occurring predominantly with other mutations may prevail and lead to life-threatening complications or a fatal outcome. Combined heart-liver transplantation should be considered in patients with restrictive cardiomyopathy.
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Liver transplanted patients with preoperative autoimmune hepatitis and immunological disorders are at increased risk for Post-Transplant Lymphoproliferative Disease (PTLD).
Eur. J. Intern. Med.
PUBLISHED: 01-31-2010
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Long term immunosuppression and therapy of acute rejections result in a 20-120-fold increased risk to develop Non Hodgkin lymphoma (NHL). Since immunosuppressive therapy and immunological disorders are major risk factors for the development of NHL in the non-transplant population we aimed to analyze risk factors for PTLD in our cohort of liver transplanted (LT) patients.
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MRI versus 64-row MDCT for diagnosis of hepatocellular carcinoma.
World J. Gastroenterol.
PUBLISHED: 12-23-2009
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To compare the diagnostic capability of multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) for the detection of hepatocellular carcinoma (HCC) tumour nodules and their effect on patient management.
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MDCT versus MRI assessment of tumor response after transarterial chemoembolization for the treatment of hepatocellular carcinoma.
Cardiovasc Intervent Radiol
PUBLISHED: 04-13-2009
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The purpose of this study was to compare the ability of multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) to evaluate treatment results after transarterial chemoembolization (TACE), with a special focus on the influence of Lipiodol on calculation of tumor necrosis according to EASL criteria. A total of 115 nodules in 20 patients (17 males, 3 females; 69.5 +/- 9.35 years) with biopsy-proven hepatocellular carcinoma were treated with TACE. Embolization was performed using a doxorubicin-Lipiodol emulsion (group I) or DC Beads loaded with doxorubicin (group II). Follow-up included triphasic contrast-enhanced 64-row MDCT (collimation, 0.625 mm; slice, 3 mm; contrast bolus, 120 ml iomeprol; delay by bolus trigger) and contrast-enhanced MRI (T1 native, T2 native; five dynamic contrast-enhanced phases; 0.1 mmol/kg body weight gadolinium-DTPA; slice thickness, 4 mm). Residual tumor and the extent of tumor necrosis were evaluated according to EASL. Contrast enhancement within tumor lesions was suspected to represent vital tumor. In the Lipiodol-based TACE protocol, MDCT underestimated residual viable tumor compared to MRI, due to Lipiodol artifacts (23.2% vs 47.7% after first, 11.9% vs 31.2% after second, and 11.4% vs 23.7% after third TACE; p = 0.0014, p < 0.001, and p < 0.001, respectively). In contrast to MDCT, MRI was completely free of any artifacts caused by Lipiodol. In the DC Bead-based Lipiodol-free TACE protocol, MRI and CT showed similar residual tumor and rating of treatment results (46.4% vs 41.2%, 31.9 vs 26.8%, and 26.0% vs 25.6%; n.s.). In conclusion, MRI is superior to MDCT for detection of viable tumor residuals after Lipiodol-based TACE. Since viable tumor tissue is superimposed by Lipiodol artifacts in MDCT, MRI is mandatory for reliable decision-making during follow-up after Lipiodol-based TACE protocols.
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Impact of a pharmaceutical care program on liver transplant patients compliance with immunosuppressive medication: a prospective, randomized, controlled trial using electronic monitoring.
Transplantation
PUBLISHED: 03-21-2009
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Compliance with immunosuppressive therapy plays a major role in the long-term success of organ transplantation. Thus, strategies to promote compliance in posttransplant care are of particular interest. At the pharmacy department of the University Hospital Mainz, a program for pharmaceutical care of organ transplant patients has been developed for the first time ever. The main objective of the presented study was to examine the influence of this program on liver transplant patients compliance with immunosuppressive therapy.
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Safety and efficacy of sorafenib in patients with advanced hepatocellular carcinoma in consideration of concomitant stage of liver cirrhosis.
J. Clin. Gastroenterol.
PUBLISHED: 02-28-2009
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The multikinase inhibitor sorafenib provides survival benefit for patients with advanced hepatocellular carcinoma (HCC) and liver cirrhosis (LCI) Child-Pugh A. We report our experiences with sorafenib in advanced HCC, particularly in patients with LCI Child-Pugh B/C, where only limited data are available in regard to safety and efficacy of sorafenib.
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EGF and HGF levels are increased during active HBV infection and enhance survival signaling through extracellular matrix interactions in primary human hepatocytes.
Int. J. Cancer
PUBLISHED: 01-08-2009
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The hepatitis B virus (HBV) is a major causative agent of chronic liver disease and subsequent liver cirrhosis worldwide. The reduced sensitivity of virus-infected liver cells to apoptosis may play a role in the failure to remove virus-infected cells and eventually promote viral chronicity. The purpose of our study was to investigate whether survival factors induced during compensatory liver regeneration may protect hepatocytes against apoptosis. We evaluated the serum levels of hepatocyte growth factor (HGF) and epidermal growth factor (EGF) in HBV-infected patients and found significant increases in HGF and EGF in patients with active virus infection. In primary human hepatocytes we show that HGF and EGF have a protective effect against CD95-mediated apoptosis and cytotoxic T-cell killing. Simultaneous treatment with both regeneration factors enhanced the cytoprotective effect. The PI 3-K/Akt kinase inhibitor, wortmannin, and the STAT3 pathway inhibitor, Tyrphostin AG490, both effectively attenuated the cytoprotective effect of HGF and EGF. Furthermore, we show an EGF/HGF-dependent upregulation of beta(1)-integrin chains, increased adhesion to extracellular matrix and an increase in focal adhesions, suggesting outside-in signaling from the extracellular matrix as an additional cytoprotective mechanism. Our study demonstrates that HGF and EGF can interfere with CD95-mediated apoptosis and the action of cytotoxic T-cells through multiple mechanisms in human hepatocytes. Together our results argue that a survival mileau generated by activation of liver regeneration factors may be a risk factor for establishing viral persistence.
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Metabolic syndrome and its association with fatty liver disease after orthotopic liver transplantation.
Transpl. Int.
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The metabolic syndrome (MetS) might contribute to morbidity after orthotopic liver transplantation (OLT). For this reason, we searched for MetS-associated risk factors and analyzed the link with nonalcoholic fatty liver disease (NAFLD) in OLT recipients. De novo MetS affected 32.9% of our cohort (n = 170) within 2 years after OLT. Multivariate analysis identified glycosylated hemoglobin (HbA1c) levels ?5% [odds ratio (OR) = 3.5; 95% confidence interval (CI) = 1.56-8.13, P = 0.003], diabetes mellitus (OR = 4.31, CI = 1.69-10.99, P = 0.002), and arterial hypertension (OR = 4.59, CI = 1.46-14.49, P = 0.009) as independent risk factors for de novo MetS. MetS incidence correlated with steroid dosage after OLT (5.2 ± 2.4 mg/day vs. 7.1 ± 4.7 mg/day, P = 0.014), and was linked to NAFLD (P = 0.001) via obesity (OR = 4.67, CI = 1.55-14.1, P = 0.006) and dyslipidemia (OR = 4.23, CI = 1.35-13.3, P = 0.013) post-OLT. In conclusion, we were able to identify low threshold HbA1c as a novel risk factor for MetS after OLT and described a link of MetS with NAFLD in transplant organs. This study also indicated that steroid treatment is associated with MetS rates after OLT.
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Clinicopathologic features and prognosis of young patients with hepatocellular carcinoma in a large German cohort.
J. Clin. Gastroenterol.
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Hepatocellular carcinoma in non-hepatitis B virus endemic areas is rare in patients younger than 40 years of age. The aim of this study was to characterize young patients in a large German cohort in comparison with older patients with regard to underlying liver disease, clinical management, and survival.
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Midterm follow-up after DC-BEAD™-TACE of hepatocellular carcinoma (HCC).
Eur J Radiol
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To determine local response, its predictors and survival and complication rates after DC-Bead™-TACE in patients with hepatocellular carcinoma (HCC).
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Frozen section diagnosis in donor liver biopsies: observer variation of semiquantitative and quantitative steatosis assessment.
Virchows Arch.
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Donor livers are not generally accepted for liver transplantation if intraoperative frozen section histology on wedge biopsies provides evidence for more severe steatosis. In this reliability study, assessment of steatosis in donor liver biopsies by different approaches (frozen sections vs. paraffin sections; macrovesicular steatosis vs. microvesicular steatosis), different observers, and different evaluation methods (conventional microscopy vs. point grid analysis on digital microphotographs) was compared. One hundred twenty consecutive donor liver biopsies were investigated. Intraoperative diagnosis was made on hematoxylin and eosin (H&E)-stained frozen sections. The residual portion of each biopsy was analyzed later on H&E-, diastase-resistant PAS-, and Elastica van Gieson-stained paraffin sections. Microvesicular steatosis and macrovesicular steatosis were classified semiquantitatively into 5 % steps. Additionally, point grid counting was applied on ten digital microphotographs per slide. The values for steatosis revealed a wide range of data between 0 and 70 or 85 % (mean values, 12.0-18.3 %), considering all types of specimens. The results of the two observers were highly correlated for macrovesicular steatosis (r???0.925) and for microvesicular steatosis (r???0.880). The values for macrovesicular and microvesicular steatosis, however, showed poor correlation (r???0.581). The rate of agreement between the two observers ranged between 84.2 and 95.8 % (?, 0.763-0.937), depending on the threshold setting. For point grid analysis, significantly lower mean values and ranges for both types of steatosis compared to conventional histopathology were found (p?
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Histological examination and evaluation of donor bile ducts received during orthotopic liver transplantation--a morphological clue to ischemic-type biliary lesion?
Virchows Arch.
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Ischemic-type biliary lesions (ITBL) belong to a group of biliary disorders that are regarded as the major complication in patients with orthotopic liver transplantation (OLT). We performed histological evaluation of donor common bile ducts received during OLT to find morphological clues to the pathomechanisms of ITBL. We investigated 93 grafts of 92 patients (recipients: mean age, 56.5 years; underlying disease: hepatocellular carcinoma (n?=?45), alcoholic cirrhosis (n?=?16), viral hepatitis with cirrhosis (n?=?9), retransplantations (n?=?9), others (n?=?14); donors: mean age, 53.2 years). Donor common bile ducts were received after recirculation of the hepatic artery prior to biliary end-to-end anastomosis and routinely processed. Statistical evaluation was performed by chi-square analysis and multivariate analysis using a logistic regression model. With regard to ITBL (observed in 19.4 %), the following phenomena were found to be statistically relevant: necrosis of the bile duct wall, arteriolonecrosis, vascular lesions (such as subintimal edema), and intramural bleeding (P?
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Solid organ transplantation for non-TTR hereditary amyloidosis: report from the 1st International Workshop on the Hereditary Renal Amyloidoses.
Amyloid
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Fibrinogen A ?-chain (AFib) and apolipoprotein AI (AApoAI) amyloidosis due to variants in the AFib and ApoAI genes are the most common types of hereditary amyloidosis in Europe and the United States. Liver is the exclusive source of the aberrant amyloidogenic protein in AFib and responsible for supplying approximately half of the circulating variant ApoAI. Nephrotic syndrome and renal impairment due to renal amyloidosis are common disease manifestations; however, recent research provides evidence to support a more diverse and systemic disease phenotype, which in turn has implications in the management of the hereditary amyloidoses with solid organ transplantation and, in particular, liver transplantation.
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Prognostic factors and outcomes of patients with hepatocellular carcinoma in non-cirrhotic liver.
Scand. J. Gastroenterol.
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To report the outcome of patients with hepatocellular carcinoma (HCC) in non-cirrhotic liver depending on the mode of primary treatment and to define clinicopathological factors influencing patients prognosis.
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Downregulation of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) in human hepatocellular carcinoma and their prognostic significance.
BMC Cancer
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Organic cation transporters (OCT) are responsible for the uptake and intracellular inactivation of a broad spectrum of endogenous substrates and detoxification of xenobiotics and chemotherapeutics. The transporters became pharmaceutically interesting, because OCTs are determinants of the cytotoxicity of platin derivates and the transport activity has been shown to correlate with the sensitivity of tumors towards tyrosine kinase inhibitors. No data exist about the relevance of OCTs in hepatocellular carcinoma (HCC).
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Sorafenib for recurrence of hepatocellular carcinoma after liver transplantation.
Dig Liver Dis
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Recurrence of hepatocellular carcinoma after orthotopic liver transplantation not amenable to surgical approaches is associated with poor outcome.
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Trends in Epidemiology, Treatment, and Survival of Hepatocellular Carcinoma Patients Between 1998 and 2009: An Analysis of 1066 Cases of a German HCC Registry.
J. Clin. Gastroenterol.
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The aim of this study was to analyze clinical presentation, course of disease, and management of patients with hepatocellular carcinoma (HCC) in a German referral center between 1998 and 2009.
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What is Visualize?

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

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