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Philip Roelandt,
Pieter Dobbels,
Mina Komuta,
Anniek Corveleyn,
Marie-Paule Emonds,
Tania Roskams,
Raymond Aerts,
Diethard Monbaliu,
Louis Libbrecht,
Wim Laleman, Chris Verslype,
Werner Van Steenbergen,
Schalk van der Merwe,
Jacques Pirenne,
Frederik Nevens,
David Cassiman
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ABSTRACT: OBJECTIVES: The Z allele (Glu342Lys) in α1-antitrypsin (AAT) deficiency is a combined deficiency and dysfunctional allele. Carrying one Z allele induces a risk of a more aggressive evolution in patients with a chronic liver disease. As most of the carriers of Z allele do not have overt liver disease, it is likely that Z allele-containing livers have been used previously for liver transplantation. We analyzed the incidence, epidemiology, and clinical features of AAT accumulation in the hepatocytes after liver transplantation. METHODS: Follow-up biopsies of liver transplant recipients were analyzed with periodic acid Schiff staining until 2006 (n=486); from 2006 on (n=303), all biopsies were stained with a specific monoclonal antibody against mutated AATZ protein. Genotyping of both recipient and donor was performed in the case of positive staining. RESULTS: Of 789 liver transplantation patients, six patients (0.8%) showed mutated AATZ accumulation in the transplanted liver. Mutation analysis confirmed the presence of the Z allele in all donor organs including one transplanted organ with the SZ phenotype. There was a clear concordance between the isoelectrical focusing of the recipient AAT after transplantation and the genotype of the donor. CONCLUSION: Presumed healthy donor organs containing the Z allele were used for transplantation in 0.8% of cases in our series. As the presence of a Z allele is an independent risk factor of aggravation of chronic liver disease, AATZ accumulation in biopsies after liver transplantation should be actively looked for.
European journal of gastroenterology & hepatology 05/2013; · 1.66 Impact Factor
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ABSTRACT: PURPOSE: To prospectively assess the performance of hydrogel-coated versus fibered microcoils in the prophylactic occlusion of the gastroduodenal artery (GDA) before yttrium-90 ((90)Y) radioembolization. MATERIALS AND METHODS: A total of 43 patients were randomized to receive fibered microcoils (n = 15), detachable hydrogel-coated microcoils (n = 13), or pushable hydrogel-coated microcoils (n = 15). Numbers of coils used, duration, dose-area product (DAP), contrast agent load, and coil migration were assessed. At the time of yttrium-90 ((90)Y) radioembolization, persistent GDA occlusion was analyzed. RESULTS: In all patients, the embolized GDA was still completely occluded at the time of (90)Y radioembolization. Mean numbers of microcoils used per patient were 11.5 (fibered microcoils), 2.9 (detachable hydrocoils), and 5.5 (pushable hydrocoils), with all numbers significantly different (P<.0001). Mean DAPs were 16,283 mGy/cm(2)±16,545 (standard deviation) for fibered microcoils, 13,786 mGy/cm(2)±5,990 for detachable hydrocoils, and 35,757 mGy/cm(2)±74,493 for pushable hydrocoils (P = .87). Mean durations of GDA coil embolization were 20 minutes for fibered microcoils, 25 minutes for detachable hydrocoils, and 32 minutes for pushable hydrocoils (P = .0015). Mean contrast agent loads were 9 mL for fibered microcoils, 11 mL for pushable hydrocoils, and 7 mL for detachable hydrocoils (P = .13). One case of coil migration occurred with each type. CONCLUSIONS: Hydrogel-coated and fibered microcoils are equally effective for prophylactic occlusion of the GDA before radioembolization. The number of coils used is higher with fibered microcoils compared with pushable and detachable hydrocoils, but the reduced number of hydrocoils comes at the cost of increased procedure duration.
Journal of vascular and interventional radiology: JVIR 04/2013; · 1.81 Impact Factor
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ABSTRACT: Sorafenib leads to a survival benefit in patients with advanced hepatocellular carcinoma but its use is hampered by the occurrence of drug resistance. To investigate the molecular mechanisms involved we developed five resistant human liver cell lines in which we studied morphology, gene expression and invasive potential. The cells changed their appearance, lost E-cadherin and KRT19 and showed high expression of vimentin, indicating epithelial-to-mesenchymal transition. Resistant cells showed reduced adherent growth, became more invasive and lost liver-specific gene expression. Furthermore, following withdrawal of sorafenib, the resistant cells showed rebound growth, a phenomenon also found in patients. This cell model was further used to investigate strategies for restoration of sensitivity to sorafenib.
Cancer letters 10/2012; · 4.86 Impact Factor
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Sofie Van Binnebeek,
Kristof Baete,
Christelle Terwinghe,
Bert Vanbilloen,
Karin Haustermans,
Luc Mortelmans,
Ivan Borbath,
Eric Van Cutsem, Chris Verslype,
Felix M Mottaghy,
Alfons Verbruggen,
Christophe M Deroose
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ABSTRACT: Peptide receptor radionuclide therapy (PRRT), with (90)Y-DOTATOC and (177)Lu-DOTATATE as most clinically used radiopeptides, is widely used in the management of metastatic neuroendocrine tumors. With respect to radiation dosimetry, the kidneys are the critical organ for (90)Y-DOTATOC. Renal irradiation is significant because of reabsorption of the radiopeptide from the proximal tubuli and the resulting retention in the interstitium, mainly in the inner cortical zone. The high energy and consequently wide range in tissue of the yttrium-90 beta particle result in high absorbed doses to the kidney cortex and medulla. Accurate renal dosimetry can help minimizing radiation nephropathy. We report a case of a 69-year-old candidate for PRRT with an acceptable kidney function at the time of screening. When performing (111)In-octreotide pretreatment dosimetry 3 weeks later, we observed a drastic deterioration in kidney function, caused by undisclosed non-steroidal anti-inflammatory drug intake. The calculated kidney biological effective dose (BED) was 153 Gy after four projected cycles. PRRT was canceled as our full-course BED limit is 37 Gy and the patient was switched to morphine analgesics. Renal function normalized after 3 months and repeated dosimetry yielded an acceptable kidney BED of 28 Gy after four projected cycles (7 Gy/cycle). This case emphasizes that acute kidney insufficiency can yield toxic kidney doses in a single therapy cycle, with an inherent risk of persistent renal insufficiency. All clinical factors which might influence kidney function should be verified at screening and before PRRT administration.
Annals of Nuclear Medicine 09/2012; · 1.50 Impact Factor
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Philip Roelandt,
Aline Antoniou,
Louis Libbrecht,
Werner Van Steenbergen,
Wim Laleman, Chris Verslype,
Schalk Van der Merwe,
Frederik Nevens,
Rita De Vos,
Evelyne Fischer,
Marco Pontoglio,
Frédéric Lemaigre,
David Cassiman
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ABSTRACT: Heterozygous deletion or mutation in hepatocyte nuclear factor 1 homeobox B/transcription factor 2 (HNF1B/TCF2) causes renal cyst and diabetes syndrome (OMIM #137920). Mice with homozygous liver-specific deletion of Hnf1β revealed that a complete lack of this factor leads to ductopenia and bile duct dysplasia, in addition to mild hepatocyte defects. However, little is known about the hepatic consequences of deficient HNF1B function in humans. Three patients with heterozygous HNF1B deficiency were found to have normal bile duct formation on radiology and routine liver pathology. Electron microscopy revealed a paucity or absence of normal primary cilia. Therefore, heterozygous HNF1B deficiency is associated with ciliary anomalies in cholangiocytes, and this may cause cholestasis.
Hepatology 06/2012; 56(3):1178-81. · 11.66 Impact Factor
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ABSTRACT: Hemobilia is an uncommon cause of gastrointestinal bleeding. The etiology is diverse, but most often, it is iatrogenic. The present study aims to reassess the clinical picture and the treatment of choice.
We describe a case series from a single center of patients who presented with nontraumatic iatrogenic hemobilia.
Over a period of 8 years, hemobilia occurred in 12 patients: following liver biopsy in six patients and after endoscopic biliary interventions in four patients, with a respective prevalence of 0.1 and 0.04%. The clinical presentation was characterized by an upper gastrointestinal bleeding (n=11) and/or biochemical signs of sudden biliary obstruction (n=9). The onset of the symptoms occurred after a median of 6 days (range: 1-23). Ultrasound and computed tomography scan missed the diagnosis in, respectively, 4/5 and 2/5 of patients. On arteriography, pseudoaneurysm (6/12) was the most common finding. Transcatheter arterial embolization controlled the bleeding in all cases (12/12) without major complications.
The delay between the intervention and the clinical presentation and the fact that imaging studies may fail to diagnose hemobilia may mislead the physician. Transcatheter arterial embolization is the treatment of choice for hemobilia. It has proven to be effective and safe and it offers a long-term definitive cure.
European journal of gastroenterology & hepatology 05/2012; 24(8):905-9. · 1.66 Impact Factor
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ABSTRACT: Pruritus is a disabling complication of cholestatic liver disorders. Its management remains challenging. Ultraviolet B (UVB) phototherapy has been successfully used to treat pruritus in other indications.
This is an observational case series. The study population consists of 13 patients (10 females, mean age 52 years) with pruritus due to different cholestatic liver disorders: PBC (n=4), PSC (n=2), drug-induced (n=3) and persistent cholestasis after liver transplantation (LT) (n=4). Serum alkaline phosphatase levels were: 686 ± 363 μ/L and serum bile acids levels: 147 ± 15 μmol/L. In all patients, conventional medical treatment had failed to control pruritus. Perception of pruritus was recorded by the visual analogue scale (VAS).
The mean follow-up was 3 years. Ten patients (77%) had more than 60% reduction in perceived pruritus of which 4 had more than an 80% reduction. Median [25-75% percentiles] VAS score before and after treatment decreased from 8.0 [8.0-10] to 2.0 [1.5-2.1] (p<0.001). The mean number of irradiations required to obtain this effect was 26 ± 17 (average duration of phototherapy: 8 weeks). No significant changes in cholestatic serum markers were observed. Four patients (30%) needed an additional phototherapy course because of recurrent pruritus and in all of them again a marked improvement of pruritus was observed. The therapy was well tolerated, except in two patients who developed, during retreatment, pronounced erythema in one case and paresthesia in the other case.
UVB phototherapy appears to be a promising and well tolerated treatment also for cholestasis-associated pruritus.
Journal of Hepatology 05/2012; 57(3):637-41. · 9.26 Impact Factor
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Hannah van Malenstein,
Mina Komuta, Chris Verslype,
Vincent Vandecaveye,
Ben Van Calster,
Baki Topal,
Wim Laleman,
David Cassiman,
Werner Van Steenbergen,
Raymond Aerts,
Dirk Vanbeckevoort,
Didier Bielen,
Jacques Pirenne,
Jos van Pelt,
Tania Roskams,
Frederik Nevens
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ABSTRACT: Aim: Hepatocellular carcinomas (HCC) have a strong biological heterogeneity. Current prognostic scores do not include histology. Information on the behavior of HCC based on histology has been characterized on retrospective data and large tissue specimens. We aimed to assess the additional value of needle biopsy and keratin 19 (K19) assessment in a prospective manner. Methods: Between 2003 and 2008, all patients with a confirmed diagnosis of HCC by a percutaneous or laparoscopic needle biopsy at the time of diagnosis, and of Barcelona Clinic Liver Cancer (BCLC) stage A, B or C, were included. The exclusion criterion was a palliative setting. Biopsies were scored for microvascular invasion, differentiation, K19, epithelial cell adhesion molecule and α-fetoprotein staining. Clinical and radiological features were registered at time of biopsy. The added value of K19 was assessed using Cox proportional hazards regression. Results: Of 74 patients screened, we included 58 patients. Based on the BCLC, 41% presented with early disease (BCLC A), 16% with intermediate disease (BCLC B) and 43% with advanced disease (BCLC C). In nine patients (16%), K19 staining was positive. Median follow up was 54 months (range 1-74) and 43 patients (72%) died. BCLC classification predicted the prognosis accurately, but histology offered additional prognostic information. In multivariate analysis, K19 was a strong predictor of overall survival (hazard ratio 4.57, 95% confidence interval 1.86-10.6), which improved predictive performance. No needle tract dissemination was observed. Conclusion: Despite the possible problem of sampling error, needle biopsy offered additional prognostic information. This is especially the case for K19 staining.
Hepatology Research 03/2012; 42(10):990-8. · 2.20 Impact Factor
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Mina Komuta,
Olivier Govaere,
Vincent Vandecaveye,
Jun Akiba,
Werner Van Steenbergen, Chris Verslype,
Wim Laleman,
Jacques Pirenne,
Raymond Aerts,
Hirohisa Yano,
Frederik Nevens,
Baki Topal,
Tania Roskams
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ABSTRACT: Cholangiocellular carcinoma (CC) originates from topographically heterogeneous cholangiocytes. The cylindrical mucin-producing cholangiocytes are located in large bile ducts and the cuboidal non-mucin-producing cholangiocytes are located in ductules containing bipotential hepatic progenitor cells (HPCs). We investigated the clinicopathological and molecular features of 85 resected CCs (14 hilar CCs [so-called Klatskin tumor], 71 intrahepatic CCs [ICCs] including 20 cholangiolocellular carcinomas [CLCs], which are thought to originate from HPCs]) and compared these with the different cholangiocyte phenotypes, including HPCs. Immunohistochemistry was performed with biliary/HPC and hepatocytic markers. Gene expression profiling was performed in different tumors and compared with nonneoplastic different cholangiocyte phenotypes obtained by laser microdissection. Invasion and cell proliferation assay were assessed using different types of CC cell lines: KMC-1, KMCH-1, and KMCH-2. Among 51 ICCs, 31 (60.8%) contained only mucin-producing CC features (muc-ICCs), whereas 39.2% displayed histological diversity: focal hepatocytic differentiation and ductular areas (mixed-ICCs). Clinicopathologically, muc-ICCs and hilar CCs showed a predominantly (peri-)hilar location, smaller tumor size, and more lymphatic and perineural invasion compared with mixed-ICCs and CLCs (predominantly peripheral location, larger tumor size, and less lymphatic and perineural invasion). Immunoreactivity was similar in muc-ICCs and hilar CCs and in mixed-ICCs and CLCs. S100P and MUC1 were significantly up-regulated in hilar CCs and muc-ICCs compared with mixed-ICCs and CLCs, whereas NCAM1 and ALB tended to be up-regulated in mixed-ICCs and CLCs compared with other tumors. KMC-1 showed significantly higher invasiveness than KMCH-1 and KMCH-2. Conclusion: Muc-ICCs had a clinicopathological, immunohistochemical, and molecular profile similar to that of hilar CCs (from mucin-producing cholangiocytes), whereas mixed-ICCs had a profile similar to that of CLCs (thought to be of HPC origin), possibly reflecting their respective cells of origin.
Hepatology 01/2012; 55(6):1876-88. · 11.66 Impact Factor
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ABSTRACT: To compare the accuracy of wedged hepatic venous pressure (WHVP) measurement with use of an end-hole catheter or an occlusion-balloon catheter versus direct portal pressure (PP) measurement in patients with cirrhosis with sinusoidal portal hypertension and to investigate the factors that affect the results of these indirect measurements.
In a cohort of 174 patients with cirrhosis referred for transjugular intrahepatic portosystemic shunt creation, indirect PP was measured with an end-hole catheter and an occlusion-balloon catheter placed in the right hepatic vein. Direct PP was measured by a pigtail catheter in the main branch of the portal vein.
PP was more accurately estimated by the occlusion-balloon technique: mean WHVP measurements were 25.5 mm Hg ± 7.9 and 30.6 mm Hg ± 13.9, respectively, for the occlusion-balloon and end-hole catheter techniques, and the direct PP measurement was 25.0 mm Hg ± 7.0. The median absolute differences between direct and the indirect methods were 6.0 mm Hg with the end-hole catheter and 2.0 mm Hg with the occlusion-balloon catheter (P < .0001, signed-rank test). Relative to direct PP measurements, the occlusion-balloon technique overestimated pressures in cases of higher Model for End-Stage Liver Disease (MELD) scores (Spearman ρ = -0.24; P = .0005).
Compared with direct PP measurements, agreement was clearly higher for indirect WHVP measurement with occlusion-balloon catheters versus end-hole catheters. However, in patients with a high MELD score, there was an overestimation of PP with the occlusion-balloon method.
Journal of vascular and interventional radiology: JVIR 11/2011; 22(11):1553-8. · 1.81 Impact Factor
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ABSTRACT: We demonstrated in an in vitro model (human HepG2 liver cells) that chronic hypoxia induced gene expression is associated with an aggressive phenotype in patients with hepatocellular carcinoma (HCC). The aim of this study was to characterize this model further using gene expression microarray, real-time PCR and immunocytochemistry. Subsequently, pathway analysis software was used to identify relevant processes. After examination, we selected 2% O2 during 72 h as conditions to study chronic hypoxia. The most affected signaling is centered on TGF-β1 and PPARα/RXRα. Cells at 2% O2 showed a shift in expression of Epithelial-to-Mesenchymal-Transition (EMT) related genes. Furthermore, a downregulation of liver specific detoxification pathways including cytochrome P450's and glutathione-S-transferases was observed. Both up- and downregulation events within different signaling cascades indicated a cellular adaptation and the onset of a new equilibrium. The prominent role of TGF-β1- and PPARα/RXRα signaling and cell motility pathways warrants their further investigation for therapeutic targets in HCC.
Cancer letters 10/2011; 315(2):178-88. · 4.86 Impact Factor
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ABSTRACT: In recent years, acute-on-chronic liver failure has been recognized as a specific clinical form of liver failure associated with cirrhosis. The syndrome refers to an acute deterioration of liver function and subsequently of other end organs over a period of weeks following a precipitating event in a patient with previously well- or reasonably well-compensated cirrhosis. These precipitating events include either an indirect (e.g., variceal hemorrhage, sepsis) or a direct (e.g., drug-induced) hepatotoxic factor. The short-term mortality for this condition is more than 50%. At present, considerable efforts are ongoing to better characterize the syndrome, to gain further insight into its pathophysiology and to optimize therapy. This article aims to highlight the current concepts of these various aspects.
Expert review of gastroenterology & hepatology 08/2011; 5(4):523-37; quiz 537.
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ABSTRACT: Caroli disease is a rare congenital disorder characterized by segmental, nonobstructive dilatation of intrahepatic bile ducts. The term Caroli syndrome is used for the association of Caroli disease with congenital hepatic fibrosis.
To provide an overview of the clinical presentation and imaging features of Caroli disease and syndrome, with an emphasis on magnetic resonance imaging.
Retrospective analysis of medical records on eight patients in whom a histologic diagnosis of Caroli disease or syndrome had been made.
Presenting signs and symptoms were (hepato)splenomegaly, hematemesis and/or melena, cholangitis, jaundice, and recurrent fever. The central dot sign, defined in the literature as a dot or bundle of strong contrast enhancement within dilated intrahepatic ducts, was found in seven cases on various imaging modalities. A 'dot-like structure' was found in one case in which only unenhanced studies were available. There was a tendency toward a right hepatic-lobe predominance.
There is an overlap between the imaging features of Caroli disease and Caroli syndrome. Our findings support earlier reports that the central dot sign is highly specific for the disease, and that it can be reliably detected by current imaging techniques.
European journal of gastroenterology & hepatology 07/2011; 23(7):578-85. · 1.66 Impact Factor
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Sofie Van Binnebeek,
Christophe M Deroose,
Kristof Baete,
Christelle Terwinghe,
Bert Vanbilloen,
Michel Koole,
Karin Haustermans,
Luc Mortelmans, Chris Verslype,
Eric Van Cutsem,
Alfons Verbruggen,
Felix M Mottaghy
Journal of Clinical Oncology 05/2011; 29(19):e579-81. · 18.37 Impact Factor
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Hannah van Malenstein,
Geert Maleux,
Diethard Monbaliu, Chris Verslype,
Mina Komuta,
Tania Roskams,
Wim Laleman,
David Cassiman,
Johan Fevery,
Raymond Aerts,
Jacques Pirenne,
Frederik Nevens
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ABSTRACT: Hepatic hemangiomas are the most common focal liver lesions and are especially prevalent in women. Giant hemangiomas are defined as hemangiomas of at least 4 cm in diameter and the majority remains stable in size over time. However, in some cases hemangiomas display growth and give rise to symptoms because of their space-occupying effect. Causes for the enlargement of the tumors are unknown, but a role of female sex hormones has been suggested. Therefore, hormone therapy should be avoided in patients who became symptomatic. In patients with important symptoms, disease control can be obtained by transcatheter arterial embolization. In selected patients, especially in case of Kasabach-Merritt syndrome, there is a good indication for liver transplantation.
European journal of gastroenterology & hepatology 03/2011; 23(5):438-43. · 1.66 Impact Factor
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ABSTRACT: Transcatheter arterial chemoembolization (TACE) is the standard treatment in selected patients with unresectable hepatocellular carcinoma (HCC). Drug-eluting particles are developed to reduce side effects and improve efficacy. We present safety data of a prospective randomized phase II study with doxorubicin-eluting superabsorbent polymer (SAP) microspheres.
We prospectively included 30 HCC patients with different Barcelona Clinic Liver Cancer (BCLC) stages (A = 3, B = 19, C = 8) and randomly assigned them to receive conventional TACE (n = 14) (control group) or doxorubicin-eluting SAP microspheres (n = 16). The doxorubicin plasma level was assessed at different time points, biochemical analysis was performed, and side effects were reported following the Common Toxicity Criteria. Tumor response was assessed at 6 weeks according to the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
There was a significantly lower plasma peak concentration (Cmax) of doxorubicin and smaller area under the curve (AUC) with SAP microspheres (mean Cmax 495 ± 293.9 ng/ml, mean AUC 69.7 ± 26.9 ng/ml min) compared to controls (mean Cmax 1,928 ± 560.8 ng/ml, mean AUC 165 ± 32.3 ng/ml/min; both p < 0.001). Furthermore, there were less grade 3 and no grade 4 adverse events in the SAP microsphere group. Tumor response was comparable between the groups.
TACE with SAP microspheres leads to low plasma levels of the cytotoxic drug and therefore minimizes toxicity compared to conventional TACE.
Onkologie 01/2011; 34(7):368-76. · 0.87 Impact Factor
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ABSTRACT: Hepatocellular carcinoma (HCC) is a major health problem worldwide responsible for 500 000 deaths annually. A number of risk factors are associated with either the induction of the disease or its progression; these include infection with hepatitis B or C virus, alcohol consumption, non-alcoholic steatohepatitis and certain congenital disorders. In around 80% of the cases, HCC is associated with cirrhosis or advanced fibrosis and with inflammation and oxidative stress. In this review we focus firstly on the different risk factors for HCC and summarize the mechanisms by which each is considered to contribute to HCC. In the second part we look at the molecular processes involved in cancer progression. HCC development is recognized as a multistep process that normally develops over many years. Over this period several mutations accumulate in the cell and that stimulate malign transformation, growth, and metastatic behavior. Over the recent years it has become evident that not only the tumor cell itself but also the tumor microenviroment plays a major role in the development of a tumor. There is a direct link between the role of inflammation and cirrhosis with this microenviroment. Both in vitro and in vivo it has been shown that tumor formation and metastatic properties are linked to epithelial-mesenchymal transition (EMT), a process by which facillitates the tumor cell's attempts to migrate to a more favourable microenviroment. Several groups have analyzed the gene expression in HCC and its surrounding tissue by microarray and this has resulted in the molecular classification into a distinct number of classes. Here we also found a role for hypoxia induced gene expression leading to a clinically more aggressive gene expression in HCC. Molecular analysis also helped to identify important cellular pathways and possible therapeutic targets. The first molecule that in this way has shown clinical application for liver cancer is the multikinase inhibitor sorafenib, others are currently in different stages of clinical studies like the mTOR inhibitor everolimus.
Acta Pharmacologica Sinica 11/2010; 31(11):1409-20. · 1.95 Impact Factor
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ABSTRACT: 'Acute-on-chronic liver failure' (ACLF) is characterised in a more advanced stage by liver failure associated with multiple other end-organ failure. The global clinical characteristics of this entity remain, however, ill-defined.
To characterise and evaluate the clinicopathological features of patients with ACLF compared with patients with chronic decompensated cirrhosis (CHD) in a prospective, homogeneous cohort of patients with histologically proven alcoholic cirrhosis from 2002 to 2007.
In total 250 patients were screened (ACLF (n=70, 28%) and CHD (n=180, 72%)). Alcoholic liver disease was observed in respectively 61/70 (87%) of patients with ACLF and 72/180 (40%) of patients with CHD. After exclusion of 31 patients, 102 patients were studied: 54 with ACLF (median age 51 years; Child-Pugh 12±2; in-hospital mortality 46% (25/54)) and 48 patients with CHD (median age 53 years; Child-Pugh 10±2; in-hospital mortality 10% (5/48)). In the patients with ACLF who survived the hospital stay, the difference in transplant-free survival compared with patients with CHD tended to attenuate with time. At admission the apparent infection of patient groups was comparable but during hospitalisation infection occurred more frequently in patients with ACLF (31/53 (58%)) than in those with CHD (12/47=26%) (p=0.007). Early signs of infection, positive systemic inflammatory response syndrome (SIRS) criteria at admission and ductular bilirubinostasis (p=0.04), were early features that predicted outcome in ACLF.
Patients with ACLF have a high short-term mortality but those who survived the acute exacerbation show a long-term outcome comparable to that of patients with CHD. Infection is the most common cause of mortality in these patients. Positive SIRS criteria and ductular bilirubinostasis are early markers of ACLF and might allow more rapid identification of high-risk patients.
Gut 11/2010; 59(11):1561-9. · 10.11 Impact Factor
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Hannah van Malenstein,
Olivier Gevaert,
Louis Libbrecht,
Anneleen Daemen,
Joke Allemeersch,
Frederik Nevens,
Eric Van Cutsem,
David Cassiman,
Bart De Moor, Chris Verslype,
Jos van Pelt
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ABSTRACT: Hepatocellular carcinomas (HCC) have an unpredictable clinical course, and molecular classification could provide better insights into prognosis and patient-directed therapy. We hypothesized that in HCC, certain microenvironmental regions exist with a characteristic gene expression related to chronic hypoxia which would induce aggressive behavior.
We determined the gene expression pattern for human HepG2 liver cells under chronic hypoxia by microarray analysis. Differentially expressed genes were selected and their clinical values were assessed. In our hypothesis-driven analysis, we included available independent microarray studies of patients with HCC in one single analysis. Three microarray studies encompassing 272 patients were used as training sets to determine a minimal prognostic gene set, and one recent study of 91 patients was used for validation.
Using computational methods, we identified seven genes (out of 3,592 differentially expressed under chronic hypoxia) that showed correlation with poor prognostic indicators in all three training sets (65/139/73 patients) and this was validated in a fourth data set (91 patients). Retrospectively, the seven-gene set was associated with poor survival (hazard ratio, 1.39; P = 0.007) and early recurrence (hazard ratio, 2.92; P = 0.007) in 135 patients. Moreover, using a hypoxia score based on this seven-gene set, we found that patients with a score of >0.35 (n = 42) had a median survival of 307 days, whereas patients with a score of < or =0.35 (n = 93) had a median survival of 1,602 days (P = 0.005).
We identified a unique, liver-specific, seven-gene signature associated with chronic hypoxia that correlates with poor prognosis in HCCs.
Clinical Cancer Research 08/2010; 16(16):4278-88. · 7.74 Impact Factor
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Alain Hendlisz,
Marc Van den Eynde,
Marc Peeters,
Geert Maleux,
Bieke Lambert,
Jaarke Vannoote,
Katrien De Keukeleire, Chris Verslype,
Luc Defreyne,
Eric Van Cutsem,
Philippe Delatte,
Thierry Delaunoit,
Nicola Personeni,
Marianne Paesmans,
Jean-Luc Van Laethem,
Patrick Flamen
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ABSTRACT: Liver dissemination is a major cause of mortality among patients with advanced colorectal cancer. Hepatic intra-arterial injection of the beta-emitting isotope yttrium-90 ((90)Y) bound to resin microspheres (radioembolization) delivers therapeutic radiation doses to liver metastases with minimal damage to adjacent tissues.
We conducted a prospective, multicenter, randomized phase III trial in patients with unresectable, chemotherapy-refractory liver-limited metastatic CRC (mCRC) comparing arm A (fluorouracil [FU] protracted intravenous infusion 300 mg/m(2) days 1 through 14 every 3 weeks) and arm B (radioembolization plus intravenous FU 225 mg/m(2) days 1 through 14 then 300 mg/m(2) days 1 through 14 every 3 weeks) until hepatic progression. The primary end point was time to liver progression (TTLP). Cross-over to radioembolization was permitted after progression in arm A.
Forty-six patients were randomly assigned and 44 were eligible for analysis (arm A, n = 23; arm B, n = 21). Median follow-up was 24.8 months. Median TTLP was 2.1 and 5.5 months in arms A and B, respectively (hazard ratio [HR] = 0.38; 95% CI, 0.20 to 0.72; P = .003). Median time to tumor progression (TTP) was 2.1 and 4.5 months, respectively (HR = 0.51; 95% CI, 0.28 to 0.94; P = .03). Grade 3 or 4 toxicities were recorded in six patients after FU monotherapy and in one patient after radioembolization plus FU treatment (P = .10). Twenty-five of 44 patients received further treatment after progression, including 10 patients in arm A who received radioembolization. Median overall survival was 7.3 and 10.0 months in arms A and B, respectively (HR = 0.92; 95% CI, 0.47 to 1.78; P = .80).
Radioembolization with (90)Y-resin microspheres plus FU is well tolerated and significantly improves TTLP and TTP compared with FU alone. This procedure is a valid therapeutic option for chemotherapy-refractory liver-limited mCRC.
Journal of Clinical Oncology 08/2010; 28(23):3687-94. · 18.37 Impact Factor
