Judith Maresch

Lymph node ratio after curative surgery for intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is rare but its incidence is rising worldwide. The value of lymph node dissection for ICC is under discussion; the current staging systems do not differentiate between numbers of involved nodes.

Gadoxetic acid-enhanced 3.0 T MR imaging versus multidetector-row CT in the detection of colorectal metastases in fatty liver using intraoperative ultrasound and histopathology as a standard of reference.

OBJECTIVE To compare the diagnostic value of gadoxetic acid-enhanced MRI at 3.0 T with 64-row MDCT in the detection of colorectal liver metastases in diffuse fatty infiltration of the liver after neoadjuvant chemotherapy. METHODS Twenty-three patients with colorectal liver metastases and at moderate to severe steatosis (25-90%) underwent prospectively preoperative tri-phasic MDCT (Somatom Sensation 64, Siemens) and gadoxetic acid-enhanced MRI (3-T Magnetom Trio, Siemens). All patients underwent surgical resection of liver metastases. Intraoperative ultrasound (IOUS) was carried out, which served as the standard of reference, together with histopathology. RESULTS Overall, 68 metastases (range, 0.4-6 cm; 31/68 metastases [46%] ≤ 1 cm) were found at histology. MDCT detected 49/68 lesions (72%), and MRI 66/68 (97%, p < 0.001). For lesions ≤ 1 cm, MDCT detected only 13/31 (41.9%) and MRI 29/31 (93%, p < 0.001). Eight false-positive lesions were detected by MDCT, seven small lesions by MRI. There was no statistically significant difference between the two modalities in the detection of lesions > 1 cm (p = 0.250). IOUS detected all metastases and revealed two false-positive diagnoses. CONCLUSION Gadoxetic acid-enhanced 3.0 T MRI is superior to 64-row MDCT in detecting colorectal liver metastases ≤ 1 cm during preoperative staging in patients with liver steatosis. A combination of MRI and IOUS may further improve the outcome of surgical treatment.

Value of hepatic venous pressure gradient measurement before liver resection for hepatocellular carcinoma.

Portal hypertension associated with liver cirrhosis increases the risk of postoperative complications after liver resection for hepatocellular carcinoma (HCC). This study assessed the role of preoperative hepatic venous pressure gradient (HVPG) assessment in identifying portal hypertension.

Liver Transplantation: Impaired Biliary Excretion of Gadoxate Is Associated With an Inferior 1-year Retransplantation-free Survival

ObjectivesThe aim of this study was to evaluate gadoxate-enhanced magnetic resonance imaging (MRI) in liver transplant recipients with regard to graft function and mortality at 1 year from imaging. Material and MethodsThis was a retrospective, proof-of-concept study of gadoxate-enhanced 3-T MRI in 51 patients with orthotopic liver transplantation. Relative liver enhancement was calculated as the ratio between the signal intensities in unenhanced and gadoxate-enhanced T1-weighted gradient echo sequences with fat saturation. Impaired excretion was defined as the absence of gadoxate visualization in the common bile duct 20 minutes after intravenous injection. ResultsOf the 51 liver transplant recipients, 31 patients showed a normal hepatobiliary excretion of gadoxate after 20 minutes (group A), whereas 20 patients showed an impaired excretion (group B). Group B had significantly higher serum levels of bilirubin (P < 0.001), aspartate-aminotransferase (P = 0.003), and alkaline phosphatase (P = 0.007), and a higher median Model for End-Stage Liver Disease score (P < 0.001). Within one-year of MRI, 55% of group B died (n = 7) or had to undergo retransplantation (n = 4), whereas all patients in group A survived without retransplantation (P < 0.001). The relative liver enhancement 20 minutes after gadoxate injection was directly related to serum levels of cholinesterase (P < 0.001) and inversely related to the serum levels of bilirubin (P = 0.0098), aspartate-aminotransferase (P = 0.007), and the Model for End-Stage Liver Disease score (P < 0.001). The relative liver enhancement 20 minutes after contrast injection was directly related to the probability of 1-year retransplantation-free survival in proportional hazard regression analysis (P = 0.005). ConclusionGadoxate-enhanced MRI may be a helpful noninvasive prognostic biomarker for chronic rejection and increased risk for 1-year mortality or retransplantation.OBJECTIVES The aim of this study was to evaluate gadoxate-enhanced magnetic resonance imaging (MRI) in liver transplant recipients with regard to graft function and mortality at 1 year from imaging. MATERIAL AND METHODS This was a retrospective, proof-of-concept study of gadoxate-enhanced 3-T MRI in 51 patients with orthotopic liver transplantation. Relative liver enhancement was calculated as the ratio between the signal intensities in unenhanced and gadoxate-enhanced T1-weighted gradient echo sequences with fat saturation. Impaired excretion was defined as the absence of gadoxate visualization in the common bile duct 20 minutes after intravenous injection. RESULTS Of the 51 liver transplant recipients, 31 patients showed a normal hepatobiliary excretion of gadoxate after 20 minutes (group A), whereas 20 patients showed an impaired excretion (group B). Group B had significantly higher serum levels of bilirubin (P < 0.001), aspartate-aminotransferase (P = 0.003), and alkaline phosphatase (P = 0.007), and a higher median Model for End-Stage Liver Disease score (P < 0.001). Within one-year of MRI, 55% of group B died (n = 7) or had to undergo retransplantation (n = 4), whereas all patients in group A survived without retransplantation (P < 0.001). The relative liver enhancement 20 minutes after gadoxate injection was directly related to serum levels of cholinesterase (P < 0.001) and inversely related to the serum levels of bilirubin (P = 0.0098), aspartate-aminotransferase (P = 0.007), and the Model for End-Stage Liver Disease score (P < 0.001). The relative liver enhancement 20 minutes after contrast injection was directly related to the probability of 1-year retransplantation-free survival in proportional hazard regression analysis (P = 0.005). CONCLUSION Gadoxate-enhanced MRI may be a helpful noninvasive prognostic biomarker for chronic rejection and increased risk for 1-year mortality or retransplantation.

Treatment of chronic hepatitis C genotype 1 patients at an academic center in Europe involved in prospective, controlled trials: is there a selection bias?

Pegylated interferon‐alpha2/ribavirin (peg‐IFN/RBV) is the standard of care (SOC) for patients with chronic hepatitis C (CHC) infection. Currently, direct‐acting antiviral agents (DAAs) are evaluated in clinical trials. The aim of this study was to compare baseline characteristics and sustained virologic response (SVR) rates in patients included in clinical trials to those receiving SOC. Medical records of all 503 treatment‐naïve patients with CHC, genotype (GT) 1, referred over a 4‐year period (January 2006‐December 2009) were reviewed. Only 310 of 503 (62%) patients received antiviral therapy, 141 were enrolled in randomized, controlled trials (“study patients”; 101 in DAA studies), and 169 received SOC. At baseline, viral load and platelet count were higher and bilirubin was lower in study patients than in SOC patients. History of psychiatric disorders was more common in SOC patients (43 [25%] versus study patients with 18 [13%]; P < 0.01). Liver biopsy was obtained in 98% of study patients, but only in 59% of SOC patients. Twenty‐nine (21%) and 40 (40%) study and SOC patients, respectively, had advanced fibrosis (F3/4; P = 0.001). By intent‐to‐treat analysis, SVR rates were higher in DAAs (64%; 95% confidence interval [CI]: 53.4‐74.4) than in SOC patients (46%; 95% CI: 37.9‐53.7; P < 0.01), but not different when calculated on a treated‐per‐protocol (TPP) basis. Interleukin (IL)28B GT was equally distributed in both cohorts. By chance, more patients treated with IFN/RBV had rs12979860 C/C‐GT (up to 44%) than DAA‐treated patients. If analyzed according to the IL28B polymorphism, TPP SVR rates did not reach statistically significant differences among study and SOC patients. Conclusions: Baseline characteristics slightly favored study patients, but IL28B GT and treatment adherence were the most important factors determining outcome. Thus, the applicability of the results of controlled studies has to be tested in a “real‐world” setting. (HEPATOLOGY 2012

Additive effect on survival of Raf kinase inhibitor protein and signal transducer and activator of transcription 3 in high-grade glioma.

Animal studies have shown cooperative contribution of the Ras/Raf/MAPK and PI3K/Akt/mTOR signaling pathways in glioblastoma formation. However, this joint action has not yet been confirmed in human studies.

HER-2 status in primary oesophageal cancer, lymph nodes and distant metastases

Some 10–15 per cent of patients with oesophageal cancer overexpress human epidermal growth factor receptor (HER) 2 at the primary tumour site, leading to the hope that specific targeted systemic therapy might favourably influence clinical and subclinical disease at locoregional and distant sites. This approach is based on primary tumour characteristics, without knowledge of expression patterns at metastatic sites. In oesophageal cancer, concordance between HER‐2 status at the primary tumour and other sites is unknown.

Hepatic steatosis assessment with 1H-spectroscopy and chemical shift imaging at 3.0 T before hepatic surgery: Reliable enough for making clinical decisions?

PURPOSE To compare the accuracy of liver fat quantification using chemical shift imaging (CSI) and H1 MR-spectroscopy (MRS) at 3.0 T in patients undergoing liver resection. METHODS Totally 35 patients were included in this prospective IRB approved study. The histopathologically assessed liver fat was compared to the hepatic fat fractions calculated with CSI (with and without spleen correction) and MRS. Spearmans rank correlation and Fisher z-test were used for correlation analysis. Sensitivity and specificity regarding the detection of marked steatosis were calculated for the different modalities and compared using the McNemar test. RESULTS MRS (r=.85) and CSI with spleen correction (r=.85) showed a significantly better correlation (p=.03) with histology compared to CSI without spleen correction (r=.67). Sensitivity and specificity for the detection of marked steatosis was 100% (12/12) and 87% (20/23) for MRS and 92% (11/12) and 83% (19/23) for CSI with spleen correction (p>.12). CONCLUSION For the assessment of hepatic steatosis both CSI with spleen correction and MRS at 3.0 T, show a good correlation with histology. CSI without spleen correction should not be used. Sensitivity and specificity for the detection of marked steatosis are high with both modalities. However, results that are scattered around the cut-off values are not reliable enough for clinical decisions.

Her-2/neu gene amplification and over-expression in stomach and esophageal adenocarcinoma: From pathology to treatment

Discovery of the over-expression of Her-2/neu or the amplification of its regulatory gene in stomach and esophageal cancer has resulted in targeted treatment directed at this protein. The fact itself and its consequences have been the topic of an abundance of studies and clinical trials. In the present report we review the current state of the art as regards diagnosis of the over-expression and amplification of Her-2/neu, its inhibition as a new therapeutic concept, treatment toxicity, and the development of resistance to Her-2/neu as a limiting factor in stomach and esophageal adenocarcinoma.

Mitochondrial toxicity is associated with virological response in patients with HIV and hepatitis C virus coinfection treated with ribavirin and highly active antiretroviral therapy.

The combination of highly active antiretroviral therapy (HAART) plus ribavirin (RBV) in patients with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection has been reported to cause mitochondrial toxicity (MT). Sixty-four patients with HIV-HCV coinfection who were receiving antiviral therapy were evaluated for MT. Patients with concomitant HAART showed greater increases in lactate levels than did patients without HAART, and this difference was more pronounced in patients who received higher dosages of RBV. The incidence of pancreatic enzyme elevations and symptomatic pancreatitis was higher among patients who received HAART and high-dose RBV. Hepatic steatosis increased in patients who received HAART and high-dose RBV. Patients who showed signs of MT achieved higher rates of sustained virologic response than did patients without MT (73% vs 44%).