Perfusion-CT monitoring of cryo-ablated renal cells tumors

<p>Abstract</p> <p>Background</p> <p>No single and thoroughly validated imaging method in monitoring of cryoablated renal cell carcinoma (RCC) is available. The purpose of our study was to determine the feasibility of dynamic contrast-enhanced perfusion CT (pCT) in evaluating the hemodynamic response of RCC.</p> <p>Methods</p> <p>15 patients (14 male, 1 female; age range, 43-81 years; mean age, 62 years) with cryoablated RCC via a transperitoneal approach, underwent to pCT 6-8 months after cryo-therapy. pCT was performed for 65 seconds after intravenous injection of contrast medium (80 mL, 370 mg iodine per millilitre, 4 mL/sec). Perfusion parameters (Time/Density curve; Blood flow, BF; Blood Volume, BV; Mean Transit Time, MTT; Permeability-Surface Area Product, PS) were sampled in the cryoablated tumor area and in ipsilateral renal cortex using deconvolution-based method. A tumor was considered to be not responsive to treatment by CT evidence of pathological contrast enhancement in the cryoablated area or renal mass persistence compared with the preoperative CT control. Written informed consent was obtained from all participants before the study.</p> <p>Results</p> <p>After cryotherapy, successfully ablated tumor (n = 13) showed decrease in BV (5,39 +/- 1,28 mL/100 g), BF (69,92 +/- 20,12 mL/100 g/min) and PS (16,66 +/- 5,67 mL/100 g/min) value and increased value of MTT (25,35 +/- 4,3 sec) compared with those of normal renal cortex (BV: 117,86 +/- 31,87 mL/100 g/min; BF: 392,39 +/- 117,32 mL/100 g/min; MTT: 18,02 +/- 3,6 sec; PS: 81,68 +/- 22,75 mL/100 g/min). In one patient, assessment of perfusion parameters was not feasible for breathing artifacts. One tumor showed poor response to treatment by the evidence of nodular contrast enhancement in the region encompassing the original lesion. Two typical enhancement patterns were obtained comparing the Time-Density curves of responsive and not responsive ablated tumors.</p> <p>Conclusion</p> <p>Perfusion CT seems to be a feasible and promising technique in monitoring the effects of cryoablation therapy.</p

A Novel Approach for Prostate Cancer Diagnosis using a Gas Sensor Array

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Portal and interface chronic inflammation are associated with the progenitor cell compartment activation during NAFLD

Background and aim: During nonalcoholic fatty liver disease (NAFLD), portal and interface chronic inflammation (PCI and ICI) are strongly associated with fibrosis by activation of hepatic stellate cell (HSC)s (Brunt et al., 2009; Vespasiani-Gentilucci et al., 2014). However, the determinants of PCI and ICI observed in NAFLD remain to be elucidated. Since portal and periportal ductular reaction is related to disease progression, we aimed to investigate if PCI and ICI are associated with hepatic progenitor cell (HPC) compartment activation. Methods: Fifty-two NAFLD patients were studied. NAFLD activity score, fibrosis, PCI and ICI were histologically evaluated. HPCs, intermediate hepatobiliary cells and bile ductules/interlobular bile ducts were evaluated by immunohistochemistry for CK-7, CK-19 and EpCAM. HSC and myofibroblast (MF) activity were determined by immunohistochemistry for α-SMA. Results: PCI and ICI strongly correlated with HPC compartment activation and with the activity of MFs (p≤0.001). Lobular inflammation, ballooning and HPC compartment activation were all associated with both PCI (p&lt;0.01) and ICI (p&lt;0.05) by univariate analysis. In the multivariate models, HPC compartment activation was independently associated with PCI and ICI (OR 4.4, 1.7-11.5; OR 3.4, 1.5-7.9, respectively). Conclusions: During NAFLD, PCI and ICI are strongly associated with HPC compartment activation and this association is likely one determinant subtending the strong association between PCI/ICI and fibrosis

Toll-like receptor-4 is involved in hepatic fibrogenesis in the course of non-alcoholic fatty liver disease

Toll-like receptor-4 (TLR4) is actively involved in liver in the response to injury from a variety of etiologies. Recently TLR4 expression by hepatic progenitor cells (HPC) and biliary epithelial cells has been associated to the progression of liver damage in chronic HCV-related hepatitis (1). HPC compartment activation in ductular reaction (DR) is a feature of progressive disease also in non-alcoholic fatty liver disease (NAFLD) (2). We aimed to investigate the association among TLR4 expression, HPC compartment activation and histopathologic features of fibrotic disease progression in NAFLD. Seventy-four patients who had undergone liver biopsy were included and immunohistochemistry for TLR4 was performed on hepatic tissue samples. CK-7 was used to evaluate HPC, bile ducts (BD)/ductules of DR and intermediate hepatocytes; α-smooth muscle actin was used to quantify the activation of hepatic stellate cells (HSC) and of portal/septal myofibroblasts (MF). HPC in BD/DR were responsible for the highest TLR4 intensity of staining. TLR4-positive HPC and BD/ DR correlated with fibrosis (p&lt;0.01 and p&lt;0.05), activity of MF (p&lt;0.001 and p&lt;0.05) and HSC (p&lt;0.001 and p&lt;0.001), portal and interface chronic inflammation (p&lt;0.01 and p=0.01). The present study indicates the activation of the TLR4 expressing HPC compartment as important determinant of the progressive liver damage in NAFLD. TLR4 stimulation could represent one of the mechanisms directly linking the activation of HPC to inflammation and fibrosis in NAFLD

Reelin expression in liver and pancreas and its correlation with liver fibrosis

Reelin is an extracellular glycoprotein secreted by a variety of cell types in both embryonic and adult tissue and plays a critical role during brain development (1,2). Reelin is up-regulated in experimental liver cirrhosis of rats in hepatic stellate cell(HSC)s, the cell type mainly implicated in liver fibrogenesis, supporting that reelin is involved in the pathogenesis of liver fibrosis (3). Pancreatic stellate cell(PSC)s share similar morphology and function to HSCs, in pancreatic fibrosis setting (4). Currently, the role of reelin in human liver and pancreas is still unclear. We investigated reelin expression in different stages of chronic liver disease in 81 liver biopsies of HCV affected patients and in pancreatic tissue near to tumoral lesions. The expression of Reelin, HSC markers (CRBP1, alpha-SMA) and Dab1, a Reelin adaptor protein, was investigated by immunohistochemistry and immunofluorescence. Reelin protein was expressed by HSCs and a strong correlation was found between Reelin expression and liver fibrosis stage (

The hepatic expression of GH/IGF1 axis components is impaired with fibrosis progression in patients with HCV-related chronic hepatitis

Background and aim: Resistance to the action of growth hormone (GH), characterized by low serum levels of insulin-like growth factor-1 (IGF1) in the face of high concentrations of GH, frequently complicates cirrhosis (Assy et al., 2008). Physiologically, the activation of GH receptor (GHR) determines phosphorylation of signal transducer and activator of transcription (STAT)-5 and the consequent induction of IGF-1 expression. The suppressor of cytokine signalling (SOCS)-3 negatively regulates this intracellular cascade. Since, to date, the hepatic expression of the GH/IGF1 axis components has been studied mainly in animal models (Blaas L et al., 2010), we aimed to evaluate their expression in the liver of patients with HCV-related chronic hepatitis. Methods: Fifty HCV patients were studied and liver samples were histologically re-evaluated for grading and staging. The expression of GH/IGF1 axis components was assessed by immunohistochemistry. Results: At the hepatocyte level, IGF-1 and phospho-STAT5 showed a negative correlation with fibrosis stage, while SOCS3 a positive one (p&lt;0,05 for all). Furthermore, the hepatocyte expression of IGF1 was negatively correlated with its expression by hepatic stellate cells (p&lt;0,05). Conclusions: IGF1 expression by hepatocytes was reduced with fibrosis progression, probably due to the impairment of GHR intracellular cascade. The inverse correlation between IGF1 expressed by hepatocytes and hepatic stellate cells suggests specific roles for IGF-I produced by different hepatic cells