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Introduction The aim of this study was to determine if neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were predictive of malignancy in mucin-producing pancreatic cystic neoplasms (MpPCN). Methods One hundred and twenty patients with MpPCN were retrospectively reviewed. Malignant neoplasms were defined as neoplasms harbouring invasive carcinoma or high grade dysplasia. A high NLR and PLR were defined as ≥2.551 and ≥208.1, respectively. Results High NLR was significantly associated with symptomatic tumors, larger tumors, solid component, main-duct IPMN, and Sendai high risk category. High PLR was significantly associated with jaundice and Sendai high risk category. On univariate analyses, symptomatic tumors, jaundice, solid component, dilated pancreatic duct, and both a high NLR and PLR were significant predictors of malignant and invasive MpPCN. On multivariate analyses, solid component and dilated pancreatic duct were independent predictors of malignant and invasive MpPCN. PLR was an independent predictor for invasive MpPCN. When MpPCN were stratified by the Fukuoka and Sendai Guidelines, both a high NLR and PLR were significantly associated with malignant neoplasms within the high risk categories. Conclusions PLR is an independent predictor of invasive carcinoma. The addition of PLR as a criterion to the FCG and SCG significantly improved the predictive value of these guidelines in detecting invasive neoplasms. J. Surg. Oncol. 2015; 112:366–371. © 2015 Wiley Periodicals, Inc.

The purpose of this study was to correlate intravoxel incoherent motion (IVIM) imaging with classical perfusion-weighted MRI metrics in human gliomas. Parametric images for slow diffusion coefficient (D), fast diffusion coefficient (D*), and fractional perfusion-related volume (f) in patients with high-grade gliomas were generated. Maps of Fp (plasma flow), vp (vascular plasma volume), PS (permeability surface–area product), ve (extravascular, extracellular volume), E (extraction ratio), ke (influx ratio into the interstitium), and tc (vascular transit time) from dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast-enhanced (DSC) MRI were also generated. A region-of-interest analysis on the contralateral healthy white matter and on the tumor areas was performed and the extracted parameter values were tested for any significant differences among tumor grades or any correlations. Only f could be significantly correlated to DSC-derived vp and tc in healthy brain tissue. Concerning the tumor regions, Fp was significantly positively correlated with D* and inversely correlated with f in DSC measurements. The D*, f, and f × D* values in the WHO grade III gliomas were non-significantly different from those in the grade IV gliomas. There was a trend to significant negative correlations between f and PS as well as between f × D* and ke in DCE experiments. Presumably due to different theoretical background, tracer properties and modeling of the tumor vasculature in the IVIM theory, there is no clearly evident link between D*, f and DSC- and DCE-derived metrics. Copyright © 2014 John Wiley & Sons, Ltd.

Contrary to the common notion that tumor necrotic regions are non-enhancing after contrast administration, recent evidence has shown that necrotic regions exhibit delayed and slow uptake of gadolinium tracer on dynamic contrast-enhanced MRI (DCE MRI). The purpose of this study is to explore whether the mapping of tumor voxels with delayed and slow enhancement on DCE MRI can be used to derive estimates of tumor necrotic fraction. Patient-derived tumor xenograft lines of seven human cancers were implanted in 26 mice which were subjected to DCE MRI performed using a spoiled gradient recalled sequence. Gadolinium tracer concentration was estimated using the variable flip angle technique. To identify tumor voxels exhibiting delayed and slow uptake of contrast medium, clustering analysis was performed using a k-means clustering algorithm that classified tumor voxels according to their contrast enhancement patterns. Comparison of the percentage of tumor voxels exhibiting delayed and slow enhancement with the tumor necrotic fraction estimated on histology showed a strong correlation (r = 0.962, p

Purpose: To devise a noninvasive imaging method for resolving the relative contribution of splenic and splanchnic blood flow to portal venous flow and derive quantitative estimates for parameters pertaining to splenic and portal hemodynamics. Methods: Tracer concentration–time curves of the aorta, portal vein, and spleen can be extracted from dynamic contrast-enhanced (DCE) CT or MR images. A combination of two tracer analysis approaches, namely arterial–venous sampling and residual tracer deconvolution, is proposed to model these concentration–time curves and derive hemodynamic parameters pertaining to splenic and portal circulation. Clinical feasibility of the proposed method was explored using DCE CT datasets of eight cirrhotic patients. Monte Carlo simulations were performed to evaluate the confidence of the parameter estimates. Results: Portal blood flow was estimated to be 763.8 ± 438.1 ml/min in cirrhotic patients and the splenic contribution was found to be elevated (0.75 ± 0.22). Estimates of splenic blood flow (582 ± 420 ml/min) and transit time (15.3 ± 10.1 s) in cirrhotic patients were consistent with reported values obtained using duplex Doppler ultrasound and dynamic scintigraphy, respectively. Conclusions: This study shows the feasibility of noninvasive assessment of splenic and portal hemodynamic parameters by DCE imaging using a combination of tracer kinetics modeling techniques.

The aim of the present study was to compare three tracer kinetics methods for the analysis of dynamic contrast-enhanced (DCE) MRI data, namely the generalized kinetics model, the distributed-parameter model and the initial area under the tumor tracer curve (IAUC) method, in a Phase I study of an anti-angiogenic drug ABT -869; and to explore their utility as biomarkers. Twenty-eight patients with a range of tumors formed the study population. DCE MRI performed at baseline and 2 weeks post-treatment was analyzed using all three methods, yielding percentage changes for various tracer kinetics parameters. Correlation analyzes were performed between these parameters and in relation to drug exposure. The association of these parameters with time-to-progression was examined using receiver-operating characteristic and Kaplan-Meier curves. Significant correlation with drug exposure was found for the following parameters: normalized IAUC (IAUC(norm)), fractional interstitial volume v(e), fractional intravascular volume v(1) and permeability PS. However, only v(e) and PS were effective in predicting late progression. A decrease in v(e) of more than 1.7% and a decrease in PS of more than 25.1% observed at 2 weeks post-treatment could be associated with late progression. All three tracer kinetics methods have biomarker potential for assessing the effects of anti-angiogenic therapy.

Neuroendocrine hepatic metastases exhibit various contrast uptake enhancement patterns in dynamic contrast-enhanced MRI. Using a dual-input two-compartment distributed parameter model, we analyzed the dynamic contrast-enhanced MRI datasets of seven patient study cases with the aim to relate the tumor contrast uptake patterns to parameters of tumor microvasculature. Simulation studies were also performed to provide further insights into the effects of individual microcirculatory parameter on the tumor concentration-time curves. Although the tumor contrast uptake patterns can be influenced by many parameters, initial results indicate that hepatic blood flow and the ratio of fractional vascular volume to fractional interstitial volume may potentially distinguish between the patterns of neuroendocrine hepatic metastases. Magn Reson Med 65: 250-260, 2011. (C) 2010 Wiley-Liss, Inc.

Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. Vascular endothelial growth factor, platelet derived growth factor and the Raf/mitogen-activated protein kinase/extracellular signal regulated kinase (Raf/MEK/ERK) signalling pathway regulates the growth, neovascularization, invasiveness and metastatic potential of HCC. In this study, we investigated the in vivo antitumour activity and mechanisms of action of sorafenib tosylate on four patient-derived HCC xenografts. Sorafenib dosed at 50 mg/kg and 100 mg/kg inhibited tumour growth by 85% and 96%, respectively. Sorafenib-induced growth suppression and apoptosis were associated with inhibition of angiogenesis, down-regulation of phospho-platelet-derived growth factor receptor beta Tyr1021, phospho-eIF4E Ser209, phospho-c-Raf Ser259, c-Raf, Mcl-1, Bcl-2, Bcl-x and positive cell cycle regulators, up-regulation of apoptosis signalling kinase-1, p27 and p21. Expression of IGF-1Rbeta and phosphorylation of c-Raf Ser338, MEK1/2 Ser217/221 and ERK1/2 Thr202/Tyr204 were increased by sorafenib treatment. Phosphorylation of mammalian target-of-rapamycin (mTOR) targets (p70S6K, S6R and 4EBP1) was reduced by sorafenib in sorafenib-sensitive lines but activated in sorafenib-less-sensitive 10-0505 xenograft. Sorafenib-induced phosphorylation of c-met, p70S6K and 4EBP1 was significantly reduced when 10-0505 cells were co-treated with anti-human anti-HGF antibody, suggesting that treatment with sorafenib leads to increased HGF secretion and activation of c-met and mTOR targets. Treatment of 10-0505 tumours with sorafenib plus rapamycin resulted in growth inhibition, inhibition of vascular endothelial growth factor receptor-2 phosphorylation, increased apoptosis and completely blocked sorafenib-induced phosphorylation of mTOR targets and cyclin B1 expression. These data also provide a strong rationale for clinical investigation of sorafenib in combination with mTOR inhibitors in patients with HCC.

Purpose To study the possibility of using independent component analysis (ICA) to identify breast lesions as separate hemodynamic sources on dynamic contrast-enhanced (DCE) MR images, as depicted by the passage of contrast medium. Materials and Methods Six patients who were histopathologically confirmed with breast carcinoma underwent DCE MRI with 5 precontrast and 60 postcontrast scans at a time-resolution of 8 s. A spatial ICA algorithm was applied on the DCE MRI data set to extract spatial component maps corresponding to source locations with different signal time–intensity patterns. To verify the present hypothesis of the ability of ICA to reveal tumor voxels as a separate hemodynamic phase, tumor margins were outlined by an experienced radiologist who was blinded from the ICA results, and the manual outlines were compared with the ICA maps. Results Consistently for each of the six patient study cases, it was found that ICA yields a tumor component map associated with typical tumor enhancement patterns of rapid enhancement with washout or plateau. Tumor outlines manually drawn by the radiologist were in good agreement with the tumor locations depicted in the tumor component maps. Conclusion ICA may provide an objective method for identifying the outlines of enhancing breast tumors on DCE MR images and to automatically extract the tumor signal intensity–time curve for subsequent tracer kinetics analysis. J. Magn. Reson. Imaging 2008. © 2008 Wiley-Liss, Inc.

Summary The aim of this study was to to evaluate the role of a computer-aided program (CAD) in assisting detection of mammographic lesions by radiologists not specifically trained in mammography and its potential utility in breast screening. Mammograms were evaluated by radiologists not specifically trained in mammography first without, and then with, the CAD. Finally, the mammograms were evaluated by experienced mammographers who formed the reference standard. Two hundred and ninety four breasts were studied. In 257 breasts (87.4%), the CAD system did not help with the detection of abnormalities. It assisted radiologists in detecting abnormalities in 21 breasts (7.1%) with potential for detecting abnormalities in a further 13 breasts (4.4%). Only in three cases (1%) did it cause confusion in interpretation. There is overall increased sensitivity in detecting mammographic abnormalities with the aid of the CAD system from 74.4 to 87.2%, which is statistically significant. However, it failed to detect suspicious abnormalities in 71 breasts (24.1%). The CAD system improved detection of suspicious mammographic abnormalities by radiologists who are not specifically trained in mammography. However, there is also a substantial failure to detect suspicious mam­mographic features that cautions against over-reliance on the system, emphasizing its role as a second reader at best.

Background: Solid pseudopapillary tumour of the pancreas is a rare pancreatic tumour that occurs predominantly in women, with very few cases reported in men. This is a tumour with low malignancy potential and surgical resection usually results in cure. Methods: A retrospective review of our experience with solid pseudopapillary tumours between April 1992 and December 2000 was undertaken. Results: Six patients were identified including one male patient. The median age was 30 years, with four patients presenting with abdominal pain and discomfort and two patients presenting with palpable abdominal masses. The mean tumour diameter was 10.2 cm and the lesions were found mainly in the body and tail of the pancreas. Only one patient had tumour at the pancreatic head. One patient had a locally invasive disease and another had peritoneal spread. None of the patients received adjuvant therapy. The mean follow up was 3.8 years (range: 1.5−10.0) and all patients were free of recurrence to date. Conclusion: SPT is a rare tumour with an unclear origin that has a distinct histology and presentation. Although preoperative diagnosis is difficult by computed tomography, magnetic resonance imaging may potentially improve this situation. In general, this is a tumour of very low malignant potential and long-term survival is excellent after resection of the tumour.