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Dynamic contrast-enhanced (DCE) CT imaging of four patients with hepatocellular carcinoma (HCC) was performed using a dual-phase imaging protocol designed with initial rapid dynamic imaging to capture the initial increase in contrast medium enhancement in order to assess perfusion, followed by a delayed imaging phase with progressively longer intervals to monitor subsequent tissue enhancement behaviour in order to assess tissue permeability. The DCE CT images were analysed using a dual-input two-compartment distributed parameter model to yield separate estimates for blood flow and permeability, as well as fractional intravascular and extravascular volumes. The HCCs and surrounding cirrhotic liver tissues were found to exhibit enhancement curves that can be appropriately described by two distinct compartments separated by a semipermeable barrier. Early contrast arrival was also found for HCC as compared with background liver. These findings are consistent with the current understanding of sinusoidal capillarization and hepatocarcinogenesis. [ABSTRACT FROM AUTHOR]

Our aim was to compare the perfusion [blood flow (BF)] values obtained by first-pass dynamic contrast-enhanced (DCE) T2-weighted magnetic resonance (MR) and computed tomography (CT) imaging of squamous cell carcinoma (SCC) in the upper aerodigestive tract in the same patient population. Seventeen patients with histologically proven primary SCC of the upper aerodigestive tract were prospectively evaluated. The perfusion CT studies were obtained using a 16-row multi-slice CT scanner running a commercial software package with a deconvolution-based technique; while the perfusion MR studies (1.5 T) were analysed with in-house-written MR perfusion software based also on a deconvolution technique. The mean perfusion values of SCC assessed by perfusion CT and MR imaging were 68.93 +/- 31.61 and 81.56 +/- 49.25 ml/min/100 g, respectively. The Bland-Altman graph showed a proportional error in the perfusion values measured by DCE-CT and -MR imaging; however, the degree of agreement was acceptable (95% limits of agreement: -66.1 to 40.8). Regression analysis of the perfusion values demonstrated significant correlation between the modalities: BF(MR) = 1.34 x BF(CT) - 10.93 (P < 0.0005, r (2) = 0.74). The parametric maps generated by both modalities provided insights into the tumour perfusion, while analysis of the obtained perfusion values demonstrated that both modalities may be used interchangeably in SCC in the upper aerodigestive tract. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate natural language processing (NLP) methods to infer metastatic sites from radiology reports., Methods: A set of 4,522 computed tomography (CT) reports of 550 patients with 14 types of cancer was used to fine-tune four clinical large language models (LLMs) for multilabel classification of metastatic sites. We also developed an NLP information extraction (IE) system (on the basis of named entity recognition, assertion status detection, and relation extraction) for comparison. Model performances were measured by F1 scores on test and three external validation sets. The best model was used to facilitate analysis of metastatic frequencies in a cohort study of 6,555 patients with 53,838 CT reports., Results: The RadBERT, BioBERT, GatorTron-base, and GatorTron-medium LLMs achieved F1 scores of 0.84, 0.87, 0.89, and 0.91, respectively, on the test set. The IE system performed best, achieving an F1 score of 0.93. F1 scores of the IE system by individual cancer type ranged from 0.89 to 0.96. The IE system attained F1 scores of 0.89, 0.83, and 0.81, respectively, on external validation sets including additional cancer types, positron emission tomography-CT ,and magnetic resonance imaging scans, respectively. In our cohort study, we found that for colorectal cancer, liver-only metastases were higher in de novo stage IV versus recurrent patients (29.7% v 12.2%; P < .001). Conversely, lung-only metastases were more frequent in recurrent versus de novo stage IV patients (17.2% v 7.3%; P < .001)., Conclusion: We developed an IE system that accurately infers metastatic sites in multiple primary cancers from radiology reports. It has explainable methods and performs better than some clinical LLMs. The inferred metastatic phenotypes could enhance cancer research databases and clinical trial matching, and identify potential patients for oligometastatic interventions.

Objective: To examine the association between the performance of mapping biopsies and surgical outcomes postexcision of extramammary Paget's disease (EMPD)., Background: Primary EMPD is a rare entity associated with poorly defined surgical margins and difficult-to-access sites of lesions. Surgical resection with clear margins remains the preferred management method. The use of mapping biopsies might be beneficial, particularly in lowering disease recurrence., Methods: Available literature was reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology before a fixed-effect meta-analysis was performed to identify the presence of a correlation between performing mapping biopsies and positive margins on permanent sections as well as disease-free survival. Additional study results not included in the quantitative assessment were qualitatively assessed and reported., Results: A total of 12 studies were shortlisted for final analysis. 294 patients who underwent mapping biopsies and 48 patients who did not undergo mapping biopsies were included in the assessment. Forest plot analysis revealed a pooled rate ratio of 0.50 (95% CI, 0.32-0.77) in the prevalence of positive margins in patients with mapping biopsies performed as compared to patients without. The pooled rate ratio of the prevalence of disease-free survival in patients with mapping biopsies performed as compared to patients without was 1.38 (95% CI, 1.03-1.84). Qualitative assessment of the remaining selected studies revealed equivocal results., Conclusions: Mapping biopsies are able to improve EMPD surgical excision outcomes but given the rarity of the disease and heterogeneity of mapping biopsy procedures, further confirmation with randomized controlled trials or a larger patient pool is necessary., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To assess large language models on their ability to accurately infer cancer disease response from free-text radiology reports., Materials and Methods: We assembled 10 602 computed tomography reports from cancer patients seen at a single institution. All reports were classified into: no evidence of disease, partial response, stable disease, or progressive disease. We applied transformer models, a bidirectional long short-term memory model, a convolutional neural network model, and conventional machine learning methods to this task. Data augmentation using sentence permutation with consistency loss as well as prompt-based fine-tuning were used on the best-performing models. Models were validated on a hold-out test set and an external validation set based on Response Evaluation Criteria in Solid Tumors (RECIST) classifications., Results: The best-performing model was the GatorTron transformer which achieved an accuracy of 0.8916 on the test set and 0.8919 on the RECIST validation set. Data augmentation further improved the accuracy to 0.8976. Prompt-based fine-tuning did not further improve accuracy but was able to reduce the number of training reports to 500 while still achieving good performance., Discussion: These models could be used by researchers to derive progression-free survival in large datasets. It may also serve as a decision support tool by providing clinicians an automated second opinion of disease response., Conclusions: Large clinical language models demonstrate potential to infer cancer disease response from radiology reports at scale. Data augmentation techniques are useful to further improve performance. Prompt-based fine-tuning can significantly reduce the size of the training dataset., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Background: The performance of MRI versus CT in the detection and evaluation of peritoneal surface malignancies (PSM) remains unclear in the current literature. Our study is the first prospective study in an Asian center comparing the two imaging modalities, validated against intra-operative findings. Methods: A total of 36 patients with PSM eligible for CRS-HIPEC underwent both MRI and CT scans up to 6 weeks before the operation. The scans were assessed for the presence and distribution of PSM and scored using the peritoneal cancer index (PCI), which were compared against PCI determined at surgery. Results: Both MRI and CT were 100% sensitive and specific in detecting the overall presence of PSM. Across all peritoneal regions, the sensitivity and specificity for PSM detection was 49.1% and 93.0% for MRI, compared to 47.8% and 95.1% for CT (p = 0.76). MRI was more sensitive than CT for small bowel disease, although the difference did not reach statistical significance. Comparing PCI on imaging with intra-operative PCI, the mean difference was found to be −3.4 ± 5.4 (p < 0.01) for MRI, and −3.9 ± 4.1 (p < 0.01) for CT. The correlation between imaging and intra-operative PCI was poor, with a concordance coefficient of 0.76 and 0.79 for MRI and CT, respectively. Within individual peritoneal regions, there was also poor agreement between imaging and intra-operative PCI for both modalities, other than in regions 1 and 3. Conclusion: MRI and CT are comparable in the detection and evaluation of PSM. While sensitive in the overall detection of PSM, they are likely to underestimate the true disease burden.

Background: Therapeutic synergism between radiotherapy and immune checkpoint blockade has been observed in preclinical models of hepatocellular carcinoma. We aimed to study the safety and efficacy of sequential radioembolisation with yttrium-90-resin microspheres (Y90-radioembolisation) followed by nivolumab in patients with advanced hepatocellular carcinoma., Methods: Patients with Child-Pugh A cirrhosis and advanced hepatocellular carcinoma not suitable for curative surgery were treated with Y90-radioembolisation followed by intravenous nivolumab 240 mg 21 days after Y90-radioembolisation and every 2 weeks thereafter. The primary endpoint, assessed in the per-protocol population, was the objective response rate, determined by RECIST version 1.1, defined as the proportion of patients with a confirmed complete or partial response observed for lesions both within and outside the Y90-radioembolisation field. This study is registered with ClinicalTrials.gov, NCT03033446 and has been completed., Findings: 40 patients were enrolled, of whom 36 received Y90-radioembolisation followed by nivolumab. One (3%) patient had a complete response and ten (28%) had a partial response; the objective response rate was 30·6% (95% CI 16·4-48·1). The most common treatment-related adverse events of any grade were pruritus (18 [50%] of 36 patients) and maculopapular rash (13 [36%]). Two (6%) patients experienced grade 3-4 treatment-related adverse events: one patient had a grade 3 increase in alanine aminotransferase levels, grade 3 bilirubin increase, and grade 4 increase in aspartate aminotransferase levels, while the other had a grade 3 maculopapular rash. Five (14%) patients had a treatment-related serious adverse event (Steven-Johnson syndrome, hepatitis E infection, fever, liver abscesses, and ascites)., Interpretation: Y90-radioembolisation followed by nivolumab resulted in an encouraging objective response rate in patients with advanced hepatocellular carcinoma, although the activity observed was not as high as the study was powered for. This strategy should be further evaluated in patients with Barcelona Clinic Liver Clinic (BCLC) stage B hepatocellular carcinoma that is ineligible or refractory to transarterial chemoembolisation and patients with BCLC C disease without extrahepatic spread., Funding: National Medical Research Council Singapore, Bristol-Myers Squibb, Sirtex., Competing Interests: Declaration of interests DT declares support for the current manuscript from Bristol-Myers Squibb, Sirtex, and NMRC Singapore (CIRG/1470/2017); payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Ipsen, Eisai, and Bristol-Myers Squibb; and consulting fees from Novartis, Bristol-Myers Squibb, and Merck Sharpe Dohme. CSP declares payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Roche, Bristol-Myers Squibb, Ipsen, Lilly, AstraZeneca, and Roche; consulting fees from Bristol-Myers Squibb, Roche, Ipsen, Servier, Eisai, and AstraZeneca; a leadership or fiduciary role for Ministry of Health Singapore Medishield Life Cancer Drug committee; and stock or stock options with Bristol-Myers Squibb. DN declares support for the present manuscript from Sirtex; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Sirtex. JL declares payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bristol-Myers Squibb, Ipsen, and Bayer; and research funding from Bayer. PKHC declares grants or contracts from Sirtex Medical, Ipsen, IQVIA, New B Innovation, Perspectum, AMiLi, MiRXES, Genentech, and Engine Biosciences; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Sirtex Medical, Ipsen, Oncosil, Bayer, Roche, New B Innovation, Merck Sharpe Dohme, BTG Plc, Eisai, Abbott, AstraZeneca, IQVIA, Genentech, Worrell Guerbet, LEK Consulting, and COR2ED; and a leadership or fiduciary role, and stock or stock options for AVATAMED. TCW declares payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events and consulting fees from Sirtex. KL, AG, NKA, TSH, TH, FI, JL, MN, TCK, KSL, CHS, GGBB, HLH, NK, RL, BG, AC, THC, TCH, TL, JY, ZWW, and CCY declared no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Real-world management of patients with hepatocellular carcinoma (HCC) is crucially challenging in the current rapidly evolving clinical environment which includes the need for respecting patient preferences and autonomy. In this context, regional/national treatment guidelines nuanced to local demographics have increasing importance in guiding disease management. We report here real-world data on clinical outcomes in HCC from a validation of the Consensus Guidelines for HCC at the National Cancer Centre Singapore (NCCS)., Method: We evaluated the NCCS guidelines using prospectively collected real-world data, comparing the efficacy of treatment received using overall survival (OS) and progression-free survival (PFS). Treatment outcomes were also independently evaluated against 2 external sets of guidelines, the Barcelona Clinic Liver Cancer (BCLC) and Hong Kong Liver Cancer (HKLC)., Results: Overall treatment compliance to the NCCS guidelines was 79.2%. Superior median OS was observed in patients receiving treatment compliant with NCCS guidelines for early (nonestimable vs. 23.5 months p < 0.0001), locally advanced (28.1 vs. 22.2 months p = 0.0216) and locally advanced with macrovascular invasion (10.3 vs. 3.3 months p = 0.0013) but not for metastatic HCC (8.1 vs. 6.8 months p = 0.6300), but PFS was similar. Better clinical outcomes were seen in BCLC C patients who received treatment compliant with NCCS guidelines than in patients with treatment only allowed by BCLC guidelines (median OS 14.2 vs. 7.4 months p = 0.0002; median PFS 6.1 vs. 4.0 months p = 0.0286). Clinical outcomes were, however, similar for patients across all HKLC stages receiving NCCS-recommended treatment regardless of whether their treatment was allowed by HKLC., Conclusion: The high overall compliance rate and satisfactory clinical outcomes of patients managed according to the NCCS guidelines confirm its validity. This validation using real-world data considers patient and treating clinician preferences, thus providing a realistic analysis of the usefulness of the NCCS guidelines when applied in the clinics., Competing Interests: Pierce K.H. Chow declares the following conflicts of interest: Editorial Board Member of Liver Cancer, Consulting or Advisory Role: Sirtex Medical, Bayer, Roche, New B Innovation, MSD, BTG PLC, Eisai, Abbott, IQVIA, Genentech, L.E.K Consulting, Astra Zeneca, Guerbet, Ipsen, OncoSil Medical, and Bristol-Myers Squibb; Speakers' Bureau: Sirtex Medical; and Research Funding: Sirtex Medical (Inst), New B Innovation (Inst), and IQVIA (Inst)., (Copyright © 2021 by S. Karger AG, Basel.)

Mammography is extensively used for breast cancer screening but has high false-positive rates. Here, prospectively collected blood samples were used to identify circulating microRNA (miRNA) biomarkers to discriminate between malignant and benign breast lesions among women with abnormal mammograms. The Discovery cohort comprised 72 patients with breast cancer and 197 patients with benign breast lesions, while the Validation cohort had 73 and 196 cancer and benign cases, respectively. Absolute expression levels of 324 miRNAs were determined using RT-qPCR. miRNA biomarker panels were identified by: (1) determining differential expression between malignant and benign breast lesions, (2) focusing on top differentially expressed miRNAs, and (3) building panels from an unbiased search among all expressed miRNAs. Two-fold cross-validation incorporating a feature selection algorithm and logistic regression was performed. A six-miRNA biomarker panel identified by the third strategy, had an area under the curve (AUC) of 0.785 and 0.774 in the Discovery and Validation cohorts, respectively, and an AUC of 0.881 when differentiating between cases versus those with benign lesions or healthy individuals with normal mammograms. Biomarker panel scores increased with tumor size, stage and number of lymph nodes involved. Our work demonstrates that circulating miRNA signatures can potentially be used with mammography to differentiate between patients with malignant and benign breast lesions.

Purpose: Overexpression of fibroblast growth factor receptor (FGFR) contributes to tumorigenesis, metastasis, and poor prognosis of hepatocellular carcinoma (HCC). Infigratinib-a pan-FGFR inhibitor-potently suppresses the growth of high-FGFR-expressing HCCs in part via alteration of the tumor microenvironment and vessel normalization. In this study, we aim to assess the utility of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) as a non-invasive imaging technique to detect microenvironment changes associated with infigratinib and sorafenib treatment in high-FGFR-expressing HCC xenografts., Procedures: Serial DCE-MRIs were performed on 12 nude mice bearing high-FGFR-expressing patient-derived HCC xenografts to quantify tumor microenvironment pre- (day 0) and post-treatment (days 3, 6, 9, and 15) of vehicle, sorafenib, and infigratinib. DCE-MRI data were analyzed using extended generalized kinetic model and two-compartment distributed parameter model. After treatment, immunohistochemistry stains were performed on the harvested tumors to confirm DCE-MRI findings., Results: By treatment day 15, infigratinib induced tumor regression (70 % volume reduction from baseline) while sorafenib induced relative growth arrest (185 % volume increase from baseline versus 694 % volume increase from baseline of control). DCE-MRI analysis revealed different changes in microcirculatory parameters upon exposure to sorafenib versus infigratinib. While sorafenib induced microenvironment changes similar to those of rapidly growing tumors, such as a decrease in blood flow (F), fractional intravascular volume (v p ), and permeability surface area product (PS), infigratinib induced the exact opposite changes as early as day 3 after treatment: increase in F, v p , and PS., Conclusions: Our study demonstrated that DCE-MRI is a reliable non-invasive imaging technique to monitor tumor microcirculatory response to FGFR inhibition and VEGF inhibition in high-FGFR-expressing HCC xenografts. Furthermore, the microcirculatory changes from FGFR inhibition manifested early upon treatment initiation and were reliably detected by DCE-MRI, creating possibilities of combinatorial therapy for synergistic effect.

Introduction: The impact on clinical practice of the international guidelines including the Sendai Guidelines (SG06) and Fukuoka Guidelines (FG12) on the management of cystic lesions of the pancreas (CLP) has not been well-studied. The primary aim was to examine the changing trends and outcomes in the surgical management of CLP in our institution over time and to determine the impact of these guidelines on our institution practice., Methods: 462 patients with surgically-treated CLP were retrospectively reviewed and classified under the 2 guidelines. The cohort was divided into 3 time periods: 1998-2006, 2007-2012 and 2013 to 2018., Results: Comparison across the 3 time periods demonstrated significantly increasing frequency of older patients, asymptomatic CLP, male gender, smaller tumor size, elevated Ca 19-9, use of magnetic resonance imaging (MRI) and use of endoscopic ultrasound (EUS) prior to surgery. There was also significantly increasing frequency of adherence to the international guidelines as evidenced by the increasing proportion of HR SG06 and HR FG12 CLP with a corresponding lower proportion of LR SG06 and LR FG12 being resected. This resulted in a significantly higher proportion of resected CLP whereby the final pathology confirmed that a surgery was actually indicated., Conclusions: Over time, there was increasing adherence to the international guidelines for the selection of patients for surgical resection as evidenced by the significantly increasing proportion of HR SG06 and HR FG06 CLPs undergoing surgery. This was associated with a significantly higher proportion of patients with a definitive indication for surgery. These suggested that over time, there was a continuous improvement in our selection of appropriate CLP for surgical treatment., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare. The authors did not receive any outside support for research, including funding, equipment and drugs., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: We hypothesized that spatial heterogeneity exists between recurrent and non-recurrent regions within a tumor. The aim of this study was to determine if there is a difference between radiomics features derived from recurrent versus non recurrent regions within the tumor based on pre-treatment MRI., Methods: A total of 14 T4NxM0 NPC patients with histologically proven "in field" recurrence in the post nasal space following curative intent IMRT were included in this study. Pretreatment MRI were co-registered with MRI at the time of recurrence for the delineation of gross tumor volume at diagnosis(GTV) and at recurrence(GTVr). A total of 7 histogram features and 40 texture features were computed from the recurrent(GTVr) and non-recurrent region(GTV-GTVr). Paired t-tests and Wilcoxon signed-rank tests were carried out on the 47 quantified radiomics features., Results: A total of 7 features were significantly different between recurrent and non-recurrent regions. Other than the variance from intensity-based histogram, the remaining six significant features were either from the gray-level size zone matrix (GLSZM) or the neighbourhood gray-tone difference matrix (NGTDM)., Conclusions: The radiomic features extracted from pre-treatment MRI can potentially reflect the difference between recurrent and non-recurrent regions within a tumor and has a potential role in pre-treatment identification of intra-tumoral radio-resistance for selective dose escalation., Competing Interests: The authors have declared that no competing interests exist.

This article explores new acquisition methods in magnetic resonance (MR) imaging to provide high spatial and temporal resolution imaging for a wide spectrum of clinical applications in the abdomen and pelvis. We present an overview of some of these advanced MR techniques, such as non-cartesian image acquisition, fast sampling and compressed sensing, diffusion quantification and quantitative MR that can improve data sampling, enhance image quality, yield quantitative measurements, and/or optimize diagnostic performance in the body., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Although mammography is the gold standard for breast cancer screening, the high rates of false-positive mammograms remain a concern. Thus, there is an unmet clinical need for a non-invasive and reliable test to differentiate between malignant and benign breast lesions in order to avoid subjecting patients with abnormal mammograms to unnecessary follow-up diagnostic procedures. Serum samples from 116 malignant breast lesions and 64 benign breast lesions were comprehensively profiled for 2,083 microRNAs (miRNAs) using next-generation sequencing. Of the 180 samples profiled, three outliers were removed based on the principal component analysis (PCA), and the remaining samples were divided into training ( n = 125) and test ( n = 52) sets at a 70:30 ratio for further analysis. In the training set, significantly differentially expressed miRNAs (adjusted p < 0.01) were identified after correcting for multiple testing using a false discovery rate. Subsequently, a predictive classification model using an eight-miRNA signature and a Bayesian logistic regression algorithm was developed. Based on the receiver operating characteristic (ROC) curve analysis in the test set, the model could achieve an area under the curve (AUC) of 0.9542. Together, this study demonstrates the potential use of circulating miRNAs as an adjunct test to stratify breast lesions in patients with abnormal screening mammograms.

Immune checkpoint inhibitors (ICIs) have demonstrated promising results in a variety of advanced cancer types. The phenomenon of hyperprogressive disease (HPD) has only been documented in recent years, however, there have been no reports of HPD in hepatocellular carcinoma. We present a case series of six patients with advanced hepatocellular carcinoma treated with ICIs who demonstrated rapid radiological progression, this was confirmed by comparing tumor growth rates before and during treatment with HPD defined as tumor growth rate ratio ≥2. Although ICIs have demonstrated profound efficacy in advanced cancer, they might also be responsible for HPD in a small subset of patients. The ability to predict treatment response to ICI is thus of importance in protecting patients from the deleterious effects of HPD.

Purpose Selective internal radiation therapy or radioembolization (RE) shows efficacy in unresectable hepatocellular carcinoma (HCC) limited to the liver. This study compared the safety and efficacy of RE and sorafenib in patients with locally advanced HCC. Patients and Methods SIRveNIB (selective internal radiation therapy v sorafenib), an open-label, investigator-initiated, phase III trial, compared yttrium-90 ( 90 Y) resin microspheres RE with sorafenib 800 mg/d in patients with locally advanced HCC in a two-tailed study designed for superiority/detriment. Patients were randomly assigned 1:1 and stratified by center and presence of portal vein thrombosis. Primary end point was overall survival (OS). Efficacy analyses were performed in the intention-to-treat population and safety analyses in the treated population. Results A total of 360 patients were randomly assigned (RE, 182; sorafenib, 178) from 11 countries in the Asia-Pacific region. In the RE and sorafenib groups, 28.6% and 9.0%, respectively, failed to receive assigned therapy without significant cross-over to either group. Median OS was 8.8 and 10.0 months with RE and sorafenib, respectively (hazard ratio, 1.1; 95% CI, 0.9 to 1.4; P = .36). A total of 1,468 treatment-emergent adverse events (AEs) were reported (RE, 437; sorafenib, 1,031). Significantly fewer patients in the RE than sorafenib group had grade ≥ 3 AEs (36 of 130 [27.7%]) v 82 of 162 [50.6%]; P < .001). The most common grade ≥ 3 AEs were ascites (five of 130 [3.8%] v four of 162 [2.5%] patients), abdominal pain (three [2.3%] v two [1.2%] patients), anemia (zero v four [2.5%] patients), and radiation hepatitis (two [1.5%] v zero [0%] patients). Fewer patients in the RE group (27 of 130 [20.8%]) than in the sorafenib group (57 of 162 [35.2%]) had serious AEs. Conclusion In patients with locally advanced HCC, OS did not differ significantly between RE and sorafenib. The improved toxicity profile of RE may inform treatment choice in selected patients.

Background: This systematic review was performed to assess the clinical utility of the Sendai Consensus Guidelines (SCG) and Fukuoka Consensus Guidelines (FCG) for intraductal papillary mucinous neoplasm (IPMN)., Methods: A computerized search of PubMed was performed to identify all the studies which evaluated the SCG and FCG in surgically resected, histologically confirmed IPMNs., Results: Ten studies evaluating the FCG, 8 evaluating the SCG and 4 evaluating both guidelines were included. In 14 studies evaluating the FCG, out of a total of 2498 neoplasms, 849 were malignant and 1649 were benign neoplasms. Pooled analysis showed that 751 of 1801 (42%) FCG+ve neoplasms were malignant and 599 neoplasms of 697 (86%) FCG-ve neoplasms were benign. PPV of the high risk and worrisome risk groups were 465/986 (47%) and 239/520 (46%) respectively. In 12 studies evaluating the SCG, 1234 neoplasms were analyzed of which 388 (31%) were malignant and 846 (69%) were benign. Pooled analysis demonstrated that 265 of 802 (33%) SCG+ve neoplasms were malignant and 238 of 266 SCG-ve (90%) neoplasms were benign., Conclusion: The FCG had a higher positive predictive value (PPV) compared to the SCG. However, the negative predictive value (NPV) of the FCG was slightly lower than that of the SCG. Malignant and even invasive IPMN may be missed according to both guidelines., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Purpose To report the safety profile and 2-year functional outcomes of in-bore magnetic resonance (MR)-guided focused ultrasound on single cancer foci in men with prostate cancer. Materials and Methods Ethics approval was obtained from the centralized institutional review board for this prospective single-arm study, and patients provided informed consent. Patients with untreated low-volume low-grade prostate cancer (clinical stage T2a or lower; Gleason score, 3+3; index tumor ≤10 mm 3 ) underwent MR-guided focused ultrasound between July 2011 and February 2013. All patients underwent robotic transperineal mapping biopsy and multiparametric MR imaging. Only those with a maximum of two lesions smaller than 10 mm at mapping biopsy were included. Target areas were sonicated with real-time MR thermometry monitoring, excluding critical areas from the beam path. Serum prostate-specific antigen (PSA) and Expanded Prostate Index Composite (EPIC) scores were obtained at baseline and at 1, 3, 6, 12, 18, and 24 months and were plotted to observe their trend. Mean EPIC subdomain score changes at each serial time point were compared with the baseline score by using paired t tests (level of significance, P < .007). Repeat transperineal biopsy was performed at 6 and 24 months. Results Fourteen men (mean age, 62.8 years; median PSA level, 8.3 ng/mL) underwent treatment, with 12 men completing 2-year follow-up. A median reduction of PSA level by 2.9 ng/mL was observed at 6 months. Seven men had Clavien-Dindo grade 1-2 complications. There was a slight insignificant deterioration of EPIC urinary symptom score (mean increase of 7.8 points compared with baseline, P = .012) noted at 1 month, but it returned to baseline by 3 months. There was a trend to deterioration in sexual function score (mean decrease, 4.4 points; P = .04 [not significant]) that normalized at 3 months. There was no significant change in EPIC subdomain scores from baseline over the 24 months. At 6-month template biopsy, one man had cancer with a Gleason score greater than 6; at 24 months, three men had cancer with a Gleason score greater than 6. Conclusion MR-guided focused ultrasound is technically feasible for focal prostate ablation and appears to have a favorable early safety and functional profile. Further clinical trials are necessary to establish oncologic efficacy. © RSNA, 2017 Online supplemental material is available for this article.

The transfer constant K trans is commonly employed in dynamic contrast-enhanced MRI studies, but the utility and interpretation of K trans as a potential biomarker of tumor vasculature remains unclear. In this study, computer simulations based on a comprehensive tracer kinetic model with multiple pathways was used to provide clarification on the interpretation and application of K trans . Tissue concentration-time curves pertaining to a wide range of transport conditions were simulated using the multiple-pathway (MP) model and fitted using the generalized kinetic (GK) and extended GK models. Relationships between K trans and plasma flow F p , vessel permeability PS and extraction rate EF p under various transport conditions were assessed by correlation and regression analysis. Results show that the MP model provides an alternative two-tier interpretation of K trans based on the vascular transit time. K trans is primarily associated with F p and EF p respectively, in the slow and rapid vascular transit states, independent of the magnitude of PS. The relative magnitudes of PS and F p only serve as secondary constraints for which K trans can be further associated with EF p and PS in the slow and rapid transit states, respectively.

Introduction: To assess if parameters in intravoxel incoherent motion (IVIM) and diffusion tensor imaging (DTI) can be used to evaluate early renal fibrosis in a mouse model of diabetic nephropathy., Materials & Methods: In a population of 38 male CD1 mice (8weeks old, 20-30g), streptozotocin induced diabetes was created in 20 mice via a single intraperitoneal injection of streptozotocin at 150mg/kg, while 18 mice served as control group. IVIM parameters were acquired at 0, 12 and 24weeks after injection of streptozotocin using a range of b values from 0 to 1200s/mm 2 . DTI parameters were obtained using 12 diffusion directions and lower b values of 0, 100 and 400s/mm 2 . DTI and IVIM parameters were obtained using region of interests drawn over the renal parenchyma. Histopathological analysis of the right kidney was performed in all mice. Results were analyzed using an unpaired t-test with P<0.05 considered statistically significant., Results: Renal cortex fractional anisotropy (FA) was significantly lower in the diabetes group at week 12 as compared with the control group. Renal cortex apparent diffusion coefficient and tissue diffusivity were significantly higher in the diabetes group at week 12 compared with the control group at 12weeks. Blood flow was significantly decreased at the renal medulla at 24weeks. Histopathological analysis confirmed fibrosis in the diabetes group at 24weeks., Conclusion: FA is significantly reduced in diabetic nephropathy. FA might serve a potential role in the detection and therapy monitoring of early diabetic nephropathy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Treatment with sorafenib, although associated with inhibition of tumour growth and angiogenesis in in vivo studies, leads to up-regulation of pERK. The addition of MEK inhibition could potentially abrogate this effect and potentiate anti-tumour activity. This phase I study investigated the maximum tolerated dose (MTD), safety, tolerability, pharmacokinetics (PK) and biomarker correlates of selumetinib combined with sorafenib in patients with advanced hepatocellular carcinoma (HCC)., Methods: Patients with Child-Pugh (CP) score ≤7 were treated with 400 mg twice daily of sorafenib with escalating doses of selumetinib in a 3 + 3 study design. The dose-limiting toxicity (DLT) evaluation period was 28 days. PK of selumetinib was determined. Angiogenic effect was evaluated with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)., Results: Twenty-seven patients of Asian ethnicity were enrolled. The MTD was selumetinib 75 mg daily with sorafenib 400 mg twice daily. DLT included grade 3 transaminitis, diarrhoea and fatigue. Most common treatment-related adverse events at MTD (all grades) were diarrhoea (85%), rash (59%), hypertension (44%), fatigue (30%), anorexia (22%) and hand-foot syndrome (22%). Four patients (15%) had PR and 13 (48%) had SD. PR or SD was observed for ≥6 months in seven patients. The median overall survival was 14.4 months. Selumetinib exposures in combination with sorafenib were comparable to other monotherapy studies. A reduction in permeability-surface area product noted in DCE-MRI with treatment correlated with worse survival outcomes., Conclusion: The MTD of selumetinib was 75 mg daily when combined with sorafenib 400 mg twice a day in CP ≤7 HCC. Acceptable adverse events and encouraging anti-tumour activity warrant further evaluation. DCE-MRI findings deserve prospective evaluation., Clinicaltrialsgov Identifier: NCT01029418., (© The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Approximately 20 % of hepatocellular carcinoma (HCC) patients diagnosed in the early stages may benefit from potentially curative ablative therapies such as surgical resection, transplantation or radiofrequency ablation. For patients not eligible for such options, prognosis is poor. Sorafenib and Selective Internal Radiation Therapy (SIRT) are clinically proven treatment options in patients with unresectable HCC, and this study aims to assess overall survival following either SIRT or Sorafenib therapy for locally advanced HCC patients., Methods: This investigator-initiated, multi-centre, open-label, randomized, controlled trial will enrol 360 patients with locally advanced HCC, as defined by Barcelona Clinic Liver Cancer stage B or stage C, without distant metastases, and which is not amenable to immediate curative treatment. Exclusion criteria include previous systemic therapy, metastatic disease, complete occlusion of the main portal vein, or a Child-Pugh score of >7. Eligible patients will be randomised 1:1 and stratified by centre and presence or absence of portal vein thrombosis to receive either a single administration of SIRT using yttrium-90 resin microspheres (SIR-Spheres®, Sirtex Medical Limited, Sydney, Australia) targeted at HCC in the liver by the trans-arterial route or continuous oral Sorafenib (Nexavar®, Bayer Pharma AG, Berlin, Germany) at a dose of 400 mg twice daily until disease progression, no further response, complete regression or unacceptable toxicity. Patients for both the Sorafenib and SIRT arms will be followed-up every 4 weeks for the first 3 months and 12 weekly thereafter. Overall survival is the primary endpoint, assessed for the intention-to-treat population. Secondary endpoints are tumour response rate, time-to-tumour progression, progression free survival, quality of life and down-staging to receive potentially curative therapy., Discussion: Definitive data comparing these two therapies will help to determine clinical practice in the large group of patients with locally advanced HCC and improve outcomes for such patients., Trial Registration: ClinicalTrials.gov identifier, NCT01135056 , first received 24, May 2010.

Background: Prolonged anti-angiogenic therapy destroys tumor vasculature, whereas vascular-normalizing doses may enhance intra-tumoral drug delivery. We hypothesize that low-dose, short-course sunitinib normalizes vasculature, enhancing chemotherapy efficacy., Patients and Methods: In phase Ib, treatment-naïve breast cancer patients received four cycles of pre-operative doxorubicin/cyclophosphamide, with sunitinib before each cycle. The optimal dose of sunitinib leading to tumor vessel normalization on immunohistochemistry was identified. In phase II, subjects were randomized to chemotherapy alone or chemotherapy plus sunitinib at the recommended phase II dose (RP2D). Primary endpoint was pathological complete response (pCR) rate. Tumor and functional imaging biomarkers were evaluated serially., Results: In phase Ib (n=9), sunitinib 12.5 mg daily for 7 days before each chemotherapy was established as RP2D. In phase II, patients receiving chemotherapy plus sunitinib (n=24) had similar pCR rates (5.0% versus 4.3%, p=1.00), but a higher incidence of chemotherapy dose delays (33.3% versus 8.7%, p=0.04), compared to those receiving chemotherapy alone (n=25). The addition of sunitinib to chemotherapy significantly increased vascular normalization index (VNI) and decreased lymphatic vessel density (D2-40) on immunohistochemistry [VNI:25.50±27.94% versus 49.29±31.84%, p=0.034; D2-40:3.29±2.70 versus 1.29±1.54, p=0.014, baseline versus post-cycle 1], and improved perfusion on DCE-MRI (Ktrans:12.6±9.6 mL/100 g/min versus 16.3±10.7 mL/100 g/min, baseline versus post-cycle 1, p=0.015). Conversely, immunohistochemical and DCE-MRI parameters were not significantly altered by chemotherapy alone., Conclusion: Low-dose, short-course sunitinib prior to anthracycline-based chemotherapy in breast cancer patients did not improve pCR and increased chemotherapy dose delays. However, the addition of sunitinib induced compelling pharmacodynamic evidence of vascular normalization. Further studies with alternative cytotoxic regimens should be explored.

Introduction: To determine if neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were predictive of malignancy in pancreatic cystic neoplasms (PCN) and if these improved the performance of the international consensus guidelines (ICG) in the initial triage of these patients., Methods: 318 patients with surgically-treated suspected PCN were retrospectively reviewed. Malignant neoplasms were defined as neoplasms harbouring invasive carcinoma. The optimal cut-off for NLR and PLR were determined by plotting the receiver operating characteristics (ROC) curves of NLR/PLR in predicting malignant PCN and utilizing the Youden index., Results: The optimal NLR and PLR cut-offs were determined to be 3.33 and 205, respectively. Univariate analyses demonstrated that symptomatic PCNs, age, obstructive jaundice, presence of solid component, dilatation of main pancreatic duct ≥10 mm, high NLR and high PLR were predictive of a malignant PCN. Multivariate analyses demonstrated that obstructive jaundice, presence of solid component, MPD ≥10 mm and high PLR but not NLR were independent predictors of a malignant PCN. A high PLR significantly predicted invasive carcinoma in patients classified within the ICG(HR) group. Comparison between the ROC curves of the ICG versus ICG plus high PLR in predicting malignant PCN demonstrated a significant improvement in the accuracy of the ICG when PLR was included [AUC 0.784 (95% CI: 0.740-0.829) vs AUC 0.822 (95% CI: 0.772-0.872) (p = 0.0032)]., Conclusions: High PLR is an independent predictor of malignancy in PCN. The addition of PLR as a criterion to the ICG improved the accuracy of these guidelines in detecting invasive neoplasms., (Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Hepatocellular carcinoma (HCC) is the 6th most common cancer in the world, but the second most common cause of cancer death. There is no universally accepted consensus practice guidelines for HCC owing to rapid developments in new treatment modalities, the heterogeneous epidemiology and clinical presentation of HCC worldwide. However, a number of regional and national guidelines currently exist which reflect practice relevant to the epidemiology and collective experience of the consensus group. In 2014, clinicians at the multidisciplinary Comprehensive Liver Cancer Clinic (CLCC) at the National Cancer Centre Singapore (NCCS) reviewed the latest published scientific data and existing international and regional practice guidelines, such as those of the National Comprehensive Cancer Network, American Association for the Study of Liver Diseases and the Asian Pacific Association for the Study of the Liver, and modified them to reflect local practice. These would serve as a template by which treatment outcomes can be collated and benchmarked against international data. The NCCS Consensus Guidelines for HCC have been successfully implemented in the CLCC since their publication online on 26(th) September 2014, and the guidelines allow outcomes of treatment to be compared to international data. These guidelines will be reviewed periodically to incorporate new data.

Purpose: To evaluate non-invasive imaging biomarkers for assessing renal fibrosis. DWI is used to assess renal function; intravoxel incoherent motion (IVIM) provides additional measures of perfusion-related diffusion (D*, blood flow; f, perfusion fraction). We aim to determine if reduced ADC seen in renal fibrosis is attributable to perfusion-related diffusion changes or to known reduction in tissue diffusivity (D)., Materials and Methods: Unilateral ureteral obstruction (UUO) was created in six mice to induce renal fibrosis. DWI was performed the day before and 7 days post-UUO. A range of b-values from 0 to 1200 s/mm(2) were used. IVIM parameters were obtained using region of interests drawn over the renal parenchyma. Histopathological analysis of both kidneys was performed in all mice. Results were analyzed using the paired t-test with P<0.05 considered statistically significant., Results: D and f were significantly lower in the ligated kidneys at Day 7 compared to before ligation and no significant difference was found for D*. Comparing non-ligated and ligated kidneys within the same mouse at Day 7, significantly lower D values were observed in the ligated kidneys, while no significant difference was found for f and D*, although the values of f were generally lower. Histopathological analysis confirmed development of fibrosis and reduction in glomeruli in all the ligated kidneys at Day 7., Conclusion: Our study shows that the reduction in ADC seen in renal fibrosis is attributable not only to reduced D as previously encountered but also a decrease in vascularity as assessed by f. Reduction in f is possibly related to a reduction in glomeruli., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: International consensus guidelines to guide management of intraductal papillary mucinous neoplasms (IPMN) were revised in Fukuoka and published in 2012. However, despite widespread acceptance of the Fukuoka Consensus Guidelines (FCG), the utility of these guidelines have not been well-validated. This systematic review was performed to evaluate the clinical utility of the FCG., Design: A computerized search of the PubMed and Scopus databases was performed to identify all studies evaluating the utility of the FCG in surgically resected IPMN. IPMN were stratified according to the FCG as high risk (HR), worrisome risk (WR), and low risk (LR). HR and WR IPMN were termed FCG+ve and LR IPMN were termed FCG-ve., Results: Seven studies analyzing 1,382 patients were included. There were 402 malignant neoplasms (29%), including 242 invasive IPMNs. There were 1,000 IPMN classified as FCG+ve. The FCG+ve group had a positive predictive value (PPV) ranging from 27 to 62% and the FCG-ve group had negative predictive value ranging from 82 to 100%. Pooled analysis demonstrated that there was 362 of 1,000 (36%) malignant FCG+ve IPMN and 342 of 382 (90%) benign FCG-ve IPMN. PPV of the HR group and the WR groups alone were 104 of 158 (66%) and 75 of 261 (29%), respectively. Forty of 382 (11%), including 22 (6%) invasive FCG-ve IPMN, were malignant. Twenty-six malignant including 18 invasive FCG-ve IPMN were reported from a single study. When the results from this study were excluded, there were only 14 of 241 malignant neoplasms (6%), including 4 of 241 (2%) invasive FCG-ve IPMN in the remaining 6 studies., Conclusion: The FCG+ve criteria had a similarly low PPV compared with the 2006 consensus criteria. Stratification of IPMN into HR and WR groups resulted in a higher PPV in the HR group. Some malignant and even invasive IPMN may be missed by the FCG criteria., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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., (© 2015 Wiley Periodicals, Inc.)

Background: To date, biomarkers to predict benefit from anti-angiogenic therapy are still lacking. Sorafenib and metronomic oral vinorelbine combination was studied and changes in blood and DCE-MRI parameters were investigated as biomarkers for benefit., Material and Methods: Patients with advanced NSCLC were recruited to 3 successive cohorts. Each cohort was given a fixed metronomic (3 times a week) dose of oral vinorelbine at 60 mg/week, 90 mg/week, or 120 mg/week respectively. Within each cohort, patients received a starting dose of sorafenib at 200mg bid for 4 weeks. In the absence of dose-limiting toxicities, each patient's dose of sorafenib was escalated to 400mg bid for 4 weeks, 600 mg bid for 4 weeks and finally 800 mg bid. Biomarkers measured include DCE-MRI parameters, circulating endothelial cells (CECs), circulating endothelial progenitor cells (CEPs), and plasma thrombospondin (TSP-1)., Results: 48 evaluable patients were analyzed. There were 4 (8.9%) patients with partial response (PR) and 7 (15.2%) with cavitary response (CaR). Two subpopulations of CECs (CEC(hi), CEC(lo)) were identified that trended in opposite directions during treatment, with CEC(hi) demonstrating an upward trend in contrast to CEC(lo). Higher baseline CEC(hi) and lower baseline blood flow (F) and fractional intravascular blood volume (V1) predicted for response. Multivariate analysis revealed a lower baseline V1, and dynamic changes of CEC during treatment (CEC increase, sum of CEC(hi) and CEC(lo)) predicted for improved survival., Conclusions: Sorafenib and metronomic oral vinorelbine is active in advanced NSCLC. Baseline levels and changes in DCE parameters and CEC may be useful predictive biomarkers., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Dynamic contrast-enhanced (DCE) images can be acquired at multiple time points and multiple slice locations of a tumor. Image segmentation and registration are important preprocessing steps that can improve subsequent analysis of DCE images by kinetic modeling. An automatic system for region-of-interest segmentation and registration of DCE images is presented. Tissue segmentation is performed using a combination of thresholding and morphological operations, and further refined using shape information from consecutive images. The segmented regions are subsequently registered based on a mutual information method that accounts for possible tissue movement between slices. The proposed segmentation and registration methods are applied on actual DCE CT datasets to illustrate feasibility of practical implementation in the clinic.

Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) allows functional characterisation of tissue perfusion characteristics and acts as a biomarker for tumour angiogenesis. It involves serial acquisition of MRI images before and after injection of contrast, as such, tissue perfusion and permeability can be assessed based on the signal enhancement kinetics. The ability to evaluate whole tumour volumes in a non-invasive manner makes DCE MRI especially attractive for potential oncological applications. Here we provide an overview of the current research involving DCE MRI as a biomarker for the diagnosis and characterisation of malignancies, prediction of the therapeutic response and survival outcomes, as well as radiation therapy planning., (Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

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.)

Background: The Sendai Consensus Guidelines (SCG) were formulated in 2006 to guide the management of mucinous cystic lesions of the pancreas (CLPs) and were updated in 2012 (International Consensus Guidelines, ICG 2012). This study aims to evaluate the clinical utility of the ICG 2012 with the SCG based on initial cross-sectional imaging findings., Methods: One hundred fourteen patients with mucinous CLPs were reviewed and classified according to the ICG 2012 as high risk (HR(ICG2012)), worrisome (W(ICG2012)), and low risk (LR(ICG2012)), and according to the SCG as high risk (HR(SCG)) and low risk (LR(SCG))., Results: On univariate analysis, the presence of symptoms, obstructive jaundice, elevated serum carcinoembryonic antigen (CEA)/carbohydrate antigen (CA)19-9, solid component, main pancreatic duct ≥ 10 mm, and main pancreatic duct ≥ 5 mm was associated with high grade dysplasia/invasive carcinoma in all mucinous CLPs. Increasing number of HR(SCG) or HR(ICG2012) features was associated with a significantly increased likelihood of malignancy. The positive predictive value of HR(SCG) and HR(ICG2012) for high grade dysplasia/invasive carcinoma was 46% and 62.5% respectively. The negative predictive value of both LR(SCG) and LR(ICG2012) was 100%., Conclusion: Both the guidelines were useful in the initial cross-sectional imaging evaluation of mucinous CLPs. The ICG 2012 guidelines were superior to the SCG guidelines., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Liver perfusion magnetic resonance (MR) imaging is currently being actively investigated as a functional imaging technique that provides physiologic information on the microcirculation and microenvironment of liver tumors and the underlying liver. It has gained importance in light of antiangiogenic therapy for hepatocellular carcinoma and colorectal liver metastases. This article explains the various model-free and model-based approaches for liver perfusion MR imaging and their relative clinical utility. Relevant published works are summarized for each approach so that the reader can understand their relative strengths and weaknesses, to make an informed choice when performing liver perfusion MR imaging studies., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The Sendai Consensus Guidelines (SCG) were formulated in 2006 and updated in Fukuoka in 2012 (FCG) to guide management of cystic mucinous neoplasms of the pancreas. This study aims to evaluate the clinical utility of the SCG and FCG in the initial triage of all suspected pancreatic cystic neoplasms., Study Design: Overall, 317 surgically-treated patients with a suspected pancreatic cystic neoplasm were classified according to the SCG as high risk (HR(SCG)) and low risk (LR(SCG)), and according to the FCG as high risk (HR(FCG)), worrisome (W(FCG)), and low risk (LR(FCG)). Cystic lesions of the pancreas (CLP) were classified as potentially malignant/malignant or benign according to the final pathology., Results: The presence of symptoms, proximal lesions with obstructive jaundice, elevated serum carcinoembryonic antigen/carbohydrate antigen 19-9 (CEA/CA 19-9), size ≥3 cm, presence of solid component, main pancreatic duct dilatation, thickened enhancing walls, and change in ductal caliber with distal atrophy were predictive of a potentially malignant/malignant CLP on univariate analyses. The positive predictive value (PPV) and negative predictive value (NPV) of HR(SCG) and HR(ICG2012) for a potentially malignant/malignant lesion was 67 and 88 %, and 88 and 92.5 %, respectively. There were no malignant lesions in both LR groups but some potentially malignant lesions such as cystic pancreatic neuroendocrine neoplasms with uncertain behavior were classified as LR., Conclusion: The updated FCG was superior to the SCG for the initial triage of all suspected pancreatic cystic neoplasms. CLP in the LR(FCG) group can be safely managed conservatively, and those in the HR(FCG) group should undergo resection.

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 < 0.001). The mapping of tumor regions with delayed and slow contrast uptake on DCE MRI correlated strongly with tumor necrotic fraction, and can potentially serve as a non-invasive imaging surrogate for the in vivo assessment of necrotic fraction., (Copyright © 2014 John Wiley & Sons, Ltd.)

A distinct feature of the tumor vasculature is its tortuosity and irregular branching of vessels, which can translate to a wider dispersion and higher variability of blood flow in the tumor. To enable tumor blood flow variability to be assessed in vivo by imaging, a tracer kinetic model that accounts for flow dispersion is developed for use with dynamic contrast-enhanced (DCE) CT. The proposed model adopts a multiple-pathway approach and allows for the quantification of relative dispersion in the blood flow distribution, which reflects flow variability in the tumor vasculature. Monte Carlo simulation experiments were performed to study the possibility of reducing the number of model parameters based on the Akaike information criterion approach and to explore possible noise and tissue conditions in which the model might be applicable. The model was used for region-of-interest analysis and to generate perfusion parameter maps for three patient DCE CT cases with cerebral tumors, to illustrate clinical applicability.

Gastrointestinal arterio-venous malformations are a known cause of gastrointestinal bleeding. We present a rare case of persistent rectal bleeding due to a rectal arterio-portal venous fistula in the setting of portal hypertension secondary to portal vein thrombosis. The portal hypertension was initially surgically treated with splenectomy and a proximal splenorenal shunt. However, rectal bleeding persisted even after surgery, presenting us with a diagnostic dilemma. The patient was re-evaluated with a computed tomography mesenteric angiogram which revealed a rectal arterio-portal fistula. Arterio-portal fistulas are a known but rare cause of portal hypertension, and possibly the underlying cause of continued rectal bleeding in this case. This was successfully treated using angiographic localization and super-selective embolization of the rectal arterio-portal venous fistula via the right internal iliac artery.The patient subsequently went on to have a full term pregnancy. Through this case report, we hope to highlight awareness of this unusual condition, discuss the diagnostic workup and our management approach.

Background: The purpose of the present study was to determine whether intrahepatic injection of (131)I-lipiodol (Lipiodol) is effective against recurrence of surgically resected hepatocellular carcinoma (HCC)., Methods: From June 2001 through March 2007, this nationwide multi-center prospective randomized controlled trial enrolled 103 patients 4-6 weeks after curative resection of HCC with complete recovery (52: Lipiodol, 51: Control). Follow-up was every 3 months for 1 year, then every 6 months. Primary and secondary endpoints were recurrence-free survival (RFS) and overall survival (OS), respectively, both of which were evaluated by the Kaplan-Meier technique and summarized by the hazard ratio (HR). The design was based on information obtained from a similar trial that had been conducted in Hong Kong., Results: The Lipiodol group showed a small, and nonsignificant, improvement over control in RFS (HR = 0.75; 95 % confidence interval [95 % CI] 0.46-1.23; p = 0.25) and OS (HR = 0.88; 95 % CI 0.51-1.51; p = 0.64). Only two serious adverse events were reported, both with hypothyroidism caused by (131)I-lipiodol and hepatic artery dissection during angiography., Conclusions: The randomized trial provides insufficient evidence to recommend the routine use of (131)I-lipiodol in these patients.

Purpose: To compare four different tracer kinetic models for the analysis of dynamic contrast material-enhanced computed tomographic (CT) data with respect to the prediction of 5-year overall survival in primary colorectal cancer., Materials and Methods: This study was approved by the ethical review board. Archival dynamic contrast-enhanced CT data from 46 patients with colorectal cancer, obtained as part of a research study, were analyzed retrospectively by using the distributed parameter, conventional compartmental, adiabatic tissue homogeneity, and generalized kinetic models. Blood flow, blood volume, mean transit time (MTT), permeability-surface area product, extraction fraction, extravascular extracellular volume (v(e)), and volume transfer constant (K(trans)) were compared by using the Friedman test, with statistical significance at 5%. Following receiver operating characteristic analysis, parameters of the different kinetic models and tumor stage were compared with respect to overall survival discrimination, with use of Kaplan Meier analysis and a univariate Cox proportional hazard model, with additional cross-validation and permutation testing., Results: Blood flow was lower with the distributed parameter model than with the conventional compartmental and adiabatic tissue homogeneity models (P < .0001), and blood flow values determined with the conventional compartmental and adiabatic tissue homogeneity models were similar. Conversely, MTT was longer with the distributed parameter model than with the conventional compartmental and adiabatic tissue homogeneity models (P < .0001). Blood volume, permeability-surface area product, and v(e) were higher with the conventional compartmental model than with the adiabatic tissue homogeneity, distributed parameter, or generalized kinetic models (P < .0001). The extraction fraction was higher with the distributed parameter model than with the adiabatic tissue homogeneity model. With respect to 5-year overall survival, only the distributed parameter model-derived v(e) was predictive of 5-year overall survival with a threshold value of 15.48 mL/100 mL after cross-validation and permutation testing., Conclusion: Parameter values differ significantly between models. Of the models investigated, the distributed parameter model was the best predictor of 5-year overall survival., Supplemental Material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120186/-/DC1., (RSNA, 2013)

Background & Aims: Preclinical studies have demonstrated the additive effect of rapamycin with bevacizumab for hepatocellular carcinoma treatment. We conducted a Phase 1 study to evaluate the safety and pharmacokinetics of the combination in patients with hepatocellular carcinoma., Methods: Adult participants with advanced hepatocellular carcinoma received intravenous bevacizumab (5mg/kg every 14 days) and oral rapamycin (1-6 mg/day; 3+3 dose escalation design). Computed tomography assessed tumour response and treatment safety. Pharmacokinetics assessment established rapamycin blood concentrations pre- and post-dose. Dynamic contrast-enhanced computed tomography analysed the tumour region for blood flow, permeability surface area product, fractional intravascular blood volume and extracellular-extravascular volume., Results: Twenty-four participants were treated. There were two dose limiting toxicities with rapamycin 5mg: grade 3 thrombocytopenia and grade 3 mucositis. The maximally tolerated dose of rapamycin was 4 mg. Adverse events (grade 1-2) included hyperglycaemia (83%), thrombocytopenia (75%), fatigue (46%), mucositis (46%), anorexia (42%), diarrhoea (33%) and proteinuria (12.5%). Of 20 evaluable participants, one reached complete response that lasted 4.5 months, two reached partial response, 14 reached stable disease and three had progressive disease. Median overall survival was 9.4 months; progression-free survival was 5.5 months. Dose level and steady state area under the concentration time curve for hour zero to infinity of rapamycin correlated inversely with blood flow rate and change in permeability-surface area. After 22 days of treatment, there were significant reductions from baseline in blood flow rate, permeability-surface area and fractional intracellular blood volume., Conclusions: The recommended Phase 2 dose of rapamycin is 4 mg in combination with bevacizumab. Evidence of anti-vascular activity was observed together with promising clinical activity., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Compartmental tracer kinetic models currently used for analysis of dynamic contrast-enhanced MRI data yield poor fittings or parameter values that are unphysiological in necrotic regions of the tumor, as these models only describe microcirculation in perfused tissue. In this study, we explore the use of Fick's law of diffusion as an alternative method for analysis of dynamic contrast-enhanced MRI data in the necrotic regions. Xenografts of various human cancer cell lines were implanted in 14 mice that were subjected to dynamic contrast-enhanced MRI performed using a spoiled gradient recalled sequence. Tracer concentration was estimated using the variable flip angle technique. Poorly perfused and necrotic tumor regions exhibiting delayed and slow enhancement were identified using a k-means clustering algorithm. Tracer behavior in necrotic regions was shown to be consistent with Fick's diffusion equation and the in vivo gadolinium diffusivity was estimated to be 2.08 (±0.88) × 10(-4) mm(2)/s. This study proposes the use of gadolinium diffusivity as an alternative parameter for quantifying tracer transport within necrotic tumor regions., (Copyright © 2012 Wiley Periodicals, Inc.)

Computer simulations based on a physiologically realistic tracer kinetic model with multiple pathways was used to provide insights on the applicability and interpretation of tissue enhancement metrics such as the maximum slope, peak enhancement and area under curve, commonly used in dynamic contrast-enhanced (DCE) MRI. Results show that physiological conditions of the tissue that could affect the accuracy of the maximal slope method include a high blood flow, increased variability of flow within the vasculature or a low vascular volume. Interestingly, changes in permeability and interstitial volume might not affect the accuracy of the maximal slope method. Time-to-peak and peak value of the tissue enhancement curve are not strictly properties of the tissue alone, and they cannot be linearly related to intrinsic tissue parameters such as blood flow, blood volume, capillary permeability, interstitial volume and mean transit time. Similar to the normalized initial area under tissue concentration curve, an alternative estimate of the total tracer distribution volume can be simply given by the ratio of tracer concentration in the tissue and artery sampled at the final DCE scan.