γδ T Cells Support Pancreatic Oncogenesis by Restraining αß T Cell Activation.

Inflammation is paramount in pancreatic oncogenesis. We identified a uniquely activated γδT cell population, which constituted ∼40% of tumor-infiltrating T cells in human pancreatic ductal adenocarcinoma (PDA). Recruitment and activation of γδT cells was contingent on diverse chemokine signals. Deletion, depletion, or blockade of γδT cell recruitment was protective against PDA and resulted in increased infiltration, activation, and Th1 polarization of αßT cells. Although αßT cells were dispensable to outcome in PDA, they became indispensable mediators of tumor protection upon γδT cell ablation. PDA-infiltrating γδT cells expressed high levels of exhaustion ligands and thereby negated adaptive anti-tumor immunity. Blockade of PD-L1 in γδT cells enhanced CD4(+) and CD8(+) T cell infiltration and immunogenicity and induced tumor protection suggesting that γδT cells are critical sources of immune-suppressive checkpoint ligands in PDA. We describe γδT cells as central regulators of effector T cell activation in cancer via novel cross-talk.

Integrated Systems Analysis of the Murine and Human Pancreatic Cancer Glycomes Reveals a Tumor-Promoting Role for ST6GAL1.

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in the United States. Glycans, such as carbohydrate antigen 19-9, are biomarkers of PDAC and are emerging as important modulators of cancer phenotypes. Herein, we used a systems-based approach integrating glycomic analysis of the well-established KC mouse, which models early events in transformation, and analysis of samples from human pancreatic cancer patients to identify glycans with potential roles in cancer formation. We observed both common and distinct patterns of glycosylation in pancreatic cancer across species. Common alterations included increased levels of α-2,3-sialic acid and α-2,6-sialic acid, bisecting GlcNAc and poly-N-acetyllactosamine. However, core fucose, which was increased in human PDAC, was not seen in the mouse, indicating that not all human glycomic changes are observed in the KC mouse model. In silico analysis of bulk and single-cell sequencing data identified ST6 beta-galactoside alpha-2,6-sialyltransferase 1, which underlies α-2,6-sialic acid, as overexpressed in human PDAC, concordant with histological data showing higher levels of this enzyme at the earliest stages. To test whether ST6 beta-galactoside alpha-2,6-sialyltransferase 1 promotes pancreatic cancer, we created a novel mouse in which a pancreas-specific genetic deletion of this enzyme overlays the KC mouse model. The analysis of our new model showed delayed cancer formation and a significant reduction in fibrosis. Our results highlight the importance of a strategic systems approach to identifying glycans whose functions can be modeled in mouse, a crucial step in the development of therapeutics targeting glycosylation in pancreatic cancer.

The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincle-induced immune suppression.

Neoplastic pancreatic epithelial cells are believed to die through caspase 8-dependent apoptotic cell death, and chemotherapy is thought to promote tumour apoptosis. Conversely, cancer cells often disrupt apoptosis to survive. Another type of programmed cell death is necroptosis (programmed necrosis), but its role in pancreatic ductal adenocarcinoma (PDA) is unclear. There are many potential inducers of necroptosis in PDA, including ligation of tumour necrosis factor receptor 1 (TNFR1), CD95, TNF-related apoptosis-inducing ligand (TRAIL) receptors, Toll-like receptors, reactive oxygen species, and chemotherapeutic drugs. Here we report that the principal components of the necrosome, receptor-interacting protein (RIP)1 and RIP3, are highly expressed in PDA and are further upregulated by the chemotherapy drug gemcitabine. Blockade of the necrosome in vitro promoted cancer cell proliferation and induced an aggressive oncogenic phenotype. By contrast, in vivo deletion of RIP3 or inhibition of RIP1 protected against oncogenic progression in mice and was associated with the development of a highly immunogenic myeloid and T cell infiltrate. The immune-suppressive tumour microenvironment associated with intact RIP1/RIP3 signalling depended in part on necroptosis-induced expression of the chemokine attractant CXCL1, and CXCL1 blockade protected against PDA. Moreover, cytoplasmic SAP130 (a subunit of the histone deacetylase complex) was expressed in PDA in a RIP1/RIP3-dependent manner, and Mincle--its cognate receptor--was upregulated in tumour-infiltrating myeloid cells. Ligation of Mincle by SAP130 promoted oncogenesis, whereas deletion of Mincle protected against oncogenesis and phenocopied the immunogenic reprogramming of the tumour microenvironment that was induced by RIP3 deletion. Cellular depletion suggested that whereas inhibitory macrophages promote tumorigenesis in PDA, they lose their immune-suppressive effects when RIP3 or Mincle is deleted. Accordingly, T cells, which are not protective against PDA progression in mice with intact RIP3 or Mincle signalling, are reprogrammed into indispensable mediators of anti-tumour immunity in the absence of RIP3 or Mincle. Our work describes parallel networks of necroptosis-induced CXCL1 and Mincle signalling that promote macrophage-induced adaptive immune suppression and thereby enable PDA progression.

Radiation Therapy Induces Macrophages to Suppress T-Cell Responses Against Pancreatic Tumors in Mice.

BACKGROUND & AIMS: The role of radiation therapy in the treatment of patients with pancreatic ductal adenocarcinoma (PDA) is controversial. Randomized controlled trials investigating the efficacy of radiation therapy in patients with locally advanced unresectable PDA have reported mixed results, with effects ranging from modest benefit to worse outcomes compared with control therapies. We investigated whether radiation causes inflammatory cells to acquire an immune-suppressive phenotype that limits the therapeutic effects of radiation on invasive PDAs and accelerates progression of preinvasive foci. METHODS: We investigated the effects of radiation therapy in p48(Cre);LSL-Kras(G12D) (KC) and p48(Cre);LSLKras(G12D);LSL-Trp53(R172H) (KPC) mice, as well as in C57BL/6 mice with orthotopic tumors grown from FC1242 cells derived from KPC mice. Some mice were given neutralizing antibodies against macrophage colony-stimulating factor 1 (CSF1 or MCSF) or F4/80. Pancreata were exposed to doses of radiation ranging from 2 to 12 Gy and analyzed by flow cytometry. RESULTS: Pancreata of KC mice exposed to radiation had a higher frequency of advanced pancreatic intraepithelial lesions and more foci of invasive cancer than pancreata of unexposed mice (controls); radiation reduced survival time by more than 6 months. A greater proportion of macrophages from radiation treated invasive and preinvasive pancreatic tumors had an immune-suppressive, M2-like phenotype compared with control mice. Pancreata from mice exposed to radiation had fewer CD8(+) T cells than controls, and greater numbers of CD4(+) T cells of T-helper 2 and T-regulatory cell phenotypes. Adoptive transfer of T cells from irradiated PDA to tumors of control mice accelerated tumor growth. Radiation induced production of MCSF by PDA cells. A neutralizing antibody against MCSF prevented radiation from altering the phenotype of macrophages in tumors, increasing the anti-tumor T-cell response and slowing tumor growth. CONCLUSIONS: Radiation treatment causes macrophages murine PDA to acquire an immune-suppressive phenotype and disabled T-cell-mediated anti-tumor responses. MCSF blockade negates this effect, allowing radiation to have increased efficacy in slowing tumor growth.

Utility of diffusion-weighted MRI for differentiating acute from chronic cholecystitis.

PURPOSE: To assess the use of diffusion-weighted imaging (DWI) for differentiating acute from chronic cholecystitis, in comparison with conventional magnetic resonance imaging (MRI) features. MATERIALS AND METHODS: Liver MRI including DWI (b-values 0/500/1000s/mm(2) ) was performed at 1.5T ≤30 days before cholecystectomy in 83 patients with abdominal pain. Two radiologists assessed cases for conventional (gallstones, wall thickening, pericholecystic fluid, pericholecystic fat changes, gallbladder distension, pericholecystic liver enhancement, mural T2 -hyperintensity, mural hyperenhancement, mural striations, abscess, intraluminal membranes, and mural defect) and DWI (increased mural signal on high b-value images, visually low apparent diffusion coefficient [ADC], and ADC values) features. RESULTS: Acute cholecystitis was present in 43%; chronic cholecystitis was present in 57%. Nine of 12 conventional features were more frequent in acute cholecystitis for both readers (P ≤ 0.003). Increased mural signal on high b-value images was more frequent (P < 0.001) in acute than chronic cholecystitis for R1 (92% vs. 32%) and R2 (83% vs. 30%). Sensitivity and specificity of increased signal on high b-value images were: R1, 92%/68%; R2, 83%/70%. Visually low ADC was more frequent in acute cholecystitis for R2 (P < 0.001) but not R1 (P = 0.406); ADC values were not different between groups for either reader (P = 0.104-0.139). Among conventional and DWI features, only increased signal on high b-value DWI was independently associated with acute cholecystitis for both readers (P = 0.006-0.012). CONCLUSION: Visually increased mural signal on high b-value DWI was highly sensitive and moderately specific for acute cholecystitis, being an independent predictor relative to conventional features for both readers. Although requiring larger studies, DWI (particularly the high b-value images) may have additive value relative to conventional MRI-suspected acute cholecystitis. J. Magn. Reson. Imaging 2016;44:89-97.

Differentiation of Malignant Omental Caking from Benign Omental Thickening using MRI.

PURPOSE: To determine multi-parametric MRI features that can help differentiate malignant omental caking from benign omental thickening in the setting of portal hypertension. METHODS: We identified 19 patients with an abnormal omentum on MRI and an available reference standard: 11 patients with portal hypertension and benign omental thickening (9 male, 2 female, mean age 58 ± 6 years) and 8 patients with metastatic omental caking (4 male, 4 female, mean age 61 ± 13 years). Criteria for benign omental thickening were no evidence of malignancy for at least 24 months of follow-up (n = 7), negative ascites cytology (n = 2), or absence of malignancy on pathologic analysis of liver explant (n = 2). Criteria for omental malignancy were positive omental biopsy (n = 6) or ascites cytology (n = 2). Two radiologists (R1 and R2) evaluated characteristics of the thickened omentum on MRI. RESULTS: Findings occurring with significantly higher frequency in malignant omental caking were hyperintensity on high b-value diffusion-weighted imaging (DWI) (R1 88% vs. 0%, R2 88% vs. 0%), hyperenhancement (R1 75% vs. 0%, R2 75% vs. 0%), and convex outer omental contour (R1 88% vs. 0%, R2 75% vs. 9%) (all p ≤ 0.001); discrete omental nodules were significantly more frequent in malignant omental thickening for R1 (63% vs. 0%, p = 0.005). Features not significantly different between groups included decreased ADC, T2 hyperintensity, vessels coursing through the omentum, moderate/large volume ascites, splenomegaly, and mesenteric edema (all p ≥ 0.058). CONCLUSION: Abnormal signal on DWI, hyperenhancement, and convex outer contour are helpful MRI features to differentiate malignant from benign omental thickening.

Comparison of MRI pulse sequences for prediction of size of hepatocellular carcinoma at explant evaluation.

OBJECTIVE: The purpose of this study was to retrospectively compare the size of hepatocellular carcinoma (HCC) on images obtained using different MRI pulse sequences with the tumor size determined at pathologic evaluation of liver explant specimens. MATERIALS AND METHODS: Ninety-two patients with HCC who underwent contrast-enhanced liver MRI within 90 days before liver transplant were included. A single pathologist measured the dominant HCC in each case. In different sessions, two abdominal radiologists (readers 1 and 2) aware only of the location of the dominant HCC independently measured lesion size on images obtained using the following sequences: T2-weighted imaging; b-500 diffusion-weighted imaging; and arterial, portal venous, and equilibrium phases of contrast enhancement. Size measurements on MR images were compared with explant measurements by use of Pearson correlation coefficients, paired t tests, and Bland-Altman plots. RESULTS: Correlation with pathologic findings was highest for reader 1 for portal venous (r = 0.890) and equilibrium (r = 0.828) phase images and for reader 2 for arterial, portal venous, and equilibrium phase images (r = 0.842-0.860). Absolute error relative to pathologic size was lowest for reader 1 using portal venous (4.3 mm) and for reader 2 using portal venous and arterial phase images (both 4.7 mm). Systematic error for both readers was lowest with portal venous and equilibrium phase images (reader 1, systematic under-measurement of 0.5 mm in both sequences; reader 2, systematic over-measurement of 0.1 mm with portal venous phase images and systematic under-measurement of 1.1 mm with equilibrium phase images). Sequences in which reader 1 made systematic over-measurements were diffusion-weighted images, arterial phase images, and T2-weighted images (by 3.5, 2.9, and 1.6 mm). Reader 2 made systematic over-measurements using arterial phase and T2-weighted images (by 1.5 and 0.4 mm). CONCLUSION: The data suggest the arterial phase may be suboptimal for measuring HCC at MRI. Portal venous phase acquisition warrants further investigation as a potential standard approach for such measurements.

Comparison of intra- and inter-reader agreement of abbreviated versus comprehensive MRCP for pancreatic cyst surveillance.

OBJECTIVE: To retrospectively compare inter- and intra-reader agreement of abbreviated MRCP (aMRCP) with comprehensive MRI (cMRCP) protocol for detection of worrisome features, high-risk stigmata, and concomitant pancreatic cancer in pancreatic cyst surveillance. METHODS: 151 patients (104 women, mean age: 69[10] years) with baseline and follow-up contrast-enhanced MRIs were included. This comprised 138 patients under cyst surveillance with 5-year follow-up showing no pancreatic ductal adenocarcinoma (PDAC), 6 with pancreatic cystic lesion-derived malignancy, and 7 with concomitant PDAC. The aMRCP protocol used four sequences (axial and coronal Half-Fourier Single-shot Turbo-spin-Echo, axial T1 fat-saturated pre-contrast, and 3D-MRCP), while cMRCP included all standard sequences, including post-contrast. Three blinded abdominal radiologists assessed baseline cyst characteristics, worrisome features, high-risk stigmata, and PDAC signs using both aMRCP and cMRCP, with a 2-week washout period. Intra- and inter-reader agreement were calculated using Fleiss' multi-rater kappa and Intra-class Correlation Coefficient (ICC). 95% confidence intervals (CI) were calculated. RESULTS: Cyst size, growth, and abrupt main pancreatic duct transition had strong intra- and inter-reader agreement. Intra-reader agreement was ICC = 0.93-0.99 for cyst size, ICC = 0.71-1.00 for cyst growth, and kappa = 0.83-1.00 for abrupt duct transition. Inter-reader agreement for cyst size was ICC = 0.86 (aMRCP) and ICC = 0.83 (cMRCP), and for abrupt duct transition was kappa = 0.84 (aMRCP) and kappa = 0.69 (cMRCP). Thickened cyst wall, mural nodule and cyst-duct communication demonstrated varying intra-reader agreements and poor inter-reader agreements. CONCLUSION: aMRCP showed high intra- and inter-reader agreement for most pancreatic cyst parameters that highly rely on T2-weighted sequences.

Enhanced Complement Expression in the Tumor Microenvironment Following Neoadjuvant Therapy: Implications for Immunomodulation and Survival in Pancreatic Ductal Adenocarcinoma.

Background: Neoadjuvant therapy (NAT) is increasingly being used for pancreatic ductal adenocarcinoma (PDAC) treatment. However, its specific effects on carcinoma cells and the tumor microenvironment (TME) are not fully understood. This study aims to investigate how NAT differentially impacts PDAC's carcinoma cells and TME. Methods: Spatial transcriptomics was used to compare gene expression profiles in carcinoma cells and the TME between 23 NAT-treated and 13 NAT-naïve PDAC patients, correlating with their clinicopathologic features. Analysis of an online single-nucleus RNA sequencing (snRNA-seq) dataset was performed for validation of the specific cell types responsible for NAT-induced gene expression alterations. Results: NAT not only induces apoptosis and inhibits proliferation in carcinoma cells but also significantly remodels the TME. Notably, NAT induces a coordinated upregulation of multiple key complement genes (C3, C1S, C1R, C4B and C7) in the TME, making the complement pathway one of the most significantly affected pathways by NAT. Patients with higher TME complement expression following NAT exhibit improved overall survival. These patients also exhibit increased immunomodulatory and neurotrophic cancer-associated fibroblasts (CAFs); more CD4+ T cells, monocytes, and mast cells; and reduced immune exhaustion gene expression. snRNA-seq analysis demonstrates C3 complement was specifically upregulated in CAFs but not in other stroma cell types. Conclusions: NAT can enhance complement production and signaling within the TME, which is associated with reduced immunosuppression in PDAC. These findings suggest that local complement dynamics could serve as a novel biomarker for prognosis, evaluating treatment response and resistance, and guiding therapeutic strategies in NAT-treated PDAC patients.

Blockade of IL1ß and PD1 with Combination Chemotherapy Reduces Systemic Myeloid Suppression in Metastatic Pancreatic Cancer with Heterogeneous Effects in the Tumor.

Innate inflammation promotes tumor development, although the role of innate inflammatory cytokines in established human tumors is unclear. Herein, we report clinical and translational results from a phase Ib trial testing whether IL1ß blockade in human pancreatic cancer would alleviate myeloid immunosuppression and reveal antitumor T-cell responses to PD1 blockade. Patients with treatment-naïve advanced pancreatic ductal adenocarcinoma (n = 10) were treated with canakinumab, a high-affinity monoclonal human antiinterleukin-1ß (IL1ß), the PD1 blocking antibody spartalizumab, and gemcitabine/n(ab)paclitaxel. Analysis of paired peripheral blood from patients in the trial versus patients receiving multiagent chemotherapy showed a modest increase in HLA-DR+CD38+ activated CD8+ T cells and a decrease in circulating monocytic myeloid-derived suppressor cells (MDSC) by flow cytometry for patients in the trial but not in controls. Similarly, we used patient serum to differentiate monocytic MDSCs in vitro and showed that functional inhibition of T-cell proliferation was reduced when using on-treatment serum samples from patients in the trial but not when using serum from patients treated with chemotherapy alone. Within the tumor, we observed few changes in suppressive myeloid-cell populations or activated T cells as assessed by single-cell transcriptional profiling or multiplex immunofluorescence, although increases in CD8+ T cells suggest that improvements in the tumor immune microenvironment might be revealed by a larger study. Overall, the data indicate that exposure to PD1 and IL1ß blockade induced a modest reactivation of peripheral CD8+ T cells and decreased circulating monocytic MDSCs; however, these changes did not lead to similarly uniform alterations in the tumor microenvironment.

Hepatocellular carcinoma: detection with diffusion-weighted versus contrast-enhanced magnetic resonance imaging in pretransplant patients.

UNLABELLED: This study evaluates the performance of diffusion-weighted magnetic resonance imaging (DWI) for the detection of hepatocellular carcinoma (HCC) in pre-liver transplantation patients, compared and combined with contrast-enhanced T1-weighted imaging (CET1WI), using liver explant as the standard of reference. We included 52 patients with cirrhosis (40 men, 12 women; mean age, 56 years) who underwent DWI and CET1WI within 90 days of liver transplantation. Magnetic resonance images were analyzed for HCC detection in three separate sessions by two independent observers: DWI images (DW-set), CET1WI (CE-set), and all images together (All-set). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), per-patient accuracy, and per-lesion PPV were calculated for each image set. A total of 72 HCCs were present in 33 patients at explant (mean size, 1.5 cm [range, 0.3-6.2 cm]). Per-patient sensitivity and NPV of CE-set were significantly higher than those of DW-set when using pooled data between observers (P = 0.02 and 0.03, respectively), whereas specificity, PPV, and accuracy were equivalent. Per-lesion sensitivity was significantly higher for CE-set versus DW-set (59.0% versus 43.8%; P = 0.008, pooled data from two observers). When stratified by lesion size, the difference was significant only for lesions with a size between 1 and 2 cm (42.0% for DW-set versus 74.0% for CE-set; P = 0.001). The addition of DWI to CET1WI improved sensitivity for the more experienced observer. CONCLUSION: DWI is outperformed by CET1WI for detection of HCC, but represents a reasonable alternative to CET1WI for detection of HCC with a size above 2 cm. The addition of DWI to CET1WI slightly increases the detection rate.

Hepatocellular carcinoma: perfusion quantification with dynamic contrast-enhanced MRI.

OBJECTIVE: The objective of our study was to report our initial experience with dynamic contrast-enhanced MRI (DCE-MRI) for perfusion quantification of hepatocellular carcinoma (HCC) and surrounding liver. SUBJECTS AND METHODS: DCE-MRI of the liver was prospectively performed on 31 patients with HCC (male-female ratio, 26:5; mean age, 61 years; age range, 41-83 years). A dynamic coronal 3D FLASH sequence was performed at 1.5 T before and after injection of gadolinium-based contrast agent with an average temporal resolution of 3.8 seconds. Regions of interest were drawn on the abdominal aorta, portal vein, liver parenchyma, and HCC lesions by two observers in consensus. Time-activity curves were analyzed using a dual-input single-compartment model. The following perfusion parameters were obtained: arterial flow, portal venous flow, arterial fraction, distribution volume, and mean transit time (MTT). RESULTS: Thirty-three HCCs (mean size, 3.9 cm; range, 1.1-12.6 cm) were evaluated in 26 patients. When compared with liver parenchyma, HCC showed significantly higher arterial hepatic blood flow and arterial fraction (p < 0.0001) and significantly lower distribution volume and portal venous hepatic blood flow (p < 0.0001-0.023), with no difference in MTT. Untreated HCCs (n = 16) had a higher arterial fraction and lower portal venous hepatic blood flow value than chemoembolized HCCs (n = 17, p < 0.04). CONCLUSION: DCE-MRI can be used to quantify perfusion metrics of HCC and liver parenchyma and to assess perfusion changes after HCC chemoembolization.

Single-cell RNA sequencing reveals the effects of chemotherapy on human pancreatic adenocarcinoma and its tumor microenvironment.

The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC) is a complex ecosystem that drives tumor progression; however, in-depth single cell characterization of the PDAC TME and its role in response to therapy is lacking. Here, we perform single-cell RNA sequencing on freshly collected human PDAC samples either before or after chemotherapy. Overall, we find a heterogeneous mixture of basal and classical cancer cell subtypes, along with distinct cancer-associated fibroblast and macrophage subpopulations. Strikingly, classical and basal-like cancer cells exhibit similar transcriptional responses to chemotherapy and do not demonstrate a shift towards a basal-like transcriptional program among treated samples. We observe decreased ligand-receptor interactions in treated samples, particularly between TIGIT on CD8 + T cells and its receptor on cancer cells, and identify TIGIT as the major inhibitory checkpoint molecule of CD8 + T cells. Our results suggest that chemotherapy profoundly impacts the PDAC TME and may promote resistance to immunotherapy.

Magnetization transfer contrast-prepared MR imaging of the liver: inability to distinguish healthy from cirrhotic liver.

PURPOSE: To evaluate the ability of magnetization transfer (MT) contrast-prepared magnetic resonance (MR) imaging to help distinguish healthy from cirrhotic liver by using a spectrum of MT pulse frequency offsets. MATERIALS AND METHODS: This HIPAA-compliant prospective study was approved by the institutional review board. Written informed consent was obtained from all subjects. After optimization of the MT sequence by using agar phantoms with protein concentrations ranging from 0% to 4%, 20 patients with cirrhosis and portal hypertension and 20 healthy volunteers with no known liver disease underwent liver MR imaging that included eight separate breath-hold MT contrast sequences, each performed by using a different MT pulse frequency offset (range, 200-2500 Hz). Regions of interest were then placed to calculate the MT ratio for the liver, fat, and muscle in the volunteer group and for the liver in the cirrhosis group. RESULTS: MT ratio increased with decreasing MT pulse frequency offset for each of the four phantoms and the assessed in vivo tissues, consistent with previous reports. At all frequency offsets, MT ratio increased with increasing phantom protein concentration. In volunteers, at frequency offsets greater than 400 Hz, the MT ratio was significantly greater for muscle (range, 34.4%-54.9%) and significantly lower for subcutaneous fat (range, 10.3%-12.6%), compared with that for the liver (range, 22.8%-46.9%; P < .001 all comparisons). However, the MT ratio was nearly identical between healthy (range, 26.0%-80.0%) and cirrhotic livers (range, 26.7%-81.2%) for all frequency offsets (P = .162-.737), aside from a minimal difference in MT ratio of 1.7% at a frequency offset of 2500 Hz (22.8% in healthy liver vs 24.5% in cirrhotic liver) that was not significant when the Bonferroni correction was applied (P = .015). CONCLUSION: Findings of this study confirm the ability of the MT contrast-prepared sequence to help distinguish substances of varying protein concentration and suggest that MT imaging is unlikely to be of clinical utility in differentiating healthy and cirrhotic livers.

Leiomyosarcoma of the splenic vein.

Leiomyosarcomas are smooth muscle-derived tumors generally found intra-abdominally in the retoperitoneum, mesentery, or omentum. Only approximately 5% of these tumors originate from vessel wall smooth muscle. Those derived from the splenic vein are exceedingly rare, with only one previously published case in the literature. We present a second case of leiomyosarcoma of the splenic vein in a 58-year-old woman with 2 months of epigastric pain. A distal pancreatectomy was performed to include the tumor found centered in the splenic vein at the splenic and portal vein confluence and growing into the pancreas in the body on the posterior aspect. A saphenous vein patch was used for reconstruction.

Hepatoportal sclerosis: CT and MRI appearance with histopathologic correlation.

OBJECTIVE: The purposes of this study were to describe the spectrum of cross-sectional imaging findings of pathologically proven hepatoportal sclerosis and to compare the features of advanced and nonadvanced hepatoportal sclerosis. MATERIALS AND METHODS: Eighteen patients with a histopathologic diagnosis of hepatoportal sclerosis who had concurrent MRI or CT images participated in the study. The following imaging features were assessed: presence of liver nodularity and liver lesions, portal vein patency, presence and degree of portal hypertension, liver volume, and caudate-to-right lobe ratio. These features were compared between patients who underwent transplant and those who did not. RESULTS: The 18 patients (11 men and one boy, six women; mean age, 46.5 years) had hepatoportal sclerosis confirmed with liver biopsy (14 patients) or explant (four patients). Fourteen patients underwent contrast-enhanced MRI, and five underwent CT. The imaging findings were as follows: liver surface nodularity, five patients (all four transplant, one nontransplant) (p = 0.0016); evidence of portal hypertension, 17 patients; increased caudate-to-right lobe ratio, 16 patients; high periportal signal intensity on T2-weighted images, six patients; portal vein occlusion with cavernous transformation, five patients. The transplant patients had smaller pretransplant liver volume than did nontransplant patients (p < 0.04). CONCLUSION: Hepatoportal sclerosis is characterized by caudate lobe hypertrophy and right hepatic lobe atrophy, preserved liver volume, and lack of the liver nodularity associated with portal hypertension. In advanced cases, liver nodularity and atrophy produce an imaging appearance indistinguishable from that of cirrhosis.

The effect of liver iron deposition on hepatic apparent diffusion coefficient values in cirrhosis.

OBJECTIVE: The purpose of this study was to assess the effect of hepatic iron deposition on apparent diffusion coefficient (ADC) values measured with single-shot echo-planar imaging (EPI) diffusion-weighted MRI (DWI) in patients with liver cirrhosis and in vitro. MATERIALS AND METHODS: Fifty-two patients with liver cirrhosis who underwent breath-hold single-shot EPI DWI at 1.5 T before liver transplantation were retrospectively assessed. Estimated signal-to-noise ratio (SNRest) and ADC were measured in the right hepatic lobe (for b values of 50 and 500 s/mm2). SNRest and ADC were compared between patients stratified by pathologic iron grade using the Mann-Whitney test. Hepatic ADC values were correlated to T2* values using the Spearman correlation test in a subset of patients. In addition, a phantom consisting of solutions of varying iron concentrations was imaged with single-shot EPI DWI and T2* imaging, and iron concentration was correlated with ADC and T2*. RESULTS: In phantoms, there was a decrease in ADC and T2* with increasing iron concentration (r=-0.95 and -0.92, respectively; p<0.05). Patients with hepatic siderosis had significantly lower SNRest and ADC compared with patients without siderosis (p<0.0001). SNRest at b=50 s/mm2 and b=500 s/mm2 and ADC had a significant negative correlation with pathologic iron grade (r=-0.67 to 0.77, p<0.0001). There was a significant correlation between liver T2* and ADC (r=0.83, p<0.0001). CONCLUSION: Hepatic siderosis lowers liver ADC and should be taken into account when using ADC for diagnosing liver cirrhosis.