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Rationale and Objectives: To date, no clinically useful classification system has been developed for reliably differentiating mucinous cystic neoplasm (MCN) from a benign hepatic cyst (BHC) in the liver. The objective was to use machine learning and a multi-center study design to develop and assess the performance of a novel classification system for predicting whether a hepatic cystic lesion represents MCN or BHC.Materials and Methods: A multi-center cohort study identified 154 surgically resected hepatic cystic lesions in 154 subjects which were pathologic confirmed as MCN (43) or BHC (111). Readers at each institution recorded seven pre-determined imaging features previously identified as potential differentiating features from prior publications. The contribution of each of these features to differentiating MCN from BHC was assessed by machine learning to develop an optimal classification system.Results: Although several of the assessed imaging features demonstrated statistical significance, only 3 imaging features were found by machine learning to significantly contribute to a potential classification system: (1) solid enhancing nodule (2) all septations arising from an external macro-lobulation (3) whether the lesion was solitary or one of multiple cystic liver lesions. The optimal classification system had only four categories and correctly identified 144/154 lesion (93.5%).Conclusion: This multi-center follow-up study was able to use machine learning to develop a highly accurate classification system for differentiation of hepatic MCN from BHC, which could be readily applied to clinical practice. [ABSTRACT FROM AUTHOR]

Summary Regulatory T (Treg) cell infiltration constitutes a prominent feature of pancreatic ductal adenocarcinoma (PDA). However, the immunomodulatory function of Treg cells in PDA is poorly understood. Here, we demonstrate that Treg cell ablation is sufficient to evoke effective anti-tumor immune response in early and advanced pancreatic tumorigenesis in mice. This response is dependent on interferon-γ (IFN-γ)-producing cytotoxic CD8 + T cells. We show that Treg cells engage in extended interactions with tumor-associated CD11c + dendritic cells (DCs) and restrain their immunogenic function by suppressing the expression of costimulatory ligands necessary for CD8 + T cell activation. Consequently, tumor-associated CD8 + T cells fail to display effector activities when Treg cell ablation is combined with DC depletion. We propose that tumor-infiltrating Treg cells can promote immune tolerance by suppressing tumor-associated DC immunogenicity. The therapeutic manipulation of this axis might provide an effective approach for the targeting of PDA. [ABSTRACT FROM AUTHOR]

Background: Diaphragmatic sarcomas are extremely rare and mostly described in children. We present the case of an adult with rhabdomyosarcoma of the diaphragm. Methods: We performed a literature review, highlighted possible diagnostic pitfalls, and discussed multidisciplinary treatment options. [ABSTRACT FROM AUTHOR]

Tumor genotype can influence the immune microenvironment, which plays a critical role in cancer development and therapy resistance. However, the immune effects of gain-of-function Trp53 mutations have not been defined in pancreatic cancer. We compare the immune profiles generated by Kras G12D -mutated mouse pancreatic ductal epithelial cells (PDECs) engineered genetically to express the Trp53 R172H mutation with their p53 wild-type control. Kras G12D/+ ; Trp53 R172H/+ tumors have a distinct immune profile characterized by an influx of CD11b+Ly6G+ neutrophils and concomitant decreases in CD3+ T cells, CD8+ T cells, and CD4+ T helper 1 cells. Knockdown of CXCL2, a neutrophil chemokine, in the tumor epithelial compartment of CRISPR Kras G12D/+ ; Trp53 R172H/+ PDEC tumors reverses the neutrophil phenotype. Neutrophil depletion of mice bearing CRISPR Kras G12D/+ ; Trp53 R172H/+ tumors augments sensitivity to combined CD40 immunotherapy and chemotherapy. These data link Trp53 R172H to the presence of intratumoral neutrophils in pancreatic cancer and suggest that tumor genotypes could inform selection of affected individuals for immunotherapy. [Display omitted] • Gain-of-function Trp53R172H promotes neutrophil recruitment to pancreatic tumors • Neutrophils in Kras G12D/+ ;Trp53 R172H/+ tumors are due to tumor-cell-derived chemokines • Neutrophils confer resistance to CD40 combination immunotherapy and chemotherapy Siolas et al. demonstrate that the gain-of-function Trp53 R172H mutation promotes CD11b+Ly6G+ neutrophil recruitment to Kras G12D pancreatic tumors, which is distinct from tumors with loss-of-function or wild-type Trp53. The presence of neutrophils in the tumor microenvironment promotes resistance to combination CD40 immunotherapy and chemotherapy treatment, suggesting that tumor genotype may guide therapy selection. [ABSTRACT FROM AUTHOR]

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. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To assess the role of apparent diffusion coefficient (ADC) measured with diffusion-weighted imaging (DWI) in predicting and assessing response of hepatocellular carcinoma (HCC) to transarterial chemoembolization (TACE). Methods: Thirty-six patients with cirrhosis and untreated HCC who underwent TACE and MRI within 3 months before and after TACE were assessed. MRI included DWI and contrast-enhanced T1-weighted imaging. Two observers measured ADC of HCCs and liver parenchyma on pre- and post-TACE MRIs and measured degree of tumor necrosis on subtracted post-contrast images on post-TACE MRI. Pre-, post-TACE tumor ADC, and changes in tumor ADC (ΔADC) were compared between lesions stratified by degree of tumor necrosis (measured on post-TACE MRI). Results: Forty seven HCCs were evaluated (mean size 4.4cm, range 1.0–14.1cm). HCCs with poor and incomplete response to TACE (<50% necrosis on post-TACE MRI) had significantly lower pre-treatment ADC and lower post TACE ADC compared to HCCs with good/complete response (≥50% necrosis): ADC pre-TACE 1.35±0.42 vs. 1.64±0.39×10−3 mm2/s (p =0.042); post-TACE ADC 1.34±0.36 vs. 1.92±0.47 (p =0.0008). There was no difference in ΔADC values. Conclusion: This preliminary data suggests that pre-TACE tumor ADC can be used to predict HCC response to TACE. [Copyright &y& Elsevier]

Summary: Stromal responses elicited by early stage neoplastic lesions can promote tumor growth. However, the molecular mechanisms that underlie the early recruitment of stromal cells to sites of neoplasia remain poorly understood. Here, we demonstrate an oncogenic KrasG12D-dependent upregulation of GM-CSF in mouse pancreatic ductal epithelial cells (PDECs). An enhanced GM-CSF production is also observed in human PanIN lesions. KrasG12D-dependent production of GM-CSF in vivo is required for the recruitment of Gr1+CD11b+ myeloid cells. The suppression of GM-CSF production inhibits the in vivo growth of Kras G12D -PDECs, and, consistent with the role of GM-CSF in Gr1+CD11b+ mobilization, this effect is mediated by CD8+ T cells. These results identify a pathway that links oncogenic activation to the evasion of antitumor immunity. [Copyright &y& Elsevier]

Purpose To compare MRI features of pathologically-proven hepatocellular carcinoma (HCC) between patients with hepatitis B (HBV) and hepatitis C (HCV) infection. Methods Two radiologists assessed 51 confirmed HCCs on MRI in HBV (n = 18) or HCV (n = 33) patients; a third, more experienced, radiologist resolved discrepancies. Results Arterial hyperenhancement occurred more frequently in HCV (90.9% vs. 66.7%; P = .032), DWI/T2WI hyperintensity more frequently in HBV [(DWI: 78.6% vs. 45.8%, T2WI: 77.8% vs. 48.5%; P = .073–0.088)]. Tumors were larger in HBV ( P ≤ .016). Washout, pseudocapsule, homogeneity, circumscribed margins, lipid, iron, and visually low ADC were not different. Conclusion Larger studies are required to confirm these preliminary findings. [ABSTRACT FROM AUTHOR]

We compared individual computed tomography (CT) and MRI findings in differentiating acute from chronic cholecystitis. Thirty-seven patients undergoing both studies before cholecystectomy were included. Two radiologists (R1/R2) independently assessed all cases. For detecting acute cholecystitis, MRI showed better sensitivity (R1) using gallbladder wall thickening, accuracy (R1) and sensitivity (R1) using gallstones, sensitivity (R1 and R2) and accuracy (R2) using gallbladder wall hyperemia, accuracy (R1 and R2) using gallbladder wall defect, and accuracy (R2) using adjacent liver hyperemia (P=.004-.063). MRI also showed better specificity (R2) using pericholecystic fat stranding (P=.016). Overall, several findings showed better sensitivity and/or accuracy for acute cholecystitis on MRI than CT. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The objective was to perform ex vivo evaluation of non-Gaussian diffusion kurtosis imaging (DKI) for assessment of hepatocellular carcinoma (HCC), including presence of treatment-related necrosis, using fresh liver explants. Methods: Twelve liver explants underwent 1.5-T magnetic resonance imaging using a DKI sequence with maximal b-value of 2000 s/mm2. A standard monoexponential fit was used to calculate apparent diffusion coefficient (ADC), and a non-Gaussian kurtosis fit was used to calculate K, a measure of excess kurtosis of diffusion, and D, a corrected diffusion coefficient accounting for this non-Gaussian behavior. The mean value of these parameters was measured for 16 HCCs based upon histologic findings. For each metric, HCC-to-liver contrast was calculated, and coefficient of variation (CV) was computed for voxels within the lesion as an indicator of heterogeneity. A single hepatopathologist determined HCC necrosis and cellularity. Results: The 16 HCCs demonstrated intermediate-to-substantial excess diffusional kurtosis, and mean corrected diffusion coefficient D was 23% greater than mean ADC (P=.002). HCC-to-liver contrast and CV of HCC were greater for K than ADC or D, although these differences were significant only for CV of HCCs (P≤.046). ADC, D and K all showed significant differences between non-, partially and completely necrotic HCCs (P≤.004). Among seven nonnecrotic HCCs, cellularity showed a strong inverse correlation with ADC (r=−0.80), a weaker inverse correlation with D (−0.24) and a direct correlation with K (r=0.48). Conclusions: We observed non-Gaussian diffusion behavior for HCCs ex vivo; this DKI model may have added value in HCC characterization in comparison with a standard monoexponential model of diffusion-weighted imaging. [Copyright &y& Elsevier]