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Morphologic irregularities of the pancreatic duct are often noted on abdominal imaging studies obtained for unrelated symptoms or conditions. We report the case of a patient who was found to have an incidental, isolated pancreatic duct dilatation on multiple imaging studies and who was found to have a nonfunctioning pancreatic endocrine neoplasm at resection. His prognosis is excellent based on the histology of the lesion and a curative resection. This case highlights the importance of fully investigating incidental pancreatic duct abnormalities regardless of the setting in which they are found. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Anastomosing hemangioma (AH) is a rare, benign vascular neoplasm with distinctive histopathology and characteristic tumor distribution. AHs show marked proclivity to involve the kidneys, gonads and the retroperitoneal soft tissues; kidney is the most common target site often in the context of end stage renal disease. Recent studies have identified activating mutations of GNA genes that drive the molecular pathogenesis of AHs. AH appears as a solitary, well-circumscribed, hypervascular tumor that charters a benign course with an excellent prognosis. The purpose of this article is to provide a current update on clinical, pathological and imaging features of anastomotic hemangioma. [ABSTRACT FROM AUTHOR]

Background: The management of ectopic pancreas is not well defined. This study aims to determine the prevalence of symptomatic ectopic pancreas and identify those who may benefit from treatment, with a particular focus on robotically assisted surgical management.Methods: Our institutional pathology database was queried to identify a cohort of ectopic pancreas specimens. Additional clinical data regarding clinical symptomatology, diagnostic studies, and treatment were obtained through chart review.Results: Nineteen cases of ectopic pancreas were found incidentally during surgery for another condition or found incidentally in a pathologic specimen (65.5%). Eleven patients (37.9%) reported prior symptoms, notably abdominal pain and/or gastrointestinal bleeding. The most common locations for ectopic pancreas were the duodenum and small bowel (31% and 27.6%, respectively). Three out of 29 cases (10.3%) had no symptoms, but had evidence of preneoplastic changes on pathology, while one harbored pancreatic cancer. Over the years, treatment of ectopic pancreas has shifted from open to laparoscopic and more recently to robotic surgery.Conclusions: Our experience is in line with existing evidence supporting surgical treatment of symptomatic or complicated ectopic pancreas. In the current era, minimally invasive and robotic surgery can be used safely and successfully for treatment of ectopic pancreas. [ABSTRACT FROM AUTHOR]

Solitary fibrous tumors (SFTs) are raremesenchymal neoplasms of fibroblastic origin. Most commonly they affect the pleura but they been described in other viscera. SFT of the pancreas is extremely rare, and only eight cases have been reported to date. We perform a literature review and report a ninth case. The patient is a 54-year-old African-American female who presented with several months of abdominal pain. Abdominal radiography demonstrated a lesion in the head of the pancreas, and she underwent a Whipple operation. Pathology demonstrated SFT of the pancreas. She is alive and well 1 year post-operatively. SFT of the pancreas predominately affects middle-aged women. These tumors are difficult to distinguish radiologically from neuroendocrine tumors. While SFT of the pancreas tend to have an indolent course, there is the potential for malignancy. We recommend complete surgical excision. [ABSTRACT FROM AUTHOR]

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. [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]

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]

Single-cell RNA sequencing (scRNA-seq) enables the systematic identification of cell populations in a tissue, but characterizing their spatial organization remains challenging. We combine a microarray-based spatial transcriptomics method that reveals spatial patterns of gene expression using an array of spots, each capturing the transcriptomes of multiple adjacent cells, with scRNA-Seq generated from the same sample. To annotate the precise cellular composition of distinct tissue regions, we introduce a method for multimodal intersection analysis. Applying multimodal intersection analysis to primary pancreatic tumors, we find that subpopulations of ductal cells, macrophages, dendritic cells and cancer cells have spatially restricted enrichments, as well as distinct coenrichments with other cell types. Furthermore, we identify colocalization of inflammatory fibroblasts and cancer cells expressing a stress-response gene module. Our approach for mapping the architecture of scRNA-seq-defined subpopulations can be applied to reveal the interactions inherent to complex tissues. Combining single-cell RNA-seq data and microarray-based spatial transcriptomics maps the location of different cell types and cell states in pancreatic tumors. [ABSTRACT FROM AUTHOR]

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]

Pancreatic ductal adenocarcinoma (PDAC) is strikingly resistant to conventional therapeutic approaches. We previously demonstrated that the histone deacetylase-associated protein SIN3B is essential for oncogene-induced senescence in cultured cells. Here, using a mouse model of pancreatic cancer, we have demonstrated that SIN3B is required for activated KRAS-induced senescence in vivo. Surprisingly, impaired senescence as the result of genetic inactivation of Sin3B was associated with delayed PDAC progression and correlated with an impaired inflammatory response. In murine and human pancreatic cells and tissues, levels of SIN3B correlated with KRAS-induced production of IL-1α. Furthermore, evaluation of human pancreatic tissue and cancer cells revealed that Sin3B was decreased in control and PDAC samples, compared with samples from patients with pancreatic inflammation. These results indicate that senescence-associated inflammation positively correlates with PDAC progression and suggest that SIN3B has potential as a therapeutic target for inhibiting inflammation-driven tumorigenesis. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is strikingly resistant to conventional therapeutic approaches. We previously demonstrated that the histone deacetylase-associated protein SIN3B is essential for oncogeneinduced senescence in cultured cells. Here, using a mouse model of pancreatic cancer, we have demonstrated that SIN3B is required for activated KRAS-induced senescence in vivo. Surprisingly, impaired senescence as the result of genetic inactivation of Sin3B was associated with delayed PDAC progression and correlated with an impaired inflammatory response. In murine and human pancreatic cells and tissues, levels of SIN3B correlated with KRAS-induced production of IL-1a. Furthermore, evaluation of human pancreatic tissue and cancer cells revealed that Sin3B was decreased in control and PDAC samples, compared with samples from patients with pancreatic inflammation. These results indicate that senescence-associated inflammation positively correlates with PDAC progression and suggest that SIN3B has potential as a therapeutic target for inhibiting inflammation-driven tumorigenesis. [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]

Pancreatic ductal adenocarcinoma is an aggressive cancer that interacts with stromal cells to produce a highly inflammatory tumor microenvironment that promotes tumor growth and invasiveness. The precise interplay between tumor and stroma remains poorly understood. TLRs mediate interactions between environmental stimuli and innate immunity and trigger proinflammatory signaling cascades. Our finding that TLR7 expres-sion is upregulated in both epithelial and stromal compartments in human and murine pancreatic cancer led us to postulate that carcinogenesis is dependent on TLR7 signaling. In a mouse model of pancreatic cancer, TLR7 ligation vigorously accelerated tumor progression and induced loss of expression of PTEN, pl6, and cyclin D1 and upregulation of p21, p27, p53, c-Myc, SHPTP1, TGF-β, PPARγ, and cyclin BL. Furthermore, TLR7 ligation induced STAT3 activation and interfaced with Notch as well as canonical NF-kB and MAP kinase pathways, but downregulated expression of Notch target genes. Moreover, blockade of TLR7 protected against carcinogenesis. Since pancreatic tumorigenesis requires stromal expansion, we proposed that TLR7 ligation modulates pancreatic cancer by driving stromal inflammation. Accordingly, we found that mice lacking TLR7 exclusively within their inflammatory cells were protected from neoplasia. These data suggest that targeting TLR7 holds promise for treatment of human pancreatic cancer. [ABSTRACT FROM AUTHOR]

R3778 --> Pancreatic ductal adenocarcinoma (PDA) is the 3rd leading cause of cancer‐death in the U.S.. Glycans, such as CA‐19‐9, are biomarkers of PDA, but their roles in PDA biology are unclear. Herein, we utilized lectin microarray technology to compare the glycomes of human and murine PDA. We observed common aberrant patterns of glycosylation across both species, including increased levels of α‐2,3‐ and α‐2,6‐sialic acids, bisecting GlcNAc and poly‐LacNAc. Using single cell sequencing and histological data, we identified ST6GAL1, which underlies α‐2,6‐sialic acid, as a potential driver in human PDA. We created a novel mouse in which a pancreas‐specific genetic deletion of ST6GAL1 overlays the well‐established KC mouse model. Analysis of our model showed delayed cancer formation and a significant reduction in fibrosis. Our results highlight the utility of the KC model as an accurate reflection of human disease and identify ST6GAL1 as a key driver of pancreatic cancer initiation and progression. [ABSTRACT FROM AUTHOR]

A Correction to this paper has been published: https://doi.org/10.1038/s41587-019-0392-8. [ABSTRACT FROM AUTHOR]

Summary 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 αβT cells. Although αβT 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. [ABSTRACT FROM AUTHOR]