Faculty Bibliography

Solitary fibrous tumors (SFTs) are rare mesenchymal 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.

Dectin-1 is a C-type lectin receptor critical in anti-fungal immunity, but Dectin-1 has not been linked to regulation of sterile inflammation or oncogenesis. We found that Dectin-1 expression is upregulated in hepatic fibrosis and liver cancer. However, Dectin-1 deletion exacerbates liver fibro-inflammatory disease and accelerates hepatocarcinogenesis. Mechanistically, we found that Dectin-1 protects against chronic liver disease by suppressing TLR4 signaling in hepatic inflammatory and stellate cells. Accordingly, Dectin-1(-/-) mice exhibited augmented cytokine production and reduced survival in lipopolysaccharide (LPS)-mediated sepsis, whereas Dectin-1 activation was protective. We showed that Dectin-1 inhibits TLR4 signaling by mitigating TLR4 and CD14 expression, which are regulated by Dectin-1-dependent macrophage colony stimulating factor (M-CSF) expression. Our study suggests that Dectin-1 is an attractive target for experimental therapeutics in hepatic fibrosis and neoplastic transformation. More broadly, our work deciphers critical cross-talk between pattern recognition receptors and implicates a role for Dectin-1 in suppression of sterile inflammation, inflammation-induced oncogenesis, and LPS-mediated sepsis.

Modulation of Toll-like receptor (TLR) signaling can have protective or protumorigenic effects on oncogenesis depending on the cancer subtype and on specific inflammatory elements within the tumor milieu. We found that TLR9 is widely expressed early during the course of pancreatic transformation and that TLR9 ligands are ubiquitous within the tumor microenvironment. TLR9 ligation markedly accelerates oncogenesis, whereas TLR9 deletion is protective. We show that TLR9 activation has distinct effects on the epithelial, inflammatory, and fibrogenic cellular subsets in pancreatic carcinoma and plays a central role in cross talk between these compartments. Specifically, TLR9 activation can induce proinflammatory signaling in transformed epithelial cells, but does not elicit oncogene expression or cancer cell proliferation. Conversely, TLR9 ligation induces pancreatic stellate cells (PSCs) to become fibrogenic and secrete chemokines that promote epithelial cell proliferation. TLR9-activated PSCs mediate their protumorigenic effects on the epithelial compartment via CCL11. Additionally, TLR9 has immune-suppressive effects in the tumor microenvironment (TME) via induction of regulatory T cell recruitment and myeloid-derived suppressor cell proliferation. Collectively, our work shows that TLR9 has protumorigenic effects in pancreatic carcinoma which are distinct from its influence in extrapancreatic malignancies and from the mechanistic effects of other TLRs on pancreatic oncogenesis.

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 /= 0.058). CONCLUSION: Abnormal signal on DWI, hyperenhancement, and convex outer contour are helpful MRI features to differentiate malignant from benign omental thickening.

PURPOSE: Transjugular liver biopsy (TJLB) is commonly performed for staging of liver fibrosis and cirrhosis among patients with coagulopathy and/or ascites. We hypothesized that device orientation during needle firing influences hepatic tissue apposition with the specimen notch and specimen quality. METHODS: Needle biopsies were performed in ex vivo bovine livers with specimen notch of the biopsy device oriented at cranial, caudal, or lateral directions with respect to the guiding metal cannula. Biopsy specimen length was measured and evaluated for fragmentation using light microscopy. In addition, a consecutive cohort of patients (n = 50) who underwent TJLB with random (n = 22) or caudal (n = 28) needle orientation was retrospectively reviewed. The number of needle passes was documented, and pathology specimen adequacy was graded using an ordinal scale. RESULTS: A total of 400 biopsies were performed (100 in each orientation) in ex vivo bovine livers. Longer specimens were obtained with caudal orientation of the needle specimen notch (p < 0.0001, ANOVA and Kruskal-Wallis tests). There was no difference in the degree of fragmentation. In the retrospective clinical study, specimen adequacy was significantly higher among patients in the caudal orientation group (p = 0.0002, Mann-Whitney U test). CONCLUSION: Caudal orientation of the needle specimen notch of the biopsy device during TJLB produces superior core biopsy specimens. This simple technical modification may assist in obtaining higher-quality biopsy specimens during TJLB.

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.