Progastrin production transitions from Bmi1+/Prox1+ to Lgr5high cells during early intestinal tumorigenesis.

Progastrin is an unprocessed soluble peptide precursor with a well-described tumor-promoting role in colorectal cancer. It is expressed at small levels in the healthy intestinal mucosa, and its expression is enhanced at early stages of intestinal tumor development, with high levels of this peptide in hyperplastic intestinal polyps being associated with poor neoplasm-free survival in patients. Yet, the precise type of progastrin-producing cells in the healthy intestinal mucosa and in early adenomas remains unclear. Here, we used a combination of immunostaining, RNAscope labelling and retrospective analysis of single cell RNAseq results to demonstrate that progastrin is produced within intestinal crypts by a subset of Bmi1+/Prox1+/LGR5low endocrine cells, previously shown to act as replacement stem cells in case of mucosal injury. In contrast, our findings indicate that intestinal stem cells, specified by expression of the Wnt signaling target LGR5, become the main source of progastrin production in early mouse and human intestinal adenomas. Collectively our results suggest that the previously identified feed-forward mechanisms between progastrin and Wnt signaling is a hallmark of early neoplastic transformation in mouse and human colonic adenomas.

Diagnostic performance of mobile cone beam computed tomography versus conventional multi-detector computed tomography in orbital floor fractures: a study on human specimens.

The aim of this study was to evaluate the diagnostic accuracy of mobile cone beam computed tomography (MCBCT) versus multi-detector computed tomography (MDCT) in orbital floor fractures. Twenty-four fresh cadaver heads were used, and one orbital floor was fractured for each head by transconjunctival approach. MDCT and MCBCT were performed on each of the heads. The images obtained were then analysed independently by eight evaluators. The radiological characteristics of the orbital floor fractures were visualized with good interpretation agreement between the two images. The location of the fracture and enophthalmos were identified in a comparable manner with strong agreement (κ=0.93 and κ=0.85, respectively). Measurements of fatty hernias and bone defects showed a strong correlation between the two imaging modalities (Pearson coefficient between 0.64 and 0.71 and between 0.67 and 0.71, respectively). The fracture limits and the presence of bone fragments, an intrasinus fatty hernia, and a fracture of the associated medial orbital wall were visualized in both examinations with good agreement (κ=0.68, κ=0.51, κ=0.57, and κ=0.46, respectively). The soft tissue study showed superiority for MDCT, with a κ<0.0009. MCBCT showed good diagnostic performance in the study of orbital floor fracture characteristics.

Non-invasive diagnosis of severe alcoholic hepatitis: Usefulness of cross-sectional imaging.

PURPOSE: To describe the computed tomography (CT) and magnetic resonance imaging (MRI) features of severe acute alcoholic hepatitis (SAAH) and estimate the capabilities of CT and MRI in differentiating SAAH from alcoholic cirrhosis and non-alcoholic steato-hepatitis (NASH) cirrhosis. MATERIALS AND METHODS: Fifty patients with pathologically proven SAAH (SAAH group) who underwent CT or MRI examinations up to 30 days before or 15 days after liver biopsy between January 2008 and June 2018 were retrospectively included. There were 31 men and 29 women with a mean age of 52±9 (SD) years (range: 33-67 years). Imaging features of the SAAH group were compared to those obtained in two control groups including 62 patients with alcoholic cirrhosis without acute alcoholic hepatitis (control group 1) and 19 patients with NASH cirrhosis (control group 2) by two independent radiologists blinded to the final diagnosis. Univariate analyses were performed to compare imaging characteristics between the three groups, followed by diagnostic performance analysis for the diagnosis of SAAH of the main CT features. RESULTS: Heterogeneous steatosis was significantly more frequent in SAAH group than in the control groups (41/50; 82% vs. 7/62; 10% and 1/19; 5% in control groups 1 and 2, respectively for reader 1 and 34/50; 68% vs. 8/62; 13% and 1/19; 5% in control groups 1 and 2, respectively for reader 2; both P=0.01). Transient perfusion disorders were more frequent in SAAH group than in the control groups (35/50; 70% vs. 12/62; 21% and 5/19; 26% in control groups 1 and 2, respectively for reader 1 and 39/50; 78% vs. 14/62; 23% and 13/19; 6% in control groups 1 and 2, respectively for reader 2; both P=0.01). The combination of these two findings yielded 100% specificity (45/45; 95% CI: 92-100) for readers 1 and 2 for the diagnosis of SAAH vs. alcoholic cirrhosis and NASH cirrhosis. CONCLUSION: The imaging features of SAAH are specific and mainly associate transient heterogeneous steatosis and liver perfusion disorders. CT/MRI may be useful to differentiate SAAH from alcoholic cirrhosis and NASH cirrhosis.