Use of ring-enhancement and focal necrosis to differentiate pancreatic adenosquamous carcinoma from pancreatic ductal adenocarcinoma on CT and MRI.

PURPOSE: To assess the ability of the ring-enhancing sign and focal necrosis to diagnose adenosquamous carcinoma (ASqC), a variant of pancreatic ductal adenocarcinoma (PDAC), on MRI and CT. METHODS: The following features of ASqC and conventional PDAC were evaluated on CT and MRI: tumor size, location, margins, borders (non-exophytic, exophytic), and T1 signal intensity. Two readers, blinded to histopathology results, rated their confidence in detecting ring-enhancement and focal necrosis (FN) on a 5-point Likert scale on both MRI and CT. Inter-reader agreement was assessed with Cohen's kappa (k). RESULTS: A total of 24 patients were included: eight patients with treatment naïve and histologically proven ASqC (six women, mean age: 63, range: 40-75) and 16 patients with PDAC (eight women, mean age: 67, range: 47-83). Statistically significant differences between ASqC and PDAC were seen in tumor size, location, presence of FN, and ring enhancement (p = 0.01-0.037). The readers were more confident in depicting the key differentiating feature ring-enhancement in ASqC on MRI compared to CT (confidence 1.71 ± 0.49 vs. 0.88 ± 0.35, p = 0.017) with moderate inter-reader agreement (k = 0.46 and 0.5, respectively). FN showed substantial inter-reader agreement on MR and moderate agreement on CT (k = 0.67 and 0.5, respectively). CONCLUSIONS: Compared to CT, MRI depicts ring-enhancement in ASqC with greater reader confidence and FN in ASqC with higher inter-reader agreement. The concurrent presence of these two imaging features should raise high suspicion for ASqC.

Activation of liver X receptor sensitizes mice to gallbladder cholesterol crystallization.

UNLABELLED: Gallstone disease is a hepatobiliary disorder due to biochemical imbalances in the gallbladder bile. In this report, we show that activation of nuclear receptor liver X receptor (LXR) sensitized mice to lithogenic diet-induced gallbladder cholesterol crystallization, which was associated with dysregulation of several hepatic transporters that efflux cholesterol, phospholipids, and bile salts. The combined effect of increased biliary concentrations of cholesterol and phospholipids and decreased biliary concentrations of bile salts in LXR-activated mice led to an increased cholesterol saturation index and the formation of cholesterol crystals. Interestingly, the lithogenic effect of LXR was completely abolished in the low-density lipoprotein receptor (Ldlr) null background or when the mice were treated with Ezetimibe, a cholesterol-lowering drug that blocks intestinal dietary cholesterol absorption. These results suggest that LDLR-mediated hepatic cholesterol uptake and intestinal cholesterol absorption play an essential role in LXR-promoted lithogenesis. CONCLUSION: The current study has revealed a novel lithogenic role of LXR as well as a functional interplay between LXR and LDLR in gallbladder cholesterol crystallization and possibly cholesterol gallstone disease (CGD). We propose that LXR is a lithogenic factor and that the LXR transgenic mice may offer a convenient CGD model to develop therapeutic interventions for this disease.

Adjuvant stereotactic body radiotherapy for resected pancreatic adenocarcinoma with close or positive margins.

PURPOSE: The aim of this study was to evaluate the role of stereotactic body radiotherapy (SBRT) as adjuvant therapy for resected pancreatic adenocarcinoma with close or positive margins. METHODS: Between September 2006 and January 2010, 24 patients were treated with adjuvant SBRT following surgical resection. Eight (33.3%) patients had close margins of 1-2.5 mm to the retroperitoneal, vascular structures, and periduodenal adipose tissue. Sixteen (66.7%) patients had positive margins at retroperitoneal margin and vascular structures. Twenty-three patients received 24 Gy (20-24 Gy) in one fraction, and one had 30 Gy in three fractions. The median target volume was 11 cc (4.5-30 cc). Eighteen patients were treated with the Cyberknife® Robotic Radiosurgery System and six patients were treated with Trilogy™ intensity-modulated radiosurgery. Kaplan-Meier survival analyses were used to estimate freedom-from-local-progression (FFLP), and overall survival (OS) rates. PET/CT or CT was used to monitor disease recurrence following SBRT. RESULTS: The median follow-up for all patients was 12.5 months (1.4-39.5 months), and among surviving patients it was 16.3 months (2-39.5 months). The FFLP rates at 6 months, 1 and 2 years were 94.7%, 66%, and 44%, respectively. Overall, FFLP was achieved in seven (87.5%) patients with close margins, and 10 (62.5%) with positive margins. After SBRT, 19 patients resumed or started a 6-month course of gemcitabine-based chemotherapy at a median interval of 18 days (range, 9-31 days) post-SBRT. The median OS was 26.7 months and the 1- and 2-year OS rates were 80.4% and 57.2%, respectively. Of the 24 patients, 12 (50%) developed distant metastases of whom two (25%) had close margins and 10 (62.5%) had positive margins. Ten patients (41.7%) were free of progression at last follow-up (range, 3-39.5 months). Three patients (12.5%) had grade 1-2 acute GI toxicities, and two patients (8.3%) had grade 1 and 2 late toxicities. No patients experienced grade 3 or 4 toxicity, including bowel perforation, secondary to SBRT. CONCLUSIONS: Our data suggest that adjuvant SBRT for resected pancreatic cancer can be achieved with minimal toxicity. This shorter treatment course allowed initiation of systemic chemotherapy shortly after the completion of SBRT.