BackgroundConcurrent chemoradiation is a standard option for locally advanced pancreatic cancer (LAPC). Concurrent conventional radiation with full-dose gemcitabine has significant toxicity. Stereotactic body radiation therapy (SBRT) may provide the opportunity to administer radiation in a shorter time frame with similar efficacy and reduced toxicity. This Pilot study assessed the safety of concurrent full-dose gemcitabine with SBRT for LAPC.MethodsPatients received gemcitabine, 1000 mg/m2 for 6 cycles. During week 4 of cycle 1, patients received SBRT (25 Gy delivered in five consecutive daily fractions of 5 Gy prescribed to the 75-83% isodose line). Acute and late toxicities were assessed using NIH CTCAE v3. Tumor response was assessed by RECIST. Patients underwent an esophagogastroduodenoscopy at baseline, 2, and 6 months to assess the duodenal mucosa. Quality of life (QoL) data was collected before and after treatment using the QLQ-C30 and QLQ-PAN26 questionnaires.ResultsBetween September 2009 and February 2011, 11 patients enrolled with one withdrawal during radiation therapy. Patients had grade 1 to 2 gastrointestinal toxicity from the start of SBRT to 2 weeks after treatment. There were no grade 3 or greater radiation-related toxicities or delays for cycle 2 of gemcitabine. On endoscopy, there were no grade 2 or higher mucosal toxicities. Two patients had a partial response. The median progression free and overall survival were 6.8 and 12.2 months, respectively. Global QoL did not change between baseline and immediately after radiation treatment.ConclusionsSBRT with concurrent full dose gemcitabine is safe when administered to patients with LAPC. There is no delay in administration of radiation or chemotherapy, and radiation is completed with minimal toxicity.

Pituitary adenylyl cyclase activating peptide (PACAP) is expressed in central, sensory, autonomic, and enteric neurons. Although it classically acts as a neurotransmitter/neuromodulator, recent studies indicate that PACAP can also regulate immune function. To this effect, PACAP has been shown to reduce clinical symptoms and inflammation in mouse models of human immunebased diseases such as rheumatoid arthritis, Crohn's Disease, septic shock and multiple sclerosis. Despite these findings, the role of the endogenous peptide in regulating immune function is unknown. To determine if endogenous PACAP plays a protective role in inflammatory bowel disease (IBD) and IBD-associated colorectal cancer in mice, PACAP-deficient (KO) mice were subjected to 3 cycles of dextran sulfate sodium (DSS) in drinking water over 2 months, an established mouse model for colitis. Compared to wild type (WT) controls, PACAP KO mice exhibited more severe clinical symptoms of colitis and had significantly higher colonic inflammation on pathological examination. Moreover, 60% of the PACAP KO mice developed colorectal tumors with an aggressive-appearing pathology. Consistent with published data, DSS-treated WT mice did not develop such tumors. The results demonstrate a new mouse model which rapidly develops inflammation-associated colorectal cancer in the absence of a carcinogen. ' 2007 Wiley-Liss, Inc.Key words: pituitary adenylyl cyclase activating peptide (PACAP); inflammation; colorectal cancer; colitis; cancer Chronic inflammatory diseases are known to be linked to the development of cancer.1 In one of the more prominent examples, colorectal cancer (CRC) occurs at a significantly higher rate in patients with inflammatory bowel disease (IBD) compared to the normal population. The increased incidence of CRC in IBD patients appears to be most pronounced in individuals with extensive and long-term ulcerative colitis.2 The rate of CRC begins to increase significantly after 10 years of colitis, with a cumulative probability of 18% after 30-year duration. Like its more common counterpart, sporadic CRC, the prognosis for IBD-associated CRC is poor: the 5-year survival rate is about 50%. Preventative treatment includes colectomy and the use of drugs. Retrospective studies suggest that chronic treatment with 5-aminosalicylic acid or related drugs can reduce the incidence of CRC in patients with IBD, although the studies are not conclusive, and the mechanism of drug action is uncertain. COX-2 inhibitors may also provide protection and appear to have less potential to aggravate IBD than other nonsteroidal antiinflammatory drugs. Despite potential preventative measures in these patients, the incidence of CRC remains high, and new therapeutic modalities must be explored. Moreover, improved animal models are needed to better understand the disease, to test new treatments, and to understand the mechanisms of action of various treatments. In this regard, several rodent models have been developed to study the pathogenesis of chronic ulcerative colitis and...

Introduction Predicting prognosis following aortic valve replacement (AVR) in patients with aortic stenosis (AS) remains challenging. Current guidelines recommend that surgery should be offered when ejection fraction (EF) is <50%. We sought to investigate the prognostic significance of EF calculated by cardiovascular magnetic resonance (CMR) in the long term survival of patients following AVR. Methods 80 patients (69 ± 11 years old at time of surgery; 55 male) scheduled for AVR underwent CMR assessment. 52 patients had severe AS (area <1cm2), 28 patients had moderate AS (area 1.0–1.5cm2) and other qualifying reasons for AVR. 44 patients had additional coronary artery disease.Patients were categorised into three groups according to EF prior to surgery: Group 1 (EF <50%; n = 26), Group 2 (EF of 50–70%; n = 26) and Group 3 (EF >70%; n = 28). A median 5.0 ± 1.8 years follow-up was completed using the National Strategic Tracing Scheme and hospital notes. Results Univariate analysis of all cause mortality using the Kaplan-Meier estimator demonstrated significantly higher mortality in patients with Group 1 (EF <50%) compared to those in group 3 (EF >70%; .03).There was no statistical difference between group 2 (EF of 50–70%) and the remaining 2 groups. Abstract 93 Figure 1 Kaplan-Meier survival curve of all cause mortality in Group 1 (EF <50%), Group 2 (EF 50–70%) and Group 3 (EF >70%) Conclusion Pre-operative EF is a significant predictor of mortality following AVR. Patients with EF <50% have the worst prognosis whereas those with EF >70% have the best prognosis. We aim to incease the sample size to determine whether a progressive decrease in EF per se even when above 50% should initiate consideration for AVR.

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