BackgroundPancreatic cancer remains one of the most difficult cancers to treat with the poorest prognosis. The key to improving survival rates in this disease is early detection and monitoring of disseminated and residual disease. However, this is hindered due to lack reliable diagnostic and predictive markers which mean that the majority of patients succumb to their condition within a few months.MethodsWe present a pilot study of the detection circulating free DNA (cfDNA) combined with tumor specific mutation detection by digital PCR as a novel minimally invasive biomarker in pancreatic ductal adenocarcinoma (PDAC). This was compared to the detection of CTC by the CellSearch® system and a novel CTC enrichment strategy based on CD45 positive cell depletion. The aim of the study was to assess tumor specific DNA detection in plasma and CTC detection as prognostic markers in PDAC.ResultsWe detected KRAS mutant cfDNA in 26 % of patients of all stages and this correlated strongly with Overall Survival (OS), 60 days (95 % CI: 19–317) for KRAS mutation positive vs 772 days for KRAS mutation negative (95 % CI: 416–1127). Although, the presence of CTC detected by the CellSearch® system did correlate significantly with OS, 88 days (95 % CI: 27–206) CTC positive vs 393 days CTC negative (95 % CI: 284–501), CTC were detected in only 20 % of patients, the majority of which had metastatic disease, whereas KRAS mutant cfDNA was detected in patients with both resectable and advanced disease.ConclusionsTumor specific cfDNA detection and CTC detection are promising markers for the management of patients with PDAC, although there is a need to validate these results in a larger patient cohort and optimize the detection of CTC in PDAC by applying the appropriate markers for their detection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1779-7) contains supplementary material, which is available to authorized users.

BackgroundTreatment with tumour necrosis factor inhibitors (TNF-i) plus methotrexate (MTX), but not MTX monotherapy alone, inhibits joint damage progression even at higher levels of disease activity. Such disassociation of disease activity and structural damage has not been shown for biological agents other than TNF-i.ObjectivesTo evaluate whether interleukin 6 (IL-6) inhibition with tocilizumab (TCZ) interferes with joint destruction beyond its effects on disease activity.MethodsA random 90% sample of data from the (The Tocilizumab Safety and the Prevention of Structural Joint Damage Study) LITHEtrial on active rheumatoid arthritis (RA) despite MTX was used, which compared addition of placebo (n=117) with addition of TCZ (n=414) every 4 weeks. Baseline and 1-year values of clinical and serological variables were correlated with changes to 1 year of the total Genant-modified Sharp score (TGSS) using a Spearman test, and the progression of TGSS, erosion and joint space narrowing (JSN) scores in groups with low and high disease activity were compared for placebo and TCZ (Kruskal–Wallis).ResultsBaseline variables were similar among the groups. Change of TGSS was lower in patients receiving TCZ than placebo (TCZ: 0.29±0.96; placebo: 0.90±1.92; p=0.0007). In patients receiving placebo, the correlation with TGSS change was significant for baseline scores of the simplified disease activity index (SDAI; r=0.18, p=0.047) and swollen joint count 28 (r=0.22, p=0.019), with similar trends for C-reactive protein. Similar correlations were seen for SDAI, clinical disease activity index, disease activity score 28 at 1 year with x-ray change during that year (r=0.26–0.28, p=0.002–0.006). In contrast, none of the baseline or 1-year variables showed significant correlation with x-ray changes in patients receiving TCZ+MTX, suggesting a disassociation of the link between disease activity and damage by TCZ. Finally, for patients in remission or with low disease activity, progression of TGSS, erosion and JSN was similar among treatment groups (TGSS: placebo, 0.4±1.1; TCZ, 0.2±0.7; p=NS), while for patients with moderate or high disease activity placebo-treated patients progression was significantly greater (TGSS: 1.2±2.2 vs 0.4±1.2; p=0.0009).ConclusionsIL-6 inhibition with TCZ plus MTX retards joint damage progression independently of its impact on disease activity. Similar effects have hitherto been reported only for TNF-i. This indicates that the effects of IL-6 inhibition on progression of joint damage in RA are among the most profound currently attainable.

Study objective:The objective of the InMEDIATE study was to evaluate the change in intensity of traumatic pain over the first 20 min in adult patients treated with methoxyflurane versus standard analgesic treatment in Spain. This the first randomized, activecontrolled, multicenter trial of methoxyflurane in the emergency setting in Europe.Methods: This was a randomized, controlled study that enrolled adult patients with acute moderate to severe (score !4 on the 11-point Numeric Rating Scale) trauma-associated pain in 14 Spanish emergency departments. Patients were randomized 1:1 to methoxyflurane (up to 2Â3 mL) or standard analgesic treatment. Coprimary endpoints were the change from baseline in Numeric Rating Scale pain intensity score during the first 20 minutes of treatment and time to first pain relief.Results: Three hundred five patients were randomized (methoxyflurane 156; standard analgesic treatment 149). Most patients in the standard analgesic treatment group (70%) received intravenous first-step analgesics and 9.4% of patients were treated with opioids. Mean decrease from baseline in Numeric Rating Scale pain intensity score was greater for methoxyflurane than standard analgesic treatment at all points, with a significant treatment difference overall up to 20 minutes (repeated-measures model 2.47 versus 1.39; treatment difference 1.00; 95% confidence interval 0.84 to 1.32). Median time to first pain relief was significantly shorter for methoxyflurane than standard analgesic treatment (3 versus 10 minutes). Methoxyflurane achieved better patient and clinician ratings for pain control and comfort of treatment than standard analgesic treatment and exceeded patient and clinician expectations of treatment in, respectively, 77% and 72% of cases compared with 38% and 19% for standard analgesic treatment. Conclusion:These results support consideration of methoxyflurane as a nonnarcotic, easy-to-administer, rapid-acting, first-line alternative to currently available analgesic treatments for trauma pain.