No abstract

No abstract

No abstract

NCT00212615.

Hyaluronan (HA) and collagen are highly expressed in pancreatic cancer (PC) stroma. HA and collagen accumulation increase tumor interstitial fluid pressure, compromising blood flow and drug penetration. The aim of this biomarker study was to determine the clinical utility of serum HA and the propeptide of type III collagen (PRO‐C3) in patients with PC. A cohort from the Danish BIOPAC study (NCT03311776) including patients with histologically confirmed pancreatic ductal adenocarcinoma (n = 809), ampullary carcinoma (n = 44), distal biliary tract cancer (n = 31), chronic pancreatitis (n = 15), intraductal papillary mucinous neoplasm (n = 41), duodenal adenoma (n = 7) and no cancer (n = 25). Healthy controls were available for serum HA (n = 141) and PRO‐C3 (n = 8). The main outcome was overall survival (OS) of patients with PC in relation to pretreatment serum HA and PRO‐C3 levels. Patients with PC had higher baseline serum HA and PRO‐C3 than healthy subjects and patients with benign conditions. Pretreatment serum baseline HA and PRO‐C3 in patients with PC were associated with poorer survival and PRO‐C3 remained prognostic also after adjusting for age, performance status, stage, the presence of liver and peritoneum metastasis, and CA19‐9. Detection of HA and PRO‐C3 may be useful in differentiating between malignant and benign pancreatic conditions. Serum HA and PRO‐C3 were prognostic for OS in patients with PC.

A biological method for precise quantification of interferons has been developed. The method is based upon the dehydrogenase system of the intact target cells, which will normally convert an artificial substrate, MTT, into formazan (blue), which, in turn, can be measured spectrophotometrically. This conversion is greatly reduced by cytocidal viruses in a dose‐dependent manner. The protection of target cells by interferon against challenge virus is reflected in a diminished reduction in the production of formazan, thus giving a very precise method for quantification of interferon. The lowest level of detection is around 0.10 international units. The intra‐ and inter‐assay variability appear to be below 10%. The assay, which makes no use of expensive ingredients, is performed in 96‐well micro‐trays and read in an inexpensive ELISA‐scanner.

Biomarkers for early diagnosis of patients with pancreatic cancer (PC) are needed. Our aim was to identify panels of miRNAs in serum in combination with CA 19-9 for use in the diagnosis of PC. Four hundred seventeen patients with PC were included prospectively from Denmark (n 5 306) and Germany (n 5 111). Controls included 59 patients with chronic pancreatitis (CP) and 248 healthy subjects (HS). MiRNAs were analyzed in pretreatment serum samples from 3 cohorts: discovery cohort (754 human miRNAs, TaqMan V R Human MicroRNA assay, Applied Biosystem; PC n 5 133, controls n 5 72); training cohort (34 miRNAs, real-time qPCR using the Fluidigm BioMark TM System; PC n 5 198, controls n 5 184); validation cohort (13 miRNAs, real-time qPCR using the Fluidigm BioMark TM System; PC n 5 86, controls n 5 51). We found that 34 miRNAs in serum from PC patients in the discovery cohort were expressed differently than in controls. These miRNAs were tested in the training cohort, and four diagnostic panels were constructed that included 5 or 12 miRNAs (miR-16, 218a, 220a, 224, 225, 227a, 229c, 230a.5p, 2191, 2323.3p, 2345 and 2483.5p). In conclusion, we identified four diagnostic panels based on 5 or 12 miRNAs in serum that could distinguish patients with PC from HS and CP.In the Western world, 280,000 subjects develop pancreatic cancer (PC) each year, and the incidence is increasing. The prognosis for these patients has improved only slightly during the last decade, and PC is the fourth-leading cause of cancer-related deaths in the US (42.000) and Europe (75.000). 1-3 <20% of patients with PC can be operated on with curative intent, because most patients have locally advanced or metastatic PC at the time of diagnosis. 4 Chemotherapy has little effect, 4 and only 20% are alive after 1 year and just 7% after 5 years.

PurposeWe tested the hypothesis that high plasma YKL-40 and IL-6 associate with pancreatic cancer and short overall survival.Patients and MethodsIn all, 559 patients with pancreatic cancer from prospective biomarker studies from Denmark (n = 448) and Germany (n = 111) were studied. Plasma YKL-40 and IL-6 were determined by ELISAs and serum CA 19.9 by chemiluminescent immunometric assay.ResultsOdds ratios (ORs) for prediction of pancreatic cancer were significant for all biomarkers, with CA 19.9 having the highest AUC (CA 19.9: OR = 2.28, 95% CI 1.97 to 2.68, p<0.0001, AUC = 0.94; YKL-40: OR = 4.50, 3.99 to 5.08, p<0.0001, AUC = 0.87; IL-6: OR = 3.68, 3.08 to 4.44, p<0.0001, AUC = 0.87). Multivariate Cox analysis (YKL-40, IL-6, CA 19.9, age, stage, gender) in patients operated on showed that high preoperative IL-6 and CA 19.9 (dichotomized according to normal values) were independently associated with short overall survival (CA 19.9: HR = 2.51, 1.22–5.15, p = 0.013; IL-6: HR = 2.03, 1.11 to 3.70, p = 0.021). Multivariate Cox analysis of non-operable patients (Stage IIB-IV) showed that high pre-treatment levels of each biomarker were independently associated with short overall survival (YKL-40: HR = 1.30, 1.03 to 1.64, p = 0.029; IL-6: HR = 1.71, 1.33 to 2.20, p<0.0001; CA 19.9: HR = 1.54, 1.06 to 2.24, p = 0.022). Patients with preoperative elevation of both IL-6 and CA 19.9 had shorter overall survival (p<0.005) compared to patients with normal levels of both biomarkers (45% vs. 92% alive after 12 months).ConclusionsPlasma YKL-40 and IL-6 had less diagnostic impact than CA 19.9. Combination of pretreatment YKL-40, IL-6, and CA 19.9 may have clinical value to identify pancreatic cancer patients with the poorest prognosis.