Repeated mutKRAS ctDNA measurements represent a novel and promising tool for early response prediction and therapy monitoring in advanced pancreatic cancer.

Background: The presence of mutated KRAS (mutKRAS ctDNA) in plasma samples has been consistently shown to be a negative prognostic indicator in pancreatic cancer (PC). Only small pilot studies have evaluated the value of serial mutKRAS ctDNA-measurements in PC. Patients and methods: The aim of the present study was to explore the potential of repeated mutKRAS ctDNA measurements for response prediction and therapy monitoring in advanced PC patients. We used the BEAMing technology to determine levels of mutKRAS ctDNA, CA 19-9, CEA and CYFRA 21-1 in 284 plasma samples of 54 patients with advanced PC receiving gemcitabine-based chemotherapy. Absolute levels and kinetics of mutKRAS ctDNA, CA 19-9, CEA and CYFRA 21-1 were correlated to radiological response, progression-free and overall survival. Results: mutKRAS ctDNA was present in a majority of advanced PC patients (n = 36/54, 67%) and indicated tissue KRAS mutation status with a high sensitivity (75%) and specificity (100%). The presence of mutKRAS ctDNA, as well as higher levels of CA 19-9, CEA and CYFRA 21-1 before initiation of the first-line chemotherapy, was significantly correlated to an adverse overall survival. During therapy, changes in mutKRAS ctDNA levels were more rapid and pronounced than changes in protein-based tumor markers. A decrease in mutKRAS ctDNA levels during therapy was an early indicator of response to therapy, while there was no significant correlation between kinetics of CA 19-9, CEA or CYFRA 21-1 and response to chemotherapy during the first four weeks of treatment. Repeated mutKRAS ctDNA measurements during follow-up appeared to be superior to protein-based tumor markers in detecting progressive disease (sensitivity: 83%, specificity: 100%). Conclusion: mutKRAS ctDNA kinetics appear to be a powerful and highly specific tool in early response prediction and therapy monitoring of advanced PC patients receiving chemotherapy.

Smoking denial in cardiovascular disease studies.

Assessment of self-reported smoking behavior in cardiovascular studies may lead to inaccurate measures of nicotine exposure. A more objective measurement of nicotine exposure can be done by measurement of plasma cotinine levels. The aim of the present study was to define the rate of discordance between the self-reported smoking behavior and biochemically defined smoking status. Data from 3,316 patients hospitalized for coronary angiography, who completed a questionnaire on smoking behavior, were analyzed. As a biochemical assessment of smoking status we used a cut-off serum cotinine level of 15 µg/l. Smoking denial, defined as a discrepancy between high cotinine levels and self-reported never- or ex-smoking status, was observed in 3.7 % of the study participants. In a logistic regression analysis with a step-wise inclusion of sex, age, CAD, previous MI, and educational level, only male sex (odds ratio male/female: 2.00, 95 % CI 1.22-3.33; p = 0.007) and age (odds ratio per year: 0.79, 95 % confidence interval 0.66-0.94, p = 0.008) were associated with smoking denial. In conclusion, a misclassification rate of 3.7 % in the evaluation of such an important risk factor may lead to blurred effects and favor false negative results. The results of the present study substantiate the importance of biochemical markers for smoking assessment in cardiovascular studies.

[Peptic ulcer and the liver]. / Peptisches Geschwür und Leber

The interorganic relations between liver and stomach are explained from the point of view of the primary diseases of each organ and the higher mechanism is also discussed. The at present well-known and partly hypothetic pathophysiological mechanisms are treated within the subject. On own combined histologo-biochemical examinations of the liver punctate is generally explained the too little regarded role of the peptic ulcer for the induction of so-called latent hepatopathies. In this respect in operations of the stomach the vagotomy as the method of choice serves the preference compared with resections of the stomach.