Stool DNA testing for early detection of colorectal cancer: systematic review using the HTA Core Model® for Rapid Relative Effectiveness Assessment.

Background: Stool DNA testing for early detection of colorectal cancer (CRC) is a non-invasive technology with the potential to supplement established CRC screening tests. The aim of this health technology assessment was to evaluate effectiveness and safety of currently CE-marked stool DNA tests, compared to other CRC tests in CRC screening strategies in an asymptomatic screening population. Methods: The assessment was carried out following the guidelines of the European Network for Health Technology Assessment (EUnetHTA). This included a systematic literature search in MED-LINE, Cochrane and EMBASE in 2018. Manufacturers were asked to provide additional data. Five patient interviews helped assessing potential ethical or social aspects and patients' experiences and preferences. We assessed the risk of bias using QUADAS-2, and the quality of the body of evidence using GRADE. Results: We identified three test accuracy studies, two of which investigated a multitarget stool DNA test (Cologuard®, compared fecal immunochemical test (FIT)) and one a combined DNA stool assay (ColoAlert®, compared to guaiac-based fecal occult blood test (gFOBT), Pyruvate Kinase Isoenzyme Type M2 (M2-PK) and combined gFOBT/M2-PK). We found five published surveys on patient satisfaction. No primary study investigating screening effects on CRC incidence or on overall mortality was found. Both stool DNA tests showed in direct comparison higher sensitivity for the detection of CRC and (advanced) adenoma compared to FIT, or gFOBT, respectively, but had lower specificity. However, these comparative results may depend on the exact type of FIT used. The reported test failure rates were higher for stool DNA testing than for FIT. The certainty of evidence was moderate to high for Cologuard® studies, and low to very low for the ColoAlert® study which refers to a former version of the product and yielded no direct evidence on the test accuracy for ad-vanced versus non-advanced adenoma. Conclusions: ColoAlert® is the only stool DNA test currently sold in Europe and is available at a lower price than Cologuard®, but reliable evidence is lacking. A screening study including the current product version of ColoAlert® and suitable comparators would, therefore, help evaluate the effectiveness of this screening option in a European context.

Effectiveness and efficacy of minimally invasive lung volume reduction surgery for emphysema.

Lung emphysema is a chronic, progressive and irreversible destruction of the lung tissue. Besides non-medical therapies and the well established medical treatment there are surgical and minimally invasive methods for lung volume reduction (LVR) to treat severe emphysema. This report deals with the effectiveness and cost-effectiveness of minimally invasive methods compared to other treatments for LVR in patients with lung emphysema. Furthermore, legal and ethical aspects are discussed. No clear benefit of minimally invasive methods compared to surgical methods can be demonstrated based on the identified and included evidence. In order to assess the different methods for LVR regarding their relative effectiveness and safety in patients with lung emphysema direct comparative studies are necessary.

Gliadin IgG antibodies and circulating immune complexes.

OBJECTIVE: Circulating immune complexes (CICs) in blood are associated with autoimmune-diseases such as systemic lupus erythematosus, immune complex glomerulonephritis, rheumatoid arthritis and vasculitis. However, slightly increased serum concentrations of such CICs are sometimes also found in healthy individuals. The objective of the current study was to assess whether food antigens could play a role in the formation of CICs. MATERIAL AND METHODS: A total of 352 (265 F, 87 M), so far, healthy individuals were tested for CICs containing C1q and immunoglobulin G (IgG) as well as for gliadin IgG antibodies using the ELISA technique. Additionally, fructose and lactose malabsorption was assessed using hydrogen breath tests. RESULTS: In our study, 15.3% (54/352) of the patients presented with elevated CIC concentrations (above 50 microg/ml) and 6.5% (23/352) of the study population were positive for gliadin IgG antibodies (above 20 U/ml). CIC concentration levels were significantly higher in the group with elevated gliadin IgG antibodies (CIC median: 49.0 microg/ml) compared with the group with normal levels of gliadin IgG antibodies (CIC median: 30.0 microg/ml; Mann-Whitney U-test, U=1992; p <0.001). As expected, there was no difference in CIC concentrations (Mann-Whitney U-test, U=6106; p=0.783) and gliadin IgG (Mann-Whitney U-test, U=3761; p=0.411) between patients in the fructose or lactose malabsorber groups and the subjects without malabsorption. CONCLUSIONS: The results of this study indicate that certain food antigens (e.g. gluten) could play a role in the formation of CICs. An association between CICs and fructose or lactose malabsorption seems to be improbable.

Implementation and interpretation of hydrogen breath tests.

Hydrogen breath tests are non-invasive and safe diagnostic tools used to investigate functional intestinal disorders. For the diagnosis of fructose or lactose malabsorption as well as for the detection of small intestinal bacterial overgrowth syndrome, hydrogen breath tests are even regarded as gold standard. However, standardization of the testing procedure and the interpretation of the test results are still lacking. In this paper, reliable information on the implementation of the most common hydrogen breath tests and precise guidelines for the interpretation of the test results are presented.