High microsatellite instability (MSI-H) is associated with distinct clinical and molecular characteristics and an improved survival in early Colon cancer (CC); real world data from the AIO molecular registry Colopredict Plus.

Colorectal cancer is one of the leading malignancies and still accounts for almost 25 000 deaths in Germany each year. Although there is accumulating data on the molecular basis, treatment and clinical outcome of patients within clinical trials evidence from the real-world setting is mostly lacking. We started the molecular registry trial Colopredict Plus in 2013 to collect clinical and molecular data from a real-world cohort of patients with early colon cancer stage II and III in 70 German colon cancer centers focusing on the prognostic impact of high microsatellite instability. In this interim report, we characterize a clinical cohort of 2615 patients, of whom 1787 tissue probes were analyzed. Microsatellite status was assessed using immunhistochemistry and fragment length analysis, with a concordance of 91.4 %. These established histopathological methods are sensitive and cost-effective. The median age was 72 years, significantly higher compared to clinical trial populations, with a median Charlson Comorbidity Index of 3. The stage-dependent incidence of microsatellite instability was 23.7 % and was associated with female gender, BRAF-mutation, UICC stage II and localization in the right colon. Survival calculated in disease free, relapse free and overall survival significantly differed between MSI-H and MSS, in favor of MSI-H patients. Multivariate age-adjusted analyses of relapse-free survival, disease-free survival, and overall survival highlighted microsatellite instability as a robust and positive prognostic marker for early colon cancer independent of age.

The asbestos fibre burden in human lungs: new insights into the chrysotile debate.

The traceability of asbestos fibres in human lungs is a matter of discussion especially for chrysotile. This issue is of high significance for differential diagnosis, risk assessment and occupational compensation. At present no intra-individual longitudinal information is available. This study addresses the question whether the asbestos fibre burden in human lungs decreases with time after exposure cessation.The database of the German Mesothelioma Register was screened for patients with asbestos body counts of at least 500 fibres per gram of wet lung, which had been analysed twice from different tissue excisions at minimum intervals of 4 years.Twelve datasets with individual longitudinal information were discovered with a median interval of about 8 years (range 4-21 years). Both examinations were performed after exposure cessation (median: surgery, 9.5 years; autopsy, 22 years). Pulmonary asbestos fibre burden was stable between both examinations (median 1623/4269 asbestos bodies per gram wet lung). Electron microscopy demonstrated a preponderance of chrysotile (median 80%).This study is the first to present longitudinal intra-individual data about the asbestos fibre burden in living human lungs. The high biopersistence of amphiboles, but also of chrysotile, offers mechanistic explanations for fibre toxicity, especially the long latency period of asbestos-related diseases.

Causes of mortality in elderly UICC stage III colon cancer (CC) patients--Tumor-related death and competing risks from the German AIO colorectal study group Colopredict Plus (CPP) registry.

BACKGROUND: Colon cancer (CC) is a disease of elderly patients (pts.) with a median age of 73 years (yrs.). Lack of data about the effects of adjuvant chemotherapy (ACT) is caused by underrepresentation of this clinically relevant cohort in interventional trials. We analyzed real-world data from the German CPP registry with regard to a possible benefit of ACT in elderly (70+ yrs.) versus younger pts. (50 to <70 yrs.) taking cause-specific deaths into account. METHODS: We analyzed the effect of age and ACT on overall survival (OS) and cause-specific death of stage III pts. using Cox regression. RESULTS: In total, 1558 pts. were analyzed and follow-up was 24.6 months. 62.6% of the elderly received ACT whereas 91.1% of younger pts. (p < 0.001). Oxaliplatin combinations were significantly less often given to older than younger pts. (38.8% vs. 88.9%; p < 0.001). Mean Charlson comorbidity score was significantly lower in pts. that received ACT (0.61) than in those without ACT (1.16; p < 0.001). ACT was an independent positive prognostic factor for cancer-related death in elderly pts. even in pts. 75+ yrs. No significant difference in the effect of ACT could be observed between age groups (interaction: cancer-specific death HR = 1.7948, p = 0.1079; death of other cause HR = 0.7384, p = 0.6705). CONCLUSION: ACT was an independent positive prognostic factor for OS. There may be a cohort of elderly with less co-morbidities who benefit from ACT.

Histological findings and lung dust analysis as the basis for occupational disease compensation in asbestos-related lung cancer in Germany.

OBJECTIVES: This study has researched the significance of histologically raised findings and lung dust analyses in the context of claiming the recognition of and thus compensation for an asbestos-associated occupational disease. MATERIAL AND METHODS: For this approach, all findings from the German Mesothelioma Register in 2015 that included lung dust analyses were evaluated and were compared with information on asbestos fiber exposure at work based on fiber years, and with the results of radiological findings. RESULTS: For 68 insured persons, recognition of an asbestos-induced lung disease according to Section 4104 of the German Ordinance on Occupational Diseases (Berufskrankheitenverordnung - BKV) could be recommended solely on the basis of the histological examinations of lung tissues and complementary lung dust analyses. Neither did the calculation of the cumulative asbestos dust exposure at work yield 25 fiber years, nor could bridge findings (e.g., plaques) be identified. In addition, the autopsies of 12 patients revealed plaques that had not been diagnosed during radiological examinations. These results show that - irrespective of the prescribed working techniques and radiological diagnosis - pathological/anatomical and histological diagnostics are often the only way for the insureds to demonstrate the causal connection between asbestos and their disease. Even after long intervals of up to 40 years post last exposure, the asbestos fibers would still be easily detectable in the lung tissues evaluated. CONCLUSIONS: Whenever suitable tissue is available, it should be examined for mild asbestosis with the aid of a lung dust analysis. Otherwise there is a risk that an occupational disease is wrongfully rejected. In the context of health insurance, the lung dust analysis and the resulting proof of the presence of asbestosis often constitute one option of providing evidence of an occupational disease. Int J Occup Med Environ Health 2018;31(3):293-305.