Molecular profiling of ctDNA in pancreatic cancer: Opportunities and challenges for clinical application

Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of cancer-related mortality within the next decade, with limited effective treatment options and a dismal long-term prognosis for patients. Genomic profiling has not yet manifested clinical benefits for diagnosis, treatment or prognosis in PDAC, due to the lack of available tissues for sequencing and the confounding effects of low tumour cellularity in many biopsy specimens. Increasing focus is now turning to the use of minimally invasive liquid biopsies to enhance the characterisation of actionable PDAC tumour genomes. Circulating tumour DNA (ctDNA) is the most comprehensively studied liquid biopsy analyte in blood and can provide insight into the molecular profile and biological characteristics of individual PDAC tumours, in real-time and in advance of traditional imaging modalities. This can pave the way for identification of new therapeutic targets, novel risk variants and markers of tumour response, to supplement diagnostic screening and provide enhanced scrutiny in treatment stratification. In the roadmap towards the application of precision medicine for clinical management in PDAC, ctDNA analyses may serve a leading role in streamlining candidate biomarkers for clinical integration. In this review, we highlight recent developments in the use of ctDNA-based liquid biopsies for PDAC and provide new insights into the technical, analytical and biological challenges that must be overcome for this potential to be realised.     

Cell biology of smooth muscle in culture: implications for atherogenesis

Smooth muscle cells are one of the most important, if not the most important component of atheromatous plaque. Smooth muscle cells from developing and regenerating arteries, as well as atheromatous plaques, show similar morphological and biochemical characteristics which differ from adult tissue. During primary culture, adult smooth muscle cells alter their morphology to resemble those of the developing, regenerating and atheromatous material. We propose that primary cell culture of smooth muscle cells provides a model for the study of smooth muscle cell changes during atheroma formation.     

Resektion singulärer Hirnmetastasen vor Ganzhirnbestrahlung

Ohne Zusammenfassung     

The effect of naloxone on the preoperative gastric volume and pH

The effect of 4 mg oral naloxone on preoperative gastric volume and pH of gastric aspirate was studied in a double-blind, randomized study. Twenty patients received 10 ml of naloxone (4 mg) mixed with 10 ml of orange juice, and 20 patients received 10 ml of isotonic saline mixed with 10 ml of orange juice, 2 h before surgery. Gastric content was obtained immediately after intubation of the trachea. No significant difference in gastric volume and pH of gastric aspirate was found between the two groups. It is concluded that naloxone does not affect gastric emptying and gastric acid secretion to a degree great enough to protect against aspiration of gastric contents into the lungs.     

Learning root debridement with curettes and power-driven instruments in vitro: the role of operator motivation and self-assessment

The influence of systematic dummy-head training with Periopolishe (PP, group A) and Gracey instruments (GRA, group B) on the effectiveness of root debridement was evaluated by Rühling et al., 2002 (9). Their results indicate that independent of the instrument used, untrained operators were only able to debride root surfaces at low levels of effectiveness. It was possible to increase effectiveness to a high level through systematic training in both groups. The aim of the present study was to assess the role of operator motivation and self-assessment on scaling effectiveness. Before baseline, operators were asked to answer a questionnaire rating the expectation of the instrument performance. Four groups of inexperienced operators (n = 11 each) received 10 weeks dummy-head training. In groups A (GRA) and B (PP), training was combined with a motivational programme. Groups C (GRA) and D (PP) received the same training, but no additional motivational programme. In a dummy-head, 10 test teeth were debrided and operators were asked to estimate their effectiveness of debridement at each test day. Effectiveness was calculated as percentage of debrided root area on 10 test teeth at different time points with an image analysis programme (NIH Image) and ANOVA. Two groups were compared using the Mann-Whitney U-test (unpaired) and the Wilcoxon signed ranks test (paired). Motivated groups (A and B) reached about 25% higher debridement results (p < 0.001) and were able to estimate their effectiveness more precisely compared to groups C and D. In the low motivation groups (C and D), overestimation of more than 20% was evident (p < 0.001). The questionnaires revealed underestimation of the GRA instruments and overestimation of PP instruments. Operator motivation and self-assessment greatly influence learning of effective root debridement.