Integration of Genomic Profiling and Organoid Development in Precision Oncology

Precision oncology involves an innovative personalized treatment strategy for each cancer patient that provides strategies and options for cancer treatment. Currently, personalized cancer medicine is primarily based on molecular matching. Next-generation sequencing and related technologies, such as single-cell whole-transcriptome sequencing, enable the accurate elucidation of the genetic landscape in individual cancer patients and consequently provide clinical benefits. Furthermore, advances in cancer organoid models that represent genetic variations and mutations in individual cancer patients have direct and important clinical implications in precision oncology. This review aimed to discuss recent advances, clinical potential, and limitations of genomic profiling and the use of organoids in breast and ovarian cancer. We also discuss the integration of genomic profiling and organoid models for applications in cancer precision medicine.

Risk evaluation of duodenoscope-associated infections in the Netherlands calls for a heightened awareness of device-related infections: a systematic review

Background The risk of exogenous infections from endoscopic procedures is often cited as almost negligible (1 infection in 1.8 million procedures); however, this risk is based on older literature and does not seem to match the number of infectious outbreaks due to contaminated duodenoscopes reported after endoscopic retrograde cholangiopancreatography (ERCP). Using Dutch data, we aimed to estimate the minimum risk of duodenoscope-associated infection (DAI) and colonization (DAC) in patients undergoing ERCP. Methods A systematic literature search identified all DAI outbreaks in the Netherlands reported between 2008 and 2019. Included cases were confirmed by molecular matching of patient and duodenoscope cultures. Risk ratios were calculated based on the total number of ERCPs performed during the study period. Results Three outbreaks were reported and published between 2008 and 2018, including 21 confirmed DAI cases and 52 confirmed DAC cases. The estimated number of ERCPs performed during the same period was 181 209–227 006. The calculated minimum estimated DAI risk was approximately 0.01 % and the minimum estimated DAC risk was 0.023 %–0.029 %. Conclusions The estimated risk of DAI in Dutch ERCP practice was at least 180 times higher than previously published risk estimates. The actual risk is likely to be (much) higher due to underreporting of infections caused by multidrug-resistant organisms and sensitive bacteria. Greater awareness by healthcare personnel involved in endoscopy and endoscope cleaning is required, as well as innovative technical solutions to contain and ultimately eliminate DAIs.

Characterization of Human Knee and Chin Adipose-Derived Stromal Cells

Animal study findings have revealed that individual fat depots are not functionally equivalent and have different embryonic origins depending on the anatomic location. Mouse bone regeneration studies have also shown that it is essential to match theHoxcode of transplanted cells and host tissues to achieve correct repair. However, subcutaneous fat depots from any donor site are often used in autologous fat grafting. Our study was thus carried out to determine the embryonic origins of human facial (chin) and limb (knee) fat depots and whether they had similar features and molecular matching patterns. Paired chin and knee fat depots were harvested from 11 subjects and gene expression profiles were determined by DNA microarray analyses. Adipose-derived stromal cells (ASCs) from both sites were isolated and analyzed for their capacity to proliferate, form clones, and differentiate. Chin and knee fat depots expressed a differentHOXcode and could have different embryonic origins. ASCs displayed a different phenotype, with chin-ASCs having the potential to differentiate into brown-like adipocytes, whereas knee-ASCs differentiated into white adipocytes. These results highlighted different features for these two fat sites and indicated that donor site selection might be an important factor to be considered when applying adipose tissue in cell-based therapies.