Introduction: b-cell regeneration is an area under active investigation for the future treatment of diabetes, but little is known about the patterns and dynamics of prenatal b-cell development in humans.In particular, the quantitative changes in b-cell mass in the developing pancreas have not been elucidated in detail. We addressed the following questions in prenatal humans: i) what is the timing of b-cell occurrence and islet growth? ii) What are the dynamics of b-cell replication and apoptosis? Methods: Pancreatic tissue was obtained from 65 human embryos and foetuses aged between 8 weeks post conception (p.c.) and birth. Sections were stained for insulin, glucagon, Ki67 (proliferation marker), TUNEL (apoptosis marker) and CD31 (blood vessel marker), and morphometric analyses were performed. Results: b-cells were detected from gestational week 9 onward, whereas glucagon expression was detected already at week 8. The fractional b-cell area of the pancreas increased in a linear fashion until birth (rZ0.60, P!0.001). The first endocrine cells were found within or adjacent to the primitive ductal epithelium. b-cell replication was readily detected in the newly forming islets already starting at week 9 p.c. (average frequency 2.8G0.4%). A small percentage of cells co-expressed insulin and glucagon during the early foetal period. There was a close relationship between the development of endocrine islets and blood vessels during all stages of prenatal pancreas development suggesting a possible interaction between both cell types. The frequency of b-cell apoptosis was relatively high throughout all ages (1.5G0.3%). Conclusions: b-cell differentiation in humans occurs from week 9 p.c. onward. The first endocrine cells are closely associated with the ductal epithelium suggesting differentiation from precursor cells. High rates of b-cell replication suggest that this mechanism plays an important role in the prenatal expansion of b-cell mass.

No abstract

Background Despite the fact that nephron-sparing treatment is considered preferable from a surgical perspective patients’ quality of life (QoL) following different types of nephron-sparing treatments remains unclear. Purpose To investigate the quality of life and complications after nephron-sparing treatment of renal cell carcinomas of stage T1. Materials and methods A systematic search of six databases was carried out. We included studies that reported the quality of life and complications in patients aged 18 years or older following nephron-sparing treatment of renal cell carcinoma stage T1. The quality assessment was performed using the Critical Appraisal Skills Programme (CASP) checklist for cohort studies and the CASP Randomized Controlled Trial Checklist. Data were analyzed using a narrative approach. Results Eight studies were included, six of which investigated QoL after partial nephrectomy and two after ablation therapies. Seven studies reported complications. Three studies reported higher QoL scores after partial nephrectomy compared to radical nephrectomy. Two studies showed that QoL increased or returned to baseline levels up to 12 months following partial nephrectomy. One study reported a gradual increase in QoL after radiofrequency ablation, and one study reported that all patients recovered to baseline QoL following cryoablation. Across studies, we found a complication rate up to 20% after partial nephrectomy and up to 12.5% after ablation therapy. Conclusions The results of this systematic review suggest that nephron-sparing treatment appears to be superior or comparable to other treatment alternatives with regard to QoL outcomes. Additionally, based on the studies included in this review, partial nephrectomy appears to have a higher complication rate compared with ablation therapies. Systematic review registration PROSPERO CRD42020155594