Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a 5-year survival rate of only 11%, due, in part, to late diagnosis, making the need to understand early events in tumorigenesis critical. Acinar-to-ductal metaplasia (ADM), when not resolved, is a PDAC precursor. Recently, we showed that ADM is constituted by a heterogenous population of cells, including hormone-producing enteroendocrine cells (EECs: gamma, delta, epsilon, and enterochromaffin cells). In this study, we employed histopathological techniques to identify and quantify the abundance of EEC subtypes throughout pancreatic tumorigenesis in mouse models and human disease. We found that EECs are most abundant in ADM and significantly decrease with lesion progression. Co-immunofluorescence identifies distinct lineages and bihormonal populations. Evaluation of EEC abundance in mice lacking Pou2f3 demonstrates that the tuft cell master regulator transcription factor is not required for EEC formation. We compared these data to human neoplasia and PDAC and observed similar trends. Lastly, we confirm that EECs are a normal cellular compartment within the murine and human pancreatic ductal trees. Altogether, these data identify EECs as a cellular compartment of the normal pancreas, which expands early in tumorigenesis and is largely lost with disease progression.

Background Joint degeneration and large or complex bone defects are a significant source of morbidity and diminished quality of life worldwide. There is an unmet need for a functional implant with near-native biomechanical properties. The potential for their generation using 3D bioprinting (3DBP)-based tissue engineering methods was assessed. We systematically reviewed the current state of 3DBP in orthoregeneration. Methods This review was performed using PubMed and Web of Science. Primary research articles reporting 3DBP of cartilage, bone, vasculature, and their osteochondral and vascular bone composites were considered. Full text English articles were analyzed. Results Over 1300 studies were retrieved, after removing duplicates, 1046 studies remained. After inclusion and exclusion criteria were applied, 114 articles were analyzed fully. Bioink material types and combinations were tallied. Cell types and testing methods were also analyzed. Nearly all papers determined the effect of 3DBP on cell survival. Bioink material physical characterization using gelation and rheology, and construct biomechanics were performed. In vitro testing methods assessed biochemistry, markers of extracellular matrix production and/or cell differentiation into respective lineages. In vivo proof-of-concept studies included full-thickness bone and joint defects as well as subcutaneous implantation in rodents followed by histological and µCT analyses to demonstrate implant growth and integration into surrounding native tissues. Conclusions Despite its relative infancy, 3DBP is making an impact in joint and bone engineering. Several groups have demonstrated preclinical efficacy of mechanically robust constructs which integrate into articular joint defects in small animals. However, notable obstacles remain. Notably, researchers encountered pitfalls in scaling up constructs and establishing implant function and viability in long term animal models. Further, to translate from the laboratory to the clinic, standardized quality control metrics such as construct stiffness and graft integration metrics should be established with investigator consensus. While there is much work to be done, 3DBP implants have great potential to treat degenerative joint diseases and provide benefit to patients globally.

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IntroductionManagement of urachal anomalies in pediatric patients has historically lacked a clear consensus between conservative and surgical management. We aimed to review and summarize the literature on the diagnosis, symptoms, and evolution in the management of urachal anomalies in pediatric patients.MethodsWe performed a scoping literature review of PubMed/Medline and WebOfScience from January 2000 to February 2022.Results32 publications were selected for inclusion in this analysis. 1,438 unique studies were identified with 32 studies meeting inclusion criteria. 15/32 studies discussed both conservative and surgical management, 14/32 studies discussed only surgical management outcomes, and 3/32 studies discussed diagnostic methods. The studies discussing conservative management supported the treatment of urachal anomalies with an initial conservative approach, which includes watchful waiting, repeated ultrasounds, lesion measurement, and antibiotic use. 5/32 of the included studies identified patients that were converted from conservative to surgical management with conversion rates ranging from 12.5% to 43.5% per study. 14/20 converted patients were identified to have a urachal cyst and 13/20 had a persistent infection.ConclusionsStrong evidence exists that supports initial conservative management over surgical management of pediatric urachal anomalies. However, predictive factors for determining which patients will require surgical management remain elusive. Treatment algorithms can potentially be developed once carefully developed prospective studies delineate statistically significant patient factors which necessitate surgical management over observation.