ABSTRACT
BACKGROUND: The diagnostic evaluation and clinical management of bladder injuries caused by blunt force trauma are variable. We aim to formulate a practice management guideline using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. METHODS: The working group, patient, intervention, comparator, outcome (PICO), formulated four questions regarding the following topics: (1) diagnostic evaluation based on patient baseline risk of bladder injury (computed tomography cystography vs. no imaging); (2) management of intraperitoneal bladder injuries (operative versus nonoperative); (3) management of extraperitoneal bladder injuries based on complexity of injury (operative vs. nonoperative); and (4) diagnostic follow-up of bladder injuries based on complexity of repair (cystography vs. no cystography). A systematic review of the MEDLINE database for English language articles with adult patients was undertaken. RevMan 5 (Review Manager (RevMan) [Computer program]. Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014) and GRADEpro (GRADEpro GDT: GRADEpro Guideline Development Tool [Software]. McMaster University, 2015) software were used. Recommendations were voted on by working group members. Consensus was obtained for each recommendation. RESULTS: Three hundred ninety-three articles were screened, resulting in a full-text review of 64 articles. Seventeen articles were used to formulate the recommendations of this guideline. Several recommendations are made. The need for initial computed tomography cystography after trauma depends on characteristics of the trauma itself, but it is not recommended in patients without gross hematuria. In general, patients with intraperitoneal bladder ruptures should undergo operative repair. This is not routinely necessary in those with extraperitoneal ruptures unless the injury is complex. The need for follow-up cystography after bladder repair depends on the risk of urine leak. Those with low risk of urine leak do not require a follow-up study. CONCLUSION: Using the GRADE process, the panel made nine recommendations based on four PICO questions concerning the evaluation and management of blunt force bladder injuries.
Subject(s)
Abdominal Injuries , Urinary Bladder/injuries , Wounds, Nonpenetrating , Abdominal Injuries/diagnosis , Abdominal Injuries/therapy , Follow-Up Studies , Humans , Practice Guidelines as Topic , Urinary Bladder/diagnostic imaging , Wounds, Nonpenetrating/complications , Wounds, Nonpenetrating/diagnosis , Wounds, Nonpenetrating/therapyABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease characterized by high expression of extracellular matrix in tumor tissue, which contributes to chemoresistance and poor prognosis. Here, we developed 3D pancreatic cancer spheroids, based on pancreatic cancer cells and fibroblast co-culture, which demonstrate innate desmoplastic properties and stay poorly permeable for model nanoparticles. Our study revealed that establishment of tumors by transplantation of spheroids significantly improved subcutaneous xenograft model of PDAC, which stays the most widely used animal model for testing of new drugs and drug delivery approaches. Spheroid based tumors abundantly produced different extracellular matrix (ECM) components including collagen I, fibronectin, laminin and hyaluronic acid. These tumors were highly reproducible with excellent uniformity in terms of ECM architecture recapitulating clinical PDAC tumors, whereas in more common cell based xenografts a significant intertumor heterogeneity in extracellular matrix production was found. Moreover, spheroid based xenografts demonstrated higher expression of pro-fibrotic and pro-survival PDAC hallmarks in opposite to cell based counterparts. We believe that future development of this model will provide an effective instrument for testing of anti-cancer drugs with improved predictive value.
