Accuracy of dual-bolus CT in the diagnosis of active arterial bleeding in adult pelvic trauma.

INTRODUCTION: A single-phase dual-bolus CT (DB-CT) simultaneously opacifies both arterial and venous systems and can be utilised in the trauma setting to aid in the diagnosis of active bleeding while also allowing for optimal assessment of the abdominal and pelvic viscera. Active bleeding can be venous or arterial, the latter being amenable to angiography and potentially embolisation. We aimed to establish the accuracy of single-phase DB-CT vs commonly performed portal venous CT (PV-CT) in the diagnosis of active bleeding when compared to formal digital subtraction angiography as the gold standard. METHODS: All patients diagnosed with active bleeding on PV-CT or DB-CT at a level 1 tertiary centre over a 6-year period and who subsequently proceeded to digital subtraction angiography (DSA) were included for analysis. The initial CT images were retrospectively reviewed by two consultant interventional radiologists who were blinded to the subsequent outcome of the DSA and to each other's results. The sensitivity, specificity and inter-observer agreement between the two readers was then able to be assessed. RESULTS: A total of 60 patients were included in the analysis. Sensitivity for the diagnosis for any active bleeding was high for both DB-CT and PV-CT (range 88.9%-100%) while diagnosis of specifically arterial bleeding was comparatively lower (51.9%-79%). Inter-observer agreement for the identification of arterial bleeding was better for DB-CT (fair) compared to PV-CT (poor). CONCLUSION: Both PV-CT and DB-CT demonstrate high sensitivity in the diagnosis of any active bleeding though identification of specifically arterial bleeding is lower for both scanning methods. Nevertheless, inter-observer reliability for the identification of arterial bleeding is higher for DB-CT. Multi-phase arterial and venous CT may yield better results and could be a focus for future studies.

Hoxa-11 maintains cell proliferation in the mouse gubernaculum to facilitate testicular descent.

INTRODUCTION: The gubernaculum is a structure vital for guiding testicular descent. The Homeobox gene, Hoxa-11, is involved in patterning embryonic structures and is necessary for gubernacular development, as Hoxa-11 knock-out mice exhibit abnormal gubernacula and undescended testes. We aimed to elucidate how testicular descent fails by examining cell proliferation and androgen receptor (AR) expression in Hoxa-11 KO mice gubernacula. METHODS: Postnatal day 2 wild type (n=6) and Hoxa-11 KO mice (n=6), were prepared for immunohistochemistry and confocal microscopy using antibodies against androgen receptor, slow skeletal myosin (My32), and Ki67, a marker of cell proliferation. RESULTS: The gubernacula of Hoxa-11 KO mice were hypocellular compared with WT. AR was present in the gubernaculum and abutting inguinal fat pad in both WT and Hoxa-11 KO with no difference in expression. Slow skeletal myosin was present in a clear 'swirl' in the growth centre of WT animals which was absent in the Hoxa-11 KO mice. Ki67, expressed in the growth centre and cremaster muscle in WT, was greatly decreased in Hoxa-11 KO. CONCLUSION: Hoxa-11 may regulate fibroblast proliferation in the gubernaculum, as it does in human uterosacral ligaments, allowing formation of the 'growth centre' within the bulb and facilitating myogenesis and elongation to the scrotum. Polymorphisms in Hoxa-11 may contribute to the aetiology of human cryptorchidism.

Wnt signalling in testicular descent: a candidate mechanism for cryptorchidism in Robinow syndrome.

BACKGROUND/AIMS: Robinow syndrome is caused by mutations in Wnt-5a or its receptor Ror2 and can lead to cryptorchidism, though the mechanisms are unclear. Wnt-5a knock-out mice fail to undergo gubernacular swelling, similar to insulin-like hormone 3 (INSl-3) knock-out mice. We aimed to characterise Wnt-5a and Ror2 expression in rat gubernacula to better understand how Wnt-5a signalling affects testicular descent. METHODS: Sprague-Dawley rats (n = 27) were collected with ethics approval (A644) at embryonic days (E) 15, 17, 19 and postnatal day (D) 2. Control and antiandrogen-treated groups were processed for immunohistochemistry for Wnt-5a, Ror2 and ß-catenin. Sagittal sections were examined using confocal microscopy. RESULTS: Wnt-5a and Ror2 were strongly expressed in the gubernacular bulb at E17 controls, their levels declining at E19 and almost absent by D2. Wnt-5a significantly co-localised with the important transcription factor ß-catenin at E17. There was no obvious difference in staining with androgen blockade. CONCLUSION: Wnt-5a, through Ror2 and ß-catenin may play a vital role in regulating the gubernacular swelling reaction downstream of INSL-3. Human mutations in Wnt-5a or Ror2 could prevent early gubernacular growth, as suggested by undescended testes in 70% of patients with Robinow Syndrome.

Gone with the Wnt: the canonical Wnt signaling axis is present and androgen dependent in the rodent gubernaculum.

BACKGROUND/AIMS: How androgens control inguinoscrotal descent remains controversial but may include canonical Wnt signaling via the transcriptional co-activator ß-catenin. The canonical Wnt pathway transcribes genes regulating mesenchymal cell migration, fate, extracellular matrix remodeling, and in addition Axin2, a feedback product that reliably identifies Wnt activation. The relationship between ß-catenin and androgen receptor warranted investigation into the involvement of the canonical Wnt pathway in testicular descent. METHODS: Gubernacula from male Sprague-Dawley control (n = 22) and flutamide-treated (n = 18) rats at E17, E19, and D0 time-points were processed for immunohistochemistry. Sagittal sections stained for presence of androgen receptor, Axin2, and ß-catenin were analyzed by fluorescent confocal microscopy. RESULTS: At E19, ß-catenin was strongly expressed in the membrane of developing cremaster muscle cells and the cytoplasm of gubernacular core cells. Axin2 expression was ubiquitous in nuclei of gubernacular mesenchymal cells, representing canonical Wnt signaling. After androgen blockade, Axin2 was conspicuously absent in the fibroblasts of the gubernacular core while remaining unaffected elsewhere. Reduced staining of Axin2 in E17 and D0 gubernacula suggests that Wnt signaling coincides with androgen programming. CONCLUSION: Axin2 expression in the E19 gubernaculum confirms canonical Wnt pathway activation. Its absence in the core of flutamide-treated gubernacula indicates Wnt down-regulation. As androgen is required for inguinoscrotal descent, downstream Wnt signaling may control initial gubernacular remodeling. Defects in this complex molecular process may play a role in cryptorchidism.