Surgery (St Vincent's) - Research Publications

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    Arthroplasty information on the internet
    Davaris, MT ; Dowsey, MM ; Bunzli, S ; Choong, PF (The British Editorial Society of Bone & Joint Surgery, 2020-04)
    Aims: Total joint replacement (TJR) is a high-cost, high-volume procedure that impacts patients’ quality of life. Informed decisions are important for patients facing TJR. The quality of information provided by websites regarding TJR is highly variable. We aimed to measure the quality of TJR information online. Methods: We identified 10,800 websites using 18 TJR-related keywords (conditions and procedures) across the Australian, French, German and Spanish Google search engines. We used the Health on the Net (HON) toolbar to evaluate the first 150 websites downloaded for every keyword in each language. The quality of information on websites was inspected, accounting for differences by language and tertiles. We also undertook an analysis of English websites to explore types of website providers. Results: ‘Total joint replacement’ had the most results returned (150 million websites), and 9% of websites are HON-accredited. Differences in information quality were seen across search terms (p < 0.001) and tertiles (p < 0.001), but not between languages (p = 0.226). A larger proportion of HON-accredited websites were seen from keywords in the condition and arthroplasty categories. The first tertile contained the highest number of HON-accredited websites for the majority of search terms. Government/educational bodies sponsored the majority of websites. Conclusion: Clinicians must consider the shortage of websites providing validated information, with disparities in both number and quality of websites for TJR conditions and procedures. As such, the challenge for clinicians is to lead the design of reliable, accurate and ethical orthopaedic websites online and direct patients to them. This stands to reward both parties greatly.
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    AAV-mediated gene delivery of the calreticulin anti-angiogenic domain inhibits ocular neovascularization
    Tu, L ; Wang, J-H ; Barathi, VA ; Prea, SM ; He, Z ; Lee, JH ; Bender, J ; King, AE ; Logan, GJ ; Alexander, IE ; Bee, Y-S ; Tai, M-H ; Dusting, GJ ; Bui, BV ; Zhong, J ; Liu, G-S (SPRINGER, 2018-02)
    Ocular neovascularization is a common pathological feature in diabetic retinopathy and neovascular age-related macular degeneration that can lead to severe vision loss. We evaluated the therapeutic efficacy of a novel endogenous inhibitor of angiogenesis, the calreticulin anti-angiogenic domain (CAD180), and its functional 112-residue fragment, CAD-like peptide 112 (CAD112), delivered using a self-complementary adeno-associated virus serotype 2 (scAAV2) in rodent models of oxygen-induced retinopathy and laser-induced choroidal neovascularization. The expression of CAD180 and CAD112 was elevated in human umbilical vein endothelial cells transduced with scAAV2-CAD180 or scAAV2-CAD112, respectively, and both inhibited angiogenic activity in vitro. Intravitreal gene delivery of scAAV2-CAD180 or scAAV2-CAD112 significantly inhibited ischemia-induced retinal neovascularization in rat eyes (CAD180: 52.7% reduction; CAD112: 49.2% reduction) compared to scAAV2-mCherry, as measured in retinal flatmounts stained with isolectin B4. Moreover, the retinal structure and function were unaffected by scAAV2-CAD180 or scAAV2-CAD112, as measured by optical coherence tomography and electroretinography. Moreover, subretinal delivery of scAAV2-CAD180 or scAAV2-CAD112 significantly attenuated laser-induced choroidal neovascularization in mouse eyes compared to scAAV2-mCherry, as measured by fundus fluorescein angiography (CAD180: 62.4% reduction; CAD112: 57.5% reduction) and choroidal flatmounts (CAD180: 40.21% reduction; CAD112: 43.03% reduction). Gene delivery using scAAV2-CAD180 or scAAV2-CAD112 has significant potential as a therapeutic option for the management of ocular neovascularization.
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    Review of the use of prophylactic drain tubes post-robotic radical prostatectomy: Dogma or decent practice?
    Nzenza, TC ; Ngweso, S ; Eapen, R ; Rajarubendra, N ; Bolton, D ; Murphy, D ; Lawrentschuk, N (WILEY, 2020-09)
    OBJECTIVE: To assess the necessity of routine prophylactic drain tube use following robot-assisted radical prostatectomy (RARP). METHOD: We performed a literature review using the Medline, Scopus, and Web of Science databases with no restriction of language from January 1900 to January 2020. The following terms we used in the literature search: prostatectomy, radical prostatectomy, robot assisted, drainage, and drain tube. RESULTS: We identified six studies that examined the use of routine prophylactic drain tubes following RARP. One of these studies was a randomized study that included 189 patients, with 97 in the pelvic drain (PD) arm and 92 in the no pelvic drain (ND) arm. This non-inferiority showed an early (90-day) complication rate of 17.4% in the ND arm versus 26.8% in the PD arm (P < .001). Another non-inferiority randomized control trial (RCT) showed a complication rate of 28.9% in the PD group versus 20.4% in the ND group (P = .254). Similarly, the other studies found no benefit of routine use of prophylactic drain tube after RARP. CONCLUSION: Drain tubes play a role during robotic-assisted radical prostatectomy, however, following a review of the current available literature, they can be safely omitted and we suggest that clinicians may be selective in their use.
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    Subinguinal orchiectomy-A minimally invasive approach to open surgery
    Anderson, E ; Pascoe, C ; Sathianathen, N ; Katz, D ; Murphy, D ; Lawrentschuk, N (WILEY, 2020-11)
    OBJECTIVES: To determine the rate of morbidity and assess the oncological outcomes for the subinguinal orchidectomy technique. BACKGROUND: Radical inguinal orchiectomy is the definitive management for a testicular mass suspicious for malignancy. The standard approach involves the division of the spermatic cord at the internal inguinal ring. In addition to the morbidity of a significant incision through skin and fascia, a known complication is damage to the nerves within the canal leading to local hypoesthesia or persistent inguinal and scrotal neuralgia. The subinguinal orchiectomy technique avoids opening the inguinal canal by excising the spermatic cord at the external inguinal ring. METHODS: Patient data from three urologists who routinely perform subinguinal orchiectomies for suspected testicular malignancy was collected. A retrospective analysis between March 2011 and March 2019 was undertaken evaluating demographic, clinical, and histological data points. Descriptive analysis of oncological and surgical outcomes of subinguinal orchiectomy for testicular mass was performed. Descriptive analysis of oncological and surgical outcomes of subinguinal orchiectomy for testicular mass was performed. RESULTS: About 42 orchiectomies performed via the subinguinal approach were identified. The median age was 38 years (range 22-72) and mean follow-up time was 18.4 months (range 0.59-61). Of the 38 patients with testicular cancer, histopathology showed 26 with pT1, 9 with pT2, and 3 with pT3 disease. Three patients had involvement of the cord, with one patient having a positive surgical margin secondary to venous invasion. No patients experienced neuropathic complications, hernia, or wound break down. CONCLUSION: These data suggest that subinguinal orchiectomy provides acceptable oncological outcomes, comparable to a traditional technique, and may decrease the risk of neuropathic injury and incisional/inguinal hernia. Further investigation with a larger, prospective series is required.
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    Tight Junction Protein Claudin-2 Promotes Self-Renewal of Human Colorectal Cancer Stem-like Cells
    Paquet-Fifield, S ; Koh, SL ; Cheng, L ; Beyit, LM ; Shembrey, C ; Molck, C ; Behrenbruch, C ; Papin, M ; Gironella, M ; Guelfi, S ; Nasr, R ; Grillet, F ; Prudhomme, M ; Bourgaux, J-F ; Castells, A ; Pascussi, J-M ; Heriot, AG ; Puisieux, A ; Davis, MJ ; Pannequin, J ; Hill, AF ; Sloan, EK ; Hollande, F (American Association for Cancer Research, 2018-06-01)
    Posttreatment recurrence of colorectal cancer, the third most lethal cancer worldwide, is often driven by a subpopulation of cancer stem cells (CSC). The tight junction (TJ) protein claudin-2 is overexpressed in human colorectal cancer, where it enhances cell proliferation, colony formation, and chemoresistance in vitro. While several of these biological processes are features of the CSC phenotype, a role for claudin-2 in the regulation of these has not been identified. Here, we report that elevated claudin-2 expression in stage II/III colorectal tumors is associated with poor recurrence-free survival following 5-fluorouracil–based chemotherapy, an outcome in which CSCs play an instrumental role. In patient-derived organoids, primary cells, and cell lines, claudin-2 promoted colorectal cancer self-renewal in vitro and in multiple mouse xenograft models. Claudin-2 enhanced self-renewal of ALDHHigh CSCs and increased their proportion in colorectal cancer cell populations, limiting their differentiation and promoting the phenotypic transition of non-CSCs toward the ALDHHigh phenotype. Next-generation sequencing in ALDHHigh cells revealed that claudin-2 regulated expression of nine miRNAs known to control stem cell signaling. Among these, miR-222-3p was instrumental for the regulation of self-renewal by claudin-2, and enhancement of this self-renewal required activation of YAP, most likely upstream from miR-222-3p. Taken together, our results indicate that overexpression of claudin-2 promotes self-renewal within colorectal cancer stem-like cells, suggesting a potential role for this protein as a therapeutic target in colorectal cancer.
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    Laminin 521 enhances self-renewal via STAT3 activation and promotes tumor progression in colorectal cancer
    Qin, Y ; Shembrey, C ; Smith, J ; Paquet-Fifield, S ; Behrenbruch, C ; Beyit, LM ; Thomson, BNJ ; Heriot, AG ; Cao, Y ; Hollande, F (ELSEVIER IRELAND LTD, 2020-04-28)
    Remodeling of basement membrane proteins contributes to tumor progression towards the metastatic stage. One of these proteins, laminin 521 (LN521), sustains embryonic and induced pluripotent stem cell self-renewal, but its putative role in cancer is poorly described. In the present study we found that LN521 promotes colorectal cancer (CRC) cell self-renewal and invasion. siRNA-mediated knockdown of endogenously-produced laminin alpha 5, as well as treatment with neutralizing antibodies against integrin α3β1 and α6β1, were able to reverse the effect of LN521 on self-renewal. Exposure of CRC cells to LN521 enhanced STAT3 phosphorylation, and incubation with STAT3 inhibitors Napabucasin and Stattic was sufficient to block the LN521-driven self-renewal increase. Robust expression of laminin alpha 5 was detected in 7/10 liver metastases tissue sections collected from CRC patients as well as in mouse liver metastasis xenografts, in most cases within areas expressing metastasis cancer stem cell markers such as c-KIT and CD44v6. Finally, retrospective analysis of multiple CRC datasets highlighted the significant association between high LN521 mRNA expression and poor clinical outcome in colorectal cancer patients. Collectively our results indicate that high Laminin 521 expression is a frequent feature of metastatic dissemination in CRC and that it promotes cell invasion and self-renewal, the latter through engagement of integrin isoforms and activation of STAT3 signaling.
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    Static force dependency of bone conduction transducer as sensory feedback for stump-socket based prosthesis
    Mayer, RM ; Mohammadi, A ; Alici, G ; Choong, P ; Oetomo, D (Australian Robotics and Automation Association, 2018-01-01)
    The dependency of a novel sensory feedback for stump-socket based prosthesis on the static force is presented using a bone conduction transducer as feedback source. The stimulation was induced onto the bony landmarks of the elbow, specifically the Ulna and presented in an interval halving method. The perception threshold in the range of tactile and auditory perception at three different force levels has been tested. The inter subject variability is bigger than the intra subject variation. The small static force variation suggests a similar approach as in bone conduction hearing aids and therefore a static force bigger than 6N should be applied to perceive a constant stimulation. A mechanical design to include such a novel feedback into a stump-socket needs to account for this requirement. The inter subject variability needs to be addressed by incorporate some kind of person to person calibration of the gain.
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    Psychometric Evaluation of Multi-Point Bone-Conducted Tactile Stimulation on the Three Bony Landmarks of the Elbow
    Mayer, RM ; Mohammadi, A ; Tan, Y ; Alici, G ; Choong, P ; Oetomo, D (IEEE, 2020)
    Sensory feedback is highly desirable in upper limb prostheses as well as in human robot interaction and other human machine interfaces. Bone conduction as sensory feedback interface is a recently studied approach showing promising properties. A combination of different feedback information is often necessary for prosthetic grasping, thus multiple feedback channels are required for effective sensory feedback. The use of multiple bone conduction stimulation sites simultaneously has not yet been studied. In this paper, the psychometric evaluation of multiple stimulation sites on the physiologically given bony landmarks on the elbow is investigated. The proposed approach is evaluated on human-subject experiments with six able-bodied subjects and one subject with transradial amputation. Vibrotactile transducers are placed on the bony landmarks of the elbow to determine the identification rate of each stimulation point separately as well as the identification rate of the number of active stimulation points for different frequencies. The outcomes show high identification rates for a frequency range from 100 to 750 Hz whilst performance deteriorates to at chance level at higher frequencies. A decreasing performance in identifying the number of active stimulation sites for an increasing number of simultaneous active transducers was observed. The obtained good performance in location identification suggests that information can be encoded via the location of the stimulation.