Surgery (Austin & Northern Health) - Research Publications

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    Metformin may offer no protective effect in men undergoing external beam radiation therapy for prostate cancer
    Ranasinghe, WKB ; Williams, S ; Ischia, J ; Wetherell, D ; Baldwin, G ; Shulkes, A ; Sengupta, S ; Bolton, D ; Patel, O (WILEY, 2019-05)
    OBJECTIVES: To assess whether metformin reduces radio-resistance and increases survival in men undergoing external beam radiation therapy (EBRT) for prostate cancer (PCa), and to determine its effect on hypoxia inducible factor 1-α (HIF1α). PATIENTS AND METHODS: All patients treated with curative intent with EBRT for PCa at a major cancer centre between 2000 and 2007 were included in this study. The outcome measures of time to biochemical failure (BF), metastasis, PCa-specific mortality and overall survival (OS) were analysed in those taking metformin vs those not, using competing risk and Cox regression models. To determine metformin's effect on HIF1α expression and survival in vitro, PC3 cells with high basal HIF1α levels were subjected to increasing doses of metformin after H2 O2 -induced oxidative stress. RESULTS: A total of 2055 eligible cases, including 113 who were on metformin, were identified, with a median follow-up of 95.7 months. There were no differences in age, initial prostate-specific antigen level, Gleason score, T-stage, D'Amico risk class or duration of androgen deprivation therapy (ADT) between patients who were or were not on metformin. Treatment with metformin did not result in any apparent improvement in time to BF, time to metastasis detection or OS, but there was a 1.5-fold increase in PCa-specific deaths (P = 0.045) in patients on metformin and ADT when adjusted for cancer risk and comorbidities. When comparing patients on high-dose metformin (>1 g/d) with those on low-dose metformin (≤1 g), there was no difference in either time to metastases or time to BF. In vitro metformin at a high concentration of 100 μM did not reduce HIF1α expression, nor did metformin affect the PC3 cell survival when exposed to oxidative stress (H2 O2 ). CONCLUSIONS: No association was found between the use of metformin and time to metastasis detection, time to BF or OS in patients undergoing radiation therapy with or without ADT for PCa. In vitro, low therapeutic concentrations of metformin had no effect on HIF1α, and this observation could explain the conflicting evidence for the effectiveness of metformin in men undergoing EBRT for PCa. Higher, more toxic doses of metformin may be required to inhibit the mammalian target of rapamycin-HIF1α pathway in this patient group.
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    Survival outcomes of younger men (< 55 years) undergoing radical prostatectomy
    Tan, L ; Wang, LL ; Ranasinghe, W ; Persad, R ; Bolton, D ; Lawrentschuk, N ; Sengupta, S (ELSEVIER INC, 2018-03)
    BACKGROUND: The aim of the paper is to investigate the outcomes of patients younger than 55 years in Victoria, Australia undergoing radical prostatectomy (RP) for prostate cancer. MATERIALS AND METHODS: Data on all men undergoing RP in Victoria between January 1, 2004 and December 31, 2014 were obtained from the Victorian Cancer Registry. Tumor characteristics including Gleason grade, stage of disease (based on final pathology specimen), and cause of death were also obtained. Statistical analysis was performed using Chi-square test, Cox proportional hazards method, and Kaplan-Meier analysis. RESULTS: A total of 14,686 men underwent RP during the defined period. Of these men 109 were aged 35-44 years and 1,998 were aged 45-54 years. Men aged 35-44 years and 45-54 years were compared against men aged 55-74 years. The majority of men between the ages of 35 years and 44 years, and 45 years and 54 years had higher rates of Gleason ≤ 7 disease compared with men aged between 55 years and 74 years (92.7% vs. 86.8% vs. 79.3%; P < 0.01) and ≤ T2 disease (82.6% vs. 75.6% vs. 49.9%; P < 0.01) but similar median prostate-specific antigen values. On a multivariate analysis adjusting for Gleason score, T stage, and prostate-specific antigen, men aged 45-54 years and 55-64 years had 67% and 46% increase in overall survival, respectively, compared to men aged 65-74 years; but these differences were not seen in the 35-44 year age group. There were no differences in prostate cancer specific deaths between the groups. The 5- and 10-year overall survival outcomes were both higher for men aged 45-54 years compared to mean aged 55-74 years (97.9% vs. 95.9% and 94.9% vs. 85.3). CONCLUSION: Men aged 45-54 years undergoing RP had better overall survival compared to men aged 55-74 years, but these effects were not seen in men aged 35-44 years. There were no differences in prostate cancer specific survival in these groups.
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    The use of organ donor blood in liver transplantation
    Tang, GT ; Shaylor, R ; Hui, V ; Przybylowski, G ; Jones, RM ; Starkey, G ; Perini, MV ; Wang, B-Z ; Zantomio, D ; Hogan, C ; Fink, MA (WILEY, 2021-09)
    BACKGROUND: Blood removed from organs during deceased donor organ procurement is routinely discarded but is a potential resource for donor-specific transfusion (DST) in subsequent liver transplantation (LT). This study retrospectively analyses the impact of DST on intraoperative bank blood product usage, long-term graft, and patient survival, as well as frequency of rejection post-LT. METHODS: A total of 992 adult LT performed from 1993 to 2018 in a single quaternary center were included. Intraoperative blood product usage, patient, and graft survival, as well as acute and chronic rejection were assessed in patients who received blood retrieved from the organ donor, the "donor blood" (DB) group (n = 437) and patients who did not, the "no donor blood" (NDB) group (n = 555). RESULTS: Processing of DB ensured safe levels of potassium, magnesium, and insulin. There were fewer units of bank red blood cells transfusion required in the DB group compared to NDB group (2 vs. 4 units, P = .01). Graft survival was significantly superior in the DB group (10-year survival 75% vs. 69%, respectively, P = .04) but DST was not an independent predictor of graft survival. There was no significant difference in patient survival or rejection between the groups. There was no difference in treated, biopsy-proven rejection between the two groups. CONCLUSIONS: This is the first large-cohort study assessing long-term outcomes of intraoperative DST in LT. The collection of organ donor blood and subsequent use in LT recipients appeared feasible with appropriate quality checks ensuring safety. DST resulted in a reduction in the use of packed red blood cells. There was no difference in the rate of rejection or graft or patient survival.