Surgery (RMH) - Research Publications

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    Intraductal carcinoma of the prostate can evade androgen deprivation, with emergence of castrate-tolerant cells
    Porter, LH ; Hashimoto, K ; Lawrence, MG ; Pezaro, C ; Clouston, D ; Wang, H ; Papargiris, M ; Thorne, H ; Li, J ; Ryan, A ; Norden, S ; Moon, D ; Bolton, DM ; Sengupta, S ; Frydenberg, M ; Murphy, DG ; Risbridger, GP ; Taylor, RA (WILEY, 2018-06)
    OBJECTIVE: To determine the relevance of intraductal carcinoma of the prostate (IDC-P) in advanced prostate cancer by first examining whether IDC-P was originally present in patients who later developed advanced prostate cancer and then using patient-derived xenografts (PDXs) to investigate the response of IDC-P to androgen deprivation therapy (ADT). MATERIALS AND METHODS: We conducted a retrospective pathology review of IDC-P in primary prostate biopsy or surgery specimens from 38 men who subsequently developed advanced prostate cancer. Overall survival was calculated using the Kaplan-Meier method. To demonstrate the response of IDC-P to ADT, we established PDXs from seven patients with familial and/or high-risk sporadic prostate cancer. After castration and testosterone restoration of host mice, we measured the volume and proliferation of IDC-P within PDX grafts. RESULTS: We found that IDC-P was a prominent feature in the primary prostate specimens, present in 63% of specimens and often co-existing with poorly differentiated adenocarcinoma. Overall survival was similar in patients with or without IDC-P. In the PDXs from all seven patients, IDC-P was identified and present at a similar volume to adenocarcinoma. Residual IDC-P lesions persisted after host castration and, similar to castrate-tolerant adenocarcinoma, testosterone restoration led to tumour regeneration. CONCLUSION: The study showed that IDC-P is prevalent in aggressive prostate cancer and contains cells that can withstand androgen deprivation. Thus, IDC-P appears functionally relevant in advanced prostate cancer. The presence of IDC-P may be a trigger to develop innovative clinical management plans.
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    Changing face of robot-assisted radical prostatectomy in Melbourne over 12 years
    Sathianathen, NJ ; Lamb, AD ; Lawrentschuk, NL ; Goad, JR ; Peters, J ; Costello, AJ ; Murphy, DG ; Moon, DA (WILEY, 2018-03)
    BACKGROUND: This study aims to characterize the trends in disease presentation for robot-assisted radical prostatectomy (RARP) over a 12-year period in Melbourne, Australia. METHODS: All patients undergoing an RARP between 2004 and October 2016 while under the care of six high-volume surgeons were included in this study. Data were collected prospectively regarding patient demographics and clinical details of their cancer. RESULTS: Over the 12-year time span of the study, 3075 men underwent an RARP with a median age of 63.01 years. Temporal analysis demonstrated that the median age of patients undergoing prostatectomy advanced with time with the median age in 2016 being 65.51 years compared with 61.0 years in 2004 (P < 0.001). There was also a significant trend to increased D'Amico risk groups over time with the percentage procedures for high-risk patients increasing from 12.6% to 28.10% from 2004 to 2016 (P < 0.001). Upgrade rates between biopsy and pathological Gleason grade scoring significantly trended down over the period of the study (P < 0.001). There was also a shift to increased pathological stage over the 12 years with 22.1% of men having T3 disease in 2004 compared with 49.8% in 2016. CONCLUSION: Our analysis demonstrates increasing treatment of older men with higher risk tumours, consistent with international trends. While this largely reflects a shift in case selection, further work is needed to assess whether the stage shift may relate partially to a decline in screening and increased presentation of higher risk disease.
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    Prostate-specific membrane antigen radioguided surgery: a promising utility
    Geurts, N ; Lamb, AD ; Lawrentschuk, N ; Murphy, DG (WILEY, 2017-07)
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    Stereotactic ablative body radiotherapy for inoperable primary kidney cancer: a prospective clinical trial
    Siva, S ; Pham, D ; Kron, T ; Bressel, M ; Lam, J ; Tan, TH ; Chesson, B ; Shaw, M ; Chander, S ; Gill, S ; Brook, NR ; Lawrentschuk, N ; Murphy, DG ; Foroudi, F (WILEY, 2017-11)
    OBJECTIVE: To assess the feasibility and safety of stereotactic ablative body radiotherapy (SABR) for renal cell carcinoma (RCC) in patients unsuitable for surgery. Secondary objectives were to assess oncological and functional outcomes. MATERIALS AND METHODS: This was a prospective interventional clinical trial with institutional ethics board approval. Inoperable patients were enrolled, after multidisciplinary consensus, for intervention with informed consent. Tumour response was defined using Response Evaluation Criteria In Solid Tumors v1.1. Toxicities were recorded using Common Terminology Criteria for Adverse Events v4.0. Time-to-event outcomes were described using the Kaplan-Meier method, and associations of baseline variables with tumour shrinkage was assessed using linear regression. Patients received either single fraction of 26 Gy or three fractions of 14 Gy, dependent on tumour size. RESULTS: Of 37 patients (median age 78 years), 62% had T1b, 35% had T1a and 3% had T2a disease. One patient presented with bilateral primaries. Histology was confirmed in 92%. In total, 33 patients and 34 kidneys received all prescribed SABR fractions (89% feasibility). The median follow-up was 24 months. Treatment-related grade 1-2 toxicities occurred in 26 patients (78%) and grade 3 toxicity in one patient (3%). No grade 4-5 toxicities were recorded and six patients (18%) reported no toxicity. Freedom from local progression, distant progression and overall survival rates at 2 years were 100%, 89% and 92%, respectively. The mean baseline glomerular filtration rate was 55 mL/min, which decreased to 44 mL/min at 1 and 2 years (P < 0.001). Neutrophil:lymphocyte ratio correlated to % change in tumour size at 1 year, r2 = 0.45 (P < 0.001). CONCLUSION: The study results show that SABR for primary RCC was feasible and well tolerated. We observed encouraging cancer control, functional preservation and early survival outcomes in an inoperable cohort. Baseline neutrophil:lymphocyte ratio may be predictive of immune-mediated response and warrants further investigation.
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    An online psychological intervention can improve the sexual satisfaction of men following treatment for localized prostate cancer: outcomes of a Randomised Controlled Trial evaluating My Road Ahead
    Wootten, AC ; Meyer, D ; Abbott, J-AM ; Chisholm, K ; Austin, DW ; Klein, B ; McCabe, M ; Murphy, DG ; Costello, AJ (WILEY, 2017-07)
    BACKGROUND: Prostate cancer treatment often results in significant psycho-sexual challenges for men following treatment; however, many men report difficulty in accessing appropriate care. METHODS: A randomized controlled trial was undertaken to assess the efficacy of a 10-week self-guided online psychological intervention called My Road Ahead (MRA) for men with localized prostate cancer in improving sexual satisfaction. Participants were randomized to 1 of 3 conditions MRA alone or MRA plus online forum, or forum access alone. Pre, post, and follow-up assessments of overall sexual satisfaction were conducted. Mixed models and structural equation modeling were used to analyze the data. RESULTS: One hundred forty-two men (mean age 61 y; SD = 7) participated. The majority of participants had undergone radical prostatectomy (88%) and all men had received treatment for localized prostate cancer. Significant differences were obtained for the 3 groups (P = .026) and a significant improvement in total sexual satisfaction was observed only for participants who were allocated to MRA + forum with a large effect size (P = .004, partial Ī·2  = 0.256). Structural equation modeling indicated that increases in sexual function, masculine self-esteem, and sexual confidence contributed significantly to overall sexual satisfaction for the MRA + forum plus forum condition. CONCLUSIONS: This study is the first, to our knowledge, that has evaluated a self-guided online psychological intervention tailored to the specific needs of men with prostate cancer. The findings indicate the potential for MRA to deliver support that men may not otherwise receive and also highlight the importance of psychological intervention to facilitate improved sexual outcomes.
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    Prostate Imaging Reporting and Data System score of four or more: active surveillance no more
    Perera, M ; Katelaris, N ; Murphy, DG ; McGrath, S ; Lawrentschuk, N (WILEY-BLACKWELL, 2017-01)
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    Validation of the novel International Society of Urological Pathology 2014 five-tier Gleason grade grouping: biochemical recurrence rates for 3+5 disease may be overestimated
    van den Bergh, RCN ; van der Kwast, TH ; de Jong, J ; Zargar, H ; Ryan, AJ ; Costello, AJ ; Murphy, DG ; van der Poel, HG (WILEY-BLACKWELL, 2016-10)
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    Going nuclear: it is time to embed the nuclear medicine physician in the prostate cancer multidisciplinary team
    Murphy, DG ; Hofman, MS ; Azad, A ; Violet, J ; Hicks, RJ ; Lawrentschuk, N (WILEY, 2019-10)
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    Adverse impact of malnutrition markers on major abdominopelvic cancer surgery
    Sathianathen, NJ ; Kwaan, M ; Lawrentschuk, N ; Weight, CJ ; Kim, SP ; Murphy, DG ; Moon, DA ; Konety, BR (WILEY, 2019-05)
    BACKGROUND: Malnutrition has been associated with adverse postoperative outcomes in a range of procedures but none have evaluated the interaction between clinical indicators of malnutrition. We aimed to comparatively evaluate how combinations of nutritional parameters impact postoperative outcomes amongst patients undergoing major cancer operations. METHODS: Major abdominopelvic cancer surgery cases (colectomy, cystectomy, esophagectomy, gastrectomy, hysterectomy, nephrectomy, pancreatectomy, pneumonectomy and prostatectomy) were identified in the American College of Surgeons National Surgical Quality Improvement Program database from 2007-2016. Malnutrition was defined by the presence of the following parameters: body mass index <18.5 kg/m2 ; preoperative serum albumin <3.0 g/dL or more than 10% weight loss in the last 6 months. Malnourished cases were matched with cases with satisfactory nutritional status using propensity scores. The primary outcome was the incidence of Clavien III-IV complications. RESULTS: Of the 30ā€‰207 cases included, 8.5% had at least one marker of malnutrition. The incidence of Clavien III-IV complications across all cases was 5.8%. In the matched cohort, malnourished cases had a higher rate of complications than those with adequate nutritional status (11.3% versus 9.6%, Pā€‰=ā€‰0.018). A correlation was observed between the number of malnutrition markers possessed and the incidence of Clavien III-V complications. Cases with all three makers had the highest likelihood of experiencing a complication (odds ratio 5.47, 95% confidence interval 1.85-16.17). CONCLUSION: Poor nutritional status confers an increased risk of major postoperative complications and being discharged to a facility in non-upper gastrointestinal cancer patients. There was a correlation between the number of malnutrition parameters and the risk of complications.