Surgery (RMH) - Research Publications
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ItemIntraductal carcinoma of the prostate can evade androgen deprivation, with emergence of castrate-tolerant cells(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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ItemChanging face of robot-assisted radical prostatectomy in Melbourne over 12 years(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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ItemAdverse impact of malnutrition markers on major abdominopelvic cancer surgery(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 30 207 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%, P = 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.
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ItemCytoreductive surgery for men with metastatic prostate cancer(ELSEVIER INC, 2016-09)BACKGROUND: Cytoreductive surgery for metastatic prostate cancer is an emerging area of interest with a potential upside that includes local control, delayed initiation of hormone therapy, and possibly improved cancer specific survival. In order for radical prostatectomy to be an effective treatment option for men in this group, the benefits must outweigh the surgical morbidity. The aim of this study was to present a case series and assess the literature feasibility of cytoreductive surgery for men with metastatic prostate cancer. METHODS: A retrospective review of clinical notes was performed to identify men with metastatic prostate cancer who underwent cytoreductive surgery between 2012 and 2014 for a group of urologists at a single institution in Melbourne. Each patient was evaluated with regard to preoperative prostate-specific antigen, grade, stage, adjuvant therapy, and surgical outcomes. RESULTS: Six cases were identified. This included 1 pelvic exenteration and 5 robot-assisted radical prostatectomies. The men who underwent RARP had uncomplicated recoveries, regained continence within 3 months and remained pad-free at follow up. All patients proceeded to additional treatment of sites of metastatic disease with a variable PSA response, however, 3 of 6 men required recommencement of ADT for biochemical progression at follow up. CONCLUSIONS: This data supports recent findings demonstrating that radical prostatectomy for metastatic prostate cancer is feasible. Further studies are needed to explore the role of cytoreductive surgery with regards to the potential oncological benefit.
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ItemUpdates of prostate cancer staging: Prostate-specific membrane antigen(KOREAN UROLOGICAL ASSOC, 2016-12)The ability to accurately stage prostate cancer in both the primary and secondary staging setting can have a major impact on management. Until recently radiological staging has relied on computer tomography, magnetic resonance imaging, and nuclear bone scans to evaluate the extent of disease. However, the utility of these imaging technologies has been limited by their sensitivity and specificity especially in detecting early recurrence. Functional imaging using positron-emission tomography with a radiolabeled ligand targeted to prostate-specific membrane antigen has transformed the prostate cancer imaging landscape. Initial results suggest that it is a substantial improvement over conventional imaging in the setting of recurrence following primary therapy by having a superior ability to detect disease and to do so at an earlier stage. Additionally, it appears that the benefits seen in the secondary staging setting may also exist in the primary staging setting.