ORCID Profile
0000-0002-6037-8895
Current Organisations
Austin Health
,
University of Melbourne
,
St Vincent's Health
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Publisher: Elsevier BV
Date: 12-2009
Publisher: BMJ
Date: 09-2022
DOI: 10.1136/BMJOPEN-2022-061815
Abstract: Prostate-specific membrane antigen positron emission tomography (PSMA-PET) has emerged as valuable imaging to assessing metastatic disease in prostate malignancy. However, there has been limited studies exploring the utility PSMA-PET as primary imaging assessing for index lesions prior to biopsy. The primary objective of this study is to compare the diagnostic accuracy of 18-fluorine PSMA (18F DCFPyL PSMA) PET scans to multiparametric MRI (mpMRI) to detect primary prostate cancer at prostate biopsy. The PEDAL trial is a multicentre, prospective, single-arm, paired comparison, non-randomised phase III trial in subjects considered for diagnostic prostate biopsy. Subjects who are eligible for a diagnostic mpMRI prostate will undergo additional same-day 18 F DCFPyl PSMA PET/CT of the chest, abdomen and pelvis. Software coregistration of the mpMRI and PSMA-PET/CT images will be performed. The reporting of the mpMRI prostate, PSMA-PET/CT and PSMA PET/MRI coregistration will be performed blinded. The diagnostic accuracy of PSMA PET/CT alone, and in combination with mpMRI, to detect prostate cancer will be assessed. Histopathology at prostate biopsy will be used as the reference standard. S le size calculations estimate that 240 subjects will need to be recruited to demonstrate 20% superiority of PSMA-PET/CT. The sensitivity, specificity, positive predictive value and negative predictive value of the combination of mpMRI prostate and PSMA PET/CT compared with targeted and systematic prostate biopsy will be evaluated. It is hypothesised that PSMA PET/CT combined with mpMRI prostate will have improved diagnostic accuracy compared with mpMRI prostate alone for detection of prostate cancer in biopsy-naïve men, resulting in a significant impact on patient management. This study was approved by the independent Human Research Ethics Committee. Results will be published in peer-reviewed medical journals with eligible investigators will significantly contribute. ACTRN12620000261910.
Publisher: Wiley
Date: 28-03-2022
DOI: 10.1002/BCO2.147
Abstract: To evaluate the diagnostic performance of FDA‐approved urinary biomarkers in the evaluation of primary haematuria for investigation of bladder cancer. The scientific databases MEDLINE, EMBASE, Pubmed and Web of Science were searched to collect studies. Studies that evaluated the diagnostic performance of FDA‐approved urinary biomarkers in investigating patients with primary haematuria without a prior history of bladder cancer were included. Quality of studies was assessed using the JBI Criteria. Bivariate mixed‐effects regression model was used to calculate pooled sensitivities and specificities for each biomarker. Eighteen studies were included in the analysis. The biomarkers assessed in these studies were CxBladder, AssureMDx, Bladder Tumour Antigen (BTA), NMP22, UroVysion and Immunocyt/uCyt+. Several biomarkers, such as AssureMDx, CxBladder and Immunocyt, were shown to have better diagnostic performance based on their sensitivity, specificity and diagnostic odds ratio, as well as positive and negative likelihood ratios. Across the six biomarkers, sensitivity ranged from 0.659 to 0.973, and the specificity ranged between 0.577 and 0.833. Despite certain biomarkers demonstrated better performance, current diagnostic abilities of the FDA‐approved biomarkers remain insufficient for their general application as a rule out test for bladder cancer diagnosis and as a triage test for cystoscopy in patients with primary haematuria. High‐quality prospective studies are required to further analyse this and also analyse the correct scenario in which urinary biomarkers may be best utilised.
Publisher: The Korean Urological Association
Date: 2017
Publisher: Hindawi Limited
Date: 25-11-2018
DOI: 10.1155/2018/9852791
Abstract: Partial nephrectomy (open or minimally invasive) usually requires temporary renal arterial occlusion to limit intraoperative bleeding and improve access to intrarenal structures. This is a time-critical step due to the critical ischemia period of renal tissue. Prolonged renal ischemia may lead to irreversible nephron damage in the remaining tissue and, ultimately, chronic kidney disease. This is potentiated by the incompletely understood ischemia-reperfusion injury (IRI). A key mechanism in IRI prevention appears to be the upregulation of an intracellular transcription protein, Hypoxia-Inducible Factor (HIF). HIF mediates metabolic adaptation, angiogenesis, erythropoiesis, cell growth, survival, and apoptosis. Upregulating HIF-1 α via ischemic preconditioning (IPC) or drugs that simulate hypoxia (hypoxia-mimetics) has been investigated as a method to reduce IRI. While many promising chemical agents have been trialed for the prevention of IRI in small animal studies, all have failed in human trials. The aim of this review is to highlight the techniques and drugs that target HIF-1 α and ameliorate IRI associated with renal ischemia. Developing a technique or drug that could reduce the risk of acute kidney injury associated with renal IRI would have an immediate worldwide impact on multisystem surgeries that would otherwise risk ischemic tissue injury.
Publisher: Wiley
Date: 28-03-2012
Publisher: Public Library of Science (PLoS)
Date: 07-07-2017
Publisher: Springer Science and Business Media LLC
Date: 28-09-2011
DOI: 10.1007/S11701-011-0313-4
Abstract: Robot-assisted laparoscopic radical prostatectomy (RALRP), increasingly used to treat localized prostate cancer, has advantages over open radical prostatectomy (ORP) in terms of reduced bleeding and quicker convalescence. However, debate continues over whether RALRP provides superior or at least equivalent surgical outcomes. This study compares positive surgical margins (+SM), as a surrogate for long-term cancer control, at RALRP and ORP performed by a single experienced surgeon during the process of taking up RALRP. 400 consecutive patients undergoing surgery for prostate cancer under a single surgeon (DW) between November 1999 and July 2009 were studied. Prior to July 2005, all patients underwent ORP after this date, most patients were treated by RALRP. Data were collected by retrospective chart review and analysed independently of the treating surgeon. +SM were defined as the presence of cancer at an inked surface. Overall, 23 (11.5%) of 200 patients undergoing RALRP had +SM, compared to 40 (20.0%) of 200 patients undergoing ORP (P < 0.05). On univariate logistic regression analysis, in addition to surgical approach (odds ratio [OR] = 1.92), patient age (OR = 1.05), pathologic stage (OR = 3.93) and specimen Gleason (GS) score (OR = 1.86) were significant predictors of +SM. On multivariate analysis, surgical approach, p-stage and specimen GS remained significant predictors of +SM. RALRP is associated with lower rates of +SM compared to ORP, even after adjusting for other known risk factors. Of note, the RALRP in this study were part of the surgeon's learning curve.
Publisher: Wiley
Date: 26-01-2015
DOI: 10.1111/BJU.12886
Abstract: To determine the expression and biology of the neuroendocrine growth factor gastrin-releasing peptide (GRP) and other proGRP-derived peptides in renal cancer. Receptor binding studies, enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay, were used to quantitate the presence of proGRP-derived peptide receptors and their ligands in renal cancer cell lines and human renal cancers. Biological activity of proGRP peptides was confirmed with proliferation, migration, and extracellular-signal-regulated kinases 1 and 2 (ERK1/2) activation assays in vitro. In vivo, ACHN renal cancer xenografts were treated with proGRP-derived peptides to assess tumour size and necrosis. hypoxia-inducible factor 1α (HIF1α) and vascular endothelial growth factor (VEGF) expression were investigated with Western blotting and ELISA respectively, to determine the possible contribution of the proGRP peptides to tumour viability. In ACHN cells that expressed both proGRP- and GRP-receptors, the expression of proGRP binding sites was 80-fold greater than the GRP-receptor (GRPR). C-terminal proGRP-derived peptides stimulated the activation of ERK1/2, but with a different time course to GRP, consistent with the suggestion that these peptides may have unique cellular functions. Both GRP and proGRP47-68 stimulated proliferation and migration of ACHN cells in vitro, but only GRP reduced the extent of tumour necrosis in ACHN xenografts. GRP, but not proGRP47-68, was able to induce HIF1α and VEGF expression in ACHN cells. This may account in part for the reduction in necrosis after GRP treatment. C-terminal proGRP-derived peptides were present in all three renal cancer cell lines and a panel of human renal cancers, but mature amidated GRP was absent. C-terminal proGRP peptides are more abundant in renal cancers and their cell lines than the more extensively studied amidated peptide, GRP. These results suggest that C-terminal proGRP-derived peptides may be a better target for novel renal cancer treatments.
Publisher: Hindawi Limited
Date: 10-04-2019
DOI: 10.1155/2019/9598038
Publisher: Wiley
Date: 11-03-2009
No related grants have been discovered for kapil sethi.