Surgery (Austin & Northern Health) - Research Publications

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    Effectiveness of epidural versus alternate analgesia for pain relief after radical prostatectomy and correlation with biochemical recurrence in men with prostate cancer
    Mir, MC ; Joseph, B ; Zhao, R ; Bolton, DM ; Gyomber, D ; Lawrentschuk, N (DOVE MEDICAL PRESS LTD, 2013)
    OBJECTIVES: Our objectives were to analyze the effectiveness of epidural anesthesia in patients who underwent open retropubic radical prostatectomy (RRP) at our institution over the past decade, and to examine subsequent oncologic outcomes, comparing those receiving with those not receiving epidural anesthesia. METHODS: A comprehensive database of all patients undergoing RRP from November 1996 to December 2006 was analyzed; 354 patients underwent RRP at our institution and were divided into those receiving or not receiving an epidural. An independent pain management team scoring technical success found epidural technique to be consistent. Oncological outcome was an endpoint of our study, comparing both analysis groups. We classed prostate-specific antigen (PSA) recurrence after RRP as a serum PSA ≥ 0.2 ng/mL at any stage of postoperative follow-up. Complications were recorded to 30 days using the modified Clavien system, and full statistical analyses were undertaken. RESULTS: Records were available for 239 men; we observed a decreased trend in the use of epidural for pain management, along with a decrease in average hospital stay and an overall epidural success rate of 64%. When dividing data into RRP with and without epidural, we found a median hospital stay of 7 days for patients receiving an epidural compared with 6 days for those not receiving an epidural. The differences were statistically significant (P < 0.048) and remained so after adjusting for complications (P < 0.0001). Regarding oncological outcome, PSA recurrence was further analyzed in this cohort. Percentage of recurrence was higher (14.8%) for patients receiving an epidural than for the non-epidural group (4.8%). The differences were statistically significant (P = 0.012). CONCLUSION: Epidural analgesia increased length of hospital stay and technical problems related to the epidural. Furthermore, men receiving an epidural showed an increased recurrence of PSA. In light of our findings, epidurals are probably not indicated for men undergoing RRP. However, as minimally invasive techniques are becoming more widespread, and epidural analgesia is being used less frequently, large randomized controlled trials to definitively support our hypotheses are unlikely to be undertaken.
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    Nephrectomy for a Renal Metastasis of Undiagnosed Hepatocellular Carcinoma Arising From an Orthotopic Liver Transplant Undertaken for Cryptogenic Cirrhosis
    Ong, KWK ; Joseph, B ; Gyomber, DV ; Bolton, DM ; Lawrentschuk, N (KOREAN UROLOGICAL ASSOC, 2013-10)
    Urological involvement of hepatocellular carcinoma (HCC) is rare; HCC arising in an orthotopic liver transplant (OLT) is exceptionally rare. Here we report the case of a 70-year-old man who was incidentally found to have metastatic HCC in the right kidney arising from his OLT undertaken for cryptogenic cirrhosis 10 years previously. Adding to the complexity of this case was the lack of an obvious liver primary HCC at the time of the radical nephrectomy, thus making the final diagnosis all but impossible. We believe this report represents the first report of HCC metastasizing to the kidney after OLT and adds to the few reports in the literature of HCC arising in transplanted livers.
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    Current role of salvage robotic-assisted laparoscopic prostatectomy
    Wetherell, D ; Bolton, D ; Kavanagh, L ; Perera, M (SPRINGER, 2013-06)
    OBJECTIVES: Salvage Robotic-Assisted Laparoscopic Prostatectomy (sRALP) is a treatment option for biochemical recurrence (BCR) in prostate cancer. It is a new and presently uncommonly performed procedure, which may be technically challenging. We aim to summarise the current literature regarding sRALP with specific reference to patient selection, complications and peri-operative functional and oncological outcomes. METHODS: A comprehensive and critical review of all peer-reviewed publications regarding sRALP. RESULTS: Within the body of literature, we identified six low-volume case-series studies analysing outcomes of sRALP. Overall, peri-operative outcomes were encouraging with low complication rates and estimated blood loss (EBL) equivocal to open and laparoscopic salvage radical prostatectomy (sRP). Long-term follow-up for functional and oncological outcomes was limited. From the limited follow-up data, the current sRALP studies show similar BCR compared to large-volume open sRP series. Potency outcomes were poor post-sRALP. CONCLUSIONS: Salvage Robotic-Assisted Laparoscopic Prostatectomy is a technically feasible operation with a low risk of significant associated complications. Robotic technology can aid the surgeon in salvage prostatectomy. Data on functional and oncological outcomes lack long-term information but initial results are encouraging. Larger series with longer follow-up periods are necessary to draw significant conclusions about the efficacy of sRALP.
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    The Role of Hypoxia-Inducible Factor 1α in Determining the Properties of Castrate-Resistant Prostate Cancers
    Ranasinghe, WKB ; Xiao, L ; Kovac, S ; Chang, M ; Michiels, C ; Bolton, D ; Shulkes, A ; Baldwin, GS ; Patel, O ; Agoulnik, IU (PUBLIC LIBRARY SCIENCE, 2013-01-16)
    BACKGROUND: Castrate-resistant prostate cancer (CRPC) is a lethal condition in patients receiving androgen deprivation therapy for prostate cancer (PC). Despite numerous studies showing the expression of HIF1α protein under normoxia in PC cell lines, the role of this normoxic HIF1α expression in chemo-resistance and migration has not been investigated previously. As no method is currently available to determine which tumors will progress to CRPC, the role of HIF1α in PC and its potential for predicting the development of CRPC was also investigated. METHODS: The effect of HIF1α protein knockdown on chemo-resistance and migration of PC3 cells was assessed by cell counting and Transwell assays, respectively. Translation efficiency of HIF1α mRNA was determined in PC cells using a HIF1α 5'UTR-luciferase construct. Clinical outcomes were correlated following the staining of 100 prostate tumors for HIF1α expression. RESULTS: The CRPC-like cell lines (PC3 and DU145) expressed more HIF1α protein than an androgen sensitive cell line (LNCaP). Migration rate and chemo-resistance were higher in the PC3 cells and both were decreased when HIF1α expression was reduced. Increased translation of HIF1α mRNA may be responsible for HIF1α overexpression in PC3 cells. Patients whose tumors expressed HIF1α had significantly decreased metastasis-free survival and the patients who were on androgen-deprivation therapy had decreased CRPC-free survival on Kaplan-Meier analysis. On multivariate analysis HIF1α was an independent risk factor for progression to metastatic PC (Hazard ratio (HR) 9.8, p = 0.017) and development of CRPC (HR 10.0, p = 0.021) in patients on androgen-deprivation therapy. Notably the tumors which did not express HIF1α did not metastasize or develop CRPC. CONCLUSIONS: HIF1α is likely to contribute to metastasis and chemo-resistance of CRPC and targeted reduction of HIF1α may increase the responsiveness of CRPCs to chemotherapy. Expression of HIF1α may be a useful screening tool for development of CRPC.