Surgery (Austin & Northern Health) - Research Publications
Now showing items 1-12 of 85
Salmonella typhimurium: a rare cause of mesh-related infection
(OXFORD UNIV PRESS, 2017-10-01)
The use of mesh in the management of abdominal wall hernias has significantly reduced the incidences of hernia recurrences. The placement of synthetic meshes to reinforce the abdominal wall is not without caveats. Synthetic meshes are associated with a risk of infection. Common causative microorganisms for mesh-related infection range from a diversity of gram positive, gram negative and anaerobic bacteria. However, non-typhoidal Salmonella spp. mesh-related infection remains poorly described in the literature. In this case, we report the management of an immunocompromised patient who developed Salmonella typhimurium mesh-related infection that was complicated by abscess formation.
Management of variceal hemorrhage: current concepts.
(FapUNIFESP (SciELO), 2014-04)
INTRODUCTION: The treatment of portal hypertension is complex and the the best strategy depends on the underlying disease (cirrhosis vs. schistosomiasis), patient's clinical condition and time on it is performed (during an acute episode of variceal bleeding or electively, as pre-primary, primary or secondary prophylaxis). With the advent of new pharmacological options and technical development of endoscopy and interventional radiology treatment of portal hypertension has changed in recent decades. AIM: To review the strategies employed in elective and emergency treatment of variceal bleeding in cirrhotic and schistosomotic patients. METHODS: Survey of publications in PubMed, Embase, Lilacs, SciELO and Cochrane databases through June 2013, using the headings: portal hypertension, esophageal and gastric varices, variceal bleeding, liver cirrhosis, schistosomiasis mansoni, surgical treatment, pharmacological treatment, secondary prophylaxis, primary prophylaxis, pre-primary prophylaxis. CONCLUSION: Pre-primary prophylaxis doesn't have specific treatment strategies; the best recommendation is treatment of the underlying disease. Primary prophylaxis should be performed in cirrhotic patients with beta-blockers or endoscopic variceal ligation. There is controversy regarding the effectiveness of primary prophylaxis in patients with schistosomiasis; when indicated, it is done with beta-blockers or endoscopic therapy in high-risk varices. Treatment of acute variceal bleeding is systematized in the literature, combination of vasoconstrictor drugs and endoscopic therapy, provided significant decline in mortality over the last decades. TIPS and surgical treatment are options as rescue therapy. Secondary prophylaxis plays a fundamental role in the reduction of recurrent bleeding, the best option in cirrhotic patients is the combination of pharmacological therapy with beta-blockers and endoscopic band ligation. TIPS or surgical treatment, are options for controlling rebleeding on failure of secondary prophylaxis. Despite the increasing evidence of the effectiveness of pharmacological and endoscopic treatment in schistosomotic patients, surgical therapy still plays an important role in secondary prophylaxis.
Zinc ion dyshomeostasis increases resistance of prostate cancer cells to oxidative stress via upregulation of HIF1α.
(Impact Journals, 2018-02-02)
Zinc ions (Zn2+) are known to influence cell survival and proliferation. However the homeostatic regulation of Zn2+ and their role in prostate cancer (PC) progression is poorly understood. Therefore the subcellular distribution and uptake of Zn2+ in PC cells were investigated. Inductively coupled plasma mass spectroscopy and fluorescent microscopy with the Zn2+-specific fluorescent probe FluoZin-3 were used to quantify total and free Zn2+, respectively, in the normal prostate epithelial cell line (PNT1A) and three human PC cell lines (PC3, DU145 and LNCaP). The effects of Zn2+ treatment on proliferation and survival were measured in vitro using MTT assays and in vivo using mouse xenografts. The ability of Zn2+ to protect against oxidative stress via a HIF1α-dependent mechanism was investigated using a HIF1α knock-down PC3 model. Our results demonstrate that the total Zn2+ concentration in normal PNT1A and PC cells is similar, but PC3 cells contain significantly higher free Zn2+ than PNT1A cells (p < 0.01). PNT1A cells can survive better in the presence of high concentrations of Zn2+ than PC3 cells. Exposure to 10 µM Zn2+ over 72 hours significantly reduces PC3 cell proliferation in vitro but not in vivo. Zn2+ increases PC3 cell survival up to 2.3-fold under oxidative stress, and this protective effect is not seen in PNT1A cells or in a HIF1α-KD PC3 cell model. A state of Zn2+ dyshomeostasis exists in PC. HIF1α is an integral component of a Zn2+-dependent protective mechanism present in PC3 cells. This pathway may be clinically significant through its contribution to castrate-resistant PC survival.
The effects of nonspecific HIF1 alpha inhibitors on development of castrate resistance and metastases in prostate cancer
Expression of hypoxia-inducible factor (HIF)1α increases the risk of castrate-resistant prostate cancer (CRPC) and metastases in patients on androgen deprivation therapy (ADT) for prostate cancer (PC). We aimed to investigate the effects of nonspecific HIF1α inhibitors (Digoxin, metformin, and angiotensin-2 receptor blockers) on development of CRPC and metastases while on ADT. A retrospective review of prospectively collected medical records was conducted of all men who had continuous ADT as first-line therapy for CRPC at the Austin Hospital from 1983 to 2011. Association between HIF1α inhibitor medications and time to develop CRPC was investigated using actuarial statistics. Ninety-eight patients meeting the criteria were identified. Eighteen patients (21.4%) were treated with the nonspecific HIF1α inhibitors. Both groups had similar characteristics, apart from patients on HIF1α inhibitors being older (70 years vs. 63.9 years). The median CRPC-free survival was longer in men using HIF1α inhibitors compared to those not on inhibitors (6.7 years vs. 2.7 years, P = 0.01) and there was a 71% reduction in the risk of developing CRPC (HR 0.29 [95% CI 0.10-0.78] P = 0.02) after adjustment for Gleason score, age, and prostate-specific antigen (PSA). The median metastasis-free survival in men on HIF1α inhibitors was also significantly longer compared to those on no inhibitors (5.1 years vs. 2.6 years, P = 0.01) with an 81% reduction in the risk of developing metastases (HR 0.19 [CI 0.05-0.76] P = 0.02) after adjustment for Gleason score, age, and PSA. Nonspecific HIF1α inhibitors appear to increase the progression-free survival and reduce the risk of developing CRPC and metastases in patients on continuous ADT.
Protective effect of zinc preconditioning against renal ischemia reperfusion injury is dose dependent
(PUBLIC LIBRARY SCIENCE, 2017-07-07)
OBJECTIVES: Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury and chronic kidney disease. Two promising preconditioning methods for the kidney, intermittent arterial clamping (IC) and treatment with the hypoxia mimetic cobalt chloride, have never been directly compared. Furthermore, the protective efficacy of the chemically related transition metal Zn2+ against renal IRI is unclear. Although Co2+ ions have been shown to protect the kidney via hypoxia inducible factor (HIF), the effect of Zn2+ ions on the induction of HIF1α, HIF2α and HIF3α has not been investigated previously. MATERIALS AND METHODS: The efficacy of different preconditioning techniques was assessed using a Sprague-Dawley rat model of renal IRI. Induction of HIF proteins following Zn2+ treatment of the human kidney cell lines HK-2 (immortalized normal tubular cells) and ACHN (renal cancer) was measured using Western Blot. RESULTS: Following 40 minutes of renal ischemia in rats, cobalt preconditioning offered greater protection against renal IRI than IC as evidenced by lower peak serum creatinine and urea concentrations. ZnCl2 (10 mg/kg) significantly lowered the creatinine and urea concentrations compared to saline-treated control rats following a clinically relevant 60 minutes of ischemia. Zn2+ induced expression of HIF1α and HIF2α but not HIF3α in HK-2 and ACHN cells. CONCLUSION: ZnCl2 preconditioning protects against renal IRI in a dose-dependent manner. Further studies are warranted to determine the possible mechanisms involved, and to assess the benefit of ZnCl2 preconditioning for clinical applications.
Bioinformatics Pipelines for Targeted Resequencing and Whole-Exome Sequencing of Human and Mouse Genomes: A Virtual Appliance Approach for Instant Deployment
(PUBLIC LIBRARY SCIENCE, 2014-04-21)
Targeted resequencing by massively parallel sequencing has become an effective and affordable way to survey small to large portions of the genome for genetic variation. Despite the rapid development in open source software for analysis of such data, the practical implementation of these tools through construction of sequencing analysis pipelines still remains a challenging and laborious activity, and a major hurdle for many small research and clinical laboratories. We developed TREVA (Targeted REsequencing Virtual Appliance), making pre-built pipelines immediately available as a virtual appliance. Based on virtual machine technologies, TREVA is a solution for rapid and efficient deployment of complex bioinformatics pipelines to laboratories of all sizes, enabling reproducible results. The analyses that are supported in TREVA include: somatic and germline single-nucleotide and insertion/deletion variant calling, copy number analysis, and cohort-based analyses such as pathway and significantly mutated genes analyses. TREVA is flexible and easy to use, and can be customised by Linux-based extensions if required. TREVA can also be deployed on the cloud (cloud computing), enabling instant access without investment overheads for additional hardware. TREVA is available at http://bioinformatics.petermac.org/treva/.
The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
(Springer Nature, 2019-11-01)
Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.
Learning outcomes for communication skills across the health professions: a systematic literature review and qualitative synthesis
(BMJ PUBLISHING GROUP, 2017-04-01)
OBJECTIVE: The aim of this study was to identify and analyse communication skills learning outcomes via a systematic review and present results in a synthesised list. Summarised results inform educators and researchers in communication skills teaching and learning across health professions. DESIGN: Systematic review and qualitative synthesis. METHODS: A systematic search of five databases (MEDLINE, PsycINFO, ERIC, CINAHL plus and Scopus), from first records until August 2016, identified published learning outcomes for communication skills in health professions education. Extracted data were analysed through an iterative process of qualitative synthesis. This process was guided by principles of person centredness and an a priori decision guide. RESULTS: 168 papers met the eligibility criteria; 1669 individual learning outcomes were extracted and refined using qualitative synthesis. A final refined set of 205 learning outcomes were constructed and are presented in 4 domains that include: (1) knowledge (eg, describe the importance of communication in healthcare), (2) content skills (eg, explore a healthcare seeker's motivation for seeking healthcare),( 3) process skills (eg, respond promptly to a communication partner's questions) and (4) perceptual skills (eg, reflect on own ways of expressing emotion). CONCLUSIONS: This study provides a list of 205 communication skills learning outcomes that provide a foundation for further research and educational design in communication education across the health professions. Areas for future investigation include greater patient involvement in communication skills education design and further identification of learning outcomes that target knowledge and perceptual skills. This work may also prompt educators to be cognisant of the quality and scope of the learning outcomes they design and their application as goals for learning.
TROG 15.03 phase II clinical trial of Focal Ablative STereotactic Radiosurgery for Cancers of the Kidney - FASTRACK II
BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is a non-invasive alternative to surgery to control primary renal cell cancer (RCC) in patients that are medically inoperable or at high-risk of post-surgical dialysis. The objective of the FASTRACK II clinical trial is to investigate the efficacy of SABR for primary RCC. METHODS: FASTRACK II is a single arm, multi-institutional phase II study. Seventy patients will be recruited over 3 years and followed for a total of 5 years. Eligible patients must have a biopsy confirmed diagnosis of primary RCC with a single lesion within a kidney, have ECOG performance ≤2 and be medically inoperable, high risk or decline surgery. Radiotherapy treatment planning is undertaken using four dimensional CT scanning to incorporate the impact of respiratory motion. Treatment must be delivered using a conformal or intensity modulated technique including IMRT, VMAT, Cyberknife or Tomotherapy. The trial includes two alternate fractionation schedules based on tumour size: for tumours ≤4 cm in maximum diameter a single fraction of 26Gy is delivered; and for tumours > 4 cm in maximum diameter 42Gy in three fractions is delivered. The primary outcome of the study is to estimate the efficacy of SABR for primary RCC. Secondary objectives include estimating tolerability, characterising overall survival and cancer specific survival, estimating the distant failure rate, describing toxicity and renal function changes after SABR, and assessment of cost-effectiveness of SABR compared with current therapies. DISCUSSION: The present study design allows for multicentre prospective validation of the efficacy of SABR for primary RCC that has been observed from prior single institutional and retrospective series. The study also allows assessment of treatment related toxicity, overall survival, cancer specific survival, freedom from distant failure and renal function post therapy. TRIAL REGISTRATION: Clinicaltrials.gov NCT02613819 , registered Nov 25th 2015.
Clinical applications of 3D T2-weighted MRI in pelvic imaging
OBJECTIVE: The purpose of this article is to illustrate clinical applications of 3D T2-weighted MRI in pelvic imaging. We review technical considerations of 3D T2-weighted MRI with clinical examples. CONCLUSION: 3D T2-weighted MRI has been increasingly utilized for pelvic applications, including imaging of rectal cancer, prostate cancer, anorectal fistulas and the female pelvis. This relatively rapid technique offers good soft-tissue contrast of the pelvic organs, with potential for more widespread clinical use.
Current role of salvage robotic-assisted laparoscopic prostatectomy.
(Springer Science and Business Media LLC, 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.
MRI and suspected acute pyelonephritis in children: comparison of diffusion-weighted imaging with gadolinium-enhanced T1-weighted imaging
OBJECTIVES: To evaluate the performance of diffusion-weighted imaging (DWI) against the reference standard of gadolinium-enhanced T1-weighted imaging (Gd-T1-WI) in children. METHODS: Thirty-nine consecutive patients (mean age 5.7 years) with suspected acute pyelonephritis underwent magnetic resonance imaging (MRI) including DWI and (the reference standard) Gd-T1-WI. Each study was read in double-blinded fashion by two radiologists. Each kidney was graded as normal or abnormal. Sensitivity and specificity of DWI were computed. Agreement between sequences and interobserver reproducibility were calculated (Cohen κ statistic and the McNemar tests). RESULTS: Thirty-two kidneys (41 %) had hypo-enhancing areas on Gd-T1-W images. The sensitivity and specificity of DWI were 100 % (32/32) and 93.5 % (43/46). DWI demonstrated excellent agreement (κ = 0.92,) with Gd-T1-W, with no significant difference (P = 0.25) in detection of abnormal lesions. Interobserver reproducibility was excellent with DWI (κ = 0.79). CONCLUSION: DWI enabled similar detection of abnormal areas to Gd-T1-WI and may provide an injection-free means of evaluation of acute pyelonephritis. KEY POINTS: • Diffusion weighted magnetic resonance imaging (DWI) can confirm acute pyelonepritis. • DWI provided comparable results to gadolinium enhanced T1-W MRI in acute pyelonepritis. • Contrast medium injection could be avoided for diagnosing acute pyelonephritis by MRI. • MRI with T2-WI and DWI provide a fast and comprehensive diagnostic tool.