Ian D McGilvray

University Health Network, Toronto, Ontario, Canada

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Publications (165)770.58 Total impact


  • No preview · Article · Jan 2016 · American Journal of Transplantation

  • No preview · Article · Jan 2016 · American Journal of Transplantation

  • No preview · Article · Jan 2016 · American Journal of Transplantation

  • No preview · Article · Jan 2016 · American Journal of Transplantation
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    ABSTRACT: The outcome of triple therapy with protease inhibitors (PI) depends on the intrinsic response to interferon. Interferon-stimulated gene (ISG) expression differs by cell type in the liver and is a strong predictor of interferon responsiveness. Patients who respond well to interferon have low/absent ISG expression in hepatocytes but significant ISG expression in macrophages. Nonresponders (NRs) show the opposite pattern. We aimed to determine the association between cell-type-specific ISG staining and treatment outcome with PI-based triple therapy. Liver biopsy tissue from consecutive patients treated with boceprevir or telaprevir with peginterferon and ribavirin was stained for myxovirus A (MxA). Staining was scored 0-3 in macrophages (M-MxA) and hepatocytes (H-MxA), and IL28B genotyping was performed. Of 56 patients included 41 achieved SVR (73%) (sustained virological response), 2 (4%) relapsed, 10 (18%) were NRs, and 3 (5%) were lost to follow-up. Median M-MxA staining was stronger and H-MxA staining was weaker in patients who achieved SVR. MxA staining correlated with IL28B genotype and with the HCV RNA decline during lead-in phase. However, unlike with dual therapy, the negative predictive value (NPV) of absent or weak M-MxA staining was poor (42%), while the positive predictive value improved (93%). Although by multivariable logistic regression M-MxA staining was significantly associated with SVR (OR 4.35, 1.32-14.28, P = 0.012), the predictive ability was inadequate to withhold therapy. The interaction between macrophages and hepatocytes plays a critical role in interferon responsiveness; however, the addition of a PI at least partially overcomes the interferon nonresponse phenotype making the predictive ability of ISG staining less clinically useful.
    No preview · Article · Dec 2015 · Journal of Viral Hepatitis
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    ABSTRACT: Pancreas transplant candidate are at very high risk of coronary vascular disease. We hypothesized that the requirement for preoperative coronary intervention (PCI) may be associated with an adverse impact on short- and long-term outcomes. Retrospective analysis of 366 consecutive primary pancreas transplants was undertaken. Outcomes were compared between recipients who had undergone PCI (n=48) and those who had not (n=318). In 48% (23/48) of instances the PCI was initiated by the transplant cardiology evaluation. The recipients undergoing PCI were older than those not undergoing PCI (47.6yrs vs. 41.9yrs respectively, p<0.0001). Although not statistically significant, there was a higher rate of postoperative major cardiovascular events (MCVE) in the PCI group (10.4%) compared to those not undergoing PCI (4.7%) although this was not statistically significant (RR [95%CI]: 2.0 [0.90-4.5]; p=0.17). In the long term, there were no differences in the rate of death with graft function (p=0.77) or rejection (p=0.17). There were no statistically significant differences between the groups with respect to patient (p=0.54), kidney (p=0.76), or pancreas (p=0.63) graft survival. PCI is not a risk factor for short-term perioperative events, and long-term transplant outcomes are equivalent to patients not requiring PCI. PCI, by itself should not be considered a contraindication for pancreas transplantation, but should raise awareness of perioperative risk. This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2015 · Clinical Transplantation
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    ABSTRACT: Purpose: The purpose of this case report is to describe a patient with a preoperative complex pain syndrome who underwent liver transplantation and was able to reduce his opioid consumption significantly following the initiation of treatment with medical cannabis. Clinical features: A 57-yr-old male with a history of hepatitis C cirrhosis underwent liver transplantation. Preoperatively, he was taking hydromorphone 2-8 mg⋅day(-1) for chronic abdominal pain. Postoperatively, he was given intravenous patient-controlled analgesia through which he received hydromorphone 30 mg⋅day(-1). Our multidisciplinary Transitional Pain Service was involved with managing his moderate to severe acute postsurgical pain in hospital and continued with weaning him from opioid medications after discharge. It was difficult to wean the patient from opioids, and he was subsequently given medical cannabis at six weeks postoperatively with remarkable effect. By the fifth postoperative month, his use of opioids had tapered to 6 mg⋅day(-1) of hydromorphone, and his functional status was excellent on this regimen. Conclusion: Reductions in opioid consumption were achieved with the administration of medical cannabis in a patient with acute postoperative pain superimposed on a chronic pain syndrome and receiving high doses of opioids. Concurrent benefits of initiating medical cannabis may include improvements in pain profile and functional status along with reductions in opioid-related side effects. This highlights the potential for medical cannabis as an adjunct medication for weaning patients from opioid use.
    Full-text · Article · Oct 2015 · Canadian Anaesthetists? Society Journal
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    ABSTRACT: Background. Patients with acute and chronic liver disease often require admission to intensive care unit (ICU) and mechanical ventilation support before liver transplantation (LT). Rapid disease progression and high mortality on LT waiting lists makes live donor LT (LDLT) an attractive option for this patient population. Methods. During 2000 to 2011, all ICU-bound and mechanically ventilated patients receiving an LDLT (n = 7) were compared to patients receiving a deceased donor LT (DDLT) (n = 38). Results. Both groups were comparable regarding length of pretransplant ICU stay (DDLT: 2 [1-31] days vs LDLT: 2 [1-8] days; P = 0.2), days under mechanical ventilation (DDLT: 2 [1-31] days vs LDLT: 2 [1-5] days; P = 0.2), pretransplant dialysis (DDLT: 45% vs LDLT: 43%; P = 1) and model for end-stage liver disease score (DDLT: 33 ± 8 vs LDLT: 33 ± 10; P = 0.911). Live donors median evaluation time was 24 hours (18-561 hours). As expected, median time on waiting list was significantly lower in the LDLT group (DDLT: 13 [0-1704] days vs LDLT: 10 [1-33] days; P = 0.008). Incidence of postoperative complications was numerically, albeit not significantly higher in the DDLT versus LDLT (68% vs 29%; P = 0.08). No difference was detected between LDLT and DDLT patients regarding 1-year (DDLT: 76% vs LDLT: 85%), 3-year (DDLT: 68% vs LDLT: 85%), and 5-year (DDLT: 68% vs LDLT: 85%) graft and patient survivals (P = 0.41). No severe donor complication occurred after live donation. Conclusions. The LDLT may provide a faster access to transplantation and therefore, offers an alternative treatment option for critically ill patients requiring ICU care and mechanical ventilation support at the time of transplantation.
    Full-text · Article · Sep 2015
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    ABSTRACT: Heme Oxygenase-1 and its product biliverdin/bilirubin have been demonstrated to protect against ischemia/reperfusion injury (IRI). We investigated if increased pre-operative bilirubin values of transplant recipients decrease IRI. Pre-operative bilirubin levels of live-donor liver recipients were correlated to post-operative liver transaminase as marker of IRI. Additionally, two recipient groups with pre-transplant bilirubin levels >24μmol/l (n=348) and ≤24μmol/l (n=118) were compared. Post-transplant liver function, complications, length of hospital stay, and patient and graft survival were assessed. Pre-operative bilirubin levels were negatively correlated to the post-operative increase in transaminases suggesting a protective effect against IRI. The maximal rise of ALT after transplantation in high vs low bilirubin patients was 288 [-210-2457] U/L vs 375 [-11-2102] U/L, P=0.006. Bilirubin remained a significant determining factor in a multivariate linear regression analysis. The MELD score and its individual components as marker of severity of chronic liver disease were significantly higher in the high vs low bilirubin group (P<0.001). Despite this, overall complication rate (21.0% vs 21.2%, P=0.88), hospital stay (13 [4-260] vs 14 [6-313] days, P=0.93), and 1-year graft survival (90.8% vs 89.0%, P=0.62) were similar in both groups. High bilirubin levels of liver recipients before live donor transplantation is associated with decreased post-operative IRI. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Full-text · Article · Jul 2015 · Transplant International
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    ABSTRACT: To compare the outcome of adult live donor liver transplantation (LDLT) with grafts from older versus younger donors. Using older donor grafts for adult LDLT may help expand the donor pool. However, the risks of LDLT with older donors remain controversial, and many centers are reluctant to use live donors aged 45 years or older for adult LDLT. Outcomes of patients receiving a LDLT graft from donors aged 50 years or older (n = 91) were compared with those receiving a live donor graft from donors younger than 50 years (n = 378). Incidences of biliary (LDLT <50: 24% vs LDLT ≥50: 23%; P = 0.89) and major complications (LDLT <50: 24% vs LDLT ≥50: 24%; P = 1) were similar between both groups of recipients. No difference was observed in 30-day recipient mortality (LDLT <50: 3% vs LDLT ≥50: 0%; P = 0.13). The 1- (90% vs 90%), 5- (82% vs 73%), and 10- (71% vs 58%) year graft survival was statistically similar between both groups (P = 0.075). Likewise, patient survival after 1- (92% vs 96%), 5- (83% vs 79%), and 10- (76% vs 69%) years was also similar (P = 0.686). Overall, donors rate of major complications (Dindo-Clavien ≥3b) within 30 days was low (n = 2.3%) and not different in older versus younger donors (P = 1). Donor median hospital stay in both groups was identical [LDLT <50: 6 (4-17) vs LDLT ≥50: 6 (4-14) days; P = 0.65]. No donor death occurred and all donors had full recovery and returned to baseline activity. Right lobe LDLT with donors aged 50 years or older results in acceptable recipient outcome without increased donor morbidity or mortality. Potential live donors should not be declined on the basis of age alone.
    Full-text · Conference Paper · Jun 2015
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    Bing Liu · Ian McGilvray · Limin Chen
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    ABSTRACT: Pegylated interferon-α and ribavirin (PEG-IFN/RBV) is widely used to treat chronic hepatitis C virus infection with notorious adverse reactions since the broad expression of IFN-α receptors on all nucleated cells. Accordingly, a Type III IFN with restricted receptors distribution is much safer as an alternative for HCV therapy. In addition, single nucleotide polymorphisms (SNPs) near the human IFN-λ3 gene, IL-28B, correlate strongly with the ability to achieve a sustained virological response (SVR) to therapy with pegylated IFN-α plus ribavirin in patients infected with chronic hepatitis C. Furthermore, we also discuss the most recent findings: IFN-λ4 predicts treatment outcomes of HCV infection. In consideration of the apparent limitations of current HCV therapy, especially high failure rate and universal side effects, prediction of treatment outcomes prior to the initiation of treatment and developing new alternative drugs are two important goals in HCV research.
    Full-text · Article · Jun 2015 · Gastroenterology Research and Practice
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    ABSTRACT: Simkania negevensis infection has been hypothesized to play a role in lung transplant rejection. The incidence of S. negevensis infection and its association with acute cellular rejection (ACR) were determined in a prospective cohort study of 78 lung transplant recipients (LTRs) in Toronto, Canada and Pittsburgh, USA from July 2007 to January 2010. S. negevensis testing was detected by quantitative polymerase chain reaction (PCR) on bronchoalveolar lavage fluid. The relationship between S. negevensis and ACR was examined using Cox proportional hazards models and generalized linear and latent mixed models. Cumulative incidence estimates for time-to-ACR in S. negevensis PCR-positive vs. PCR-negative LTRs were 52.7% vs. 31.1% at 6 months and 68.9% vs. 44.6% at 1 year, respectively. Although not statistically significant, there was a trend towards a higher risk of ACR among S. negevensis PCR-positive vs. PCR-negative LTRs in all statistical models. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    No preview · Article · May 2015 · Clinical Transplantation
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    ABSTRACT: Donor-specific antibodies (DSA) have been associated with increased rejection and lower kidney transplant survival. The impact of DSA on pancreas transplant outcomes in patients with negative T-cell cytotoxicity cross-matches remains unclear. We performed a retrospective analysis of DSA in 171 (69 PAK and 102 SPK) consecutive pancreas transplants from a single center since January 2009, when routine DSA examination using luminex single antigen assays began. Pre-transplant DSA (Pre-DSA) was detected in 36 (21%) recipients, and was more prevalent in PAK than SPK recipients (32% vs. 16%, p=0.02). All patients with pre-DSA had a negative CDC or flow cross-match and were treated routinely with IVIG during surgery. De novo DSA developed in 44 (33%) recipients during follow-up (33% in PAK vs. 32% in SPK, p=0.89). Kidney and/or pancreas rejection occurred in 25% (42), and most 64% (22) of these occurred in the presence of DSA (p=0.012). The presence of DSA also increased the risk of having > 1 rejection episode (p=0.004). DSA became undetectable in 21 (26%) patients: in 5 patients, the same DSA reappeared in 3 and new DSA developed in 2 (reappearance of DSA was associated with an acute rejection episode in 4 of 5 recipients); in 16 patients in whom DSA remained undetectable, 5 had a subsequent rejection episode with no evidence of new DSA. Pancreas graft survival among those with and without pre-transplant DSA was 92% and 88% at 1-year and 80% and 88% at 3-years (p=0.26). Similarly, pancreas graft survival among those with and without de novo DSA was 86% and 91% at 1-year and 81% and 89% at 3-years (p=0.14). 24 graft failures occurred during follow-up time (9 in the DSA- and 15 in the DSA+), only 6 were due to rejection (3 in the DSA- and 3 in the DSA+; p=0.64). Pre-transplant DSA also did not increase the risk graft loss from rejection (13% in Pre-DSA- and 28% of Pre-DSA+; p=0.57). Conclusion: Pre-transplant DSA with a negative cross-match and post-transplant de novo DSA are risk factors for rejection, but have little impact on early pancreas transplant survival.
    No preview · Conference Paper · May 2015
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    ABSTRACT: Due to a persistent discrepancy between the demand for liver transplantation and the supply of deceased donor organs, there is an interest in increasing live donation rates at centres trained in this method of transplantation. We examined a large socioeconomically heterogeneous cohort of patients listed for liver transplantation to identify recipient factors associated with live donation. We retrospectively reviewed 491 consecutive patients who were listed for liver transplantation at our centre over a 24 month period. Demographic, medical, and socioeconomic data were extracted from electronic records and compared between those who had a potential live donor volunteer for assessment, and those who did not. 245 patients (50%) had at least one potential live donor volunteer for assessment. Multivariate logistic regression analysis identified that patients with a live donor were more likely to have Child-Pugh C disease (OR 2.44, p=0.019), and less likely to be older (OR 0.96, p=0.002), single (OR 0.34, p=0.006), divorced (OR 0.53, p=0.03), immigrants (OR 0.38, p=0.049) or from the lowest income quintile (OR 0.44, p=0.016). This analysis has identified several factors associated with access to live donation. More research is warranted to define and overcome barriers to live donor liver transplant through targeted interventions in underrepresented populations. This article is protected by copyright. All rights reserved. © 2015 American Association for the Study of Liver Diseases.
    No preview · Article · Apr 2015 · Liver Transplantation
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    ABSTRACT: Long-term biliary complications after living donor liver transplantation (LDLT) are not well described in the literature. This study was undertaken to determine the long-term impact of biliary complications after adult right-lobe LDLT. This retrospective review analyzed an 11-year experience of 344 consecutive right-lobe LDLT with at least 2 years of follow-up. Biliary leaks occurred in 50 patients (14.5%), and strictures occurred in 67 patients (19.5%). Cumulative biliary complication rates at 1, 2, 5, and 10 years were 29%, 32%, 36%, and 37%, respectively. Most early biliary leaks were treated with surgical drainage (N = 29, 62%). Most biliary strictures were treated first with endoscopic retrograde cholangiography (42%). There was no association between biliary strictures and the number of ducts (hazard ratio [HR] 1.017 [0.65-1.592]), p = 0.94), but freedom from biliary stricture was associated with a more recent era (2006-2010) (HR 0.457 [0.247-0.845], p = 0.01). Long-term graft survival did not differ between those who had or did not have biliary complications (66% versus 67% at 10 years). Biliary strictures are common after LDLT but may decline with a center's experience. With careful follow-up, they can be successfully treated, with excellent long-term graft survival rates. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    No preview · Article · Mar 2015 · Clinical Transplantation
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    ABSTRACT: We report the outcome of live donor liver transplantation (LDLT) for patients suffering from acute liver failure (ALF). From 2006 to 2013, all patients with ALF who received a LDLT (n = 7) at our institution were compared to all ALF patients receiving a deceased donor liver transplantation (DDLT = 26). Groups were comparable regarding pretransplant ICU stay (DDLT: 1 [0-7] vs. LDLT: 1 days [0-10]; p = 0.38), mechanical ventilation support (DDLT: 69% vs. LDLT: 57%; p = 0.66), inotropic drug requirement (DDLT: 27% vs. LDLT: 43%; p = 0.64) and dialysis (DDLT: 2 vs. LDLT: 0 patients; p = 1). Median evaluation time for live donors was 24 h (18-72 h). LDLT versus DDLT had similar incidence of overall postoperative complications (31% vs. 43%; p = 0.66). No difference was detected between LDLT and DDLT patients regarding 1- (DDLT: 92% vs. LDLT: 86%), 3- (DDLT: 92% vs. LDLT: 86%), and 5- (DDLT: 92% vs. LDLT: 86%) year graft and patient survival (p = 0.63). No severe donor complication (Dindo-Clavien ≥3 b) occurred after live liver donation. ALF is a severe disease with high mortality on liver transplant waiting lists worldwide. Therefore, LDLT is an attractive option since live donor work-up can be expedited and liver transplantation can be performed within 24 h with excellent short- and long-term outcomes. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.
    Full-text · Article · Mar 2015 · American Journal of Transplantation
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    ABSTRACT: Background Pancreas-kidney transplantation with enteric drainage has become a standard treatment in diabetic patients with renal failure. Leaks of the graft duodenum (DL) remain a significant complication after transplantation. We studied incidence and predisposing factors of DLs in both simultaneous pancreas-kidney (SPK) and pancreas after kidney (PAK) transplantation.Method Between January 2002 and April 2013 284 pancreas transplantations were performed including 191 SPK (67.3%) and 93 PAK (32.7%). Patient data were analyzed for occurrence of DLs, risk factors, leak etiology, and graft survival.ResultsOf 18 DLs (incidence 6.3%), 12 (67%) occurred within the first 100 days after transplantation. Six grafts (33%) were rescued by duodenal segment resection. Risk factors for a DL were: PAK transplantation sequence (odds ratio 3.526, p=0.008) and preoperative immunosuppression (odds ratio 3.328, p=0.012). In the SPK subgroup, postoperative peak amylase as marker of preservation/reperfusion injury and recipient pre-transplantation cardiovascular interventions as marker of atherosclerosis severity were associated with an increased incidence of DLs. CMV mismatch constellations showed an increased incidence in the SPK subgroup, however without significance probability.Conclusion Long-term immunosuppression in PAK transplantation is a major risk factor for DLs. Early surgical revision offers the chance of graft rescue.This article is protected by copyright. All rights reserved.
    Full-text · Article · Feb 2015 · Transplant International
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    ABSTRACT: Data regarding transplantation outcomes in ventilated intensive care unit (ICU)-dependent patients with end-stage liver disease (ESLD) are conflicting. This single-center cohort study investigated the outcomes of patients with ESLD who were intubated with mechanical support before liver transplantation (LT). The ICU plus intubation group consisted of 42 patients with decompensated cirrhosis and mechanical ventilation before transplantation. LT was considered for intubated ICU patients if the fraction of inspired oxygen was ≤40% with a positive end-expiratory pressure ≤ 10, low pressor requirements, and the absence of an active infection. Intubated ICU patients were compared to 80 patients requiring ICU admission before transplantation without intubation and to 126 matched non-ICU-bound patients. Patients requiring ICU care with intubation and ICU care alone had more severe postoperative complications than non-ICU-bound patients. Intubation before transplantation was associated with more postoperative pneumonias (15% in intubated ICU transplant candidates, 5% in ICU-bound but not intubated patients, and 3% in control group patients; P = 0.02). Parameters of reperfusion injury and renal function on postoperative day (POD) 2 and POD 7 were similar in all groups. Bilirubin levels were higher in the ICU plus intubation group at POD 2 and POD 7 after transplantation but were normalized in all groups within 3 months. The ICU plus intubation group versus the ICU-only group and the non-ICU group had decreased 1-, 3-, and 5-year graft survival (81% versus 84% versus 92%, 76% versus 78% versus 87%, and 71% versus 77% versus 84%, respectively; P = 0.19), but statistical significance was not reached. A Glasgow coma scale score of <7 versus >7 before transplantation was associated with high postoperative mortality in ICU-bound patients requiring intubation (38% versus 23%; P = 0.01). In conclusion, ICU admission and mechanical ventilation should not be considered contraindications for LT. With careful patient selection, acceptable long-term outcomes can be achieved despite increased postoperative complications. This article is protected by copyright. All rights reserved. © 2015 American Association for the Study of Liver Diseases.
    Full-text · Article · Jan 2015 · Liver Transplantation
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    ABSTRACT: Unlabelled: In nonalcoholic fatty liver disease, hepatic gene expression and fatty acid (FA) composition have been reported independently, but a comprehensive gene expression profiling in relation to FA composition is lacking. The aim was to assess this relationship. In a cross-sectional study, hepatic gene expression (Illumina Microarray) was first compared among 20 patients with simple steatosis (SS), 19 with nonalcoholic steatohepatitis (NASH), and 24 healthy controls. The FA composition in hepatic total lipids was compared between SS and NASH, and associations between gene expression and FAs were examined. Gene expression differed mainly between healthy controls and patients (SS and NASH), including genes related to unsaturated FA metabolism. Twenty-two genes were differentially expressed between NASH and SS; most of them correlated with disease severity and related more to cancer progression than to lipid metabolism. Biologically active long-chain polyunsaturated FAs (PUFAs; eicosapentaenoic acid + docosahexaenoic acid, arachidonic acid) in hepatic total lipids were lower in NASH than in SS. This may be related to overexpression of FADS1, FADS2, and PNPLA3. The degree and direction of correlations between PUFAs and gene expression were different among SS and NASH, which may suggest that low PUFA content in NASH modulates gene expression in a different way compared with SS or, alternatively, that gene expression influences PUFA content differently depending on disease severity (SS versus NASH). Conclusion: Well-defined subjects with either healthy liver, SS, or NASH showed distinct hepatic gene expression profiles including genes involved in unsaturated FA metabolism. In patients with NASH, hepatic PUFAs were lower and associations with gene expression were different compared to SS.
    No preview · Article · Jan 2015 · Hepatology

  • No preview · Conference Paper · Jan 2015

Publication Stats

3k Citations
770.58 Total Impact Points

Institutions

  • 2010-2015
    • University Health Network
      • • Department of Surgery
      • • Department of General Surgery
      Toronto, Ontario, Canada
  • 2004-2015
    • UHN: Toronto General Hospital
      Toronto, Ontario, Canada
  • 1997-2015
    • University of Toronto
      • • Department of Surgery
      • • Division of General Surgery
      • • Institute of Medical Sciences
      • • Department of Medicine
      Toronto, Ontario, Canada