Ian D McGilvray

University of Toronto, Toronto, Ontario, Canada

Are you Ian D McGilvray?

Claim your profile

Publications (129)530.44 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: To identify prognostic factors after hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). We retrospectively reviewed the combined experience at Toronto General Hospital and Hospital Vall d'Hebron managing HCC recurrence after LT (n = 121) between 2000 and 2012. We analyzed prognostic factors by uni- and multi-variate analysis. Median follow-up from LT was 29.5 (range 2-129.4) months. Median follow-up from HCC recurrence was 12.2 (range 0.1-112.5) months. At recurrence, 31.4 % were treated with curative-intent treatments (surgery or ablation), 42.1 % received palliative treatment, and 26.4 % received best supportive care. The 1-, 3-, and 5-year survivals, respectively, after HCC recurrence were 75, 60, and 31 %, vs. 60, 19, and 12 %, vs. 52, 4, and 5 % (p < 0.001). By multivariate analysis, not being amenable to a curative-intent treatment [hazard ratio (HR) 4.7, 95 % confidence interval (CI) 2.7-8.3, p < 0.001], α-fetoprotein of ≥100 ng/mL at the time of HCC recurrence (HR 2.1, 95 % CI 1.3-2.3, p = 0.002) and early recurrence (<12 months) after LT (HR 1.6, 95 % CI 1.1-2.5, p = 0.03) were found to be poor prognosis factors. A prognostic score was devised on the basis of these three independent variables. Patients were divided into three groups, as follows: good prognosis, 0 points (n = 22); moderate prognosis, 1 or 2 points (n = 84); and poor prognosis, 3 points (n = 15). The 1-, 3-, and 5-year actuarial survival for each group was 91, 50, and 50 %, vs. 52, 7, and 2 %, vs. 13, 0, and 0 %, respectively (p < 0.001). Patients with HCC recurrence after transplant amenable to curative-intent treatments can experience significant long-term survival (~50 % at 5 years), so aggressive management should be offered. Poor prognosis factors after recurrence are not being amenable to a curative-intent treatment, α-fetoprotein of ≥100 ng/mL, and early (<1 year) recurrence after LT.
    Annals of Surgical Oncology 12/2014; · 3.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Liver transplantation from donation-after-circulatory death (DCD) donors has been associated with a high rate of ischemic-type biliary strictures (ITBS) and inferior graft survival. To investigate the impact of intraoperative tissue plasminogen activator (tPA) on outcomes following DCD liver transplantation (DCD-LT), we conducted a retrospective analysis of DCD liver transplants at the Toronto General Hospital (TGH) and Ochsner Medical Center (OMC). Between 2009 and 2013, 85 DCD liver transplants were performed with intraoperative tPA injection (N=30 TGH, 55 OMC) and compared to 33 DCD liver transplants without tPA. Donor and recipient characteristics were similar between both groups. There was no significant difference in intra-operative packed red blood cell transfusion requirement (3.2 ± 3.4 vs 3.1 ± 2.3, P=0.74). Overall, biliary strictures occurred less commonly in the tPA treated group (16.5% vs 33.3%, P=0.07) with a much lower rate of diffuse intra-hepatic strictures (3.5% vs 21.2%, P=0.005). After 1- and 3-years the tPA vs non tPA group had superior patient survival (97.6% vs 87.0% and 92.7% vs 79.7%; P=0.016) and graft survival (96.4% vs 69.7% and 90.2% vs 63.6%; p<0.001). In conclusion, tPA injection into the hepatic artery during DCD liver transplantation reduces ITBS and improves graft and patient survival without increasing the risk for bleeding. This article is protected by copyright. All rights reserved.
    Liver Transplantation 12/2014; · 3.79 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: IntroductionOncological implications of laparoscopic resection in primary hepatic malignancy are not well defined. Laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) in comparison to an open liver resection (OLR) in peri-operative and long-term oncological outcomes are described from a single North American institution.Methods From 2006 to 2013, all forty-three LLR patients for HCC were evaluated. Each patient was matched to two OLR patients for age at operation, maximal tumour size and tumour number.ResultsWhen compared with OLR, LLR had a lower severity of complication (0% versus 27%, P = 0.050) and lower 30-day readmission rate (2.3% versus 18.6%, P = 0.010). The length of stay (LOS) was shorter in LLR patients (5 versus 7 days, P < 0.001) and the estimated blood loss was also lower in LLR (300 versus 700 ml, P = 0.004). Admission to intensive care unit (ICU), emergency room (ER) visits and complication rates were similar. Overall, recurrence-free and intra-hepatic recurrence-free survival were comparable between LLR and OLR.DiscussionLLR confers the widely-accepted benefits of laparoscopic surgery, namely severity of complication, 30-day readmission rate, LOS and blood loss. Further studies are required to examine intra- and extra-hepatic recurrence after LLR. LLR for HCC should be considered for appropriately selected patients in centres with requisite volume and expertise.
    HPB 11/2014; · 2.05 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Outcomes of living versus deceased donor liver transplantation in patients with chronic liver disease and hepatorenal syndrome (HRS) was compared using a matched pair study design. Thirty patients with HRS receiving a live donor liver transplantation (LDLT) and 90 HRS patients receiving a full graft deceased donor liver transplantation (DDLT) were compared. LDLT versus DDLT of patients with HRS was associated with decreased peak aspartate aminotransferase levels (339 ± 214 vs. 935 ± 1253 U/L; p = 0.0001), and similar 7-day bilirubin (8.42 ± 7.89 vs. 6.95 ± 7.13 mg/dL; p = 0.35), and international normalized ratio levels (1.93 ± 0.62 vs. 1.78 ± 0.78; p = 0.314). LDLT vs. DDLT had a decreased intensive care unit (2 [1–39] vs. 4 [0–93] days; p = 0.004), and hospital stay (17 [4–313] vs. 26 [0–126] days; p = 0.016) and a similar incidence of overall postoperative complications (20% vs. 27%; p = 0.62). No difference was detected between LDLT and DDLT patients regarding graft survival at 1 (80% vs. 82%), at 3 (69% vs. 76%) and 5 years (65% vs. 76%) (p = 0.63), as well as patient survival at 1 (83% vs. 82%), 3 (72% vs. 77%) and 5 years (72% vs. 77%) (p = 0.93). The incidence of chronic kidney disease post-LT (10% vs. 6%; p = 0.4) was similar between both groups. LDLT results in identical long-term outcome when compared with DDLT in patients with HRS.
    American Journal of Transplantation 10/2014; · 6.19 Impact Factor
  • Transplantation 09/2014; · 3.78 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Pancreas transplant recipient obesity has been associated with increased risk of peri-operative complications, graft failure and death. Cardiovascular co-morbidity is the key risk for the obese candidate. Methods We compared the outcomes of pancreas transplant recipients with body mass index (BMI) >30kg/m 2(n=60) to those with BMI <30kg/m 2 (n=308) between 1996 and 2013. All patients were assessed by a cardiologist prior to, and annually after transplantation. There was a low threshold for cardiovascular intervention both pre- and post-operatively. Results There were no differences in the pre-transplant recipient or donor characteristics apart from BMI. There was an increased incidence of surgical site infections in the BMI>30 group compared to the BMI<30 group (12% vs 3.2% respectively; p=0.03). Despite this, the median length of hospital stay was shorter in the BMI>30 group (9 days vs. 10 days in the BMI<30 group; p=0.02). There were no other significant differences in the complications in the first three post-operative months. The BMI>30 group were more likely to suffer a rejection episode (43% vs 29%; p=0.03) compared to the BMI<30 group, and the median time to first rejection was also shorter (1 vs. 6 months; p=0.04) in the BMI>30 group. There was no difference in the rate of patient survival, pancreas or kidney graft survival or difference in graft function between the two groups. Conclusion Although there was an increased risk of rejection and wound infection in the obese group, there was no difference in the rate of patient or graft survival. This finding, when compared with previous reports, may be related to stringent recipient selection and post-transplant care particularly with respect to cardiovascular disease.
    The World Transplant Congress, San Francisco; 06/2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background:Steroids are known to be associated with several adverse metabolic and cardiovascular (CV) side effects. Given the increase in risk of CV disease in patients with diabetes, pancreas transplant recipients may benefit from steroid withdrawal after transplant. However, the impact of steroid withdrawal on acute rejection and graft survival is controversial. Methods:A retrospective cohort study was conducted at our institution. Simultaneous pancreas-kidney (SPK) and pancreas after kidney (PAK) transplant recipients between Feb 1997 and May 2005 were included in the study and followed until April 2010. Exposure to steroids was modeled as a time-varying exposure. Cox proportional hazards models were used to examine the relation between steroid withdrawal and acute rejection as well as graft survival. Traditional CV risk factors were evaluated using parametric and non-parametric methods as appropriate. Results:141 SPK and PAK transplant recipients were included in the cohort, of which 42 underwent steroid withdrawal. 41 patients experienced acute rejection, with 17 episodes occurring in the steroid withdrawal group (36%) compared to 24 occurring in the non-steroid withdrawal group (25%). Withdrawal of steroids was associated with an increased risk of acute rejection (HR 4.74, [95% CI 1.9, 11.8], p value 0.001) but was not associated with an increased risk of graft failure (HR 1.42, [95% CI 0.64, 3.16], p value 0.4). There were no clinically significant differences in lipid profile, blood pressure and glucose tolerance at 1 year after steroid withdrawal. Conclusion:In a cohort of SPK and PAK transplant recipients at our institution, steroid withdrawal was associated with a significantly increased risk of acute rejection but no clinically meaningful changes in traditional CV risk factors. Further study is needed to determine whether steroid withdrawal may be beneficial in a subgroup of carefully selected patients.
    The World Transplant Congress, San Francisco, California; 06/2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Evaluation for pancreas transplantation in this centre requires routine cardiovascular consultation with a low threshold for intervention. We hypothesized that the requirement for pre-operative cardiovascular intervention (PCVI) may be associated with an adverse impact on outcome after pancreas transplantation. Methods Retrospective analysis of a prospectively collected database was undertaken, including 366 consecutive primary pancreas transplants performed between 1995 and 2013. Outcomes including postoperative complications, rejection, as well as graft and patient survival were compared between recipients who had undergone PCVI (n=48) and those who had not (n=318). Results The recipients undergoing PCVI were older than those not undergoing PCVI (47.6yrs (+/- 7.9) vs. 41.9yrs (+/- 7.6) respectively, p<0.0001) and the cohort included more males (73% vs. 62% respectively, p=0.02). There was a higher rate of post-operative cardiovascular events or interventions in the PCVI group (11.9% vs. 2.2% respectively, p=0.02). In the long term, there were no difference 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. Conclusion PCVI is a risk factor for short term peri-operative cardiovascular events. However, the long-term transplant outcomes are equivalent to patients not requiring PCVI. The requirement for PCVI by itself should not be considered a contraindication for pancreas transplantation, but should raise awareness of increased peri-operative risk.
    The World Transplant Congress, San Francisco, California; 06/2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Although commonly applied in many centers, there are limited data to validate age alone as a selection criterion for pancreas transplantation. We analyzed the impact of recipient age ( ≥55yrs) on outcome of pancreas transplantation. Methods Retrospective analysis of a prospectively collected database was undertaken, including 382 consecutive pancreas transplants performed between 1995 and 2013. Outcomes including postoperative complications, rejection, as well as graft and patient survival were compared between recipients ≥55years (n=30) and <55 yrs (n=352). Results The recipients ≥55years had a significantly higher rate of pre-operative cardiac intervention (46% vs. 13%, p=<0.001) than those <55years. However, there were no differences in the incidence of infectious and non-infectious post-operative complications between the groups. The rate of rejection in the first three months after transplant of recipients ≥55yrs was significantly lower (13% vs. 33%, p=0.02) than recipients <55years. There were no differences in kidney or pancreas graft function. There were no statistically significant differences between the groups with respect to patient (p=0.25), kidney (p=0.71), or pancreas (p=0.14) graft survival. Conclusion Pancreas transplantation in carefully selected recipients ≥55yrs of age can yield equivalent outcomes to transplantation of recipients of a younger age. Advanced recipient age by itself should not be considered a contraindication for pancreas transplantation.
    The World Transplant Congress, San Francisco, California; 06/2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: There is a paucity of contemporary data describing the results of pancreas retransplantation (PRT). As a measure of utility, we wished to determine whether PRT could produce equivalent short-term and long-term recipient outcomes to primary pancreas after kidney (PAK) transplantation.
    Transplantation 06/2014; · 3.78 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hepatitis B (HBV) and hepatitis C (HCV) are well-recognized risk factors for hepatocellular carcinoma (HCC). The characteristics and clinical outcomes of HCC arising from these conditions may differ. This study was conducted to compare the outcomes of HCC associated with HBV and HCV after liver resection. Of 386 liver resections for HCC performed between July 1992 and April 2011, 181 patients had HBV and 74 patients had HCV. Patients with HBV/HCV coinfections (n = 20), non-HBV/HCV etiology (n = 94), and postoperative death within 3 months (n = 17) were excluded. Patient, tumor characteristics, and perioperative and oncologic outcomes were compared between patients with HBV and HCV. The patients with HBV had better overall survival (OS) than patients with HCV (68 vs. 59 months, p = 0.03); however, there was no difference in recurrence-free survival (RFS) between the groups (44 vs. 45 months, p = 0.1). The factors predictive of OS based on multivariate analyses included: vascular invasion [p < 0.01, hazard ratio (HR) = 3.4], Child-Pugh Score (p < 0.01, HR = 4.8), and underlying liver disease (HCV vs HBV) (p = 0.01, HR = 1.9). Vascular invasion and tumor number (p < 0.01, HR = 2.3 and p < 0.01, HR = 2.1) were independent predictors of RFS. OS but not RFS after liver resection for HCC is better in patients with HBV than HCV. This survival advantage for HBV patients may be due to differences in tumor biology and outcomes after disease recurrence.
    Annals of Surgical Oncology 05/2014; · 3.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: SUMMARYHCV infection is a major world health problem, leading to both end-stage liver disease and primary liver cancer. Great efforts have been made in developing new therapies for HCV infection; however, combination therapy with pegylated IFN-α and ribavirin (pegIFN-RBV) remains the first choice of treatment for chronic HCV infection in most countries. The treatment response to pegIFN-RBV remains relatively low. Understanding the molecular mechanisms of persistent HCV infection and pegIFN-RBV resistance will suggest ways of improving the current standard of care and offers new antiviral therapies for both HCV and other viral infections. Recent data suggest that increased expression of hepatic IFN-stimulated genes (ISGs) before treatment is associated with treatment nonresponse in patients chronically infected with HCV. Although ISGs are generally antiviral in nature, in the case of HCV, the virus may exploit some of them to its benefit. This is not unique to HCV: Blockade of type I IFN signaling has been shown to control persistent LCMV infection. Thus, in certain viral infections, preactivation or overactivation of type I IFN signaling may contribute to viral persistence. In this review, we briefly summarize the findings from high-throughput gene expression profiling from patients chronically infected with HCV, then focus on a novel ubiquitin-like signaling pathway (ISG15/USP18) and its potential role in HCV persistence. Finally, the role of activation of endogenous type I IFN signaling in persistent HCV infection will be discussed in the context of recent studies indicating that blocking IFN signaling controls persistent LCMV infection. Copyright © 2014 John Wiley & Sons, Ltd.
    Reviews in Medical Virology 05/2014; · 5.76 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Combined pancreaticoduodenectomy (PD) and colonic resection may be necessary to achieve an R0 resection of peri-ampullary tumours. The aim of this study was to examine the morbidity and mortality associated with this procedure.MethodsA retrospective cohort study was performed comparing 607 patients who underwent a standard pancreaticoduodenectomy (S-PD) to 28 patients who had a concomitant colon resection and PD (PD-colon) over a 10-year period at an academic centre.ResultsPatients in the PD-colon group were more likely to have received neoadjuvant chemotherapy ± radiation (3/28, 11% versus 14/607, 2%, P = 0.024). Operative time was also longer (530 versus 410 min, P < 0.001) and they were more likely to have had portal vein resections (9/28, 32% versus 76/607, 13%, P = 0.007). There was no difference in the intra-operative blood loss, length of stay, or overall complication rates. The PD-colon group had a higher rate of severe post-operative bleeding (4/28, 11% versus 8/607, 1%, P = 0.002). The post-operative mortality rates for the PD-colon and PD groups were 2/28 (7%) and 8/607 (1%), respectively (P = 0.068).ConclusionsPD-colon has an acceptable risk of peri-operative morbidity compared with S-PD in well-selected patients.
    HPB 05/2014; · 2.05 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Coronaviruses express a de-ubiquitinating protein, the papain-like protease-2 (PLP2), that removes both ubiquitin and the ubiquitin-like Interferon (IFN) Stimulated Gene 15 (ISG15) protein from target proteins. ISG15 has antiviral activity against a number of viruses therefore, we examined the effect of ISG15 conjugation (ISGylation) in a model of acute viral hepatitis induced by the murine hepatitis virus (MHV)-3 coronavirus. Mice deficient in the ISG15 deconjugating enzyme, ubiquitin specific peptidase-18 (USP18), accumulate high levels of ISG15-conjugated proteins and are hypersensitive to type I IFN. Infecting USP18(-/-) mice with MHV-3 resulted in extended survival (8 ± 1.2 vs. 4 days), and improved liver histology, a decreased inflammatory response, and 1-2 logs lower viral titers compared to USP18(+/+) mice. The suppression of viral replication was not due to increased IFN, since infected USP18(-/-) mice had neither increased hepatic IFN-α, -β or -γ mRNA nor circulating protein. Instead, delayed MHV-3 replication coincided with high levels of cellular ISGylation. Decreasing ISGylation by knockdown of the ISG15 E1 enzyme, Ube1L, in primary USP18(+/+) and USP18(-/-) hepatocytes led to increased MHV-3 replication. Both in vitro and in vivo, increasing MHV-3 titers were coincident with increased PLP2 mRNA and decreased ISGylation over the course of infection. The pharmacologic inhibition of the PLP2 enzyme in vitro led to decreased MHV-3 replication. Overall, these results demonstrate the antiviral effect of ISGylation in an in vivo model of coronavirus-induced mouse hepatitis and illustrate that PLP2 manipulates the host innate immune response through the ISG15/USP18 pathway. There have been a number of serious worldwide pandemics due to widespread infections by Coronavirus. This virus (in its many forms) is difficult to treat, in part because it is very good at finding "holes" in the way that the host (the infected individual) tries to control and eliminate the virus. In this study we demonstrate that an important host viral defence - the ISG15 pathway - is only partially effective in controlling severe Coronavirus infection. Activation of the pathway is very good at suppressing viral production, but over time the virus overwhelms the host response and the effects of the ISG15 pathway. This data provides insight into the host-viral interactions during Coronavirus infection and suggests that the ISG15 pathway is a reasonable target for controlling severe Coronavirus infection, though the best treatment will likely involve multiple pathways and targets.
    Journal of Virology 03/2014; · 4.65 Impact Factor
  • Journal of the American College of Surgeons 02/2014; 218(2):306-7. · 4.45 Impact Factor
  • Source
    S Li, X Duan, Y Li, B Liu, I McGilvray, L Chen
    [Show abstract] [Hide abstract]
    ABSTRACT: Hepatitis C virus (HCV) infection is a major cause of chronic hepatitis and hepatocellular carcinoma. Currently pegylated interferon (IFN) combined with ribavirin remains the best therapeutic approach, although patients infected with HCV genotype I may benefit from adding protease inhibitors as 'triple therapy'. MicroRNAs (miRNAs) are endogenous small noncoding RNAs that regulate gene expression and have recently been shown to play an important role in human innate immune response and as an antiviral in chimpanzees. We studied the effect of miR-130a on the HCV replication. We found that miR-130a significantly inhibits HCV replication in both HCV replicon and J6-/JFH1-infected cells. Over expression of miR-130a upregulated the expression of type I IFN (IFN-α/IFN -β), ISG15, USP18 and MxA, which are involved in innate immune response and decreased expression of miR-122, a well-defined miRNA promoting HCV production. In conclusion, miR-130a inhibits HCV replication/production by restoring host innate immune responses and/or downregulating pro-HCV miR-122. miR-130a might be a potential drug target by modulating host innate immune responses to combat HCV infection.
    Journal of Viral Hepatitis 02/2014; 21(2):121-8. · 3.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Solid pseudopapillary tumors (SPT) are rare, generally low grade pancreatic neoplasms that occasionally display malignant behavior. To analyze the clinical and pathological features associated with increased risk of recurrence of SPT. Cohort study of patients with SPT who underwent resection of the primary tumor and in selected cases resection of metastatic disease from 1999-2013 at a single tertiary care Hepatopancreatobiliary center. Risk factors for recurrence were statistically analyzed. There were 32 patients. The mean age was 35.65 years (standard deviation: 12.26), 26/32, 81.25% were female. Median size of resected tumors was 4.7cm (1.1-14.5). Most were solid and cystic (22/32, 68.75%), encapsulated (27/32, 84.4%) and located in the pancreatic body or tail (22/32, 68.75%). All displayed strong β-catenin, cyclin D1, CD56, and progesterone receptor staining with loss of E-cadherin. Most stained positive for vimentin (15/16, 93.75%) and CD10 (17/18, 94.4%). Median follow-up was 43 months (range: 3-207); 3/32, 9.38% recurred (all after 5-years from curative resection) and 1 died by the end of the study period, 11 years after diagnosis. Patients who developed recurrences (n=3) more commonly had synchronous metastases at presentation (P=0.006), lymphovascular invasion (P=0.04) and invasion of tumor capsule (P=0.08) compared to those who did not have disease recurrence. Lymphovascular invasion, synchronous metastases and local invasion of tumor capsule are associated with aggressive behavior. Since recurrences may occur >5 years from resection, this high-risk group should undergo extended follow-up. Progression and recurrence is slow, therefore, resection of liver metastases can offer long-term survival.
    JOP: Journal of the pancreas 01/2014; 15(6):561-8.
  • [Show abstract] [Hide abstract]
    ABSTRACT: The role of liver resection in patients with multifocal hepatocellular carcinoma (HCC) with well preserved liver function is controversial. This study was conducted to evaluate the outcomes of such patients. This was a retrospective analysis of patients who underwent liver resection for multifocal HCC between 1992 and 2011. Postoperative outcomes, survival and predictors of outcomes were analysed. Of 46 patients who underwent hepatic resection for multifocal HCC, 38 had Barcelona Clinic Liver Cancer stage B disease. Major hepatectomy was performed in 27 patients, and major complications occurred in nine (20 per cent). The 90-day postoperative mortality rate was 7 per cent. Overall 1-, 2-, 3- and 5-year survival rates were 78, 64, 59 and 53 per cent respectively (median 70 months), whereas corresponding recurrence-free survival rates were 53, 32, 30 and 27 per cent (median 14 months). Recurrence developed in 28 (61 per cent) of the 46 patients, affecting the liver only in 22. Three-quarters of patients with recurrence underwent further therapy. Major hepatectomy (hazard ratio (HR) 0.37, 95 per cent confidence interval 0.14 to 0·95; P = 0·038), microvascular (HR 3·44, 1·35 to 8·74; P = 0·009) and macrovascular (HR 2·68, 1·11 to 6·43; P = 0·028) invasion, and cirrhosis (HR 3·15, 1·12 to 8·86; P = 0·029) were associated with overall survival. Microvascular invasion (HR 2·81, 1·06 to 7·40; P = 0·037), cirrhosis (HR 3·12, 1·41 to 6·88; P < 0·001) and bilobar disease (HR 2·93, 1·09 to 7·88; P = 0·033) were associated with recurrence-free survival. In selected patients with multifocal HCC and well preserved liver function, long-term survival is possible after liver resection and subsequent aggressive treatment of recurrence.
    British Journal of Surgery 10/2013; 100(11):1516-22. · 4.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pancreatic neuroendocrine tumors (pNETs) are the second most common pancreatic neoplasms, exhibiting a complex spectrum of clinical behaviors. To examine the clinico-pathological characteristics associated with long-term prognosis we reviewed 119 patients with pNETs treated in a tertiary referral center using the WHO 2010 grading and the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging systems, with a median follow-up of 38 months. Tumor size, immunohistochemistry (IHC) profiling and patient characteristics-determining stage were analyzed. Primary clinical outcomes were disease progression or death. The mean age at presentation was 52 years; 55% were female patients, 11% were associated with MEN1 (multiple endocrine neoplasia 1) or VHL (Von Hippel-Lindau); mean tumor diameter was 3.3 cm (standard deviation, SD) (2.92). The clinical presentation was incidental in 39% with endocrine hypersecretion syndromes in only 24% of cases. Nevertheless, endocrine hormone tissue immunoreactivity was identified in 67 (56.3%) cases. According to WHO 2010 grading, 50 (42%), 38 (31.9%), and 3 (2.5%) of tumors were low grade (G1), intermediate grade (G2), and high grade (G3), respectively. Disease progression occurred more frequently in higher WHO grades (G1: 6%, G2: 10.5%, G3: 67%, P = 0.026) and in more advanced AJCC stages (I: 2%, IV: 63%, P = 0.033). Shorter progression free survival (PFS) was noted in higher grades (G3 vs. G2; 21 vs. 144 months; P = 0.015) and in more advanced AJCC stages (stage I: 218 months, IV: 24 months, P < 0.001). Liver involvement (20 vs. 173 months, P < 0.001) or histologically positive lymph nodes (33 vs. 208 months, P < 0.001) were independently associated with shorter PFS. Conversely, tissue endocrine hormone immunoreactivity, independent of circulating levels was significantly associated with less aggressive disease. Age, gender, number of primary tumors, and heredity were not significantly associated with prognosis. Although the AJCC staging and WHO 2010 grading systems are useful in predicting disease progression, tissue endocrine hormone profiling provides additional information of potentially important prognostic value.
    Cancer Medicine 10/2013; 2(5):701-711.
  • [Show abstract] [Hide abstract]
    ABSTRACT: The management of portal vein (PV) involvement by pancreatic adenocarcinoma during pancreaticoduodenectomy (PD) is controversial. The aim of this study was to compare the outcomes of unplanned and planned PV resections as part of PD. An analysis of PD over 11 years was performed. Patients who had undergone PV resection (PV-PD) were identified, and categorized into those who had undergone planned or unplanned resection. Postoperative and oncological outcomes were compared. Of 249 patients who underwent PD for pancreatic adenocarcinoma, 66 (26·5 per cent) had PV-PD, including 27 (41 per cent) planned and 39 (59 per cent) unplanned PV resections. Twenty-five of 27 planned PV resections were circumferential PV-PD, whereas 25 of 39 unplanned PV resections were partial PV-PD. Planned PV resections were performed in slightly younger patients (mean(s.d.) 60(9) versus 65(10) years; P = 0·031), and associated with longer operating times (mean(s.d.) 602(131) versus 458(83) min; P < 0·001) and more major complications (26 versus 5 per cent; P = 0·026). Planned PV resections were associated with a lower rate of positive margins (4 versus 44 per cent; P < 0·001) despite being carried out for larger tumours (mean(s.d.) 3·9(1·4) versus 2·9(1·0) cm; P = 0·002). There was no difference in survival between the two groups (P = 0·998). On multivariable analysis, margin status was a significant predictor of survival. Although planned PV resections for pancreatic adenocarcinoma were associated with higher rates of postoperative morbidity than unplanned resections, R0 resection rates were better.
    British Journal of Surgery 09/2013; 100(10):1349-56. · 4.84 Impact Factor

Publication Stats

2k Citations
530.44 Total Impact Points

Institutions

  • 1996–2014
    • University of Toronto
      • • Department of Surgery
      • • Division of General Surgery
      • • Banting and Best Department of Medical Research
      • • Institute of Medical Sciences
      Toronto, Ontario, Canada
  • 2009–2013
    • University Health Network
      Toronto, Ontario, Canada
  • 2011
    • Peking Union Medical College Hospital
      Peping, Beijing, China
  • 2004–2009
    • UHN: Toronto General Hospital
      Toronto, Ontario, Canada
    • National and Kapodistrian University of Athens
      • Division of Surgery V
      Athens, Attiki, Greece
  • 2006
    • The Rockefeller University
      • Center for the Study of Hepatitis C
      New York City, NY, United States
    • University of Pennsylvania
      Philadelphia, Pennsylvania, United States