Roberto Hernandez-Alejandro

The University of Western Ontario, London, Ontario, Canada

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Publications (27)47.93 Total impact

  • Keegan Selby, Roberto Hernandez-Alejandro
    05/2014;
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    ABSTRACT: Portal vein occlusion to increase the size of the future liver remnant (FLR) is well established, using portal vein ligation (PVL) or embolization (PVE) followed by resection 4-8 weeks later. Associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) combines PVL and complete parenchymal transection, followed by hepatectomy within 1-2 weeks. ALPPS has been recently introduced but remains controversial. We compare the ability of ALPPS versus PVE or PVL for complete tumor resection. A retrospective review of all patients undergoing ALPPS or conventional staged hepatectomies using PVL or PVE at four high-volume HPB centres between 2003 and 2012 was performed. Patients with primary liver tumors and liver metastases were included. Primary endpoint was complete tumor resection. Secondary endpoints include 90-day mortality, complications, FLR increase, time to resection, and tumor recurrence. Forty-eight patients with ALPPS were compared with 83 patients with conventional-staged hepatectomies. Eighty-three percent (40/48 patients) of ALPPS patients achieved complete resection compared with 66 % (55/83 patients) in PVE/PVL (odds ratio 3.34, p = 0.027). Ninety-day mortality in ALPPS and PVE/PVL was 15 and 6 %, respectively (p = 0.2). Extrapolated growth rate was 11 times higher in ALPPS (34.8 cc/day; interquartile range (IQR) 26-49) compared with PVE/PVL (3 cc/day; IQR2-6; p = 0.001). Tumor recurrence at 1 year was 54 versus 52 % for ALPPS and PVE/PVL, respectively (p = 0.7). This study provides evidence that ALPPS offers a better chance of complete resection in patients with primarily unresectable liver tumors at the cost of a high mortality. The technique is promising but should currently not be used outside of studies and registries.
    World Journal of Surgery 04/2014; · 2.23 Impact Factor
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    ABSTRACT: The optimal initial treatment of splanchnic vein thrombosis is uncertain. Anticoagulant therapy has been shown to be associated with vessel recanalization and decreased recurrence. Furthermore, information regarding potential predictors of chronic complications is not well understood. A retrospective cohort study involving consecutive patients diagnosed with first-episode noncirrhotic splanchnic vein thrombosis referred to the thrombosis clinic of the authors' institution between 2008 and 2011 was conducted. Demographic and clinical information was collected. The response to initial anticoagulant therapy was evaluated by determining radiographic recanalization of vessels and clinical resolution (defined as the absence of ongoing splanchnic vein thrombosis symptoms or complications requiring treatment beyond anticoagulant therapy). Twenty-two patients were included. Anticoagulant therapy alone resulted in vessel recanalization in 41% of patients and 68% achieved clinical resolution. Two patients experienced bleeding events. Factors associated with a lack of clinical resolution included signs of portal hypertension⁄liver failure on presentation, complete vessel occlusion at diagnosis, presence of a myeloproliferative disorder or JAK2V617F tyrosine kinase mutation and the absence of a local⁄transient predisposing factor. Anticoagulant therapy appeared to be an effective initial treatment in patients with splanchnic vein thrombosis. Clinical factors may help to identify patients who are at risk for developing complications thus requiring closer monitoring. These findings were limited by the small sample size and need to be explored in larger prospective studies.
    Canadian journal of gastroenterology & hepatology. 04/2014; 28(4):207-11.
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    Malcolm Wells, Kris M Croome, Toni Janik, Roberto M Hernandez-Alejandro, Natasha M Chandok
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    ABSTRACT: Liver transplantation (LT) using organs donated after cardiac death (DCD) is increasing due, in large part, to a shortage of organs. The outcome of using DCD organs in recipients with hepatits C virus (HCV) infection remains unclear due to the limited experience and number of publications addressing this issue. OBJECTIVE: To evaluate the clinical outcomes of DCD versus donation after brain death (DBD) in HCV-positive patients undergoing LT. METHODS: Studies comparing DCD versus DBD LT in HCV-positive patients were identified based on systematic searches of seven electronic databases and multiple sources of gray literature. Results: The search identified 58 citations, including three studies, with 324 patients meeting eligibility criteria. The use of DCD livers was associated with a significantly higher risk of primary nonfunction (RR 5.49 [95% CI 1.53 to 19.64]; P=0.009; I2=0%), while not associated with a significantly different patient survival (RR 0.89 [95% CI 0.37 to 2.11]; P=0.79; I2=51%), graft survival (RR 0.40 [95% CI 0.14 to 1.11]; P=0.08; I2=34%), rate of recurrence of severe HCV infection (RR 2.74 [95% CI 0.36 to 20.92]; P=0.33; I2=84%), retransplantation or liver disease-related death (RR 1.79 [95% CI 0.66 to 4.84]; P=0.25; I2=44%), and biliary complications. CONCLUSIONS: While the literature and quality of studies assessing DCD versus DBD grafts are limited, there was significantly more primary nonfunction and a trend toward decreased graft survival, but no significant difference in biliary complications or recipient mortality rates between DCD and DBD LT in patients with HCV infection. There is insufficient literature on the topic to draw any definitive conclusions.
    Canadian journal of gastroenterology = Journal canadien de gastroenterologie. 01/2014; 28(2):103-8.
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    ABSTRACT: On behalf of the ALPPS Registry Group Objectives: To assess safety and outcomes of the novel 2-stage hepatectomy, Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS), using an international registry. Background: ALPPS induces accelerated growth of small future liver rem-nants (FLR) to allow curative resection of liver tumors. There is concern about safety based on reports of higher morbidity and mortality. Methods: A Web-based data entry system was created with password access and data pseudoencryption (NCT01924741). All patients with com-plete 90-day data were included. Multivariate logistic regression analysis was performed to identify independent risk factors for severe complications and mortality and volume growth of the FLR. Results: Complete data were available for 202 patients. A total of 141 (70%) patients had colorectal liver metastases (CRLM). Median starting standard-ized future liver remnants of 21% increased by 80% within a median of 7 days. Ninety-day mortality was 19/202 (9%). Severe complications including mortalities (Clavien-Dindo ≥IIIb) occurred in 27% of patients. Independent factors for severe complications were red blood cell transfusion [odds ratio (OR), 5.2), ALLPS stage I operating time greater than 300 minutes (OR, 4.4), age more than 60 years (OR, 3.8), and non-CRLM (OR, 2.7). Age, use of Pringle maneuver, and histologic changes led to less volume growth. In patients younger than 60 years with CRLM, 90-day mortality was similar to conventional 2-stage hepatectomies for CRLM. Conclusions: This is the first analysis of the ALPPS registry showing that ALPPS shows increased perioperative morbidity and mortality in older patients but better outcomes in patients with CRLM.
    Annals of surgery 01/2014; · 7.90 Impact Factor
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    ABSTRACT: The influence of donor-recipient gender mismatch on outcomes after liver transplantation (LT) is controversial. The aim of this study was to evaluate the effect of donor and recipient gender discordance on graft survival. All patients who underwent primary LT from 1994-2012 at a single-center were identified prospectively. Clinico-demographic data were collected at the time of LT and last follow-up. Gender match included both male donor to male recipient (MM) and female donor to female recipient (FF), while gender mismatch included female donor to male recipient (FM) and male donor to female recipient (MF). Survival curves for graft survival were generated using Kaplan-Meier method and compared by log-rank test. Unadjusted and multivariate adjusted COX regression analyzing graft survival at up to 10 years post-transplant was performed. A total of 1,042 subjects fulfilled the criteria. Graft survival in patients receiving a donor-recipient gender match was better than those receiving a gender mismatch (P = 0.047). Female-to-male transplants had the worst graft survival of all combinations (P < 0.001); this difference was maintained in multivariate regression after adjustment for recipient and donor variables (hazards ratio 2.09, P = 0.013). Female-to-male liver transplants are associated with a statistically significant poorer graft survival as compared with other donor-recipient gender groups.
    Journal of hepato-biliary-pancreatic sciences. 09/2013;
  • Canadian journal of gastroenterology = Journal canadien de gastroenterologie. 09/2013;
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    ABSTRACT: Portal vein ligation (PVL) or embolization (PVE) are standard approaches to induce liver hypertrophy of the future liver remnant (FLR) prior to hepatectomy in primarily non-resectable liver tumors. However, this approach fails in about one third of patients. Recently, the new "ALPPS" approach has been described that combines PVL with parenchymal transection to induce rapid liver hypertrophy. This series explores whether isolated parenchymal transection boosts liver hypertrophy in scenarios of failed PVL/PVE. A multicenter database with 170 patients undergoing portal vein manipulation to increase the size of the FLR was screened for patients undergoing isolated parenchymal transection as a salvage procedure. Three patients who underwent PVL/PVE with subsequent insufficient volume gain and subsequently underwent parenchymal liver transection as a salvage procedure were identified. Patient characteristics, volume increase, postoperative complications and outcomes were analyzed. The first patient underwent liver transection 16 weeks after failed PVL with a standardized FLR (sFLR) of 30%, which increased to 47% in 7 days. The second patient showed a sFLR of 25% 28 weeks after PVL and subsequent PVE of segment IV, which increased to 41% in 7 days after transection. The third patient underwent liver partition 8 weeks after PVE with a sFLR of 19%, which increased to 37% in six days. All patients underwent a R0 resection. Failed PVE or PVL appears to represent a good indication for the isolated parenchymal liver transection according to the newly developed ALPPS approach.
    European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 08/2013; · 2.56 Impact Factor
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    ABSTRACT: Background: Liver organ donor characteristics have a significant impact on graft quality and in turn recipient outcome. In this study, we examined deceased liver donor characteristics and Donor Risk Index (DRI) trends in Canada over the past decade. Methods: Data were extracted from the Canadian Organ Replacement Register (CORR) and Quebec Transplant for the decade (2000-2010). Trends in the DRI and donor characteristics were examined including: age, race, height, cause of death (COD), location, cold ischemia time (CIT), and type of donation. Results: 3745 transplants using deceased liver donors were analyzed. Donor age, proportion of black donors, proportion of cerebrovascular accident as a COD, and proportion of donation after cardiac death (DCD) donors all increased over the aforementioned time period. The proportion of transplants classified geographically as local increased and the CIT for donor livers decreased. Although many of the parameters that adversely affect DRI increased over the study period, the DRI only showed a small significant trend in increasing value. The increase in these parameters has been counteracted by a decrease in modifiable risk factors such as CIT and distance traveled. Recipient 5-year survival rates increased from 71.43% (1999-2001) to 75.5% (2005-2007), however this trend was not significant. Although there was an increase in the utilization of older and DCD donor organs, recipient survival was not compromised. Conclusions: Liver donor demographic trends in Canada suggest an increase in utilization of higher risk donors. However, overall graft quality is not compromised due to a decreasing trend in CIT and increase in local transplants. Better coordination and allocation practices in liver transplantation across Canada minimize the risk for graft failure and results in good recipient outcomes. Liver Transpl , 2013. © 2013 AASLD.
    Liver Transplantation 08/2013; · 3.94 Impact Factor
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    ABSTRACT: Background: The impact of Ischemia reperfusion Injury (IRI) in the setting of transplantation for Hepatocellular Carcinoma (HCC) has not been thoroughly investigated. Methods: The present study examined data from the Scientific Registry of Transplant Recipients (SRTR) on all deceased donor liver transplant recipients performed from January 1 1995 to October 31 2011. Results: On multivariate Cox analysis significant predictors of graft and patient survival included a diagnosis of HCC (p<0.001), receiving a DCD allograft (p<0.001), HCV+ status (p<0.001), recipient age (p<0.001), donor age (p<0.001), and MELD score (p<0.001) recipient race and an AFP level>400 at the time of transplant.. In order to test if the decreased survival seen in Group 3(HCC DCD) was more than would be expected given the inferior nature of DCD grafts and having a diagnosis of HCC, an interaction term was created between receiving a DCD allograft and a diagnosis of HCC to examine for potentiation of effect. In the multivariate analysis adjusting for all other covariates this interaction term was statistically significant (p=0.049) confirming that there was potentiation of inferior survival with the use of DCD allografts in recipients with HCC. In a subgroup survival analysis on HCC recipients receiving a DCD allograft, recipients with a donor Warm ischemia time (WIT) ≤15min had a trend of better survival than recipients with a WIT>15min. In addition recipients with Cold ischemia time (CIT) <380min (6h 20min) had significantly better survival than recipients with CIT>380min (p<0.036). Conclusion: There is an inferior patient and graft survival in HCC recipients of DCD allografts compared to those receiving DBD allografts. This potentiation of effect of inferior survival remains even after adjustment for the inherent inferiority observed in DCD allografts as well as other known risk factors. It is hypothesized that this difference could reflect an increased rate of recurrence of HCC. Liver Transpl, 2013. © 2013 AASLD.
    Liver Transplantation 08/2013; · 3.94 Impact Factor
  • Aman Arya, Roberto Hernandez-Alejandro, Paul Marotta, Julia Uhanova, Natasha Chandok
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    ABSTRACT: Candidacy for liver transplantation is determined through standardized evaluation. There are limited data on the frequency and reasons for denial of transplantation after assessment; analysis may shed light on the short-term utility of the assessment. We sought to describe the frequency and reasons for ineligibility for liver transplantation among referred adults. We studied all prospectively followed recipient candidates at a single centre who were deemed unsuitable for liver transplantation after assessment. Inclusion criteria were age 18 years and older and completion of a standard liver transplantation evaluation over a 3-year period. Patients were excluded if they had a history of prior assessment or liver transplantation within the study period. Demographic and baseline clinical data and reasons for recipient ineligibility were recorded. In all, 337 patients underwent their first liver transplantation evaluation during the study period; 166 (49.3%) fulfilled inclusion criteria. The mean age was 55.4 years, and 106 (63.9%) were men. The 3 most common reasons for denial of listing were patient too well (n = 82, 49.4%), medical comorbidities and/or need for medical optimization (n = 43, 25.9%) and need for addiction rehabilitation (n = 28, 16.9%). Ineligibility for transplantation after assessment was common, occurring in nearly half of the cohort. Most denied candidates could be identified with more discriminate screening before the resource-intensive assessment; however, the assessment likely provides unforeseen positive impacts on patient care.
    Canadian journal of surgery. Journal canadien de chirurgie 06/2013; 56(3):E39-E43. · 1.63 Impact Factor
  • K P Croome, R Hernandez-Alejandro, N Chandok
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    ABSTRACT: There are limited data on length of stay (LOS) following liver transplantation (LT), yet this is an important health services metric that directly correlates with early post-LT health care costs. The primary objective of this study was to examine the relationship between early allograft dysfunction (EAD) and LOS after LT. The secondary objective was to identify additional recipient, donor, and operative factors associated with LOS. Adult patients undergoing primary LT over a 32-month period were prospectively examined at a single center. Subjects fulfilling standard criteria for EAD were compared with those not meeting the definition. Variables associated with increased LOS on ordinal logistic regression were identified. Subjects with EAD had longer mean hospital LOS than those without (42.5 ± 38.9 days vs 27.4 ± 31 days; P = .003). Subjects with EAD also had longer mean intensive care LOS (8.61 ± 10.28 days vs 5.45 ± 11.6 days; P = .048). Additional factors significantly associated with LOS included Model for End-Stage Liver Disease (MELD) score, recipient location before LT, and postoperative surgical complications. EAD is associated with longer hospitalization after LT. MELD score, preoperative recipient location, and postoperative complications were significantly associated with LOS. From a cost-containment perspective, these findings have implications on resource allocation.
    Transplantation Proceedings 01/2013; 45(1):259-64. · 0.95 Impact Factor
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    ABSTRACT: Previous studies have shown a higher incidence of biliary complications following donation after cardiac death (DCD) liver transplantation compared with donation after brain death (DBD) liver transplantation. The endoscopic management of ischemic type biliary strictures in patients who have undergone DCD liver transplants needs to be characterized further. A retrospective institutional review of all patients who underwent DCD liver transplant from January 2006 to September 2011 was performed. These patients were compared with all patients who underwent DBD liver transplantation in the same time period. A descriptive analysis of all DCD patients who developed biliary complications and their subsequent endoscopic management was also performed. Of the 36 patients who received DCD liver transplants, 25% developed biliary complications compared with 13% of patients who received DBD liver transplants (P=0.062). All DCD allograft recipients who developed biliary complications became symptomatic within three months of transplantation. Ischemic type biliary strictures in DCD allograft recipients included disseminated biliary strictures in two patients, biliary strictures of the hepatic duct bifurcation in three patients and biliary strictures of the donor common hepatic duct in three patients. There was a trend toward increasing incidence of total biliary complications in recipients of DCD liver allografts compared with those receiving DBD livers, and the rate of diffuse ischemic cholangiopathy was significantly higher. Focal ischemic type biliary strictures can be treated effectively in DCD liver transplant recipients with favourable results. Diffuse ischemic type biliary strictures in DCD liver transplant recipients ultimately requires retransplantation.
    Canadian journal of gastroenterology = Journal canadien de gastroenterologie 09/2012; 26(9):607-10. · 1.53 Impact Factor
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    ABSTRACT: To compare the clinical outcome and pathologic features of non-alcoholic steatohepatitis (NASH) patients with hepatocellular carcinoma (HCC) and hepatitic C virus (HCV) patients with HCC (another group in which HCC is commonly seen) undergoing liver transplantation. Patients transplanted for HCV and NASH at our institution from January 2000 to April 2011 were analyzed. All explanted liver histology and pre-transplant liver biopsies were examined by two specialist liver histopathologists. Patient demographics, disease free survival, explant liver characteristics and HCC features (tumour number, cumulative tumour size, vascular invasion and differentiation) were compared between HCV and NASH liver transplant recipients. A total of 102 patients with NASH and 283 patients with HCV were transplanted. The incidence of HCC in NASH transplant recipients was 16.7% (17/102). The incidence of HCC in HCV transplant recipients was 22.6% (64/283). Patients with NASH-HCC were statistically older than HCV-HCC patients (P < 0.001). A significantly higher proportion of HCV-HCC patients had vascular invasion (23.4% vs 6.4%, P = 0.002) and poorly differentiated HCC (4.7% vs 0%, P < 0.001) compared to the NASH-HCC group. A trend of poorer recurrence free survival at 5 years was seen in HCV-HCC patients compared to NASH-HCC who underwent a Liver transplantation (P = 0.11). Patients transplanted for NASH-HCC appear to have less aggressive tumour features compared to those with HCV-HCC, which likely in part accounts for their improved recurrence free survival.
    World Journal of Gastroenterology 08/2012; 18(31):4145-9. · 2.55 Impact Factor
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    ABSTRACT: An updated definition of early allograft dysfunction (EAD) was recently validated in a multicenter study of 300 deceased donor liver transplant recipients. This analysis did not differentiate between donation after brain death (DBD) and donation after cardiac death (DCD) allograft recipients. We reviewed our prospectively entered database for all DBD (n=377) and DCD (n=38) liver transplantations between January 1, 2006 and October 30, 2011. The incidence of EAD as well as its ability to predict graft failure and survival was compared between DBD and DCD groups. EAD was a valid predictor of both graft and patient survival at six months in DBD allograft recipients, but in DCD allograft recipients there was no significant difference in the rate of graft failure in those with EAD (11.5%) compared with those without EAD (16.7%) (P=0.664) or in the rate of death in recipients with EAD (3.8%) compared with those without EAD (8.3%) (P=0.565). The graft failure rate in the first 6 months in those with international normalized ratio ≥1.6 on day 7 who received a DCD allograft was 37.5% compared with 6.7% for those with international normalized ratio <1.6 on day 7 (P=0.022). The recently validated definition of EAD is a valid predictor of patient and graft survival in recipients of DBD allografts. On initial assessment, it does not appear to be a useful predictor of patient and graft survival in recipients of DCD allografts, however a study with a larger sample size of DCD allografts is needed to confirm these findings. The high ALT/AST levels in most recipients of DCD livers as well as the predisposition to biliary complications and early cholestasis make these parameters as poor predictors of graft failure. An alternative definition of EAD that gives greater weight to the INR on day 7 may be more relevant in this population.
    Hepatobiliary & pancreatic diseases international: HBPD INT 08/2012; 11(4):372-6. · 1.26 Impact Factor
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    ABSTRACT: There is a global tendency to justify transplanting extended criteria organs (ECD; Donor Risk Index [DRI] ≥ 1.7) into recipients with a lower Model for End-Stage Liver Disease (MELD) score and to transplant standard criteria organs (DRI < 1.7) into recipients with a higher MELD scores. There is a lack of evidence in the current literature to justify this assumption. A review of our prospectively entered database for donation after brain death (DBD) liver transplantation (n = 310) between January 1, 2006, and September 30, 2010, was performed. DRI was dichotomized as <1.7 and ≥ 1.7. Recipients were divided into 3 strata, those with high (≥ 27), moderate (15-26), and low MELD (<15) scores. The recently validated definition of early allograft dysfunction (EAD) was used. We analyzed EAD and its relation with donor DRI and recipient MELD scores. The overall incidence of EAD was 24.5%. Mortality in the first 6 months in recipients with EAD was 20% compared with 3.4% for those without EAD (relative risk [RR], 5.56, 95% confidence interval [CI], 1.96-15.73; P < .001). Graft failure rate in the first 6 months in those with EAD was 27% compared with 5.8% for those without EAD (RR, 4.63; 95% CI, 2.02-10.6; P < .001). In patients with low MELD scores, a significantly increased rate of EAD (25%) was seen in patients transplanted with a high DRI liver compared with those transplanted with a low DRI liver (6.25%; P = .012). In moderate and high MELD recipients, there was no significant difference in the rate of EAD in patients transplanted with a high DRI liver (62%) compared with those transplanted with a low DRI liver (59%). These results suggest that contrary to common belief it is not justified to preferentially allocate organs with higher DRI to recipients with lower MELD scores.
    Transplantation Proceedings 06/2012; 44(5):1303-6. · 0.95 Impact Factor
  • Jiwei Huang, Roberto Hernandez-Alejandro, Kristopher P Croome, Yong Zeng, Hong Wu, Zheyu Chen
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    ABSTRACT: BACKGROUND: Surgical resection has routinely not been recommended for patients with huge (>15 cm) multinodular lesions and macrovascular invasion (advanced-stage hepatocellular carcinoma [HCC] patients) because of high operative mortality, recurrence rate, and lack of survival benefit. METHODS: A retrospective study of 1425 patients was carried out, of which 1245 patients met EASL/AASLD criteria for hepatic resection (HR-EA group), 116 were surgically treated advanced-stage HCC patients (HR-AS group), and 64 were advanced-stage HCC patients receiving nonsurgical treatments (N-AS group). CONCLUSION: HR may still be suitable for the HCC patients with huge (>15 cm) multinodular lesions and macrovascular invasion in selected cases. Advanced-stage HCC patients without liver cirrhosis and with a tumor-free resection margin could enjoy longer survival and lower recurrence. Preoperative and/or postoperative TACE provides no survival benefits for advanced-stage HCC patients.
    Journal of Surgical Research 05/2012; · 2.02 Impact Factor
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    D Lam, Kp Croome, R Hernandez-Alejandro
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    ABSTRACT: A duodenal adenocarcinoma arising from the junction of the second and third portion of the duodenum, which was resected by pancreas-sparing duodenectomy, is reported. The completely obstructing tumour was circumferential and measured 6.5cm x 3.5cm x 1.0 cm. There was no evidence of pancreas invasion, nor any lymph node metastasis. Pancreas-sparing duodenectomy was performed, with dissection of the pancreaticoduodenal lymph nodes. The proximal duodenum was transected just distal to the ampula of Vater and jejunum was transected just distal to the ligament of Treitz. A hand-sewn side-to-side anastomosis for the duodenojejunostomy was performed. There were no postoperative complications. Pathology reported a duodenal adenocarcinoma resected with negative margins. Pancreaticoduodenectomy is the treatment of choice for a duodenal adenocarcinoma, however, pancreas-sparing duodenectomy may be a safe alternative for duodenal tumours not involving the 2(nd) portion, especially in elderly patients with multiple medical comorbidities.
    Journal of surgical case reports. 01/2012; 2012(8):13.
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    ABSTRACT: Tumor necrosis factor-alpha (TNF-α) is a central mediator in the hepatic response to ischemia/reperfusion. Short hairpin RNA (shRNA) has been proven to be an effective means of harnessing the RNA interference pathway in mammalian cells. In the current study, we investigated whether silencing TNF-α gene with shRNA can prevent liver ischemic reperfusion injury (IRI). Male BalB/c mice were randomized to TNF-α shRNA, scramble shRNA, or sham operation groups. TNF-α shRNA and scramble shRNA groups were injected 48 h before inducing IRI. IRI was induced via microaneurysm clamps applied to the left hepatic artery and portal vein. Six hours after reperfusion, IRI injury was examined by serum level of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), liver histopathology, MPO, and MDA level, as well as by relative quantities of TNF-α mRNA. TNF-α expression induced by ischemia reperfusion in the liver was significantly suppressed after treatment with TNF-α shRNA compared with the group treated with scramble shRNA (P < 0.001). Mice treated with TNF-α shRNA showed lower peak values of AST and ALT than scramble shRNA treated mice (P < 0.001). On histopathologic slides, mice treated with TNF-α shRNA had significantly less ischemia/reperfusion injury based on Suzuki score than the scramble shRNA group, 3.57 ± 2.30 and 8.83 ± 0.98 respectively (P < 0.001), while the sham group was not significantly different from the TNF-alpha shRNA group, 0 ± 0 and 3.57 ± 2.30, respectively (P = 0.075). Liver tissue MDA levels were significantly lower in mice treated with TNF-α shRNA as compared with the group treated with scramble shRNA (P < 0.01). Immunohistochemical staining for MPO was significantly lower in mice treated with TNF-α shRNA compared with the group treated with shRNA (compared with treated with scramble shRNA group.) Liver IRI can be minimized through gene silencing of TNF-α. This may represent a novel therapy in the setting of transplantation and in other conditions associated with IRI of the liver.
    Journal of Surgical Research 11/2011; 176(2):614-20. · 2.02 Impact Factor
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    ABSTRACT: Liver transplantation (LT) is a costly but effective treatment for end-stage liver disease (ESLD). However, there are minimal data on the patterns of and risk factors for hospital readmission after LT. The aim of this study was to determine the frequency of and risk factors for rehospitalization after LT. Consecutive adult patients who underwent LT at a single center (n = 208) were prospectively studied over a 30-month period. Within 90 days of LT, 30.3% of LT recipients were readmitted to the hospital. Recipient and donor age, Model for End-Stage Liver Disease score, cold ischemia time, type of hepatic graft, length of hospitalization after LT, and occurrence of operative/postoperative complications had no association with the risk for readmission (P>.05). The length of stay in intensive care was negatively correlated with readmission (hazard ratio, 0.92; P=.028). ESLD from hepatitis C virus (HCV) infection as an indication for LT was the only factor associated with an increased risk for readmission (hazard ratio, 1.91 ; P=.010). Further studies are needed to explore the reasons for readmission among LT recipients, particularly those with HCV infection, in order to devise cost-savings policies for post-LT care.
    Gastroenterology and Hepatology 09/2011; 7(9):585-90.

Publication Stats

66 Citations
47.93 Total Impact Points

Institutions

  • 2010–2014
    • The University of Western Ontario
      • • Schulich School of Medicine and Dentistry
      • • Division of Gastroenterology
      • • Department of Surgery
      London, Ontario, Canada
  • 2011–2012
    • London Health Sciences Centre
      • Department of Surgery
      London, Ontario, Canada