Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 35
Filter
1.
Ann Med Surg (Lond) ; 77: 103645, 2022 May.
Article in English | MEDLINE | ID: mdl-35637985

ABSTRACT

Background: Curative-intent therapies for hepatocellular carcinoma (HCC) include radiofrequency ablation (RFA), liver resection (LR), and liver transplantation (LT). Controversy exists in treatment selection for early-stage tumours. We sought to evaluate the oncologic outcomes of patients who received either RFA, LR, or LT as first-line treatment for solitary HCC ≤ 3 cm in an intention-to-treat analysis. Materials and methods: All patients with solitary HCC ≤ 3 cm who underwent RFA, LR, or were listed for LT between Feb-2000 and Nov-2018 were analyzed. Cox regression analysis was then performed to compare intention-to-treat (ITT) survival by initial treatment allocation and disease-free survival (DFS) by treatment received in patients eligible for all three treatments. Results: A total of 119 patients were identified (RFA n = 83; LR n = 25; LT n = 11). The overall intention-to-treat survival was similar between the three groups. The overall DFS was highest for the LT group. This was significantly higher than RFA (p = 0.02), but not statistically significantly different from LR (p = 0.14). After multivariable adjustment, ITT survival was similar in the LR and LT groups relative to RFA (LR HR:1.13, 95%CI 0.33-3.82; p = 0.80; LT HR:1.39, 95%CI 0.35-5.44; p = 0.60). On multivariable DFS analysis, only LT was better relative to RFA (LR HR:0.52, 95%CI 0.26-1.02; p = 0.06; LT HR:0.15, 95%CI 0.03-0.67; p = 0.01). Compared to LR, LT was associated with a numerically lower hazard on multivariable DFS analysis, though this did not reach statistical significance (HR 0.30, 95%CI 0.06-1.43; p = 0.13). Conclusion: For treatment-naïve patients with solitary HCC ≤ 3 cm who are eligible for RFA, LR, and LT, adjusted ITT survival is equivalent amongst the treatment modalities, however, DFS is better with LR and LT, compared with RFA. Differences in recurrence between treatment modalities and equipoise in ITT survival provides support for a future prospective trial in this setting.

2.
Am J Transplant ; 17(3): 754-760, 2017 03.
Article in English | MEDLINE | ID: mdl-27545327

ABSTRACT

The increased prevalence of obesity worldwide threatens the pool of living liver donors. Although the negative effects of graft steatosis on liver donation and transplantation are well known, the impact of obesity in the absence of hepatic steatosis on outcome of living donor liver transplantation (LDLT) is unknown. Consequently, we compared the outcome of LDLT using donors with BMI <30 versus donors with BMI ≥30. Between April 2000 and May 2014, 105 patients received a right-lobe liver graft from donors with BMI ≥30, whereas 364 recipients were transplanted with grafts from donors with BMI <30. Liver steatosis >10% was excluded in all donors with BMI >30 by imaging and liver biopsies. None of the donors had any other comorbidity. Donors with BMI <30 versus ≥30 had similar postoperative complication rates (Dindo-Clavien ≥3b: 2% vs. 3%; p = 0.71) and lengths of hospital stay (6 vs. 6 days; p = 0.13). Recipient graft function, assessed by posttransplant peak serum bilirubin and international normalized ratio was identical. Furthermore, no difference was observed in recipient complication rates (Dindo-Clavien ≥3b: 25% vs. 20%; p = 0.3) or lengths of hospital stay between groups. We concluded that donors with BMI ≥30, in the absence of graft steatosis, are not contraindicated for LDLT.


Subject(s)
Body Mass Index , Liver Transplantation/methods , Living Donors , Patient Selection , Postoperative Complications , Tissue and Organ Procurement/methods , Adult , Female , Follow-Up Studies , Graft Survival , Humans , Liver Function Tests , Male , Middle Aged , Obesity/physiopathology , Prognosis , Retrospective Studies , Risk Factors
3.
Nutr Diabetes ; 6(7): e220, 2016 07 18.
Article in English | MEDLINE | ID: mdl-27428872

ABSTRACT

BACKGROUND: There is growing evidence that nonalcoholic fatty liver disease (NAFLD) is associated with perturbations in liver lipid metabolism. Liver phospholipid and fatty acid composition have been shown to be altered in NAFLD. However, detailed profiles of circulating lipids in the pathogenesis of NAFLD are lacking. OBJECTIVE: Therefore, the objective of the present study was to examine circulating lipids and potential mechanisms related to hepatic gene expression between liver biopsy-proven simple steatosis (SS), nonalcoholic steatohepatitis (NASH) and healthy subjects. SUBJECTS: Plasma phospholipid and fatty acid composition were determined in 31 healthy living liver donors as healthy controls (HC), 26 patients with simple hepatic steatosis (SS) and 20 with progressive NASH. Hepatic gene expression was analyzed by Illumina microarray in a subset of 22 HC, 16 SS and 14 NASH. RESULTS: Concentrations of phosphatidylethanolamine (PE) increased relative to disease progression, HC

Subject(s)
Fatty Acids/blood , Liver/pathology , Non-alcoholic Fatty Liver Disease/blood , Phospholipids/blood , Adult , Cross-Sectional Studies , Fatty Liver/blood , Fatty Liver/diagnosis , Fatty Liver/pathology , Female , Healthy Volunteers , Humans , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/pathology , Young Adult
4.
Am J Transplant ; 16(12): 3512-3521, 2016 12.
Article in English | MEDLINE | ID: mdl-27088432

ABSTRACT

Liver transplantation (LT) is the treatment of choice for end-stage autoimmune liver diseases. However, the underlying disease may recur in the graft in some 20% of cases. The aim of this study is to determine whether LT using living donor grafts from first-degree relatives results in higher rates of recurrence than grafts from more distant/unrelated donors. Two hundred sixty-three patients, who underwent a first LT in the Toronto liver transplant program between January 2000 and March 2015 for autoimmune liver diseases, and had at least 6 months of post-LT follow-up, were included in this study. Of these, 72 (27%) received a graft from a first-degree living-related donor, 56 (21%) from a distant/unrelated living donor, and 135 (51%) from a deceased donor for primary sclerosing cholangitis (PSC) (n = 138, 52%), primary biliary cholangitis (PBC) (n = 69, 26%), autoimmune hepatitis (AIH) (n = 44, 17%), and overlap syndromes (n = 12, 5%). Recurrence occurred in 52 (20%) patients. Recurrence rates for each autoimmune liver disease were not significantly different after first-degree living-related, living-unrelated, or deceased-donor LT. Similarly, time to recurrence, recurrence-related graft failure, graft survival, and patient survival were not significantly different between groups. In conclusion, first-degree living-related donor LT for PSC, PBC, or AIH is not associated with an increased risk of disease recurrence.


Subject(s)
Autoimmune Diseases/surgery , Family , Graft Rejection/etiology , Liver Diseases/surgery , Liver Transplantation/adverse effects , Living Donors , Postoperative Complications/etiology , Adult , Female , Follow-Up Studies , Graft Survival , Humans , Male , Middle Aged , Prognosis , Recurrence , Risk Factors
5.
J Viral Hepat ; 23(5): 340-7, 2016 May.
Article in English | MEDLINE | ID: mdl-26710754

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.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/immunology , Interferon-alpha/therapeutic use , Protease Inhibitors/therapeutic use , Adult , Aged , Biopsy , Female , Gene Expression Profiling , Hepatocytes/immunology , Humans , Interferon-alpha/immunology , Liver/pathology , Macrophages/immunology , Male , Middle Aged , Oligopeptides/therapeutic use , Proline/analogs & derivatives , Proline/therapeutic use , Ribavirin/therapeutic use , Staining and Labeling
6.
Am J Transplant ; 15(6): 1591-7, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25799890

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.


Subject(s)
Critical Illness , Liver Failure, Acute/surgery , Liver Transplantation , Living Donors , Tissue Donors , Adult , Aged , Canada , Female , Humans , Incidence , Male , Middle Aged , Postoperative Complications/epidemiology , Retrospective Studies , Severity of Illness Index , Treatment Outcome
7.
Ann Surg Oncol ; 22(7): 2286-94, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25472651

ABSTRACT

PURPOSE: To identify prognostic factors after hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.


Subject(s)
Carcinoma, Hepatocellular/surgery , Catheter Ablation , Liver Neoplasms/surgery , Liver Transplantation/adverse effects , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/surgery , Postoperative Complications , Adult , Aged , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Europe/epidemiology , Female , Follow-Up Studies , Humans , Incidence , Intention , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Multivariate Analysis , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/etiology , Neoplasm Staging , Prognosis , Prospective Studies , Retrospective Studies , Risk Factors , Survival Rate , United States/epidemiology , Young Adult , alpha-Fetoproteins/analysis
8.
Am J Transplant ; 14(12): 2788-95, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25277134

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.


Subject(s)
Graft Rejection/epidemiology , Hepatorenal Syndrome/surgery , Kidney Failure, Chronic/epidemiology , Liver Transplantation , Living Donors , Postoperative Complications , Adult , Cadaver , Case-Control Studies , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Rejection/mortality , Graft Survival , Humans , Incidence , Kidney Failure, Chronic/mortality , Kidney Function Tests , Male , Middle Aged , Prognosis , Prospective Studies , Risk Factors , Survival Rate
9.
J Viral Hepat ; 21(2): 121-8, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24383925

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 -ß), 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.


Subject(s)
Hepacivirus/immunology , Hepacivirus/physiology , Hepatocytes/immunology , Hepatocytes/virology , Immunity, Innate , MicroRNAs/metabolism , Virus Replication , Cell Line , Humans
10.
Br J Surg ; 100(11): 1516-22, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24037575

ABSTRACT

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.


Subject(s)
Carcinoma, Hepatocellular/surgery , Hepatectomy/methods , Liver Neoplasms/surgery , Neoplasm Recurrence, Local/surgery , Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/pathology , Combined Modality Therapy , Disease-Free Survival , Female , Hepatectomy/mortality , Hepatitis B, Chronic/complications , Hepatitis C, Chronic , Humans , Liver Cirrhosis/complications , Liver Neoplasms/pathology , Liver Transplantation/statistics & numerical data , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness/pathology , Postoperative Complications , Retrospective Studies , Treatment Outcome , Tumor Burden
11.
Br J Surg ; 100(10): 1349-56, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23939847

ABSTRACT

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Although planned PV resections for pancreatic adenocarcinoma were associated with higher rates of postoperative morbidity than unplanned resections, R0 resection rates were better.


Subject(s)
Adenocarcinoma/surgery , Mesenteric Veins/surgery , Pancreatic Neoplasms/surgery , Pancreaticoduodenectomy/methods , Portal Vein/surgery , Blood Loss, Surgical , Blood Vessel Prosthesis Implantation/methods , Female , Humans , Length of Stay , Male , Middle Aged , Neoplasm Invasiveness , Operative Time , Patient Care Planning , Portal Vein/injuries , Postoperative Complications/etiology , Treatment Outcome , Vascular Neoplasms/surgery
12.
Am J Transplant ; 13(6): 1441-9, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23668775

ABSTRACT

We compared cold static with acellular normothermic ex vivo liver perfusion (NEVLP) as a novel preservation technique in a pig model of DCD liver injury. DCD livers (60 min warm ischemia) were cold stored for 4 h, or treated with 4 h cold storage plus 8 h NEVLP. First, the livers were reperfused with diluted blood as a model of transplantation. Liver injury was determined by ALT, oxygen extraction, histology, bile content analysis and hepatic artery (HA) angiography. Second, AST levels and bile production were assessed after DCD liver transplantation. Cold stored versus NEVLP grafts had higher ALT levels (350 ± 125 vs. 55 ± 35 U/L; p < 0.0001), decreased oxygen extraction (250 ± 65 mmHg vs. 410 ± 58 mmHg, p < 0.01) and increased hepatocyte necrosis (45% vs. 10%, p = 0.01). Levels of bilirubin, phospholipids and bile salts were fivefold decreased, while LDH was sixfold higher in cold stored versus NEVLP grafts. HA perfusion was decreased (twofold), and bile duct necrosis was increased (100% vs. 5%, p < 0.0001) in cold stored versus NEVLP livers. Following transplantation, mean serum AST level was higher in the cold stored versus NEVLP group (1809 ± 205 U/L vs. 524 ± 187 U/L, p < 0.05), with similar bile production (2.5 ± 1.2 cc/h vs. 2.8 ± 1.4 cc/h; p = 0.2). NEVLP improved HA perfusion and decreased markers of liver duct injury in DCD grafts.


Subject(s)
Bile Duct Diseases/prevention & control , Brain Death , Liver Transplantation , Organ Preservation/methods , Perfusion/methods , Reperfusion Injury/prevention & control , Angiography , Animals , Bile Duct Diseases/diagnostic imaging , Disease Models, Animal , Male , Reperfusion Injury/diagnostic imaging , Swine , Temperature , Tomography, X-Ray Computed
13.
Transplant Proc ; 44(5): 1351-6, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22664014

ABSTRACT

BACKGROUND: Routine induction therapy in living donor liver transplantation (LDLT) has not been well described. METHODS: We reviewed outcomes of induction therapy with rabbit antithymocyte globulin (rATG) or basiliximab within 1 year of LDLT. RESULTS: Between 2002 and 2007, 184 adults underwent LDLT and received induction therapy in addition to standard immunosuppression. Acute cellular rejection (ACR) developed in 17 of 130 patients (13.1%) who received rATG and 13 of 54 patients (24.1%) who received basiliximab (P = .066). The interval between transplantation and rejection as well as rejection severity was similar in patients who received rATG and those who received basiliximab. Hepatitis C (HCV) recurrence requiring initiation of antiviral therapy was more common in patients who received rATG compared with basiliximab (34.5% vs 8.7%; P = .021), and in those who received induction combined with tacrolimus as opposed to cyclosporine (38.5% vs 3.9%; P = .001). rATG and basiliximab were associated with excellent patient and graft survivals well as low rates of opportunistic infections and malignancies. CONCLUSION: Induction with rATG or basiliximab was well tolerated and highly effective at preventing ACR within 1 year of LDLT, but may be associated with a higher risk of clinically significant HCV recurrence in some patients.


Subject(s)
Antibodies, Monoclonal/adverse effects , Antilymphocyte Serum/adverse effects , Graft Rejection/prevention & control , Hepatitis C/complications , Immunosuppressive Agents/adverse effects , Liver Cirrhosis/surgery , Liver Transplantation/adverse effects , Living Donors , Recombinant Fusion Proteins/adverse effects , Transplantation Conditioning/adverse effects , Adult , Antiviral Agents/therapeutic use , Basiliximab , Chi-Square Distribution , Female , Graft Rejection/immunology , Hepatitis C/diagnosis , Hepatitis C/drug therapy , Humans , Liver Cirrhosis/virology , Liver Transplantation/immunology , Male , Middle Aged , Ontario , Recurrence , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Virus Activation
14.
Am J Transplant ; 12(1): 226-32, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22054257

ABSTRACT

Portal venous (PV) and systemic venous (SV) drainage methods are used in pancreas transplantation. The impact of the reconstruction technique on long-term outcome remains unclear. We compared the efficacy and side effects of both methods in 192 recipients who received synchronous pancreas kidney transplants between November 1995 and November 2007. SV and PV drainage were used in 147 and 45 cases, respectively. Pancreas function was determined by hemoglobin A1c levels and annual oral glucose tolerance test. Serum creatinine assessed kidney function. Serum lipid (low-density lipoprotein, high-density lipoprotein and cholesterol) levels and body mass index were measured annually. Patient and graft survival were calculated by log-rank analysis. Pancreas survival for SV versus PV patients was similar after 5 years (81.8% vs. 75.5%) and 10 years (65.1% vs. 60%; p = NS). Similarly, no difference was detected between the groups regarding kidney survival after 5 years (92.9% vs. 84.4%) and 10 years (81.6% vs. 75.5%; p = NS). Patient survival did not differ at 5 years (94.3% vs. 88.8%) and 10 years (85.1% vs. 84.4%; p = NS). Pancreas and kidney function and the lipid profiles were similar in both groups. SV and PV drainage of pancreas grafts offer similar long-term graft survival and function and choice of method should remain the preference of the surgeon.


Subject(s)
Pancreas Transplantation/methods , Portal Vein/physiopathology , Adult , Creatinine/blood , Female , Glucose Tolerance Test , Humans , Kidney Function Tests , Male
15.
Am J Transplant ; 10(2): 364-71, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20415904

ABSTRACT

Right lobe living donor liver transplantation is an effective treatment for selected individuals with end-stage liver disease. Although 1 year donor morbidity and mortality have been reported, little is known about outcomes beyond 1 year. Our objective was to analyze the outcomes of the first 202 consecutive donors performed at our center with a minimum follow-up of 12 months (range 12-96 months). All physical complications were prospectively recorded and categorized according to the modified Clavien classification system. Donors were seen by a dedicated family physician at 2 weeks, 1, 3 and 12 months postoperatively and yearly thereafter. The cohort included 108 males and 94 females (mean age 37.3 +/- 11.5 years). Donor survival was 100%. A total of 39.6% of donors experienced a medical complication during the first year after surgery (21 Grade 1, 27 Grade 2, 32 Grade 3). After 1 year, three donors experienced a medical complication (1 Grade 1, 1 Grade 2, 1 Grade 3). All donors returned to predonation employment or studies although four donors (2%) experienced a psychiatric complication. This prospective study suggests that living liver donation can be performed safely without any serious late medical complications and suggests that long-term follow-up may contribute to favorable donor outcomes.


Subject(s)
Liver Transplantation , Living Donors , Tissue Donors , Adult , Female , Humans , Liver/surgery , Liver Failure/surgery , Male , Morbidity , Prospective Studies , Treatment Outcome , Universities
16.
Am J Transplant ; 10(3): 612-8, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20121746

ABSTRACT

Donor safety is the paramount concern of living donor liver transplantation (LDLT). Although LDLT is employed worldwide, there is little data on rates and causes of 'no go' hepatectomies-patients brought to the operating room for possible donor hepatectomy whose procedure was aborted. We performed a single-center, retrospective review of all patients brought to the operating room for donor hepatectomy between October 2000 and November 2008. Of 257 right lobe donors, the donor operation was aborted in 12 cases (4.7%). The main reasons for stopping the operation were aberrant ductal or vascular anatomy (seven cases), unsuitable liver quality (three cases) or unexpected intraoperative events (two cases). Over the median period of follow-up of 23 months, there were no long-term complications of patients with aborted donor procedures. This report focuses exclusively on an important issue: the frequency and causes of no go decisions at a single large volume North American LDLT center. The rate of no go donor hepatectomies should be as low as possible without compromising donor safety--however, even with rigorous preoperative evaluation the rate of donor abortions will be significant. The default surgical position should always be to abort the donor operation if there is an unexpected finding that places the donor at increased risk.


Subject(s)
Donor Selection , Hepatectomy/methods , Liver Transplantation/methods , Adult , Female , Hepatic Artery/abnormalities , Hepatic Artery/pathology , Humans , Living Donors , Male , Middle Aged , Retrospective Studies , Safety , Tissue and Organ Harvesting/methods , Treatment Outcome
17.
Br J Surg ; 96(12): 1429-36, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19918862

ABSTRACT

BACKGROUND: The in situ hypothermic liver preservation technique may allow a more aggressive approach to tumours of the caval confluence and/or all three hepatic veins, which would otherwise be deemed irresectable. METHODS: All descriptive data regarding patient demographics, operative characteristics, perioperative complications and outcomes of nine patients in whom this technique was used were collected prospectively. RESULTS: Seven patients underwent liver trisegmentectomy and two had primary retrohepatic venal caval resection. Total hepatic vascular occlusion with in situ hypothermic liver preservation was used for venous reconstruction in all patients. The vena cava was reconstructed with prosthetic graft in seven patients. All main hepatic veins were reconstructed in the seven liver resections. In situ hypothermic liver preservation was well tolerated as evidenced by preserved hepatic synthetic function early after operation. One patient died 66 days after surgery. There were two recurrences after a median follow-up of 14 (range 2-33) months; local recurrence was identified in one patient after 4 months and distant metastasis in another after 8 months. CONCLUSION: The in situ hypothermic liver preservation technique appears to be a useful adjunct to radical hepatobiliary tumour excision procedures that require total hepatic vascular exclusion and major vascular reconstruction.


Subject(s)
Hepatectomy/methods , Hypothermia, Induced/methods , Liver Neoplasms/surgery , Vascular Neoplasms/surgery , Vascular Surgical Procedures/methods , Adult , Aged , Anticoagulants/therapeutic use , Cholangiocarcinoma/surgery , Hepatic Veins/surgery , Humans , Intraoperative Care , Leiomyosarcoma/surgery , Liver Neoplasms/blood supply , Middle Aged , Neoplasm Recurrence, Local/surgery , Neurilemmoma/surgery , Reoperation , Reperfusion/methods , Tissue Preservation , Tomography, X-Ray Computed , Venae Cavae/surgery
18.
Am J Transplant ; 7(4): 998-1002, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17391140

ABSTRACT

Right lobe living donor liver transplantation (RLDLT) is not yet a fully accepted therapy for patients with end-stage liver failure in the Western hemisphere because of concerns about donor safety and inferior recipient outcomes. An outcome analysis from the time of listing for all adult patients who were listed for liver transplantation (LT) at our center was performed. From 2000 to 2006, 1091 patients were listed for LT. One hundred fifty-four patients (LRD; 14%) had suitable live donors and 153 (99%) underwent RLDLT. Of the remaining patients (DD/Waiting List; n = 937), 350 underwent deceased donor liver transplant (DDLT); 312 died or dropped off the waiting list; and 275 were still waiting at the time of this analysis. The LRD group had shorter mean waiting times (6.0 months vs. 9.8 months; p < 0.001). Although medical model for end-stage liver disease (MELD) scores were similar at the time of listing, MELD scores at LT were significantly higher in the DD/Waiting List group (15.4 vs. 19.5; p = 0.002). Patients in Group 1 had a survival advantage with RLDLT from the time of listing (1-year survival 90% vs. 80%; p < 0.001). To our knowledge, this is the first report to document a survival advantage at time of listing for RLDLT over DDLT.


Subject(s)
Hepatectomy/methods , Liver Transplantation/physiology , Living Donors/statistics & numerical data , Tissue Donors/statistics & numerical data , Tissue and Organ Harvesting/methods , Waiting Lists , Adult , Cadaver , Humans , Liver Transplantation/mortality , Patient Selection , Retrospective Studies , Survival Analysis , Time Factors , Treatment Outcome
19.
Cardiovasc Intervent Radiol ; 30(2): 241-7, 2007.
Article in English | MEDLINE | ID: mdl-17200905

ABSTRACT

Fine needles with an end hole or multiple side holes have traditionally been used for percutaneous ethanol injection (PEI) of hepatomas. This study retrospectively evaluates the safety and efficacy of PEI of unresectable medium-to-large (3.5-9 cm) hepatomas using a multipronged needle and with conscious sedation. Twelve patients, eight men and four women (age 51-77 years; mean: 69) received PEI for hepatomas, mostly subcapsular or exophytic in location with average tumor size of 5.6 cm (range: 3.5-9.0 cm). Patients were consciously sedated and an 18G retractable multipronged needle (Quadrafuse needle; Rex Medical, Philadelphia, PA) was used for injection under real-time ultrasound guidance. By varying the length of the prongs and rotating the needle, the alcohol was widely distributed within the tumor. The progress of ablation was monitored by contrast-enhanced ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) after each weekly injection and within a month after the final (third) injection and 3 months thereafter. An average total of 63 mL (range: 20-154 ml) of alcohol was injected per patient in an average of 2.3 sessions. Contrast-enhanced CT, ultrasound, or MRI was used to determine the degree of necrosis. Complete necrosis was noted in eight patients (67%), near-complete necrosis (90-99%) in two (16.7%), and partial success (50-89%) in two (16.7%). Follow-up in the first 9 months showed local recurrence in two patients and new lesions in another. There was no mortality. One patient developed renal failure, liver failure, and localized perforation of the stomach. He responded to medical treatment and surgery was not required for the perforation. One patient had severe postprocedural abdominal pain and fever, and another had transient hyperbilirubinemia; both recovered with conservative treatment. PEI with a multipronged needle is a new, safe, and efficacious method in treating medium-to-large-sized hepatocellular carcinoma under conscious sedation. Its survival benefits require further investigations.


Subject(s)
Carcinoma, Hepatocellular/pathology , Ethanol/administration & dosage , Liver Neoplasms/pathology , Needles , Solvents/administration & dosage , Administration, Cutaneous , Aged , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/surgery , Catheter Ablation , Equipment Safety , Female , Follow-Up Studies , Humans , Injections/instrumentation , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/surgery , Male , Middle Aged , Necrosis , Neoplasm Recurrence, Local , Retrospective Studies , Severity of Illness Index , Tomography, X-Ray Computed , Treatment Outcome
20.
Am J Transplant ; 7(1): 142-50, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17227563

ABSTRACT

Many centers are reluctant to use older donors (>44 years) for adult right-lobe living donor liver transplantation (RLDLT) due to concerns about possible increased morbidity in donors and poorer outcomes in recipients. Since 2000, 130 adult RLDLTs have been performed at our institution. Recipients were divided into those who received a right lobe graft from a donor 44 (n = 41, 32%; mean age 52). The two donor and recipient populations had similar demographic and operative profiles. With a median follow-up of 29 months, the severity and number of complications in older donors were similar to those in younger donors. No living donor died. Older donor allografts had initial allograft dysfunction compared to younger donors. Complication rates were similar among recipients in both groups but there was a higher bile duct stricture rate with older donor grafts (27% vs. 12%; p = 0.04). One-year recipient graft survival was 86% for older donors and 85% for younger donors (p = 0.95). Early experience with the use of selected older adults (>44 years) for RLDLT is encouraging, but may be associated with a higher rate of biliary complications in the recipient.


Subject(s)
Liver Transplantation/adverse effects , Liver Transplantation/methods , Living Donors , Adolescent , Adult , Age Distribution , Age Factors , Algorithms , Cholestasis , Delayed Graft Function , Female , Graft Survival , Humans , Liver Transplantation/mortality , Male , Middle Aged , Postoperative Complications , Retrospective Studies , Survival Analysis
SELECTION OF CITATIONS
SEARCH DETAIL
...