David R. Grant

Survival after hepatic resection for colorectal metastases: a 10-year experience.

BackgroundMetastatic colorectal cancer is a major cause of cancer death in North America. Hepatic resection offers the potential for cure in selected patients. We report the long-term outcomes of patients who underwent hepatic resection for colorectal metastases over a 10-year period at a single hepatobiliary surgical oncology center.MethodsAll patients who underwent liver resection for metastatic colorectal cancer between 1992 and 2002 were identified. Data were retrospectively obtained through chart review. Major outcome variables were disease-free survival and overall survival. Risk factors for disease recurrence and mortality were identified by multivariate analysis by using the Cox proportional hazard method.ResultsA total of 423 hepatectomies were performed for metastatic colorectal cancer. Most operations (n = 276; 65%) were major (four or more segments) hepatectomies. Perioperative morbidity occurred in 74 (17%) patients. There were seven (1.6%) perioperative deaths. The disease-free survival at 1, 5, and 10 years was 64%, 27%, and 22%, respectively. The overall survival at 1, 5, and 10 years was 93%, 47%, and 28%, respectively. Multivariate analysis identified four negative predictive factors for overall survival (hazard ratio; 95% confidence interval): a positive surgical margin (2.9; 1.5–5.3), large metastases (>5 cm; 1.5; 1.1–2.0), multiple metastases (1.4; 1.1–1.9), and age >60 years (1.4; 1.1–1.9).ConclusionsHepatic resection for metastatic colorectal cancer is safe and provides good long-term overall survival rates of 47% at 5 years and 28% at 10 years. An aggressive approach is justified by the low operative mortality rate and good long-term survival, even in individuals with multiple bilobar metastases.Metastatic colorectal cancer is a major cause of cancer death in North America. Hepatic resection offers the potential for cure in selected patients. We report the long-term outcomes of patients who underwent hepatic resection for colorectal metastases over a 10-year period at a single hepatobiliary surgical oncology center. All patients who underwent liver resection for metastatic colorectal cancer between 1992 and 2002 were identified. Data were retrospectively obtained through chart review. Major outcome variables were disease-free survival and overall survival. Risk factors for disease recurrence and mortality were identified by multivariate analysis by using the Cox proportional hazard method. A total of 423 hepatectomies were performed for metastatic colorectal cancer. Most operations (n = 276; 65%) were major (four or more segments) hepatectomies. Perioperative morbidity occurred in 74 (17%) patients. There were seven (1.6%) perioperative deaths. The disease-free survival at 1, 5, and 10 years was 64%, 27%, and 22%, respectively. The overall survival at 1, 5, and 10 years was 93%, 47%, and 28%, respectively. Multivariate analysis identified four negative predictive factors for overall survival (hazard ratio; 95% confidence interval): a positive surgical margin (2.9; 1.5–5.3), large metastases (>5 cm; 1.5; 1.1–2.0), multiple metastases (1.4; 1.1–1.9), and age >60 years (1.4; 1.1–1.9). Hepatic resection for metastatic colorectal cancer is safe and provides good long-term overall survival rates of 47% at 5 years and 28% at 10 years. An aggressive approach is justified by the low operative mortality rate and good long-term survival, even in individuals with multiple bilobar metastases.

Total tumor volume predicts risk of recurrence following liver transplantation in patients with hepatocellular carcinoma

Criteria for the selection of candidates for liver transplantation in the presence of hepatocellular carcinoma (HCC) should accurately predict posttransplant recurrence while not excluding excessive numbers of patients from candidacy. Existing criteria are challenged by the limited accuracy of radiological assessment. The total tumor volume (TTV) was calculated by the addition of the volume of each individual tumor. A preliminary analysis was carried out on HCC patient data from the Alberta Liver Transplant Program (52 patients) and then validated on the populations of the Universities of Toronto and Colorado programs (154 and 82 patients). A TTV cutoff of 115 cm3 was chosen on the basis of the risk of recurrence with use of a receiver operating characteristic curve. Radiology correlated more closely to pathology with TTV than with Milan and University of California at San Francisco (UCSF) criteria (91% versus 69% and 75% of patients, P < 0.0001). Although more patients met qualifying criteria for transplant with TTV (28%‐53% more than Milan and 16%‐26% more than UCSF), no deterioration of outcome was demonstrated in an analysis of patients within TTV ≤ 115 cm3 in comparison with those meeting Milan or UCSF classifications at all institutions. Patients with TTV > 115 cm3 experienced more recurrences and lower patient survival in the Alberta and Colorado series (P < 0.05). When TTV with a cutoff of 115 cm3 is used for candidate selection, the accuracy of pretransplant radiological assessment is enhanced, with posttransplant outcomes not different from those achieved with Milan and UCSF classifications despite a more inclusive patient population. Liver Transpl 14:1107–1115, 2008.

Needle Tract Seeding after Radiofrequency Ablation of Hepatic Tumors

PURPOSE To determine the incidence and risk factors associated with needle tract seeding after radiofrequency ablation (RFA) of liver tumors. MATERIALS AND METHODS A prospective data base of patients with hepatic tumors treated by RFA from December 1999 until August 2003 was reviewed to identify patients with needle tract seeding. During this period, 200 patients (148 men, 52 women) with 299 lesions underwent 298 treatment sessions. Patients with both primary (153 hepatocellular carcinoma, two cholangiocarcinoma) and a variety of secondary tumors (35 colorectal, 10 other) were treated. RFA was performed percutaneously with computed tomography (CT) and/or ultrasound (US) guidance, or with US guidance at laparoscopy or laparotomy. All procedures were performed with a LeVeen needle electrode. The needle tract was not routinely coagulated or embolized. RESULTS Eight patients out of 200 (4%) were identified with needle tract seeding, based on imaging findings or surgical reintervention. This corresponds to a rate of eight of 298 (2.7%) per treatment session and eight of 299 (2.7%) per lesion. Statistically significant risk factors for neoplastic seeding included treatment of a subcapsular lesion (OR = 11.57, P = .007), multiple treatment sessions (OR = 2.0, P = .037), and multiple electrode placements (OR = 1.4, P = .006). CONCLUSIONS Neoplastic seeding may occur after RFA of liver tumors. The results show that the frequency of this complication is not insignificant, and are at the upper end of rates reported in the literature of 0.5% to 2.8%. Specific risk factors identified in this study include treatment of subcapsular lesions, patients treated in multiple sessions, and lesions requiring more than one electrode placement.

Intestine transplantation in the United States, 1999-2008.

Improving short‐term results with intestine transplantation have allowed more patients to benefit with nearly 700 patients alive in the United States with a functioning allograft at the end of 2007. This success has led to an increase in demand. Time to transplant and waiting list mortality have significantly improved over the decade, but mortality remains high, especially for infants and adults with concomitant liver failure. The approximately 200 intestines recovered annually from deceased donors represent less than 3% of donors who have at least one organ recovered. Consent practice varies widely by OPTN region. Opportunities for improving intestine recovery and utilization include improving consent rates and standardizing donor selection criteria. One‐year patient and intestine graft survival is 89% and 79% for intestine‐only recipients and 72% and 69% for liver‐intestine recipients, respectively. By 10 years, patient and intestine survival falls to 46% and 29% for intestine‐only recipients, and 42% and 39% for liver‐intestine, respectively. Immunosuppression practice employs peri‐operative antibody induction therapy in 60% of cases; acute rejection is reported in 30%–40% of recipients at one year. Data on long‐term nutritional outcomes and morbidities are limited, while the cause and therapy for late graft loss from chronic rejection are areas of ongoing investigation.

Derivation of a risk index for the prediction of massive blood transfusion in liver transplantation.

Massive blood transfusion (MBT) remains a serious and common occurrence in liver transplantation surgery. This retrospective cohort study was undertaken to identify preoperative predictors of MBT and to develop a risk index for MBT in liver transplantation. Data were retrospectively collected on all liver transplantations carried out at a single institution between January 1998 and March 2004. Multivariable logistic regression analysis was used to identify independent predictor variables of MBT, defined as ≥6 units of red blood cell concentrate (RBC) in the first 24 hours of surgery. The model was internally validated by bootstrapping. Of the 460 liver transplant recipients, 193 (42%) received ≥6 units of RBC within 24 hours of surgery. Unadjusted analyses identified 12 preoperative predictors of MBT: age, height, gender, repeat transplantation, etiology of liver failure, and preoperative laboratory values (hemoglobin concentration, platelet count, international normalized ratio for prothrombin activity [INR], albumin, total bilirubin, and creatinine). In multivariable logistic regression, 7 independent predictors of MBT were identified: age (>40 years), hemoglobin concentration (≤10.0 g/dL), INR (1.2‐1.99, and >2.0), platelet count (≤70 × 109/L), creatinine (≥110 μmol/L for female subjects and ≥120 μmol/L for male subjects), albumin (< 28 g/L), and repeat transplantation. The area under the receiver‐operating characteristic curve (ROC) for the model was 0.82. By using the regression β coefficients to derive weights for each of these predictors, a risk index was developed that assigned each patient a score between 0 and 8. The ROC for this risk index was 0.79. MBT in liver transplantation surgery can be accurately predicted by 7 readily available preoperative predictors. Liver Transpl, 2006.

Adult living liver donors have excellent long-term medical outcomes: the University of Toronto liver transplant experience.

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.

Adult Right-Lobe Living Liver Donors: Quality of Life, Attitudes and Predictors of Donor Outcomes

To refine selection criteria for adult living liver donors and improve donor quality of care, risk factors for poor postdonation health‐related quality of life (HRQOL) must be identified. This cross‐sectional study examined donors who underwent a right hepatectomy at the University of Toronto between 2000 and 2007 (n = 143), and investigated predictors of (1) physical and mental health postdonation, as well as (2) willingness to participate in the donor process again. Participants completed a standardized HRQOL measure (SF‐36) and measures of the pre‐ and postdonation process. Donor scores on the SF‐36 physical and mental health indices were equivalent to, or greater than, population norms. Greater predonation concerns, a psychiatric diagnosis and a graduate degree were associated with lower mental health postdonation whereas older donors reported better mental health. The majority of donors (80%) stated they would donate again but those who perceived that their recipient engaged in risky health behaviors were more hesitant. Prospective donors with risk factors for lower postdonation satisfaction and mental health may require more extensive predonation counseling and postdonation psychosocial follow‐up. Risk factors identified in this study should be prospectively evaluated in future research.

The Difference in the Fibrosis Progression of Recurrent Hepatitis C After Live Donor Liver Transplantation Versus Deceased Donor Liver Transplantation Is Attributable to the Difference in Donor Age

Hepatitis C recurs universally after liver transplantation (LT). Whether its progression differs after live donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT) is still debated. We retrospectively analyzed 201 consecutive LTs performed at our institution for hepatitis C–related end‐stage liver disease between April 2000 and December 2005 (46 LDLTs and 155 DDLTs). Patients were followed with protocol biopsies for medians of 29 (LDLT) and 39 months (DDLT; P = 0.7). Although overall graft and patient survival did not differ, the mean fibrosis stage (Metavir) was significantly higher at 12 to 48 months post‐LT (all P < 0.05), and the rate of fibrosis progression tended to be faster after DDLT than LDLT (0.19 versus 0.11 stage/year, P = 0.05). In univariate analysis, donor age, cold ischemic time, and DDLT were significantly associated with a fibrosis stage ≥ 1 at 1 year and a fibrosis stage of 3 or 4 at 2 years post‐LT. In multivariate analysis, however, donor age was the sole variable independently associated with both surrogate outcomes. Thus, donor age > 45 years carried a relative risk of 8.17 (confidence interval = 2.6–25.5, P = 0.001) for reaching fibrosis stage 3 or 4 at 2 years post‐LT. In conclusion, donor age, rather than the transplant approach, determines the progression of recurrent hepatitis C after LT. LDLT, allowing for the selection of younger donors, may particularly benefit hepatitis C patients. Liver Transpl 14:1778–1786, 2008.

Reduced Mortality with Right-Lobe Living Donor Compared to Deceased-Donor Liver Transplantation When Analyzed from the Time of Listing

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.

Living donor liver transplantation versus deceased donor liver transplantation for hepatocellular carcinoma: Comparable survival and recurrence

Several studies have reported higher rates of recurrent hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) versus deceased donor liver transplantation (DDLT). It is unclear whether this difference is due to a specific biological effect unique to the LDLT procedure or to other factors such as patient selection. We compared the overall survival (OS) rates and the rates of HCC recurrence after LDLT and DDLT at our center. Between January 1996 and September 2009, 345 patients with HCC were identified: 287 (83%) had DDLT and 58 (17%) had LDLT. The OS rates were calculated with the Kaplan‐Meier method, whereas competing risks methods were used to determine the HCC recurrence rates. The LDLT and DDLT groups were similar with respect to most clinical parameters, but they had different median waiting times (3.1 versus 5.3 months, P = 0.003) and median follow‐up times (30 versus 38.1 months, P = 0.02). The type of transplant did not affect any of the measured cancer outcomes. The OS rates at 1, 3, and 5 years were equivalent: 91.3%, 75.2%, and 75.2%, respectively, for the LDLT group and 90.5%, 79.7%, and 74.6%, respectively, for DDLT (P = 0.62). The 1‐, 3‐, and 5‐year HCC recurrence rates were also similar: 8.8%, 10.7%, and 15.4%, respectively, for the LDLT group and 7.5%, 14.8%, and 17.0%, respectively, for the DDLT group (P = 0.54). A regression analysis identified microvascular invasion (but not the graft type) as a predictor of HCC recurrence. In conclusion, in well‐matched cohorts of LDLT and DDLT recipients, LDLT and DDLT provide similarly low recurrence rates and high survival rates for the treatment of HCC. Liver Transpl 18:315–322, 2012.