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Objectives To assess the added value of gadoxetic-acid–enhanced T1-weighted magnetic resonance Cholangiography (T1W-MRC) including controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA)-Volumetric Interpolated Breathhold (VIBE) technique compared to T2-weighted MR Cholangiography (T2W-MRC) in depicting biliary anatomy in potential living liver donors. Methods Eighty-five potential donors including 34 men with a mean age of 35.6 years (range, 18–55 years) and 51 women with a mean age of 36.7 years (range, 23–57 years), were enrolled in this ethics-approved retrospective study. Image quality for depiction of bile ducts was evaluated by two readers in consensus in 3 separate reading sessions: 1) T2W-MRC alone, 2) T1W-MRC alone (including CAIPI-VIBE and generalized autocalibrating partially parallel acquisitions (GRAPPA)-VIBE techniques, and 3) combined T1W/T2W-MRC. Accuracy of T2W-MRC, T1W-MRC, and combined T1W/T2W-MRC for the identification/classification of the biliary variants was calculated using intraoperative cholangiogram (IOC) as the reference standard. Image quality and reader diagnostic confidence provided by CAIPI-VIBE technique was compared with GRAPPA-VIBE technique. Datasets were compared using the Wilcoxon signed-rank test. Results Image quality for depiction of the bile ducts was significantly superior in the combined T1W/T2W-MRC group, when compared to each of T2W-MRC and T1W-MRC groups independently (P value = 0.001–0.034). The combination of CAIPI-VIBE and GRAPPA-VIBE was superior compared to each of the sequences individually. The accuracy of T2W-MRC and T1W-MRC was 93% and 91%, respectively. T1W-MRC depicted four biliary variants better than T2W-MRC. Two variants not well seen in T2W-MRC were clearly shown on T1W-MRC. Conclusion Gadoxetic-acid–enhanced T1W-MRC and conventional T2W-MRC techniques are complementary for depiction of biliary variants in potential liver donors and the combination of the two improves the results. The combination of CAIPI-VIBE and GRAPPA-VIBE techniques appear to be complementary for optimal diagnostic yield of T1W-MRC.

Radiofrequency ablation (RFA) is an effective treatment for single hepatocellular carcinoma (HCC) ≤3 cm. Disease recurrence is common, and in some patients will occur outside transplant criteria. We aimed to assess the incidence and risk factors for recurrence beyond Milan criteria in potentially transplantable patients treated with RFA as first-line therapy.We performed a retrospective cohort study of potentially transplantable patients with new diagnoses of unifocal HCC ≤3 cm that underwent RFA as first-line therapy between 2000-2015. We defined potentially transplantable patients as those aged70 years without any comorbidities that would preclude transplant surgery. Incidence of recurrence beyond Milan criteria was compared across 2 groups according to HCC diameter at the time of ablation: (HCC ≤2 cm vs. HCC2 cm). Competing risks Cox regression was used to identify predictors of recurrence beyond Milan criteria.We included 301 patients (167 HCC ≤2 cm and 134 HCC2 cm). Recurrence beyond Milan criteria occurred in 36 (21.6%) and 47 (35.1%) patients in the HCC ≤2 cm and the HCC2 cm groups, respectively (p = 0.01). The 1-, 3- and 5-year actuarial survival rates after RFA were 98.2%, 86.2% and 79.0% in the HCC ≤2 cm group vs. 93.3%, 77.6% and 70.9% in the HCC2 cm group (p = 0.01). Tumor size2 cm (hazard ratio 1.94; 95%CI 1.25-3.02) and alpha-fetoprotein levels at the time of ablation (100-1,000 ng/ml: hazard ratio 2.05; 95%CI 1.10-3.83) were found to be predictors of post-RFA recurrence outside Milan criteria.RFA for single HCC ≤3 cm provides excellent short- to medium-term survival. However, we identified patients at higher risk of recurrence beyond Milan criteria. For these patients, liver transplantation should be considered immediately after the first HCC recurrence following RFA.Radiofrequency ablation and liver transplantation are treatment options for early stages of hepatocellular carcinoma (HCC). After ablation some patients will experience recurrence or metastatic spread of the initial tumor or may develop new tumors within the liver. Despite close follow-up, these recurrences can progress rapidly and exceed transplant criteria, preventing the patient from receiving a transplant. We identified that patients with HCC2 cm and higher serum alpha-fetoprotein are at greater risk of recurrence beyond the transplant criteria. These data suggest that liver transplantation should be considered immediately after the first HCC recurrence for these patients.

Normothermic ex vivo kidney perfusion (NEVKP) demonstrated superior results compared to hypothermic storage in donation after circulatory death (DCD) kidney transplantation. It is unknown whether an optimal perfusion time exists following hypothermic storage to allow for the recovery of renal grafts from cold ischemic injury. In a porcine model of DCD kidney autotransplantation, the impact of initial static cold storage (SCS) (8 h) followed by various periods of NEVKP recovery was investigated: group A, 8 hSCS only (control); group B, 8 hSCS + 1 hNEVKP (brief NEVKP); group C, 8 hSCS + 8 hNEVKP (intermediate NEVKP); and group D, 8 hSCS + 16 hNEVKP (prolonged NEVKP). All grafts were preserved and transplanted successfully. One animal in group D was sacrificed and excluded by postoperative day 3 due to hind limb paralysis, but demonstrated good renal function. Postoperative graft assessment during 8 days' follow-up demonstrated lowest levels of peak serum creatinine for intermediate (C) and prolonged (D) NEVKP (p = 0.027). Histological assessment on day 8 demonstrated a significant difference in tubular injury (p = 0.001), with highest values for group B. These results suggest that longer periods of NEVKP following SCS are feasible and safe for postponing surgical transplant procedure and superior to brief NEVKP, reducing the damage caused during cold ischemic storage of renal grafts.

Normothermic ex vivo liver perfusion (NEVLP) offers the potential to optimize graft function prior to liver transplantation (LT). Hepatitis C virus (HCV) is dependent on the presence of miRNA(microRNA)-122. Miravirsen, a locked-nucleic acid oligonucleotide, sequesters miR-122 and inhibits HCV replication. The aim of this study was to assess the efficacy of delivering miravirsen during NEVLP to inhibit miR-122 function in a pig LT model. Pig livers were treated with miravirsen during NEVLP or cold storage (CS). Miravirsen absorption, miR-122 sequestration, and miR-122 target gene derepression were determined before and after LT. The effect of miravirsen treatment on HCV infection of hepatoma cells was also assessed. NEVLP improved miravirsen uptake versus CS. Significant miR-122 sequestration and miR-122 target gene derepression were seen with NEVLP but not with CS. In vitro data confirmed miravirsen suppression of HCV replication after established infection and prevented HCV infection with pretreatment of cells, analogous to the pretreatment of grafts in the transplant setting. In conclusion, miravirsen delivery during NEVLP is a potential strategy to prevent HCV reinfection after LT. This is the first large-animal study to provide "proof of concept" for using NEVLP to modify and optimize liver grafts for transplantation.

Fibrinogen-like protein 2 (FGL2) is an immunomodulatory protein that is expressed by regulatory T cells (Tregs). The objective of this study was to determine if recombinant FGL2 (rFGL2) treatment or constitutive FGL2 overexpression could promote transplant tolerance in mice. Although rFGL2 treatment prevented rejection of fully mismatched cardiac allografts, all grafts were rejected after stopping treatment. Next, we generated FGL2 transgenic mice (fgl2(Tg) ) that ubiquitously overexpressed FGL2. These mice developed normally and had no evidence of the autoimmune glomerulonephritis seen in fgl2(-/-) mice. Immune characterization showed fgl2(Tg) T cells were hypoproliferative to stimulation with alloantigens or anti-CD3 and anti-CD28 stimulation, and fgl2(Tg) Tregs had increased immunosuppressive activity compared with fgl2(+/+) Tregs. To determine if FGL2 overexpression can promote tolerance, we transplanted fully mismatched cardiac allografts into fgl2(Tg) recipients. Fifty percent of cardiac grafts were accepted indefinitely in fgl2(Tg) recipients without any immunosuppression. Tolerant fgl2(Tg) grafts had increased numbers and proportions of Tregs and tolerant fgl2(Tg) mice had reduced proliferation to donor but not third party antigens. These data show that tolerance in fgl2(Tg) recipients involves changes in Treg and T cell activity that contribute to a higher intragraft Treg-to-T cell ratio and acceptance of fully mismatched allografts.

Purpose To determine whether response to transarterial chemoembolization can predict survival in patients with hepatocellular carcinoma (HCC) who are candidates for orthotopic liver transplantation (LT) and if either European Association for Study of the Liver (EASL) criteria or Response Evaluation Criteria in Solid Tumors (RECIST) criteria are more accurate for this purpose. Materials and Methods A retrospective review of all patients who underwent LT after transarterial chemoembolization between January 2005 and June 2011 was performed. Follow-up imaging with multiphasic computed tomography or magnetic resonance imaging was performed 1 month after transarterial chemoembolization and every 3 months thereafter until LT. Treatment response was evaluated at each imaging time point using RECIST criteria and EASL criteria. The relationship between survival and objective response (OR), time to response (TTR), time to progression (TTP), and time interval between transarterial chemoembolization and LT was assessed. Results A median of one transarterial chemoembolization procedure was performed before LT in 58 patients (52 men, 6 women; mean age, 57 y). OR was shown by 28 (48%) patients and 51 (88%) patients at 1 month by EASL criteria and RECIST criteria, respectively. OR at 1-month follow-up using RECIST criteria was associated with increased survival compared with patients with no response (NR) ( P = .03). Using RECIST criteria, 5-year survival in the OR group was 66.7% versus 0% in the NR group ( P = .015). There was no significant difference in survival in patients who showed OR at 1 month using EASL criteria. There was poor agreement between RECIST and EASL response assessments (κ = 0.23). There was no significant association between survival and TTR, TTP, or time interval between transarterial chemoembolization and LT. Conclusions Patients with objective response to transarterial chemoembolization at 1 month using RECIST criteria showed improved survival over nonresponders. RECIST criteria demonstrated better accuracy compared with EASL criteria for predicting survival in patients after LT who had transarterial chemoembolization as a "bridge."

There are no published series of the assessment process, profiles and outcomes of anonymous, directed or nondirected live liver donation. The outcomes of 29 consecutive potential anonymous liver donors at our center were assessed. We used our standard live liver assessment process, augmented with the following additional acceptance criteria: a logical rationale for donation, a history of social altruism, strong social supports and a willingness to maintain confidentiality of patient information. Seventeen potential donors were rejected and 12 donors were ultimately accepted (six male, six female). All donors were strongly motivated by a desire and sense of responsibility to help others. Four donations were directed toward recipients who undertook media appeals. The donor operations included five left lateral segmentectomies and seven right hepatectomies. The overall donor morbidity was 40% with one patient having a transient Clavien level 3 complication (a pneumothorax). All donors are currently well. None expressed regret about their decision to donate, and all volunteered the opinion that donation had improved their lives. The standard live liver donor assessment process plus our additional requirements appears to provide a robust assessment process for the selection of anonymous live liver donors. Acceptance of anonymous donors enlarges the donor liver pool.

Note on sources: The articles in this report are based on the reference tables in the 2009 OPTN/SRTR Annual Report, which are not included in this publication. Many relevant data appear in the figures and tables included here. All of the tables may be found online at: http://www.ustransplant.org. 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 intestineonly 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.

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.

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.

Purpose Complete resection with adjuvant chemotherapy is the accepted treatment for hepatoblastoma. The aim of this study is to evaluate our results of liver transplantation (LT) for tumors still unresectable after adequate chemotherapy. Methods All patients transplanted for hepatoblastoma from 2 institutions between 1990 and 2004 were included. Variables reviewed to determine impact on survival included the following: previous tumor resection, metastatic disease at diagnosis, microscopic vascular invasion, α -fetoprotein (AFP) levels at diagnosis and at transplant, tumor histology, and administration of posttransplantation chemotherapy. Effectiveness of pretransplantation chemotherapy was defined as a drop of more than 99% in peak AFP levels. Results Fourteen patients were transplanted: 9 boys and 5 girls (age range, 18 months-13 years; mean age, 57 ± 48 months). Patients were transplanted a mean of 4 ± 1 months after diagnosis. Overall survival was 71% (10/14) with a mean follow-up of 46 months. All deaths were secondary to recurrent tumor. Of 10 patients who underwent a primary LT, 9 survived compared to only 1 of 4 transplanted for unresectable tumor recurrence after primary resection (90% vs 25%; P = .02). Decline in peak AFP of more than 99% was also associated with better survival (100% vs 56%; P = .08). Similarly, patients who received posttransplantation chemotherapy had 100% survival compared with 56% without chemotherapy ( P = .08). Other variables had little effect on survival. Conclusions Liver transplantation is a successful treatment option for children with unresectable hepatoblastoma with a 90% survival rate for primary transplantation. Rescue LT for recurrent hepatoblastoma after previous resection has a poor survival outcome and should be considered a relative contraindication. Posttransplantation chemotherapy improves survival. A prospective multicenter collaboration to validate these findings with a larger patient population is necessary. Until that time, patients who receive rescue transplants should receive posttransplantation chemotherapy.

Background Tumor recurrence remains the major cause of death after curative resection for hepatocellular carcinoma (HCC). The purpose of this study was to identify risk factors for the recurrence of HCC and to examine long-term outcomes after resection. Methods From July 1992 to July 2004, 193 consecutive patients who underwent hepatic resection as primary therapy with curative intent for HCC were included in this single-center analysis. The perioperative mortality rate was 5%. Time to recurrence (disease-free survival) and overall survival were determined by Kaplan-Meier analysis. Demographic, tumor, and treatment characteristics were tested for their prognostic significance by univariate and multivariate analysis with the log-rank test and the Cox proportional hazards model, respectively. Results Median overall survival for the entire cohort was 71 ± 11 months; disease-free survival was 34 months (range, 1-149 months). After a median follow-up time of 34 months, 98 patients (51%) experienced recurrent cancer; initial tumor recurrence was confined to the liver in 86 patients (88%). With the use of multivariate analysis, preoperative vascular invasion detected on radiologic imaging studies; postoperative vascular invasion found on pathologic assessment, and intermediate and poor tumor differentiation and tumor size and number were significant predictors of disease-free survival. Of the 98 patients who had tumor recurrence, 53 patients (54%) underwent additional therapy (ablation, 31 patients; re-resection, 11 patients; transarterial chemoembolization, 8 patients; liver transplantation, 3 patients) with improvement in survival. Conclusion Despite recurrences in >50% of patients, long-term survival can be achieved after resection of HCC. Identification of risk factors, close follow-up evaluation, and early detection are mandatory because recurrences that are confined to the liver may be amenable to treatment with an additional survival benefit.

Biliary strictures remain the most challenging aspect of adult right lobe living donor liver transplantation (RLDLT). Between 04/2000 and 10/2005, 130 consecutive RLDLTs were performed in our center and followed prospectively. Median follow-up was 23 months (range 3-67) and 1-year graft and patient survival was 85% and 87%, respectively. Overall incidence of biliary leaks (n = 19) or strictures (n = 22) was 32% (41/128) in 33 patients (26%). A duct-to-duct (D-D) or Roux-en-Y (R-Y) anastomosis were performed equally (n = 64 each) with no difference in stricture rate (p = 0.31). The use of ductoplasty increased the number of grafts with a single duct for anastomosis and reduced the biliary complication rate compared to grafts/=2 ducts (17% vs. 46%; p = 0.02). Independent risk factors for strictures included older donor age and previous history of a bile leak. All strictures were managed nonsurgically initially but four patients ultimately required conversion from D-D to R-Y. Ninety-six percent (123/128) of patients are currently free of any biliary complications. D-D anastomosis is safe after RLDLT and provides access for future endoscopic therapy in cases of leak or stricture. When presented with multiple bile ducts, ductoplasty should be considered to reduce the potential chance of stricture.

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/=age 44 (n = 89, 68%; median age 30) and those who received a liver graft from a donor age44 (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.

Background. High-pressure water-jet dissection was originally developed for industry where ultra-precise cutting and engraving were desirable. This technology has been adapted for medical applications with favorable results, but little is understood about its performance in hepatic resections. Blood loss may be limited by the thin laminar liquid-jet effect that provides precise, controllable, tissue-selective dissection with excellent visualization and minimal trauma to surrounding fibrous structures. Patients and methods. The efficacy of the Water-jet system for hepatic parenchymal dissection was examined in a consecutive case series of 101 hepatic resections (including 22 living donor transplantation resections) performed over 11 months. Perioperative outcomes, including blood loss, transfusion requirements, complications, and length of stay (LOS), were assessed. Results. Three-quarters of the cases were major hepatectomies and 22% were cirrhotic. Malignancy was the most common indication (77%). Median operative time was 289min. Median estimated blood loss (EBL) was 900ml for all cases, and only 14% of patients had >2000ml EBL. Furthermore, EBL was 1000ml for major resections, 775ml for living donor resections, 600ml in cirrhotic patients, and 1950ml for steatotic livers. In all, 14% of patients received heterologous packed red blood cell (PRBC) transfusions for an average of 0.59 units per case. Median LOS was 7 days. EBL, transfusion requirements, and LOS were slightly increased in the major resection cohort. There was one mortality (1%) overall. These results are equivalent to, or better than, those from our contemporary series of resections performed with ultrasonic dissection. Conclusion. Water-jet dissection minimizes large blood volume loss, requirements for transfusion, and complications. This initial experience suggests that this precision tool is safe and effective for hepatic division, and compares favorably to other established methods for hepatic parenchymal transection.

Background The role of isolated liver transplantation in infants with parenteral nutrition–associated cholestasis (PNAC) associated with short bowel syndrome (SBS) is unclear. Methods We performed a retrospective descriptive study of infants with PNAC and SBS who received an isolated liver transplant at our institution. Review of the literature was also performed. Results Three infants (aged 7, 8, and 13 months) with SBS and PNAC received an isolated liver transplant. Etiology of SBS was necrotizing enterocolitis, gastroschisis, and volvulus. Two patients with pretransplant small bowel length of 40 and 80 cm, who were receiving 65% and 79% of intake enterally, demonstrated good graft function (bilirubin, 0 and 7 μ mol/L) at 41 and 58 months posttransplant. Despite full tolerance of enteral feeds, both remain on parenteral nutrition (PN) (4 and 7 nights per week) for poor weight gain. One child with 25 cm of small bowel, who received 65% of energy enterally pretransplant, died 7 months posttransplant from PNAC. A literature review revealed 22 cases of isolated liver transplant for PNAC associated with SBS. Overall survival was 77%, with 76% of survivors demonstrating independence from PN. Conclusions Isolated liver transplantation is an acceptable option for select infants with PNAC associated with SBS when further intestinal adaptation and freedom from PN are anticipated.

During liver transplantation, the donor graft is subjected to a number of acute stresses whose molecular basis is not well-understood. The effects of surgical stress, preservation and reperfusion injury were studied in 24 consecutive living donor liver transplant (LDLT) operations. Liver biopsies were taken early in the donor operation (OPENING), after transection of the donor liver (PRECLAMP) and following implantation of the graft (post hepatic artery, [PHA]); these were evaluated for histology, tissue glutathione content and gene expression using a 19K-human cDNA microarray. LDLT was associated with an ischemia/reperfusion injury, with accumulation of small numbers of neutrophils and decreased glutathione in the PHA biopsies. Following reperfusion, the expression of 129 genes increased and 106 genes decreased when compared to OPENING levels (> or

The shortage of deceased organ donors has created a need for right lobe living donor liver transplantation (RLDLT) in adults. Concerns regarding donor safety, however, necessitate continuous assessment of donor acceptance criteria and documentation of donor morbidity. We report the outcomes of our first 101 donors who underwent right lobectomy between April 2000 and November 2004. The cohort comprised 58 men and 43 women with a median age of 37.8 years (range: 18.6-55 years); median follow-up is 24 months. The middle hepatic vein (MHV) was taken with the graft in 55 donors. All complications were recorded prospectively and stratified by grade according to Clavien's classification. Overall morbidity rate was 37%; all complications were either grade 1 or 2, and the majority occurred during the first 30 days after surgery. Removal of the MHV did not affect morbidity rate. There were significantly fewer complications in the later half of our experience. All donors are well and have returned to full activities. With careful donor selection and specialized patient care, low morbidity rates can be achieved after right hepatectomy for living donor liver transplantation.

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.

The role of small bowel-derived epithelial cells in regulating the accumulation of inflammatory cells within the inflamed gut epithelium is poorly understood because of the difficulties in culturing the epithelial cells in vitro. We have recently developed a cloned epithelial cell line (IEC-4.1) derived from the small intestine of BALB/c mice. In the present study, we examined whether IEC-4.1 cells could express adhesion molecules ICAM-1 and VCAM-1 and the molecular basis of macrophage adhesion to the epithelial cells. Northern blot analysis demonstrated that IEC-4.1 cells constitutively expressed ICAM-1 and VCAM-1 mRNA at low levels. Stimulation with LPS (12 microg/ml) or TNF-alpha (2.5 ng/ml) markedly upregulated ICAM-1 and VCAM-1 gene expression in IEC-4.1 cells. ICAM-1 mRNA started to increase 2 hr after LPS stimulation, peaked at 4 hr, and then decreased rapidly to the basal level at 8 hr. VCAM-1 mRNA had the similar pattern of upregulation but the increased VCAM-1 mRNA sustained over a longer period of time and did not return to the basal level until 24 hr after the stimulation. IEC-4.1 cells expressed very low basal levels of ICAM-1 and VCAM-1 on the cell surface as demonstrated by immunofluorescence staining and FACS analysis. Stimulation of IEC-4.1 cells with LPS or TNF-alpha markedly increased the surface expression of both ICAM-1 and VCAM-1, which correlated with the increased binding of macrophages to the stimulated IEC-4.1 cells. Adherence of macrophages to the IEC-4.1 cells was mediated by both LFA-1/ICAM-1 and VLA-4/VCAM-1 since blocking both adhesion pathways inhibited macrophage adhesion by about 90%. These findings suggest that small bowel-derived epithelial cells may be capable of expressing a defined set of functional adhesion molecules during mucosal inflammation.

To compare the metabolic effects of portal and systemic delivery of insulin, we used portal-caval transposition (PCT) in rats to provide total systemic diversion of splanchnic venous blood. PCT rats exhibited normal weight gain, liver histology, liver-function tests, glycosylated hemoglobin, arterial blood pressure, and hepatic blood flow. Mean liver weight relative to body weight was 12% lower in PCT rats than in sham-operated control (CTR) rats 30 days following transposition. Indwelling venous catheters were established to facilitate metabolic studies in conscious, minimally restrained animals. Postabsorptive plasma glucose and C-peptide (CPEP) levels were similar in PCT and CTR rats; however, postabsorptive immunoreactive insulin (IRI) levels were elevated in PCT rats (67 ± 3.1 v 49 ± 3.5 pmol · L−1, P < .002, n = 11 v 11), as were postabsorptive plasma glucagon levels (570 ± 67 v 240 ± 11 ng · L−1, P < .001, n = 11 v 16) at similar body weights. The postabsorptive CPEP/IRI concentration ratio was lower in PCT than in CTR rats (4.0 ± 0.3 v 6.0 ± 0.6, P < .02), suggesting reduced hepatic extraction of insulin. Insulin sensitivity (IS), determined by minimal model analysis of frequently sampled intravenous glucose tolerance tests yielding the sensitivity index (SI), was reduced in PCT compared with CTR (61 ± 5.6 v 86 ± 9.0 (μmol · L−1)−1 · min−1, P < .04, n = 9 v 10). During euglycemic-hyperinsulinemic clamps, glucose infusion rates (GIRs) from 60 to 120 minutes were lower in PCT than in CTR rats (6.0 ± 0.3 v 8.0 ± 0.4 g · kg−1 · min−1, P < .002, n = 9 v 7) with matching plasma IRI levels, confirming the reduced IS in PCT rats. Areas under the concentration curves ([AUCs] 0 to 150 minutes) for glucose tolerance tests (gavage) indicated that plasma glucose excursion was similar in PCT and CTR rats whereas AUC IRI was significantly higher in PCT than in CTR rats (23 ± 1.3 v 18 ± 0.6 nmol · L−1 · min, P < .009, n = 11 v 11). However, AUC CPEP for oral glucose tolerance tests was lower in PCT than in CTR rats (55 ± 3.4 v 68 ± 4.8 nmol · L−1 · min, P < .05), indicating decreased insulin secretion. Thus, the mean ratio AUC CPEP/AUC IRI was significantly lower in PCT rats (2.5 ± 0.2 v 3.8 ± 0.3, P < .002), again suggesting reduced hepatic extraction of insulin. Thus, euglycemia after PCT was accompanied by elevated postabsorptive and glucose-stimulated levels of IRI in systemic blood, postabsorptive hyperglucagonemia, and decreased insulin secretion in response to glucose challenge (gavage), with diminished hepatic extraction of insulin and decreased IS. The PCT model illustrates the insulin-resistant adaptive state that results from systemic delivery of insulin, and indicates the importance of hepatic portal delivery of insulin and possibly of other gastroenteropancreatic hormones in the maintenance of IS and physiological metabolic control.

The problems, progress, and future prospects of small bowel transplantation are reviewed. Recent advances include the development of techniques for successful combined liver/small bowel transplantation, isolated small bowel transplantation, and colon transplantation. Bowel transplantation appears destined to become the preferred treatment for patients with end-stage intestinal failure. Current protocols, however, need to be refined to achieve (1) lower rates of rejection and infections and (2) more consistent graft function.

ND-STAGE CHRONIC liver disease (ESCLD) due to hepatitis C virus (HCV) infection is now the most frequent indication for orthotopic liver transplantation (OLT) in North America. HCV is a lymphotrophic virus and has the potential to stimulate immune-mediated diseases. Other lymphotrophic viruses such as cytomegalovirus have been associated with increased risk of rejection following OLT, but little information is available regarding the role of HCV in this respect. 1 In the setting of organ transplantation the immunostimulatory effects of HCV may increase the risk of acute and chronic allograft rejection. A recent report in renal transplant recipients suggests an increased risk of renal allograft rejection in patients with HCV. 2 To investigate the role of HCV in liver allograft rejection and survival, we identified all recipients of first OLT with ESCLD secondary to HCV at our unit during the 5-year period from January 1, 1992 to December 31, 1996 and compared them to contemporaneous patients with nonviral causes of liver disease (non-HCV).

Isogeneic intestinal transplantation of iron-loaded and iron-deficient intestine into iron-deficient rats was performed in 20 Lewis rats to isolate the effect of intestinal mucosal iron on iron absorption. Rats were iron loaded with three weekly IM injections of 50 mg of iron dextran and were rendered iron deficient with an iron-deficient diet for 3 weeks. Iron status was assessed by hepatic and gut mucosal iron determination. Uptake and transfer of 59Fe-ascorbate was measured in an isolated perfused segment of transplanted intestine 48 hours after transplantation. The mean rate of uptake of 59Fe from an iron-loaded intestine (mean mucosal iron concentration, 7.97 +/- 2.02 mumol/g) was 431 +/- 27 nmol/30 min, and from an iron-deficient intestine (mean mucosal iron concentration, 1.35 +/- .84 mumol/g), 743 +/- 222 nmol/30 min (P less than 0.001). The mean transfer of 59Fe from the mucosal cell to the body through an iron-loaded intestine was 63 +/- 22 nmol/30 min, and through an iron-deficient intestine was 86 +/- 32 nmol/30 min (P less than 0.05). These results suggest that the gut mucosal iron concentration regulates the uptake and transfer of iron in the intestine.

Reported side-effects of tacrolimus, a potent immunosuppressive agent, have not included cardiotoxicity. We describe 5 consecutive paediatric transplant recipients (3 small bowel with or without liver and 2 liver) who received tacrolimus. 2 developed congestive heart failure and hypertrophic obstructive cardiomyopathy which resolved after changing to cyclosporin. In the other 3 patients the cardiomyopathy regressed or improved with a lower dose of tacrolimus or after stopping the drug.

Intestinal permeability was studied after accessory intestinal transplantation in Lewis rats. Five groups were evaluated: Group 1--isografts (N = 6); Group 2--Lewis X Brown Norway F1 (LBN-F1) allografts (N = 6); Group 3--isografts treated with CsA 2 mg/kg/day X 10 days (N = 6); Group 4--LBN-F1 allografts treated with CsA 2 mg/kg/day X 10 days (N = 6); Group 5--LBN-F1 allografts treated with CsA 4 mg/kg/day X 28 days (N = 6). Chromium-labeled ethylenedimianetetraacetate (51Cr-EDTA) was given through the proximal stoma of the graft. Renal clearance of 51Cr-EDTA and mucosal biopsies were followed post-transplant. The biopsies of the intestinal graft showed no rejection in Groups 1, 3, and 5; fulminant rejection in Group 2; and mild atypical rejection in Group 4. 51Cr-EDTA clearance was elevated in all groups during the first 7 days post-transplant. Thereafter, 51Cr-EDTA excretion fell to lower levels in the animals with histologically normal grafts (Groups 1, 3, and 5). 51Cr-EDTA excretion in Group 4 was increased with the first histological evidence of rejection on Day 14 and remained elevated until sacrifice (P less than 0.02 compared to Groups 3 and 5). A transient permeability defect occurs after intestinal grafting. Once the graft has recovered from this injury, 51Cr-EDTA is a sensitive marker for intestinal rejection.