J.M. Kim

Primary Versus Salvage Living Donor Liver Transplantation for Patients With Hepatocellular Carcinoma: Impact of Microvascular Invasion on Survival

OBJECTIVEnSalvage liver transplantation (LT) has been proposed for patients with a small hepatocellular carcinoma (HCC) and preserved liver function. Few reports have been issued on salvage LT in a living-donor (LD) LT setting. Therefore, we performed this study to evaluate differences in tumor invasiveness and other risk factors on survival after salvage versus primary LDLT.nnnMETHODSnBetween September 1996 and December 2008, 324 patients with HCC underwent LT. We excluded 138 patient from the analysis, leaving 186 HCC patients for analysis, including 17 (9.1%) who had undergone earlier resection, the salvage LDLT cohort. The other 169 patients underwent primary LDLT.nnnRESULTSnIntrahepatic metastasis, Edmonson-Steiner histologic grade, microscopic vascular invasion, and preoperative serum alpha-fetoprotein levels significantly influenced tumor recurrence. Microscopic vascular invasion, intrahepatic metastasis, Edmonson-Steiner histologic grade, and treatment by salvage LDLT were significantly associated with poor patient survival univariate analysis. However, only microscopic vascular invasion was significant on multivariate analysis. The treatment modality (primary or salvage LDLT) was not observed to affect overall or disease-free survival significantly on multivariate analysis. Disease-free survival was significantly better in the primary than in the salvage LDLT group. Furthermore, patients in the primary LDLT group tended to show better survival. However, when stratified by the presence or absence of microscopic vascular invasion, no significant group difference was found for overall or disease-free survival among those without versus with microscopic vascular invasion.nnnCONCLUSIONSnFive-year overall survival after primary versus salvage LDLT were similar when differences in tumor pathologic features, such as microscopic vascular invasion, were taken into account. Multivariate analysis showed that the treatment itself was not a significant prognostic factor for survival.

Living Donor Liver Transplantation in Budd-Chiari Syndrome: A Single-Center Experience

Budd-Chiari syndrome (BCS), which is characterized by hepatic venous outflow obstruction due to occlusion of the major hepatic vein and/or the inferior vena cava (IVC), is rare. Traditionally, a caval resection is advocated for these patients; however, such a maneuver renders living donor liver transplantation (LDLT) impossible. We encountered BCS in 4/377 LDLT patients during a 5-year period (January 2003 to December 2007). This report examine the various surgical modifications in these 4 patients, who underwent to LDLT for BCS. Resection of right hepatic vein (RHV) with an adjacent fibrotic part of the IVC with direct anastomosis of the graft RHV to the IVC was performed in 2 patients. One patient underwent retrohepatic IVC excision and reconstruction with a cryopreserved autologous IVC graft. The fourth patient, with a preexisting mesoatrial shunt for BCS, underwent conversion of this to a RHV atrial shunt. Graft and patient survivals were 100%. There were few complications in either donors or recipients. LDLT for BCS can be performed safely with adequate venous drainage techniques and with anticoagulant therapy and good follow-up for early diagnosis and treatment of recurrence leading to excellent long-term results.

Risk Factors for Portal Vein Complications After Pediatric Living Donor Liver Transplantation With Left-sided Grafts

PURPOSEnPortal vein complications (PVC) after pediatric living donor liver transplantation (LDLT) have rarely been reported. We evaluated the long-term incidence and of the risk factors for PVC after pediatric LDLT.nnnMETHODSnFrom April 1997 to November 2008, 96 pediatric patients underwent LDLT using left lateral segments or left lobes. We investigated recipient factors, donor factors, and operative factors through medical records. The portal vein sizes in 96 recipients ranged from 2.7 mm to 13.0 mm (median=5.0 mm). Portal vein reconstruction was usually performed with the graft portal vein anastomosed to the bifurcation of the recipient right and left portal veins, the so-called branch patch.nnnRESULTSnPVC occurred in 11 patients (11.5%) including early PVC (n=3), late PVC (n=8). The disease-free survivals at 1, 5, and 10 years after LDLT were 94.7%, 88.7%, and 86.0%. Upon univariate analysis, a portal vein size<5 mm graft-to-recipient weight ratio (GRWR)>or=4%, transfusion volume>or=270 mL were significant risk factors for PVC. Body weight<8 kg and previous operative history tendes to be adverse for PVC. Upon multivariate analysis by Cox regression, portal vein size<5 mm was a highly significant factor for PVC after pediatric LDLT (hazard ratio=5.627, P=.027).nnnCONCLUSIONnThe disease-free survival at 10 years after LDLT was 86.0%. If the recipients portal vein size<5 mm received a large-for-size graft (GRWR>or=4%), it is important to observe by regular Doppler ultrasonography follow-up to detect PVC.

The Risk Factors of Delayed Graft Function and Comparison of Clinical Outcomes After Deceased Donor Kidney Transplantation: Single-Center Study

INTRODUCTIONnThe aim of this study was to analyze risk factors for delayed graft function (DGF) after deceased donor kidney transplantation and to compare the clinical outcomes of non-DGF versus DGF recipients.nnnPATIENTS AND METHODSnFrom January 2004 to June 2008, 75/154 kidneys were transplanted into 74 recipients. We classified the recipients into two groups: group 1 (n=61) without DGF and group 2 (n=13) with DGF.nnnRESULTSnOn univariate analysis, recipient age (P=.048) cause of brain death (traumatic brain injury vs disease, P=.016), blood urea nitrogen (P=.002), serum creatinine (P=.001), arterial pH (P=.019), and serum sodium level (P=.012) just before organ procurement showed significant differences. On multivariate analysis, the cause of brain death (P=.015, hazard ratio [HR]: 7.086), the terminal serum creatinine>or=1.5 mg/dL before organ procurement (P=.007, HR: 10.132), and recipient age over >or=50 years (P=.021, HR: 7.767) were independent risk factors for the development of DGF. Graft failures occurred among 5/74 recipients with 5-year graft survivals between group 1 and group 2 of 91.7% and 84.6%, respectively. Patient death occurred in five cases, most by due to infection. The 5-year patient survival between groups 1 and 2 were 93.9% and 84.6%, respectively (P = .106).nnnCONCLUSIONnThe independent risk factors for DGF were the cause of brain death, the terminal creatinine level, and the recipient age. In deceased donor kidney transplantation, DGF may have less effect on long-term patient and graft survivals.

Enhancement of the immunosuppressive effect of human adipose tissue-derived mesenchymal stromal cells through HLA-G1 expression

BACKGROUND AIMSnMesenchymal stromal cells (MSC) from several tissues have immunomodulatory properties that involve various immunosuppressive molecules. An example is human leukocyte antigen (HLA)-G, a non-classical major histocompatibility complex (MHC) class I molecule that induces tolerance via interactions with inhibitory receptors present on major immune effector cells. Recently, the molecular mechanisms that regulate MSC-mediated immunosuppression have come under investigation. Our goal was to determine whether HLA-G plays a crucial role in immunosuppression and whether human adipose tissure (hAT) MSC can be used as a tool for biologic immunosuppression with HLA-G in transplantation.nnnMETHODSnMSC were characterized by fluorescence-activated cell sorting (FACS) analysis, reverse transcriptase (RT)-polymerase chain reaction (PCR) and staining for differentiation. The immunogenicity and immunomodulatory effects of MSC were monitored by peripheral blood mononuclear cell (PBMC) proliferation assay with or without phytohemagglutinin (PHA) stimulation. Stable expression of HLA-G1 in MSC was done using a lentiviral system. Results. MSC from different tissues had similar morphology, immunophenotypic characters and differentiation potential. We also found that the immunosuppressive effect of MSC was monitored along with their endogenous HLA-G mRNA and protein levels. Stable expression of HLA-G1 appeared to enhance the immunosuppressive effect of hAT MSC, and the function of HLA-G1 was significantly decreased by HLA-G antagonistic antibody in PBMC proliferation assays.nnnCONCLUSIONSnAlthough the HLA-G molecule is not the sole factor for MSC-mediated immunosuppression, our data provide evidence that HLA-G plays an important role in immunosuppression and that hAT MSC can be used as a tool for biologic immunosuppression during transplantation procedures.

Expanded Criteria for Liver Transplantation in Patients with Hepatocellular Carcinoma

Liver transplantation (LT) is one of the few effective treatment options for hepatocellular carcinoma (HCC). Our aim in this study was to evaluate the risk factors for HCC recurrence and propose new criteria for LT based on pretransplantation findings. One hundred eighty patients who underwent LT for HCC between 2002 and 2008 were reviewed retrospectively. Outcome measures included maximal tumor size and number of tumors revealed by radiological studies before transplantation, demographics, and tumor recurrence. Maximal tumor size >6 cm, >7 tumors, and alpha-fetoprotein (AFP) levels >1000 ng/mL were identified as independent prognostic factors of HCC recurrence in univariate and multivariate analysis. Disease-free survival rate in patients with a maximal tumor sizexa0≤6 cm,xa0≤7 tumors, and/or AFP levelsxa0≤1000 ng/mL at 1, 3, and 5 years was 97.9%, 91.5%, and 90.0%, respectively, but the 1-, 3-, and 5-year disease-free survival rate of patients who had a maximal tumor size >6 cm, >7 tumors, and/or AFP levels >1000 ng/mL was 61.9%, 47.6%, and 47.6%, respectively (Pxa0< .001). In conclusion, LT can improve the survival of patients with advanced HCC if they have a maximal tumor sizexa0≤6 cm, tumor numberxa0≤7, and/or AFP levelsxa0≤1000 ng/mL.

Can Immune Function Assay Predict Infection or Recovery

BACKGROUNDnRecently, the ImmuKnow assay (Cylex Inc., Columbia, Md) has been reported to be a global immune monitoring tool for organ transplants recipients. We assessed whether immunKnow ATP values predicted infectious syndromes.nnnMETHODSnWe prospectively enrolled 71 kidney transplant patients between September 2008 and May 2011. lmmuKnow assay monitoring was performed at one dav before as well as 4, 8, 12, 16, 20, 24, 36, and 52 weeks after the operation. ImmuKnow assay values were compared as well as BK viral infection pre-infection(PI), at first detection of infectious syndrome (DI), 4 weeks there after (4W), 8 weeks there after (8W) and 12 weeks there after (12W) and pre-recovery (PR), recovery (R) times.nnnRESULTSnSerial ImmuKnow assays showed significant differences over time and BK viral infectious state (P = .026). Interestingly, PI was significantly lower than DI and PR but PR significant greater than PI, 8W and 12W. However, we did not observe an adequate or absolute cutoff value of ImmuKnow by ROC curve: 377 ng/mL ImmuKnow showed 0.471 of AUC and 57.1% and 56.2%, of sensitivity and specificity.nnnCONCLUSIONnLongitudinal evaluation and adjustment of the value of ImmuKnow assay seemed to be a favorable modality to monitor infectious syndromes especially those involving BK virus.

Can Preemptive Kidney Transplantation Guarantee Longer Graft Survival in Living-Donor Kidney Transplantation? Single-Center Study

INTRODUCTIONnThe benefit of preemptive kidney transplantation (KTx) for graft survival compared with nonpreemptive KTx is controversial.nnnOBJECTIVEnTo analyze the influence of preemptive KTx on graft survival.nnnPATIENTS AND METHODSnThe study included 476 of 531 patients who had undergone living-donor KTx between January 2000 and June 2007. Pediatric patients and those who had previously undergone KTx were excluded. Recipients were divided into 2 groups; group 1 included 413 patients (86.8%) who received grafts after institution of maintenance dialysis, and group 2 included 63 patients (13.2%) who underwent preemptive KTx.nnnRESULTSnDonor type and HLA mismatch demonstrated significant differences between the 2 groups. Group 1 had more living donors and fewer HLA mismatches. Warm ischemia time in group 2 was significantly shorter than in group 1. The serum creatinine concentration in group 1 on postoperative day 7 was significantly higher than in group 2. Five- and 10-year graft survival in groups 1 and 2, respectively, were 95.3% and 81.3% vs 92.9% and 92.9%. Graft survival was not significant insofar as duration and method of dialysis. At our institution, independent risk factors for graft survival in living-donor KTx are primary end-stage renal disease, acute cellular rejection episodes, and recipient age.nnnCONCLUSIONnWe observed no benefit on graft survival in recipients of living-donor KTx insofar as whether they had undergone previous dialysis.

Risk factors for posttransplant lymphoproliferative disorder in pediatric liver transplant recipients with cytomegalovirus antigenemia.

Epstein-Barr virus (EBV) infections, associated with posttransplant lymphoproliferative disorder (PTLD) are known to develop in cytomegalovirus (CMV)-infected transplant recipients due to the indirect effects of CMV. This study evaluated risk factors for PTLD among pediatric liver transplant recipients with CMV infections. We reviewed the medical records of 119 patients<or=18 years old who underwent liver transplantation between September 1996 and April 2009. Sixty-six subjects (55.5%) displayed CMV antigenemia during the study period; 15 (12.6%) developed PTLD. Of these, 10 developed PTLD after CMV antigenemia. The other patients (n=5) were excluded due to negative CMV antigenemia. The incidence of PTLD influenced by CMV infection was not significantly different from the incidence of PTLD without underlying CMV (P=.258). There were no differences in age, gender, antiviral prophylaxis, type of liver transplantation, or acute rejection episodes in the incidence of between patients with versus without PTLD. EBV but not CMV high-risk groups were a predictor for the development of PTLD (P=.035). CMV syndrome, tissue-invasive CMV disease, and CMV peak titer were not associated with an increased risk of PTLD. The primary risk factor for PTLD was EBV high-risk patients (donor positive/recipient negative). CMV disease was not associated with PTLD in pediatric liver transplant recipients with CMV infections.

Effectiveness of Locoregional Therapy Before Living Donor Liver Transplantation in Patients With Hepatocellular Carcinoma Who Meet the Milan Criteria

BACKGROUNDnMany patients are diagnosed with hepatocellular carcinoma (HCC) within the Milan criteria. In Korea, these patients are preferentially treated with locoregional therapy (LRT) instead of living donor liver transplantation. We investigated the effectiveness of LRT in liver transplant recipients who met the Milan criteria at the time of HCC diagnosis and investigated risk factors for HCC recurrence.nnnMETHODSnWe retrospectively reviewed the medical records of patients diagnosed with HCC who met the Milan criteria between 2002 and 2008.nnnRESULTSnWe performed 101 liver transplants for HCC during the study period. Seventy-one patients (70%) underwent pretransplant LRT. The disease-free survival rates at 1, 3, and 5 years in patients who received LRT were 96.6%, 93.1%, and 93.1%, and in those who did not receive LRT, 94.2%, 83.4%, and 83.4%, respectively. There were no differences between the 2 groups. Multivariate analysis showed that a low Model for End-Stage Liver Disease (MELD) score and microvascular invasion were independent predictors of HCC recurrence after transplantation. The MELD scores and rate of microvascular invasion were not statistically different in patients with or without previous LRT.nnnCONCLUSIONnPretransplant LRT for patients with HCC who met the Milan criteria at the time of diagnosis did not provide a clear benefit with respect to HCC recurrence after transplantation. If patients have suitable living donors, those who meet the Milan criteria should undergo a liver transplantation as soon as possible.