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1.
Yonsei Medical Journal ; : 647-657, 2023.
Article in English | WPRIM | ID: wpr-1003236

ABSTRACT

Purpose@#The model for end-stage liver disease (MELD) 3.0 has recently been suggested for determining liver allocation. We aimed to apply MELD 3.0 to a Korean population and to discover differences between patients with and without hepatocellular carcinoma (HCC). @*Materials and Methods@#This study is a retrospective study of 2203 patients diagnosed with liver cirrhosis at Severance Hospital between 2016–2022. Harrell’s concordance index was used to validate the ability of MELD scores to predict 90-day survival. @*Results@#During a mean follow-up of 12.9 months, 90-day survival was 61.9% in all patients, 50.4% in the HCC patients, and 74.8% in the non-HCC patients. Within the HCC patients, the concordance index for patients on the waitlist was 0.653 using MELD, which increased to 0.753 using MELD 3.0. Among waitlisted patients, the 90-day survival of HCC patients was worse than that of non-HCC patients with MELD scores of 31–37 only (69.7% vs. 30.0%, p=0.001). Applying MELD 3.0, the 90-day survival of HCC patients was worse than that of non-HCC patients across a wider range of MELD 3.0 scores, compared to MELD, with MELD 3.0 scores of 21–30 and 31–37 (82.0% vs. 72.5% and 72.3% vs. 24.3%, p=0.02 and p<0.001, respectively). @*Conclusion@#MELD 3.0 predicted 90-day survival of the HCC patients more accurately than original MELD score; however, the disparity between HCC and non-HCC patients increased, particularly in patients with MELD scores of 21–30. Therefore, a novel exception score is needed or the current exception score system should be modified.

2.
Journal of Korean Medical Science ; : e274-2023.
Article in English | WPRIM | ID: wpr-1001223

ABSTRACT

Background@#The model for end-stage liver disease 3.0 (MELD3.0) is expected to address the flaws of the current allocation system for deceased donor liver transplantation (DDLT). We aimed to validate MELD3.0 in the Korean population where living donor liver transplantation is predominant due to organ shortages. @*Methods@#Korean large-volume single-centric waitlist data were merged with the Korean Network for Organ Sharing (KONOS) data. The 90-day mortality was compared between MELD and MELD3.0 using the C-index in 2,353 eligible patients registered for liver transplantation. Patient numbers and outcomes were compared based on changes in KONOS-MELD categorization using MELD3.0. Possible gains in MELD points and reduced waitlist mortality were analyzed. @*Results@#MELD3.0 performed better than MELD (C-index 0.893 for MELD3.0 vs. 0.889 for MELD). When stratified according to the KONOS-MELD categories, 15.9% of the total patients and 35.2% of the deceased patients were up-categorized using MELD3.0 versus MELD categories. The mean gain of MELD points was higher in women (2.6 ± 2.1) than men (2.1 ± 1.9, P < 0.001), and higher in patients with severe ascites (3.3 ± 1.8) than in controls (1.9 ± 1.8, P< 0.001); however, this trend was not significant when the MELD score was higher than 30. When the possible increase in DDLT chance was calculated via up-categorizing using MELD3.0, reducible waitlist mortality was 2.7%. @*Conclusion@#MELD3.0 could predict better waitlist mortality than MELD; however, the merit for women and patients with severe ascites is uncertain, and reduced waitlist mortality from implementing MELD3.0 is limited in regions suffering from organ shortage, as in Korea.

3.
Gut and Liver ; : 443-455, 2022.
Article in English | WPRIM | ID: wpr-925024

ABSTRACT

Background/aims@#Circulating tumor cells (CTCs) with cancer stemness have been demonstrated to be a direct cause of tumor recurrence, and only few studies have reported the role of CTCs in liver transplantation (LT) for hepatocellular carcinoma (HCC). @*Methods@#Epithelial cell adhesion molecule+ (EpCAM+), cluster of differentiation 90+ (CD90+) and EpCAM+/CD90+ CTCs were sorted via fluorescence-activated cell sorting, and transcripts level of EpCAM, K19 and CD90 in the peripheral blood were analyzed via real-time polymerase chain reaction preoperatively and on postoperative days 1 and 7 in 25 patients who underwent living donor liver transplantation (LDLT) for HCC. EpCAM protein was assessed in HCC tissue using immunohistochemical staining. The median follow-up duration was 40 months. @*Results@#HCC after LDLT recurred in four out of 25 patients. Detection of EpCAM+ or CD90+ CTCs correlated well with their messenger RNA levels (p100 mAU/mL and postoperative day 1 EpCAM+/CD90+ CTCs were independent risk factors for HCC recurrence (hazard ratio, 14.64; 95% confidence interval, 1.08 to 198.20; p=0.043 and hazard ratio, 26.88; 95% confidence interval, 1.86 to 387.51; p=0.016, respectively). @*Conclusions@#EpCAM+/CD90+ CTCs can be used preoperatively and 1 day after LDLT as key biological markers in LT candidate selection and post-LDLT management.

4.
Journal of Liver Cancer ; : 181-186, 2021.
Article in English | WPRIM | ID: wpr-900276

ABSTRACT

Hepatocellular carcinoma (HCC) with distant metastasis is an absolute contraindication for liver transplantation (LT). However, it is still unclear whether LT is feasible or acceptable in such patients, albeit after being treated with a multidisciplinary approach and after any metastatic lesion is ruled out. We report one such successful treatment with living donor LT (LDLT) after completely controlling far-advanced HCC with inferior vena cava tumor thrombosis and multiple lung metastases. The patient has been doing well without HCC recurrence for eight years since LDLT. The current patient could be an anecdotal case, but provides a case for expanding LDLT indications in the context of advanced HCC and suchlike.

5.
Clinical and Molecular Hepatology ; : 589-602, 2021.
Article in English | WPRIM | ID: wpr-897689

ABSTRACT

Background/Aims@#This study aimed to investigate whether everolimus (EVR) affects long-term survival after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). @*Methods@#The data from 303 consecutive patients with HCC who had undergone LT from January 2012 to July 2018 were retrospectively reviewed. The patients were divided into two groups: 1) patients treated with EVR in combination with calcineurin inhibitors (CNIs) (EVR group; n=114) and 2) patients treated with CNI-based therapy without EVR (non-EVR group; n=189). Time to recurrence (TTR) and overall survival (OS) after propensity score (PS) matching were compared between the groups, and prognostic factors for TTR and OS were evaluated. @*Results@#The EVR group exhibited more aggressive tumor biology than the non-EVR group, such as a higher number of tumors (P=0.003), a higher prevalence of microscopic vascular invasion (P=0.017) and exceeding Milan criteria (P=0.029). Compared with the PS-matched non-EVR group, the PS-matched EVR group had significantly better TTR (P<0.001) and OS (P<0.001). In multivariable analysis, EVR was identified as an independent prognostic factor for TTR (hazard ratio [HR], 0.248; P=0.001) and OS (HR, 0.145; P<0.001). @*Conclusions@#Combined with CNIs, EVR has the potential to prolong long-term survival in patients undergoing LT for HCC. These findings warrant further investigation in a well-designed prospective study.

6.
Journal of Liver Cancer ; : 181-186, 2021.
Article in English | WPRIM | ID: wpr-892572

ABSTRACT

Hepatocellular carcinoma (HCC) with distant metastasis is an absolute contraindication for liver transplantation (LT). However, it is still unclear whether LT is feasible or acceptable in such patients, albeit after being treated with a multidisciplinary approach and after any metastatic lesion is ruled out. We report one such successful treatment with living donor LT (LDLT) after completely controlling far-advanced HCC with inferior vena cava tumor thrombosis and multiple lung metastases. The patient has been doing well without HCC recurrence for eight years since LDLT. The current patient could be an anecdotal case, but provides a case for expanding LDLT indications in the context of advanced HCC and suchlike.

7.
Clinical and Molecular Hepatology ; : 589-602, 2021.
Article in English | WPRIM | ID: wpr-889985

ABSTRACT

Background/Aims@#This study aimed to investigate whether everolimus (EVR) affects long-term survival after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). @*Methods@#The data from 303 consecutive patients with HCC who had undergone LT from January 2012 to July 2018 were retrospectively reviewed. The patients were divided into two groups: 1) patients treated with EVR in combination with calcineurin inhibitors (CNIs) (EVR group; n=114) and 2) patients treated with CNI-based therapy without EVR (non-EVR group; n=189). Time to recurrence (TTR) and overall survival (OS) after propensity score (PS) matching were compared between the groups, and prognostic factors for TTR and OS were evaluated. @*Results@#The EVR group exhibited more aggressive tumor biology than the non-EVR group, such as a higher number of tumors (P=0.003), a higher prevalence of microscopic vascular invasion (P=0.017) and exceeding Milan criteria (P=0.029). Compared with the PS-matched non-EVR group, the PS-matched EVR group had significantly better TTR (P<0.001) and OS (P<0.001). In multivariable analysis, EVR was identified as an independent prognostic factor for TTR (hazard ratio [HR], 0.248; P=0.001) and OS (HR, 0.145; P<0.001). @*Conclusions@#Combined with CNIs, EVR has the potential to prolong long-term survival in patients undergoing LT for HCC. These findings warrant further investigation in a well-designed prospective study.

8.
The Korean Journal of Gastroenterology ; : 4-11, 2021.
Article in English | WPRIM | ID: wpr-875419

ABSTRACT

The organ allocation system should be fair and efficient to predict the prognosis of patients with end-stage organ failure. The liver allocation system in Korea was changed to the model for end-stage liver disease (MELD) score system from Child-Turcotte-Pugh score-based status system in 2016. Since then, there have been some changes in matching liver graft to recipients in deceased liver transplantation. The severity of sickness of the end-stage liver failure patients has been increased in the MELD era than before. Since 2013, liver transplantation for alcoholic liver disease has been gradually increasing in Korea. We should take proper evaluation into consideration when we decide early liver transplantation particularly for patients with severe alcoholic hepatitis, who have a high MELD score. Above all, overcoming organ shortage, it is necessary for us to try to increase the number of deceased donors to meet the need for liver transplantation for end-stage liver disease patients.

9.
The Journal of the Korean Society for Transplantation ; : 6-12, 2016.
Article in Korean | WPRIM | ID: wpr-194386

ABSTRACT

BACKGROUND: Duct-to-duct anastomosis is the most common biliary reconstruction method in living donor liver transplantation. However, biliary complications can frequently occur. The objective of this study was to examine biliary complications and related risk factors of patients with living donor liver transplantation during the last 12 years in our institution. METHODS: Surgical outcomes of 252 consecutive patients with duct-to-duct anastomosis for biliary reconstruction in living donor liver transplantation between December 2000 and July 2012 were analyzed retrospectively. RESULTS: Among the 252 patients, there were 65 cases (25.8%) of biliary complications. Before 2010, the incidence of biliary complications was 30.4% (56 of 184 cases). After 2011, the incidence was significantly (P<0.05) decreased to 13.2% (nine out of 68 cases). The complication rate of anastomosis of two separated bile ducts of graft to recipient two separated bile ducts using cystic duct and common bile duct of recipient was 50% (10 out of 20), which was relatively higher compared to that of single to single duct anastomosis (47 out of 191, 24.6%) or multiple duct to single duct anastomosis (eight out of 41, 19.5%). CONCLUSIONS: Duct to duct anastomosis between two separated bile ducts of a graft to two separated bile ducts of a recipient, the most common biliary reconstruction method, was associated with higher rate of biliary complications. Complications related to biliary reconstruction of living donor liver transplantation was gradually decreased. Standardization of bile duct anastomosis might lead to sequential reduction of biliary complications in living donor liver transplantations.


Subject(s)
Humans , Bile Ducts , Common Bile Duct , Cystic Duct , Incidence , Liver Transplantation , Liver , Living Donors , Postoperative Complications , Retrospective Studies , Risk Factors , Transplants
10.
Yonsei Medical Journal ; : 1276-1281, 2016.
Article in English | WPRIM | ID: wpr-79763

ABSTRACT

Locally advanced hepatocellular carcinoma (HCC) with portal vein thrombosis carries a 1-year survival rate <10%. Localized concurrent chemoradiotherapy (CCRT), followed by hepatic arterial infusion chemotherapy (HAIC), was recently introduced in this setting. Here, we report our early experience with living donor liver transplantation (LDLT) in such patients after successful down-staging of HCC through CCRT and HAIC. Between December 2011 and September 2012, eight patients with locally advanced HCC at initial diagnosis were given CCRT, followed by HAIC, and underwent LDLT at the Severance Hospital, Seoul, Korea. CCRT [45 Gy over 5 weeks with 5-fluorouracil (5-FU) as HAIC] was followed by HAIC (5-FU/cisplatin combination every 4 weeks for 3-12 months), adjusted for tumor response. Down-staging succeeded in all eight patients, leaving no viable tumor thrombi in major vessels, although three patients first underwent hepatic resections. Due to deteriorating liver function, transplantation was the sole therapeutic option and offered a chance for cure. The 1-year disease-free survival rate was 87.5%. There were three instances of post-transplantation tumor recurrence during follow-up monitoring (median, 17 months; range, 10-22 months), but no deaths occurred. Median survival time from initial diagnosis was 33 months. Four postoperative complications recorded in three patients (anastomotic strictures: portal vein, 2; bile duct, 2) were resolved through radiologic interventions. Using an intensive tumor down-staging protocol of CCRT followed by HAIC, LDLT may be a therapeutic option for selected patients with locally advanced HCC and portal vein tumor thrombosis.


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Carcinoma, Hepatocellular/complications , Chemoradiotherapy , Cisplatin/therapeutic use , Disease-Free Survival , Fluorouracil/therapeutic use , Liver Neoplasms/complications , Liver Transplantation , Living Donors , Neoplasm Recurrence, Local , Portal Vein , Venous Thrombosis/complications
12.
The Journal of the Korean Society for Transplantation ; : 118-129, 2015.
Article in English | WPRIM | ID: wpr-220923

ABSTRACT

BACKGROUNDS: Type I diabetes mellitus (T1DM), an autoimmune disease, is associated with insulin deficiency due to the death of beta-cells. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are capable of tissue repair and thus are a promising source of beta-cell surrogates. METHODS: In this study, the therapeutic potential of BM-MSCs as beta-cell replacements was analyzed both in vitro and in vivo. First, we used retinoic acid (RA) to induce rat BM-MSCs to differentiate into cells of endodermal/pancreatic lineage. Then, differentiated rat BM-MSCs were syngeneically injected under the renal capsule of rats. RESULTS: Analysis of gene expression revealed that rat BM-MSCs showed signs of early pancreatic development, and differentiated cells were qualitatively and quantitatively confirmed to produce insulin in vitro. In vivo study was performed for short-term (3 weeks) and long-term (8 weeks) period of time. Rats that were injected with differentiated MSCs exhibited a reduction in blood glucose levels throughout 8 weeks, and grafted cells survived in vivo for at least 3 weeks. CONCLUSIONS: These findings show that RA can induce differentiation of MSCs into the beta-cell lineage and demonstrate the potential of BM-MSCs to serve as therapeutic tools for T1DM.


Subject(s)
Animals , Rats , Autoimmune Diseases , Blood Glucose , Diabetes Mellitus , Diabetes Mellitus, Type 1 , Gene Expression , Insulin , Insulin-Secreting Cells , Mesenchymal Stem Cells , Transplants , Tretinoin
13.
Annals of Surgical Treatment and Research ; : 100-105, 2015.
Article in English | WPRIM | ID: wpr-23005

ABSTRACT

PURPOSE: Preformed circulating donor-specific antibodies (DSAs) immunologically challenge vascular endothelium and the bile duct. However, the liver is an immune-tolerant organ and can avoid immunological challenges. This study was undertaken to analyze the effects of DSAs after adult living donor liver transplantation (LDLT). METHODS: We retrospectively reviewed 219 LDLT patients' records treated at our center. RESULTS: Of the 219 patients, 32 (14.6%) were DSA (+) and 187 (85.4%) were DSA (-). Class I DSAs were present in 18 patients, class II in seven patients, and both in seven patients. Seven patients (3.2%) showed DSA to HLA-A, four (1.8%) to HLA-B, seven (3.2%) to HLA-DR, and 14 (6.4%) to two or more HLAs. More DSAs were observed in female recipients than male recipients in the DSA (+) group. The DSA (+) group showed significantly higher levels of class I and II panel reactive antibody (PRA) than did the DSA (-) group. No significant intergroup differences were found between incidences of primary nonfunction, acute rejection, vascular complication, or biliary complication. There were no significant differences in graft survival rates between the two groups. However, the recipients with multiple DSAs tended to have more acute rejection episodes and events of biliary stricture and lower graft survival rates than did patients in the DSA (-) group. CONCLUSION: In LDLT, the presence of multiple DSAs and high PRA seemed to be associated with poor graft outcomes, although our results did not reach statistical significance. Large cohort studies are necessary to clarify the impact of DSA and PRA in LDLT.


Subject(s)
Adult , Female , Humans , Male , Antibodies , Bile Ducts , Cohort Studies , Constriction, Pathologic , Endothelium, Vascular , Graft Survival , HLA-A Antigens , HLA-B Antigens , HLA-DR Antigens , Incidence , Liver Transplantation , Liver , Living Donors , Retrospective Studies , Transplantation , Transplants
14.
The Journal of the Korean Society for Transplantation ; : 135-143, 2014.
Article in Korean | WPRIM | ID: wpr-86708

ABSTRACT

BACKGROUND: Kidney injury molecule-1 (KIM-1) is known as a good ancillary marker of acute kidney injury (AKI) and its expression has also been observed in acute rejection and chronic graft dysfunction. We tested usefulness of KIM-1 as an indicator of acute and chronic renal graft injury by correlating KIM-1 expression with renal graft function and histology. METHODS: A total of 133 zero-time biopsies and 42 follow-up biopsies obtained within 1 year posttransplantation were selected. Renal tubular KIM-1 staining was graded semiquantitatively from 0 to 3 and the extent of staining was expressed as the ratio of KIM-1 positive/CD10 positive proximal tubules using Image J program. RESULTS: KIM-1 was positive in 39.8% of zero-time biopsies. KIM-1 positive cases were predominantly male and had received grafts from donors with older age, deceased donors, and poor renal function at the time of donation, compared with KIM-1 negative cases. KIM-1 expression showed correlation with delayed graft function and acute tubular necrosis. In comparison of KIM-1 expression between stable grafts (n=23) and grafts with dysfunction (n=19) at the time of repeated biopsy, the intensity/extent of KIM-1 staining and renal histology at zero-time did not differ significantly between the two groups. Histologically, KIM-1 expression was significantly increased with both acute and chronic changes of glomeruli, tubules and interstitium, peritubular capillaritis, and arteriolar hyalinosis. CONCLUSIONS: KIM-1 can be used as an ancillary marker of AKI and a nonspecific indicator of acute inflammation and tubulointerstitial fibrosis. However, KIM-1 expression at zero-time is not suitable for prediction of long-term graft dysfunction.


Subject(s)
Humans , Male , Acute Kidney Injury , Allografts , Biopsy , Delayed Graft Function , Fibrosis , Follow-Up Studies , Inflammation , Kidney , Necrosis , Tissue Donors , Transplants
15.
Journal of Korean Medical Science ; : 1069-1076, 2014.
Article in English | WPRIM | ID: wpr-208226

ABSTRACT

This study was designed to evaluate whether sirolimus (SRL) conversion effectively improves renal function and histopathology in calcineurin inhibitor (CNI)-treated renal recipients with mild to moderate renal insufficiency. SRL conversion from CNI was performed in patients who underwent kidney transplantation from 6 months to 5 yr prior to screening. Forty-five patients were enrolled. The effect of SRL conversion on graft function was evaluated, and protocol biopsies were performed preconversion and 1 yr after conversion. Overall graft function after SRL conversion gradually improved, and the improvement in renal function was closely associated with the shorter duration of CNI exposure. When we divided the patients by the duration of CNI exposure, the patients with less than 1 yr of CNI exposure demonstrated significant improvement, but patients with a greater than 1 yr CNI exposure did not exhibit significant improvement. In contrast, protocol biopsies demonstrated no significant improvements in the modified "ah" score or other Banff scores after SRL conversion. Furthermore, the duration of CNI treatment prior to SRL conversion was not associated with histological findings 1 yr after SRL conversion. SRL conversion improved graft function in renal recipients with mild to moderate renal insufficiency, but this effect is not accompanied by histological improvement.


Subject(s)
Adult , Female , Humans , Male , Calcineurin Inhibitors/administration & dosage , Drug Synergism , Graft Rejection/etiology , Graft Survival/drug effects , Immunosuppressive Agents , Kidney Transplantation/adverse effects , Renal Insufficiency/diagnosis , Republic of Korea , Severity of Illness Index , Sirolimus/administration & dosage , Transplantation Tolerance/drug effects , Treatment Outcome
16.
The Journal of the Korean Society for Transplantation ; : 121-127, 2013.
Article in Korean | WPRIM | ID: wpr-29959

ABSTRACT

BACKGROUND: The occurrence of malignancy following kidney transplantation has been estimated three to five times the incidence compared to that of the general population. It is estimated that particularly in renal cell carcinoma (RCC), the relative risk increases. The aim of this study was to analyze the characteristics, risk factors, and prognosis of RCC following kidney transplantation. METHODS: Total number of 3,272 kidney recipients who underwent transplantation from April 1979 to December 2012 and patients who had RCC following kidney transplantation were retrospectively reviewed and analyzed. RESULTS: We found that among 232 cases of posttransplant malignancies, 25 recipients were diagnosed with RCC. We have observed in our study that it took an average of 175.2+/-71.0 months to develop RCC after their first kidney transplantation. However, with longer follow up period, interval incidence of RCC increased. Fourteen patients (56%) were diagnosed with RCC 15 years after transplantation. We also found that with reference to the risk factor analysis for posttransplant RCC, the long-term follow-up period was the only independent risk factor. In our study, 21 patients with RCC were treated with radical nephrectomy. Of them, 16 patients survived, and four RCC-related deaths occurred. Furthermore, the patient survival rate of RCC recipients was lower than that of the nonmalignancy group despite the graft survival rate were not different. CONCLUSIONS: We conclude that the incidence of RCC increased in a time-dependent manner following kidney transplantation. Therefore, we strongly recommend the procedure of regular-interval screening for the patients who are on compulsive long-term immunosuppression.


Subject(s)
Humans , Carcinoma, Renal Cell , Follow-Up Studies , Graft Survival , Immunosuppression Therapy , Incidence , Kidney , Kidney Transplantation , Mass Screening , Nephrectomy , Prognosis , Retrospective Studies , Risk Factors , Survival Rate , Transplants
17.
Korean Journal of Urology ; : 870-875, 2013.
Article in English | WPRIM | ID: wpr-13285

ABSTRACT

PURPOSE: We propose an equation that predicts graft function after kidney transplantation by using donated kidney volume and recipient body surface area (BSA). MATERIALS AND METHODS: Included were 261 cases of living kidney transplantation between 2007 and 2009. Preoperative computed tomography scans were performed and the donated kidney volume was measured by use of a three-dimensional reconstruction program (Ripidia). The estimated glomerular filtration rate (eGFR) was calculated by using the modification of diet in renal disease formula. Donated kidney volume, preoperative renal function, and demographic factors of both donors and recipients were evaluated as predictors. RESULTS: The mean ages of the donors and recipients were 40.8 and 41.6 years, respectively. The mean donated kidney volume and donated kidney volume/recipient BSA ratio were 153.4 mL and 96.9 mL/m2, respectively. Mean preoperative and postoperative 12-month eGFR of recipients were 7.1 and 59.7 mL/min, respectively, and the mean preoperative eGFR of donors was 92.2 mL/min. Donated kidney volume/recipient BSA ratio, donor age, and recipient gender were the significant predictors of eGFR level (p<0.001) and eGFR<45 mL/min at postoperative 12 months (p=0.005, p<0.001, and p=0.006). From the multiple linear regression equation and predicted probability from logistic regression, we could calculate the equation for the ratio of living donor kidney volume to recipient BSA on graft function. CONCLUSIONS: Graft kidney volume/recipient BSA ratio, donor age, and recipient gender were predictors of graft function 12 months after kidney transplantation. Although we are concerned only with the preoperative, this equation model could help physicians to counsel patients concerning their postoperative prognosis and to avoid insufficient volume donations.


Subject(s)
Humans , Body Surface Area , Delayed Graft Function , Demography , Diet , Glomerular Filtration Rate , Kidney Transplantation , Kidney , Linear Models , Living Donors , Logistic Models , Organ Size , Prognosis , Tissue Donors , Transplantation , Transplants
18.
The Journal of the Korean Society for Transplantation ; : 248-253, 2012.
Article in English | WPRIM | ID: wpr-127069

ABSTRACT

BACKGROUND: AEB071, an orally available PKC inhibitor, prevents organ rejection after transplantation in rodents and man. Furthermore, pro-inflammatory cytokines and inflammatory processes are important mediators of transplanted organ rejection. We therefore examined whether single or combination therapies of AEB071 and/or tacrolimus affect cytokine profiles in a rat cardiac allograft model. METHODS: AEB071 (60 mg/kg twice a day) and tacrolimus (0.6 or 1.2 mg/kg once a day) were orally administered daily after cardiac transplantation. Interferon (IFN)-gamma, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-10, and tumor necrosis factor (TNF)-alpha levels in serum were subsequently measured 5 days after cardiac transplantation using a multiplex protein assay system. RESULTS: All cytokine levels were significantly depressed in cardiac transplanted rats treated with AEB071, whereas tacrolimus only reduced IFN-gamma, IL-2, IL-4, IL-6, and IL-10 levels. When administered in combination, AEB071 and low- or high-dose tacrolimus had additive effects on IFN-gamma, IL-4, IL-6, and TNF-alpha. CONCLUSIONS: These results suggest that AEB071 inhibits T cell activation by blocking the production of proinflammatory cytokines, and that tacrolimus combined with AEB071 can effectively regulate inflammatory cytokines in the transplantation setting.


Subject(s)
Animals , Rats , Cytokines , Heart Transplantation , Immunosuppression Therapy , Interferons , Interleukin-10 , Interleukin-2 , Interleukin-4 , Interleukin-6 , Interleukins , Pyrroles , Quinazolines , Rejection, Psychology , Rodentia , Tacrolimus , Transplantation, Homologous , Transplants , Tumor Necrosis Factor-alpha
19.
The Journal of the Korean Society for Transplantation ; : 32-37, 2012.
Article in Korean | WPRIM | ID: wpr-209735

ABSTRACT

BACKGROUND: The kidney recovery rate associated with deceased donors has increased after the establishment of the Korean Network for Organ Sharing (KONOS). And the KONOS organ allocation system gives priority to candidates affiliated with a Hospital based Organ Procurement Organization (HOPO) and/or donor recovery hospital. Regardless of whether or not this organ allocation system is fair, it can make an important impact on the waiting time for an organ transplant. METHODS: A total of 157 deceased donor kidney transplantations were performed at Severance Hospital between January 2006 and April 2011. The recipients of these transplantations were retrospectively divided into five groups according to their allocation types; general allocation group (GA, n=54), HOPO priority group (HP, n=65), zero antigen mismatching group (ZM, n=23), marginal donor allocation group (MD, n=7), and the combined organ transplant allocation group (CT, n=8). The five groups were assessed in terms of their waiting time for organ allocation, cold ischemia time, and post-transplant graft outcome. RESULTS: Mean waiting time for organ allocation of the HP group (69.5+/-27.4 months) was significantly shorter than for the GA group (90.0+/-34.0 months)(P<0.05). However, the degree of HLA mismatching was not different between each group. The cold ischemia time for the HP group (301.5+/-133.9 min) was significantly shorter than all other groups, except for the ZM group. There were no differences between groups in terms of acute rejection episodes, delayed graft function events or graft survival rates. CONCLUSIONS: Our retrospective analysis of the kidney allocation pattern showed that there were disparities in distribution by priority of allocation. We should make a consensus within the Korean transplant society in order to further develop the allocation system to decease donor kidney transplantation time.


Subject(s)
Humans , Cold Ischemia , Consensus , Delayed Graft Function , Graft Survival , Kidney , Kidney Transplantation , Rejection, Psychology , Retrospective Studies , Tissue and Organ Procurement , Tissue Donors , Transplants
20.
Journal of the Korean Surgical Society ; : 335-339, 2012.
Article in English | WPRIM | ID: wpr-207564

ABSTRACT

PURPOSE: Highly sensitized patients with a high level of panel reactive antibody (PRA) experience more episodes of antibody-mediated rejection (AMR) and poorer graft survival than non-sensitized patients. Rituximab is a well-known monoclonal anti-CD20 antibody that causes the depletion of B lymphocytes. The aim of this study was to compare a rituximab-administered and a non-administered group of highly sensitized recipients. METHODS: Forty-three kidney recipients with a PRA level of > or =50% were included. Sixteen (group R) received one dose of rituximab at 2 days prior to transplantation and 27 patients (group NR) did not. RESULTS: Patients' demographics, such as age, sex, dialysis duration, and type of immunosuppressive agent were not different in the two groups. No side effects due to rituximab administration were observed in group R. Class I PRA of group R (75.6 +/- 37.7%) was higher than that of group NR (45.7 +/- 35.8%, P = 0.013). More acute rejection episodes occurred within 1 year after transplantation in group NR but the difference between the groups was not significant (18.8% in group R vs. 29.6% in group NR, P = 0.631). However, two AMR episodes occurred only in group NR. Renal functions were not different in the two groups. In group R, CD19 and CD20 rapidly decreased 2 days after rituximab infusion. Furthermore, the administration of rituximab was not linked to acute rejection. CONCLUSION: To confirm the long-term anti-rejection and beneficial effects of rituximab, further studies should be performed with a larger cohort. In conclusion, rituximab administration 2 days prior to transplantation is both effective and safe.


Subject(s)
Humans , Antibodies, Monoclonal, Murine-Derived , B-Lymphocytes , Cohort Studies , Demography , Dialysis , Graft Survival , Immunization , Kidney , Kidney Transplantation , Rejection, Psychology , Rituximab , Transplants
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