Coculture With Ischemia/Reperfusion-Preconditioned Hepatocytes Improves Islet Function and Survival.

In clinical islet transplantation, hepatic ischemia and insufficient neovascularization of transplanted islets are barriers to islet survival and function. However, hepatocytes have a potency to protect themselves against ischemia. We hypothesized that ischemia/reperfusion preconditioning (IRP) of hepatocytes might beneficially affect islet cells in a coculture system. Primary islets were cocultured with primary hepatocytes, and hepatocyte IRP was conducted by subjecting cells to hypoxic conditions for single 15-minute/30-minute hypoxia, or 2 tandem 15-minute/30-minute hypoxic treatments (hypoxic-normoxic-hypoxic). We show that gene expression levels of insulin-like growth factor 1 (IGF-1), hepatocyte growth factor (HGF), transforming growth factor-α (TGF-α), and TGF-ß1 in hepatocytes were increased by IRP. IRP hepatocytes secreted hepatocyte growth factor and insulin-like growth factor-1. Coculture of islets with IRP hepatocytes enhanced islet insulin secretion in glucose challenge test and expression of the survival-related gene Bcl-2 and the regenerating gene-1α (Reg-1α). Islets cocultured with the 30-minute double-IRP hepatocytes displayed significantly higher viability in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and terminal deoxynucleotidyl transferase dUTP nick end labeling stain compared with that of islets subjected to 30 minutes of hypoxia. These results suggest that islet coculture with IRP hepatocytes can improve islet survival and insulin secretion.

Development and Applicability of the A-P 200 Criteria for Liver Transplantation for Hepatocellular Carcinoma.

BACKGROUND: The Milan criteria are widely accepted for indicating liver transplantation in patients with hepatocellular carcinoma (HCC). However, a 7% to 20% possibility of HCC recurrence remains, even among patients who fulfill the Milan criteria. METHODS: We retrospectively reviewed 88 patients with HCC who underwent liver transplantation at Pusan National University Yangsan Hospital between May 2010 and December 2014. The risk factors for HCC recurrence were analyzed, and the overall survival and disease-free survival rates were calculated based on each risk factor. RESULTS: Seventeen patients (19.3%) experienced HCC recurrence. Multivariate analyses revealed that the independent risk factors for HCC recurrence were protein induced by vitamin K absence or antagonist II (PIVKA-II) levels of >200 mAU/mL, levels of >200 for alpha-fetoprotein (ng/mL) or PIVKA-II (mAU/mL), and microvascular invasion. Therefore, we defined the A-P 200 criteria as simultaneously exhibiting alpha-fetoprotein levels of ≤200 ng/mL and PIVKA-II levels of ≤200 mAU/mL. The 3-year overall survival rates among patients who fulfilled or exceeded the A-P 200 criteria were 89.2% and 80.0%, respectively (P = .79). The 3-year disease-free survival rates among patients who fulfilled or exceeded the A-P 200 criteria were 89.9% and 43.1%, respectively (P < .001). We also applied the A-P 200 criteria to patient data from another major center and observed similar results. CONCLUSION: These findings confirm that the A-P 200 criteria can be used to predict recurrence after liver transplantation among patients with HCC.

Significance of Time-Zero Biopsy for Graft Renal Function After Deceased Donor Kidney Transplantation.

BACKGROUND: Donor organ quality from deceased donors affects graft survival after kidney transplantation. This study was performed to identify clinico-histological factors that affect early graft outcome, using time-zero biopsies of deceased donors. METHODS: Between December 2006 and July 2011, 135 recipients of deceased donor kidneys were included, and data concerning donor and recipient-related clinical characteristics and histological findings of time-zero biopsies categorized by use of the Banff 07 scoring system were included in the analysis. Mean donor age was 44.3 ± 12.3 years. Mean terminal serum creatinine level and cold ischemic time were 1.50 ± 0.96 mg/dL and 349 ± 166 minutes. Mean follow-up time after transplantation was 37 ± 16 months, and all recipients were followed for at least 1 year. RESULTS: Global glomerulosclerosis (38.5%), tubular atrophy (37.8%), arteriolar hyaline thickening (25.9%), interstitial fibrosis (23%), vascular fibrous intimal thickening (21.5%), and interstitial inflammation (20%) were the major pathologic findings of time-zero biopsies. The majority of pathologic scores were of mild degree. Among histological findings, arteriolar hyaline thickening and interstitial fibrosis were only significantly associated with early post-transplant renal function in multivariate analyses. CONCLUSIONS: Considerations of clinico-histological findings were found to be valuable for predicting early graft outcome after deceased donor kidney transplantation.

Role of Thalidomide on the Expression of OX40, 4-1BB, and GITR in T Cell Subsets.

BACKGROUND: Thalidomide (TM) is known to have anti-cancer and anti-inflammatory properties; however, its mechanism on T cells is still unclear. We previously showed the immune modulatory effect of TM on T cells and its therapeutic effect on lupus nephritis models. Here we examined the changes in the expression of tumor necrosis factor receptor superfamilies (TNFRSFs), including OX40, 4-1BB, and glucocorticoid-induced TNFR-related protein (GITR) in T cell subsets by TM treatments. METHODS: Splenic naïve T cells (Tnaives) from C57BL/6 mice were sort-purified and cultured for CD4(+) T cell proliferation and regulatory T cells (Tregs) conversion with TM treatments. All samples were analyzed by flow cytometry after stained with anti-mouse CD4, Foxp3, OX40, 4-1BB, or GITR antibodies. RESULTS: Expressions of OX40, 4-1BB, and GITR on CD4(+) T cells showed a decreasing tendency by TM treatments. Especially, downregulation of these molecules on CD4(+)CFSE(low) T cells was significant in TM treatment groups. On the condition of Treg conversion, OX40 was downregulated significantly. In contrast, the expression of GITR was increased, and that of 4-1BB had shown no particular change under the condition of Treg. CONCLUSION: Considering these results, TM may have an immune modulatory role through the T cell subset-specific change of OX40, 4-1BB, and GITR expression. Further study is required to elucidate the effect of thalidomide on T cells.

Results of ABO-incompatible liver transplantation using a simplified protocol at a single institution.

BACKGROUND: Because of the development of various desensitization strategies, ABO-incompatible (ABOi) living donor liver transplantation (LDLT) has become a feasible option for patients with end-stage liver disease. However, there has been no united desensitization protocol for ABOi LDLT. We analyzed the outcomes after establishment of simplified protocol without splenectomy, intravenous immunoglobulin, and local infusion therapy. METHODS: We analyzed 19 ABOi LDLT cases that had been performed between January 2012 and December 2013, without splenectomy and local infusion. We used a single dose of rituximab (375 mg/m(2)) 10 days before transplantation and several series of plasma exchange according to the recipients' iso-agglutinin titer-to-target titer ratio of 1:32. RESULTS: Nineteen recipients received ABOi LTs from living donors. The mean initial immunoglobulin (Ig) M and IgG anti-ABO titers were 76.63 ± 78.81 (range, 8∼256) and 162.53 ± 464.1 (0∼2048). We performed preoperative plasma exchange to 16 recipients (mean number of sessions, 3.58; range, 1-10). After surgery, 9 patients received plasma exchange (mean, 1.84; range 1∼14). One death occurred as the result of pneumonia (5.3%). There were 4 cases of acute rejections (21.1%), and all of them were treated successfully with steroid pulse or thymoglobulin. Antibody-mediated rejection and graft failure did not occur. Six cases of postoperative complications (31.6%) occurred, including 3 cases of infections. There were 2 cases of biliary anastomotic stricture (10.5%) and 1 case of portal vein stenosis (5.3%). CONCLUSIONS: ABOi LDLT with the use of simplified protocol can be safely performed without increased risk of antibody-mediated rejection and other complications.

PRMT3: new binding molecule to RhoGDI-α during mycophenolic acid-induced ß-cell death.

Mycophenolic acid (MPA)-induced beta cell toxicity limits islet graft survival. However, the signal transduction mechanisms underlying MPA-induced ß-cell toxicity have not been fully elucidated. Previously, we showed that MPA-induced pancreatic ß-cell apoptosis proceeds via RhoGDI-α down-regulation linked to Rac1 activation. In the present study, we investigated factors affecting RhoGDI-α during MPA-induced ß-cell apoptosis. The presence of RhoGDI-α-related protein was determined with the use of yeast 2-hybrid (Y2H) analysis. Y2H screening of RhoGDI-α was performed in yeast PBN204 strain containing 3 reporters (URA3, lacZ, and ADE2) under the control of different GAL promoters. INS-1E cells (an insulin-secreting pancreatic ß-cell line) were treated with MPA for 12, 24, and 36 hours. Eighty-three real positives were obtained by Y2H analysis, and of these, arginine N-methyltransferase 3 (PRMT3) protein interacted with RhoGDI-α in INS-1E cells. PRMT3 gene expressions and its protein levels were significantly decreased during MPA-induced apoptosis. In summary, PRMT3 and RhoGDI-α were found to interact in INS-1E cells. Furthermore, MPA was found to regulate this interaction in INS-1E cells by down-regulating the gene expression of PRMT3. These findings suggest that control of the interaction between PRMT3 and RhoGDI-α could be used to prevent MPA-induced ß-cell death.

Do the abnormal results of an implantation renal biopsy affect the donor renal function?

BACKGROUND: Living kidney donation has become an important source for renal transplantation. Thus, renal function after donation is an important issue. In this study, we examined histological abnormalities in implantation biopsy specimens from living kidney donors and analyzed the renal function of the remaining kidney. METHODS: Using the 2007 Banff classification system, we analyzed 121 kidneys from living donors who underwent implantation biopsies (IBs) between 2010 and 2011. Donor characteristics, intraoperative factors, and perioperative renal functions, such as serum creatinine and glomerular filtration rate (GFR), were evaluated. Univariate and multivariate regression analyses were performed to identify the factors related to each histological abnormality and postoperative 1-year donor renal function. RESULTS: Most histological abnormalities in healthy living donors were scored as 1 on the Banff scale. Univariate and multivariate analyses revealed that donor age was the only preoperative factor related to tubular atrophy (odds ratio [OR] = 1.104; P = .012) and glomerular sclerosis (OR = 1.050; P = .019). Intraoperative factors were not related to histological parameters. And histological abnormalities did not affect postoperative 1-year renal function. In contrast, donor age, preoperative GFR, and estimated blood loss were significantly related to 1-year postoperative GFR. CONCLUSION: Most histological abnormalities in healthy living donors were minor. The incidence of abnormalities correlated with donor age. However, postoperative renal functions in living donors were not affected by histological abnormalities. Larger-scale investigations with long-term follow-up analysis will be needed.

The impact of time-zero biopsy on early graft outcomes after living donor kidney transplantation.

BACKGROUND: In contrast with deceased donor transplantation, the clinical significance of pathologic findings in time-zero biopsies after living donor kidney transplantation are rarely reported, due to the expectation that histologic findings and renal function are normal. The aim of this study was to identify subclinical pathologic findings in living donors and examine the effect on early graft renal function. METHODS: Between December 2006 and July 2011, 146 living-donor kidney transplant recipients were enrolled in this study. We retrospectively analyzed donor and recipient-related clinical parameters, and post-transplant 6 months and 1 year estimated glomerular filtration rate (eGFR) as early graft renal function. Time-zero biopsies were evaluated using the 2007 Banff criteria. RESULTS: Most abnormal histologic findings were of mild degree as determined by Banff scores. Global glomerulosclerosis (GS, 35.6%), tubular atrophy (CT, 36.3%), interstitial fibrosis (CI, 20.5%), vascular fibrous intimal thickening (CV, 4.1%), arteriolar hyaline thickening (AH, 14.4%), interstitial inflammation (I, 3.4%) were pathologic findings in time-zero biopsies. The univariate analysis revealed that donor age and gender were significantly associated with eGFR at post-transplant 6 months and at 1 year (P < .05). Furthermore, GS and CT were significantly associated with early graft renal function (P < .05). However, multivariate linear regression analysis showed only donor age was significantly associated with early graft renal function (P = .001). CONCLUSION: A mild degree of subclinical, pathologic findings on time-zero biopsy did not affect early graft renal function in living-donor kidney transplantation.

Mizoribine versus mycophenolate mofetil in combination therapy with tacrolimus for de novo kidney transplantation: evaluation of efficacy and safety.

The present study compared the efficacy and safety of mizoribine (MZR) with mycophenolate mofetil (MMF) in kidney transplantation. This multicenter, randomized clinical trial. Employed doses of study drug tailored to the immunosuppressive need. The primary efficacy outcome was the incidence of biopsy-proven acute rejection episodes (BPAR). The safety of the study drug was assessed using the incidences of adverse events, drug discontinuations, and abnormal laboratory results. The 7 (6.4%) BPARs above grade II were observed in the MZR group noninferior to the 2 (1.8%) in the MMF group (95% confidence interval, -0.007-0.097 > noninferiority limit [-0.2]). BPAR was significantly decreased in the MZR group after the dose change (17/41 [41.4%] vs 8/69 [11.6%]; P < .0001) and the incidence of BPAR was similar between the MZR and MMF groups after the dose change (P = .592). The uric acid level was significantly elevated in the MZR group (P = .002). In conclusion, the efficacy and safety of MZR were similar and statistically noninferior to MMF in combination therapy with tacrolimus.

Laparoscopic fenestration versus percutaneous catheter drainage for lymphocele treatment after kidney transplantation.

BACKGROUND: Laparoscopic fenestration (LF) and percutaneous catheter drainage (PCD) are widely accepted treatments for symptomatic lymphoceles. The aim of this study was to review the results and compare the outcomes of LF with those of PCD. PATIENTS AND METHODS: Among 1363 patients who underwent kidney transplantation at our institute between 1999 and 2011, 35 (2.5%) developed symptomatic lymphoceles. Among them, 7 were treated by LF after PCD; 10, LF only, and 18 PCD only. The patients were divided into 2 groups based upon the treatment method: LF (n = 17) and PCD-only groups (n = 18). RESULTS: No intergroup differences in age, gender, diabetes prevalence, retransplant rate, delayed graft function, or serum creatinine was observed at 7 days after the treatment. However, acute rejection episodes and sirolimus use were more frequent among the LF group (P = .028). Furthermore, median drainage on the first day was significantly greater in the LF versus PCD group. After catheter insertion, the PCD group showed a significant decrease in drainage on the following day, but no decrease was observed in the LF group. CONCLUSIONS: LF is a safe treatment for symptomatic lymphocele. LF should be held in reserve for treatment failures after PCD. LF seems to be a more reasonable first-line treatment for symptomatic lymphoceles in patients at high risk for graft dysfunction.

Cellular function of RhoGDI-α mediates the cycling of Rac1 and the regulation of pancreatic beta cell death.

Mycophenolic acid (MPA) is an immunosuppressive agent that is widely used in clinical therapy, including pancreas and islet transplantation. Previously, we showed that MPA induces significant apoptosis of insulin-secreting cells by downregulating RhoGDI-α and increasing JNK expression. In this study, we investigated Rac1 directly associated with RhoGDI-α during MPA-induced apoptosis in INS-1E cells (an insulin-secreting cell line). Cells were treated with MPA for 24 and 36 hours. Immunoprecipitation was used to examine physical interactions between RhoGDI-α and Rac1. Activation and immunoprecipitation assays showed expressions of Rac1 and RhoGDI-α to be directly correlated. Rac1 binding to RhoGDI-α decreased after MPA treatment, and Rac1 was induced and subsequently activated by MPA. We concluded that this novel RhoGDI-α/Rac1/JNK pathway induced apoptosis of transplanted islet cells after MPA treatment.

Hybrid cellular spheroids from hepatocellular carcinoma and insulin-secreting cell lines.

During islet transplantation into the portal vein of the liver, the islet cells are expected to have complex interactions with hepatocytes. However, the mechanism underlying this interaction is not yet understood. Hence, we developed cellular complexes containing a mixture of human hepatocellular carcinoma cell line (Hep-G2) and rat insulin-secreting cell line (RIN-5F) by using a co-culture model and studied the function and morphology of the resultant hybrid cellular spheroids (HCSs). The RIN-5F and Hep-G2 cells were suspension cultured and, within 5 days of culture, the two types of cells aggregated to yield spheroids. The functionality of the thus formed HCSs was evaluated by measuring the levels of insulin and albumin in the culture supernatant. The HCSs retained their insulin- and albumin-secreting ability and their morphology, as revealed by immunohistological staining. The insulin and albumin levels secreted by the HCSs were considerably higher than those secreted by spheroids of single-cell origin. Generally, obtaining complexes from more than two types of cells is difficult. However, we were able to generate HCSs. We believe that this culture method could have various applications such as studying the in vitro cell-cell interactions and developing new cell transplantation models.

Impact of coculture with ischemic preconditioned hepatocellular carcinoma cell line (Hep-G2) cells on insulin secreting function of rat insulin-secreting cell line (RIN-5F) cells.

INTRODUCTION: Although Islet cell isolation and culture have been well developed, there has been little progress to prolong transplanted islet survival. Hepatic ischemia and insufficient neovascularization of islets are considered to be the barriers to long-term survival, Hepatocytes that survive ischemic injury have been reported to protect themeslves and regenerate using the IL-6 interleukin 6 and STAT3 pathways. MATERIALS AND METHODS: The hepatocellular carcinoma (Hep-G2) cell line preconditioned for 0, 2, 4, 6, and 24 hours in a hypoxic chamber, was cocultured with rat insulin-secreting celline (RIN-5F) cells. We measured cell viabilities, insulin secretion, and p-STAT3, IL-6, and NF-κB levels. RESULTS: Cocultured Hep-G2 and RIN-5F cells aggregated to form spheroids. Viabilities of Hep-G2 cells were no different after various ischemic preconditioning times, but insulin secretion increased in a time-dependent fashion with preconditioning. Western blotting showed p-STAT3, NF-κB, and IL-6 levels to increase with preconditioning time. CONCLUSION: The IL-6/STAT3 pathway of Hep-G2 cells after ischemic injury showed beneficial effects on insulin secretion of RIN-5f cells cocultured with themselves.

Long-term viability of transplanted hybrid cellular spheroids within chondrocyte sheets.

Encapsulation of transplanted cells within an immunoisolating membrane may provide a new strategy for protecting these cells from recipient immune responses without the use of immunosuppressive drugs. We have previously reported a novel concept of immunoisolation and immunodelusion using recipient cells instead of traditional artificial materials. We developed a chondrocyte sheeting immunodelusive immunoisolated bioartificial pancreas (CSI-BAP) that would enable transplantation of cells across allogeneic and xenogeneic barriers without the cells being recognized as donor cells and without the need for immunosuppression. Recently, we have constructed hybrid cellular spheroids (HCSs) containing cells from two different cell lines (RIN-5F, an insulin-secreting cell line, and Hep-G2, a hepatocellular carcinoma cell line) to enhance the function and biocompatibility of the HCSs. These HCSs were then encapsulated with multiple layers of chondrocyte sheets obtained from the auricular cartilage of Sprague-Dawley (SD) rats. The in vitro ability of the CSI-BAP to secrete insulin was tested before transplantation. Histological evaluation of CSI-BAP chondrocyte microencapsulated immunoisolated islet morphology and viability of allogeneic or xenogeneic cell lines was performed 100 days after the CSI-BAP was transplanted into SD rats. Morphological evaluations revealed good viability of the islets and progression of islet encapsulation. In vitro insulin secretion from the CSI-BAP was well maintained. Additionally, insulin and albumin secretion from the CSI-BAP was confirmed by in vivo immunohistochemical examination. Moreover, the cell lines transplanted into the subcutaneous space in the form of HCSs within the chondrocyte sheets showed good viability of more than 100 days and sustained insulin and albumin secreting ability.

Analysis of transplant outcomes after five or six human leukocyte antigen-mismatched living donor kidney transplantation.

BACKGROUND: Recently, the impact of human leukocyte antigen (HLA) mismatch (MM) on graft outcome has diminished since the introduction of potent immunosuppressive agents, whereas previous reports support the notion that greater numbers of HLA matches are beneficial. This study was undertaken to evaluate outcomes after five or six HLA-mismatched living donor kidney transplantations (LDKT). METHODS: The authors retrospectively reviewed graft function after 2687 LDKTs performed between June 1984 and February 2010. A database of 1364 living related and 1063 living-unrelated donor (LURD) kidney transplantations was used for this study. LURD kidney transplantations were classified into three groups; (1) zero to one HLA MM (n = 158); (2) two to four HLA MM (n = 851); and (3) five to six MM (n = 54). An acute rejection episode was diagnosed based on clinical deterioration of graft function or biopsy findings. Graft survival was calculated using the Kaplan-Meier method. RESULTS: Graft survivals in the zero to one HLA MM, two to four HLA MM, five to six HLA MM, and one-haplo MM LDKT were not significantly different. The rates of acute rejection episodes within 1 year after transplantation were similar irrespective of the HLA MM; (1) zero to one HLA MM (37.3%), (2) two to four HLA MM (35.3%), (3) five to six HLA MM (33.3%; P = .832). CONCLUSIONS: Survival of five or six HLA-mismatched LDKTs was comparable to that of one-haplo MM and relatively well-matched LDKT. The study showed that the presence of five or six HLA MM was not a risk factor for graft survival after LDKT.

Quality of life comparison between open and retroperitoneal video-assisted minilaparotomy surgery for kidney donors.

This study compared open and video-assisted minilaparotomy surgery in live kidney donors for quality of life (QoL), pain, cosmesis, and recovery. Between January 2003 and March 2006, we reviewed data from 205 patients who underwent live-donor nephrectomy: 116 by video-assisted minilaparotomy and 89 by open surgery. Pain and satisfaction were evaluated using scales from 1 to 10, and QoL, with the 36-item Short Form questionnaire. Hospital stay was significantly shorter among the video-assisted (5.1 +/- 1.6 days) than the open group (6.9 +/- 1.3 days; P < .01). Time to resumption of walking without difficulty and normal activity was significantly shorter among the video-assisted than the open group (P<.01). The video-assisted group showed better QoL scores in 6 of 8 QoL categories, including physical role (P < .01), bodily pain (P < .01), general health (P < .01), vitality (P < .01), emotional health (P < .01), and mental health (P < .01). Patients in the video-assisted group (score, 7.3 +/- 2.4) were more satisfied with the cosmetic outcome than those in the open group (score, 5.1 +/- 3.0; P < .01). In conclusion, donors who underwent nephrectomy via video-assisted minilaparotomy showed better outcomes regarding pain, convalescence, cosmesis, and QoL than those who underwent open surgery.

Change in serum lipid peroxide as an oxidative stress marker and its effects on kidney function after successful kidney transplantation.

BACKGROUND: Reactive oxygen species are believed to be responsible for organ injury after reperfusion. We evaluated serial changes in lipid peroxide (LPO) as an oxidative stress marker after kidney transplantation and investigated its effects on graft function. METHODS: Fifty-nine kidney transplant recipients were enrolled between September 2006 and March 2009. The control group consisted of kidney donors (n=40). Serum LPO concentrations were measured by a thiobarbituric acid reaction. The serum creatinine concentration and estimated glomerular filtration rate (eGFR) were used to evaluate graft function. Blood samples were obtained preoperatively, on postoperative day (POD) 5, and at 1 year posttransplantation. The median concentration of LPO on POD 5 was used as a cut-off. RESULTS: The mean preoperative LPO concentration was greater than the control group. The mean LPO concentration on POD 5 was increased compared with the preoperative level. However, the mean LPO concentration at 1 year was significantly decreased compared with the preoperative day, but greater than the control group. On POD 5, the mean serum creatinine concentration in the low LPO group was lower than that in the high LPO group. The mean eGFR in the low LPO group was significantly higher than that in the high LPO group. There was no difference in mean serum creatinine concentrations and eGFR at 1 year between the groups. CONCLUSION: Oxidative stress showed a significant impact on graft function in the immediate posttransplant period.

Invasive pulmonary aspergillosis after solid organ transplantation: diagnosis and treatment based on 28 years of transplantation experience.

Invasive pulmonary aspergillosis (IPA) is a serious and lethal complication among organ transplant recipients. This report described the clinical manifestations and treatment of IPA over a 28-year period. From January 1979 to December 2007, 3215 organ transplant patients (2954 kidney and 261 liver recipients) were enrolled in the study. Nine patients developed IPA (7 kidney and 2 liver recipients), yielding an incidence of 0.003% (9/3215). Five IPA patients (55.6%) were diagnosed by transbronchial lung biopsy or autopsy, and 3 (33.3%) by sputum culture study. One patient was diagnosed through clinical manifestations and observations of IPA characteristics on chest X ray. We used amphotericin B (n = 4; 44.4%), voriconazole (n = 2; 22.2%), or fluconazole (n = 1; 11.1%) as the primary antifungal agents, but 2 patients could not receive antifungal agents due to rapid disease progression and sequential mortality. This study showed a high mortality rate among IPA patients (55.6%; 5/9). Only patients who received early antifungal agent thereby after a prompt diagnosis recovered from IPA. This survival advantage warrants careful monitoring for invasive fungal infections after organ transplantation with immediate administration of antifungal agents or surgical intervention.