Sung Shin

Recombinant human epidermal growth factor treatment of radiation-induced severe oral mucositis in patients with head and neck malignancies

Mucositis of the oral cavity and pharynx is a major dose-limiting factor in the application of radiotherapy (RT) to patients with head and neck cancer. Therefore, we evaluated the wound healing effect of human recombinant epidermal growth factor (rhEGF) in head and neck cancer and lymphoma patients with irradiation (with or without combined chemotherapy-induced oral mucositis). Patients at Asan Medical Center who had undergone definitive RT of the head and neck region with or without combined chemotherapy and who had developed severe oral mucositis (higher than the Radiation Therapy Oncology Group grade 3) were treated with topical rhEGF twice daily for 7 days. The evaluation of response with regard to oral mucositis was performed 1 week later. Of the 11 treated patients, three had nasopharyngeal carcinoma, three had carcinoma of the oropharynx, two had carcinoma of the oral cavity, one had carcinoma of the hypopharynx and two had lymphoma of the head and neck. Six patients received RT only, and five patients received concurrent chemoradiotherapy. All patients showed improvements in their oral mucositis after topical treatment with rhEGF in that the Radiation Therapy Oncology Group grade was significantly decreased (P = 0.0000). This finding suggests that rhEGF is effective and safe for the treatment of radiation-induced mucositis. Further studies are needed to determine the optimal dosage and fractionation schedule.

Isoniazid treatment to prevent TB in kidney and pancreas transplant recipients based on an interferon-γ-releasing assay: an exploratory randomized controlled trial

BACKGROUND We performed a randomized trial of isoniazid treatment based on interferon-γ-releasing assay (IGRA) in kidney transplant (KT) recipients in an intermediate-TB-burden country. METHODS All adult patients admitted to a KT institute between June 2010 and May 2013 were enrolled. The IGRA (T-SPOT.TB assay) was performed on all patients, and isoniazid treatment was given to those with clinical risk factors for latent TB infection (LTBI). Patients with positive IGRA who had no clinical risk factors for LTBI were randomly assigned to isoniazid treatment or a control group. The development of TB after KT was monitored between June 2010 and November 2013. The primary endpoint was the development of TB. RESULTS Of the 784 patients who had no clinical risk factors for LTBI, 445 (57%) gave negative results in the IGRA, 76 (10%) indeterminate results and 263 (33%) positive results. Of the latter, 131 were allocated to isoniazid treatment and 132 to the control group. Three (2%) of the control group developed TB, whereas none of the isoniazid treatment group developed TB (rate difference 1.22 per 100 person-years, P = 0.09). Of the 521 patients with negative or indeterminate IGRA results, 4 [0.8%, 0.43 per 100 person-years (95% CI 0.12-1.09)] developed TB after KT. CONCLUSIONS IGRA-based isoniazid treatment has a trend towards reducing TB development in KT recipients without clinical risk factors, but careful monitoring of TB development is needed in negative-IGRA KT recipients.

Differences of cytomegalovirus diseases between kidney and hematopoietic stem cell transplant recipients during preemptive therapy

Background/Aims: Cytomegalovirus (CMV) surveillance and preemptive therapy is a widely-used strategy for preventing CMV disease in transplant recipients. However, there are limited data on the incidence and patterns of CMV disease during the preemptive period. Thus, we investigated the incidence and pattern of tissue-invasive CMV disease in CMV seropositive kidney transplantation (KT) and hematopoietic stem cell transplantation (HCT) recipients during preemptive therapy. Methods: We prospectively identified patients with tissue-invasive CMV disease among 664 KT (90%) and 496 HCT (96%) recipients who were D+/R+ (both donor and recipient seropositive) during a 4-year period. Results: The incidence rates of CMV disease were 4.1/100 person-years (4%, 27/664) in KT recipients and 5.0/100 person-years (4%, 21/496) in HCT recipients. Twenty-six (96%) of the KT recipients with CMV disease had gastrointestinal CMV, whereas 17 (81%) of the HCT recipients had gastrointestinal CMV and 4 (19%) had CMV retinitis. Thus, CMV retinitis was more common among HCT recipients (p = 0.03). All 27 KT recipients with CMV disease suffered abrupt onset of CMV disease before or during preemptive therapy; 10 (48%) of the 21 HCT recipients with CMV disease were also classified in this way but the other 11 (52%) were classified as CMV disease following successful ganciclovir preemptive therapy (p < 0.001). Conclusions: The incidence of CMV disease was about 4% in both KT and HCT recipients during preemptive therapy. However, CMV retinitis and CMV disease as a relapsed infection were more frequently found among HCT recipients.

Diagnostic Usefulness of Cytomegalovirus (CMV)-Specific T Cell Immunity in Predicting CMV Infection after Kidney Transplantation: A Pilot Proof-of-Concept Study

Background Cytomegalovirus (CMV) is one of the most important opportunistic infections in transplant recipients. Currently sero-positivity for CMV IgG before solid organ transplantation is the laboratory test of choice for stratifying the risk of CMV reactivation after solid organ transplantation. Theoretically, CMV-specific cell-mediated immune responses before solid organ transplantation should further categorize patients as high or low risk of CMV development. We therefore evaluated the usefulness of the CMV-specific enzyme-linked immunospot (ELISPOT) assay in kidney transplant (KT) candidates for predicting the development of CMV infections after transplantation. Materials and Methods All adult CMV IgG (+) recipients admitted to the KT institute between March 2014 and June 2014 were enrolled, and CMV infections after KT were observed between March 2014 and December 2014. All patients underwent CMV pp65 and IE1-specific ELISPOT assays before transplantation. CMV infection was defined in the presence of CMV antigenemia, CMV syndrome, or tissue-invasive CMV disease. We used the data to select optimal cut-off values for pp65 and IE1, respectively, on ROC curves. Results A total of 69 transplant recipients involving 54 (78%) living-donor KT, 9 (13%) deceased-donor KT, 3 (4%) kidney-pancreas transplants, and 3 (4%) pancreas transplants were enrolled. Of the 69 patients, 27 (39%) developed CMV infections. There was no association between the IE1-specific ELISPOT assay and CMV infection. However, only 15 (31%) of the 48 patients with positive pp65-specific ELISPOT results (>10 spots/2.0 × 105 cells) developed CMV infections, whereas 12 (57%) of the 21 patients with negative pp65-specific ELISPOT results developed CMV infection (P = 0.04). Conclusion Negative pp65-specific ELISPOT assay results before transplantation appear to predict the subsequent development of CMV infections after transplantation in CMV IgG (+) KT recipients. Therefore, risk stratification of CMV IgG (+) recipients using the CMV-specific ELISPOT, together with preventive strategies, may further reduce CMV development.

Pancreas Transplantation From Living Donors: A Single Center Experience of 20 Cases.

Living donor pancreas transplantation (LDPT) has several advantages over deceased donor pancreas transplantation (DDPT), including better HLA matching, shorter ischemic time, and shorter waiting time. It remains an attractive option for diabetes mellitus (DM) patients with end stage renal disease. We reviewed 20 cases of LDPT performed in Asan Medical Center between October 1992 and March 2015. Six cases (30%) were pancreas transplantation alone (PTA), and the rest (70%) were simultaneous pancreas and kidney transplantation (SPK). Relations of donor and recipient were parents in 7 (35%), siblings in 6 (30%), spouse in 6 (30%), and cousin in 1 (5%). Graft survival in SPK at 1, 3, 5, and 10 years was 91.7%, 83.3%, 83.3%, and 83.3%, respectively, and that in PTA recipients was 50%, 33.3%, 16.7%, and 16.7%, respectively (p = 0.005). Causes of graft failure in SPK were thrombosis (one case), and rejection (one case), whereas those in PTA were noncompliance (two cases), thrombosis (one case), reflux pancreatitis (one case), and chronic rejection (one case). In terms of pancreas exocrine drainage, two grafts (25%) maintained their function in bladder drainage, while all grafts maintained in enteric drainage p < 0.05). Seven (35%) donors experienced minor pancreatic juice leakage and one underwent reoperation due to postoperative hematoma. Most donors maintained normoglycemia and normal renal function. However, two donors developed DM (at 1 and 90 months postdonation), and were treated with oral hypoglycemic agents. Graft survival in PTA recipients was poorer than in SPK due to poor compliance and bladder drainage–related problems. The surgical and metabolic complication rates of donors can be minimized by applying strict donor criteria. Therefore, LDPT with enteric drainage is an acceptable treatment for SPK.

Long‐term impact of human leukocyte antigen mismatches combined with expanded criteria donor on allograft outcomes in deceased donor kidney transplantation

The long‐term impact of human leukocyte antigen (HLA) mismatches combined with expanded criteria donors (ECD) on clinical outcomes has not been fully evaluated in recipients of deceased donor (DD) kidney transplantations. Of 595 DD renal transplant recipients in our center between 1991 and 2011, 210 recipients (36%) had 0–3 HLA mismatches/standard criteria donor (SCD), 353 (59%) had 4–6 HLA mismatches/SCD or 0–3 HLA mismatches/ECD, and 32 (5%) had 4–6 HLA mismatches/ECD. The mortality rate was significantly highest in the patients with 4–6 HLA mismatches/ECD (p = 0.040). The most common cause of death in this group was infection (50%). There were no significant differences in overall graft survival and death‐censored graft survival. The biopsy‐proven acute rejection rate was significantly higher in the 4–6 HLA mismatches/ECD group (p = 0.011). Cox‐regression multivariate analyses showed that 4–6 HLA mismatches plus ECD (adjusted hazard ratio [AHR], 3.2; 95% confidence interval [CI], 1.17–10.56) and diabetes (AHR, 4.3; 95% CI, 1.50–12.28) were significant predictors of recipient mortality. In conclusion, ≥4 HLA mismatches plus ECD were associated with significantly higher rates of biopsy‐proven acute rejection and mortality compared with other groups undergoing DD kidney transplantation.

Long-term Effects of Delayed Graft Function on Pancreas Graft Survival After Pancreas Transplantation.

Background Compared with the impact of delayed graft function (DGF) after renal transplantation, DGF after pancreas transplantation has not been fully evaluated. Methods We retrospectively verified the impact of DGF on long-term pancreas graft survival in surgically successful cases. Pancreas graft failure was defined by the recipient’s return to exogenous insulin administration. Results Between May 2004 and April 2013, we performed 135 technically successful primary pancreas transplantations. Delayed graft function was defined as a total cumulative insulin requirement of 19 UI or greater within postoperative 7 days. Of the 135 recipients in our study cohort, 47 (34.8%) developed DGF after the pancreas transplantation. By multivariate analysis, DGF was found to be associated with a donor age of 30 years or older (odds ratio, 3.4; 95% confidence interval, 1.50–7.69; P=0.003) and the increased ratio of body mass index in a recipient to a donor (odds ratio, 26.1; 95% confidence interval, 2.53–270.0; P=0.006). There was a trend toward higher acute rejection (P=0.622) and mortality (P=0.49) rates in recipients with versus without DGF, although this did not reach statistical significance. Delayed graft function was found to be associated with a greater risk of overall pancreas graft failure (P=0.016) and death-censored graft failure (P=0.037). Conclusion Delayed graft function after pancreas transplantation was found to be associated with a greater risk of overall pancreas graft failure and death-censored graft failure.

How to reduce lethal infectious complications in ABO-incompatible kidney transplantation.

BACKGROUND ABO-incompatible organ transplants are good options for expanding the living donor pool; however, the necessary pre-conditioning to remove ABO antibodies before surgery can evoke critical infectious complications after surgery. METHODS Between February 2009 and July 2013, we performed ABO-incompatible kidney transplantation on 182 patients. We analyzed the first 85 patients for post-operative infectious complications in a cross-sectional cohort of patients (group 1, n = 85) who had received an ABO-incompatible kidney transplant and, in light of the results, amended the pre-conditioning (lower dose of rituximab, selective use of calcineurin inhibitors, anti-metabolite reduction, and prophylactic strategy) given to a prospective cohort (group 2, n = 97). RESULTS The characteristics of the two groups did not differ significantly. Infectious complications decreased significantly in group 2, including cytomegalovirus (anti-genemia 64.7% vs 27.8%, P < .001) and BK viremia (35.2% vs 18.6%, P = .008). The acute rejection rate and death-censored graft survival were similar in both groups. Notably, with the modified protocol, there were no deaths (8.2% vs 0.0%, P = .03). CONCLUSIONS Pre-conditioning for ABO-incompatible kidney transplantation is a prerequisite for successful outcome; its drawbacks can be limited with the use of a modified immunosuppressive strategy. If immunosuppression is modified according to host conditions, ABO-incompatible kidney transplantation can be performed safely with a successful graft outcome.

Outcomes of En Bloc Kidney Transplantation From Pediatric Donors: A Single-Center Experience

BACKGROUND To overcome a shortage of donors, cadaveric pediatric en bloc kidneys can be used to expand the donor pool. Recent evidence shows that en bloc kidney transplantation (EBKT) has better outcomes than standard-criteria deceased adult donor kidney transplantation. We reviewed our experiences of EBKT and their outcomes. METHODS From September 1996 to January 2016, 15 EBKTs were performed in Asan Medical Center. The characteristics of donors and recipients were analyzed. Graft survival was analyzed by means of serum creatinine levels. RESULTS Nine male and 6 female donors were used. The mean age and body weight of donors was 2.79 years (range, 0.25-14) and 13.14 kg (range, 5.5-35). The mean weight of en bloc kidneys was 117.43 g (range, 36-146). Recipient median age was 39.13 years and body weight was 49.47 kg. Ureteral anastomosis was performed by means of side-to-side anastomosis and then bladder anastomosis in 9 patients and by bladder patch anastomosis in 4 patients. Serum creatinine levels at discharge and latest follow-up were 0.97 mg/dL (range, 0.7-1.54) and 0.89 mg/dL (range, 0.44-2.58). Delayed graft function developed in 3 patients and clinical rejection developed in 2 patients. We performed graftectomy on post-operative day 1 because of graft thrombosis. The rest maintained their graft function well. Graft survival was comparable with that of kidney transplantation from standard donors. CONCLUSIONS EBKT showed excellent graft function and outcomes at our center. As an approach to expand the donor pool and improve graft utilization, EBKT is acceptable and should be more widely used.

Incidence and differential characteristics of culture‐negative fever following pancreas transplantation with anti‐thymocyte globulin induction

Limited data are available on the incidence and characteristics of culture‐negative fever following pancreas transplantation (PTx) with anti‐thymocyte globulin (ATG) induction. Our study aims to better define the features of culture‐negative fever, so it can be delineated from infectious fever, hopefully helping clinicians to guide antibiotic therapy in this high‐risk patient population.