Case-matched comparison of ABO-incompatible and ABO-compatible living donor liver transplantation.

BACKGROUND: ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) has a high success rate. There are few detailed comparisons regarding biliary complications, infective complications and patient survival between ABO-compatible (ABO-C) and ABO-I LDLT. The aim was to compare the outcomes of ABO-I LDLT with those of ABO-C LDLT using the matched-pairs method. METHODS: Patients who underwent ABO-I LDLT procedures between 2010 and 2013 were studied. They were matched for significant variables with patients who had ABO-C LDLT (1:2 matching). RESULTS: Forty-seven ABO-I LDLT procedures were included. Ninety-four patients who had ABO-C LDLT were selected as a comparator group. The incidence of cytomegalovirus, bacterial and fungal infections during the first 3 months was similar after ABO-I LDLT and ABO-C LDLT (85 versus 76 per cent, 28 versus 37 per cent, and 13 versus 20 per cent, respectively). Antibody-mediated rejection occurred after two procedures within 2 weeks of transplantation, but liver function improved with plasma exchange in both patients. There were no differences in the rate of acute rejection and biliary complications between ABO-I and ABO-C groups (P = 0.478 and P = 0.511 respectively). Three patients who had ABO-I LDLT developed diffuse intrahepatic biliary complications and progressed to graft failure. The 1-, 2- and 3-year patient survival rates after ABO-I LDLT and ABO-C LDLT were 89 versus 87 per cent, 85 versus 83 per cent, and 85 versus 79 per cent, respectively. CONCLUSION: The short-term outcomes of ABO-I LDLT were comparable to those of ABO-C LDLT in this study. ABO-I LDLT is an effective and safe transplant option with the potential to expand the pool of live donors.

Generic piperacillin/tazobactam is not associated with galactomannan false-positivity in adult patients with cancer: a case-control study.

Recent products of piperacillin/tazobactam (PTZ) from the original manufacturer, previously considered a major cause of galactomannan (GM) false-positivity, are reported not to be related to it. However, data regarding generic PTZ are limited and controversial. To evaluate the effect of generic PTZ on GM false-positivity in Korea, we performed a case-control study in adult patients with cancer. A case-control study was designed. Electronic medical records of cancer patients who were admitted and tested for serum GM between March and June 2014 at a tertiary care university hospital were reviewed. During the study period, a single generic PTZ (C manufacturer, Korea) was used. Patients who received PTZ within 24 h prior to serum GM testing were enrolled. Age- and GM test date-matched non-PTZ patients were selected as controls. A total of 110 patients received PTZ within 24 h prior to serum GM testing during the study period. The GM optical density index (ODI) of the PTZ group did not vary significantly from that of the control group (p = 0.251). The percentage of false-positive patients in the PTZ group was also similar to that of the control group (p = 0.538). There was no statistical relationship between GM ODI titer and time interval from PTZ administration (p = 0.095) or cumulative PTZ dose (p = 0.416). In a case-control study that evaluated 220 patients, a generic PTZ in Korea was not related to GM false-positivity.

The impact of drug-resistant cytomegalovirus in pediatric allogeneic hematopoietic cell transplant recipients: a prospective monitoring of UL97 and UL54 gene mutations.

BACKGROUND: Cytomegalovirus (CMV) infection is a major cause of morbidity in allogeneic hematopoietic cell transplant (alloHCT) recipients. Little is known about the epidemiology of antiviral resistance in the pediatric population. We performed the prospective study to assess the impact of drug-resistant CMV infections in pediatric alloHCT recipients. METHODS: Pediatric alloHCT recipients who developed CMV infection were consecutively enrolled from May 2009 to April 2012. CMV polymerase chain reaction amplification and sequencing analysis for UL97 and UL54 genes were performed at enrollment and during follow-up. RESULTS: In total, 208 sequence data from viruses in 49 recipients were eligible for the final analysis. Resistant CMV infection caused by UL97 and UL54 mutations occurred in 4.1% (2/49) and 2.0% (1/49), respectively. Known UL97 mutations, M460V and C592G, were observed in each of 2 patients. One patient with the M460V UL97 mutation had an additional T700A UL54 mutation. Drug-resistant CMV attributable mortality was 2.0% (1/49). One or more known sequence variants (drug-sensitive) were observed in all 49 patients. Thirty-one (63.3%) and 28 patients (60.9%) already had known UL97 and UL54 sequence variants before antiviral therapy, respectively. CONCLUSION: This study provides comprehensive information on the epidemiology of both UL97 and UL54 variants and mutations in alloHCT recipients.

Ligand-activated peroxisome proliferator-activated receptor-δ and -γ inhibit lipopolysaccharide-primed release of high mobility group box 1 through upregulation of SIRT1.

Peroxisome proliferator-activated receptors (PPARs) inhibit lipopolysaccharide (LPS)-primed release of high mobility group box 1 (HMGB1), a late proinflammatory mediator, but the underlying molecular mechanism is not completely understood. In this study, we demonstrated that the inhibition of HMGB1 release by PPAR-δ and -γ is associated with the deacetylase activity of SIRT1. Ligand-activated PPAR-δ and -γ inhibited LPS-primed release of HMGB1, concomitant with elevation in SIRT1 expression and promoter activity. These effects were significantly reduced in the presence of small interfering (si)RNAs against PPAR, indicating that PPAR-δ and -γ are involved in both HMGB1 release and SIRT1 expression. In addition, modulation of SIRT1 expression and activity by siRNA or chemicals correspondingly influenced the effects of PPARs on HMGB1 release, suggesting a mechanism in which SIRT1 modulates HMGB1 release. Furthermore, we showed for the first time that HMGB1 acetylated in response to LPS or p300/CBP-associated factor (PCAF) is an effective substrate for SIRT1, and that deacetylation of HMGB1 is responsible for blockade of HMGB1 release in macrophages. Finally, acetylation of HMGB1 was elevated in mouse embryonic fibroblasts from SIRT1-knockout mice, whereas this increase was completely reversed by ectopic expression of SIRT1. These results indicate that PPAR-mediated upregulation of SIRT1 modulates the status of HMGB1 acetylation, which, in turn, has a critical role in the cellular response to inflammation through deacetylation-mediated regulation of HMGB1 release.

Incidence and risk factors of poor mobilization in adult autologous peripheral blood stem cell transplantation: a single-centre experience.

BACKGROUND AND OBJECTIVES: Collection of sufficient CD34+ cells for autologous peripheral blood stem cell (PBSC) transplantation is frequently failed in patients with lymphoma or multiple myeloma (MM). We investigated the incidence and the predictive factors for poor mobilization. MATERIALS AND METHODS: A total of 205 adult patients (101 lymphoma and 104 MM) were retrospectively included for identifying the incidence of mobilization failure and the predictive factors for poor mobilization in conventional G-CSF-based mobilization regimen. Another 17 patients who used plerixafor for mobilization were included. RESULTS: Overall, 14·1% of patients (21·8% of patients with lymphoma, 6·7% of patients with MM) were poor mobilizers. Univariate analysis and multivariate analysis revealed an interval from G-CSF administration to PBSC collection exceeding 10 days and peripheral blood mononuclear cells count on the first day of collection were predictive factors for poor mobilization in lymphoma, but not in MM. Among plerixafor-treated patient group, 9 of 11 poor mobilizers who received second-cycle plerixafor mobilization were able to collect higher number of CD34+ cells than that of CD34+ cells during the G-CSF-based first mobilization. All patients who had received initial plerixafor mobilization reached 2·0 × 10(6) CD34+ cells/kg during the four leukaphereses. CONCLUSION: In conventional G-CSF-based mobilization, early PBSC collection after G-CSF administration might enhance CD34+ cell yield. A combination of a new mobilizing agent, plerixafor, would be helpful to harvest sufficient number of CD34+ cells for successful transplantation outcome while reducing the effort of collection procedures in poor mobilizers.

Prediction of biliary complications after living-donor liver transplantation based on serum cytokine profile.

Biliary tract complications are the main concern associated with living-donor liver transplantation (LDLT). Many laboratory parameters have been studied for the early detection of post-LDLT complications, including various cytokines. To explore immunologic activation status and its clinical significance, the cytokine secretion patterns of LDLT patients who developed biliary complications were analyzed. Serum samples from LDLT recipients were collected 1 day before and 3, 7, 14, and 30 days after transplantation. Each sample was tested for interleukin (IL) 2, IL-4, IL-6, IL-8, IL-10, IL-12, interferon-α, and tumor necrosis factor α with the use of multiplex bead flow cytometry. Fifteen patients without any complications and 6 patients with biliary complications showed differential serum cytokine profiles. The biliary complication group (4 biliary stricture and 2 biliary obstruction patients) displayed significantly increased concentrations of IL-2 and IL-12 on post-transplantation days 3 and 7 and of IL-4 on post-transplantation day 7. Profiling cytokine secretion in the serum of patients in the first month of LDLT may be helpful for the prediction and diagnosis of biliary complications within 1 year.

15-Deoxy-Δ(12,14)-prostaglandin J2 prevents oxidative injury by upregulating the expression of aldose reductase in vascular smooth muscle cells.

The omega-6 fatty acid derivative 15-Deoxy-Δ(12,14)-prostaglandin J2 (15d-PGJ2) is believed to play a role in cellular protection against oxidative stress in diverse cell systems. However, the cellular mechanisms by which protection is afforded by 15d-PGJ2 are not fully elucidated in vascular smooth muscle cells (VSMCs). In this study, we report the finding that 15d-PGJ2 elicited a time and concentration- dependent increase in aldose reductase (AR) expression. This induction was independent of the activation of peroxisome proliferator- activated receptor γ. Inhibition of phosphatidylinositol 3-kinase (PI3K) significantly suppressed the increase in expression and promoter activity of AR induced by 15d-PGJ2. Luciferase reporter assays demonstrated that 15d-PGJ2 targets the multiple stress response regions comprising the antioxidant response element in the promoter of the AR gene. 15d-PGJ2-mediated induction of AR promoter activity was potentiated in the presence of nuclear factor-erythroid 2-related factor 2 (Nrf2), but not in cells expressing dominant negative Nrf2. Cells treated with 15d-PGJ2 were resistant to oxidant-induced apoptotic cell death by inhibiting production of reactive oxygen species. These effects were significantly attenuated in the presence of an AR inhibitor or small interfering RNA against AR, indicating that AR plays a protective role against oxidative injury. Taken together, these findings demonstrate that activation of PI3K by 15d-PGJ2 increases the expression of AR through Nrf2, and increased AR activity may function as an important cellular response against oxidative injury.

Evaluation of overnight storage conditions for autologous peripheral blood stem cell products: comparison of three different conditions.

BACKGROUND: Overnight (ON) storage of peripheral blood stem cell (PBSC) occurs frequently in clinical settings. However, there are no standard guidelines for optimal storage conditions of freshly harvested PBSC. The aim of this study was to investigate the influence of storage temperatures on the quality of autologous PBSC and establish optimal storage conditions before cryopreservation. METHODS: A retrospective analysis was performed on 260 PBSC harvests according to pre-cryopreservation conditions: immediate processing or ON storage at room temperature (RT). For direct comparison, 30 autologous PBSC products were collected prospectively and prepared under three different pre-cryopreservation conditions: immediate processing, ON storage at 4°C and ON storage at RT. The recovery of CD34(+) cells, post-thaw CFU-GM count and viability were analysed. RESULTS: Retrospective analysis revealed that post-thaw CFU-GM count was significantly lower when PBSC were stored ON at RT compared to when immediately processed (136·4 vs. 409·6/µl). Prospective analysis showed a mean recovery of CD34(+) cells of 65·5 ± 25·1%, 70·5 ± 27·4% and 35·9 ± 25·1% for immediate processing, ON storage at 4°C and ON storage at RT, respectively. Similarly, mean viability and CFU-GM counts were significantly reduced when stored ON at RT compared to when immediately processed or stored ON at 4°C (60·4 ± 25·6 vs. 84·1 ± 12·9 vs. 82·7 ± 12·6%, 15·7 ± 25·7 vs. 398·5 ± 906·2 vs. 350·0 ± 847·9/µl, respectively). CONCLUSIONS: ON storage of autologous PBSC at RT significantly decreased the quality of HPCs. These data indicate that ON storage of autologous PBSC at 4°C would be the most reasonable approach for maintaining the quality of HPCs when immediate processing is not possible.

Frequencies of 10 autosomal minor histocompatibility antigens in Korean population and estimated disparities in unrelated hematopoietic stem cell transplantation.

Disparity of minor histocompatibility antigens (mHAs) is known to induce graft-versus-tumor and graft-versus-host disease reactions in stem cell transplantation. Not much information is available on genotypic and phenotypic distributions of the currently identified mHAs, especially in Korean population. Therefore, we report genotype and phenotype frequency analyses of 10 autosomal mHAs in 329 unrelated healthy Koreans using the Sequenom MassARRAY matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) system and polymerase chain reaction-sequence specific primers (PCR-SSP). Estimates of the probability of immunogenic mismatches between donor/recipient pairs were made from observed phenotypic frequencies. HA-1 was the most favorable mHA for clinical application with the highest disparity of 7.0%. Similar results were obtained in ACC-1. The Korean population can benefit the most in a setting of matched major histocompatibility complex (MHC)-restricted mHAs-mismatched unrelated hematopoietic stem cell transplantations with the disparity rate of 27.5% with eight hematopoietic mHAs. This is the first comprehensive report on the genotypic and phenotypic frequency distributions of human mHAs in the Korean population. It can contribute to not only donor selection before transplantation but also therapeutic approaches after transplantation. It is expected that mHA-based immunotherapy will lead to a new treatment modality tailored for patients at high risk of relapse following allogeneic hematopoietic cell transplantation.

Prophylactic use of lamivudine for hepatitis B exacerbation in post-operative breast cancer patients receiving anthracycline-based adjuvant chemotherapy.

BACKGROUND: With the increasing incidence of breast cancer worldwide, in particular in southeast Asia (including Korea), and the common use of anthracyclines in the adjuvant and metastatic settings, the occurrence of Hepatitis B virus (HBV) reactivation may develop in this patient population. The use of prophylactic antiviral agents in cancer patients may result in a reduced HBV exacerbation. The purpose of the current study was to assess the efficacy of prophylactic lamivudine in reducing the incidence and severity of HBV reactivation in post-operative breast cancer patients undergoing adjuvant doxorubicin-containing chemotherapy. METHODS: The medical records of patients undergoing anthracycline-based adjuvant chemotherapy at Samsung Medical Center between January 2001 and September 2008 were reviewed. RESULTS: From the database, 1912 breast cancer patients who had received anthracycline-based adjuvant chemotherapy were identified. Of 131 patients who were HBV surface antigen positive, 55 and 76 did and did not receive prophylactic lamivudine, respectively. In all, 30 patients (23%) developed hepatitis during doxorubicin-containing adjuvant chemotherapy. Of the 30 patients, 5 (9%) were in the prophylactic lamivudine group and 25 (33%) in the control group (P=0.001). In the prophylactic lamivudine group, there was significantly less HBV reactivation (1 patient (2%) vs 20 patients (16%); P=0.002), less disruption of chemotherapy (7 vs 14%; P=0.04), and less severe hepatitis (0 vs 17%; P=0.002). CONCLUSION: Prophylactic lamivudine significantly reduced the incidence and severity of HBV reactivation in breast cancer patients undergoing anthracycline-based adjuvant chemotherapy.

Musculofascial lengthening for the treatment of patients with medial epicondylitis and coexistent ulnar neuropathy.

The outcome of surgery in patients with medial epicondylitis of the elbow is less favourable in those with co-existent symptoms from the ulnar nerve. We wanted to know whether we could successfully treat such patients by using musculofascial lengthening of the flexor-pronator origin with simultaneous deep transposition of the ulnar nerve. We retrospectively reviewed 19 patients who were treated in this way. Seven had grade I and 12 had grade IIa ulnar neuropathy. At a mean follow-up of 38 months (24 to 48), the mean visual analogue scale pain scores improved from 3.7 to 0.3 at rest, from 6.6 to 2.1 with activities of daily living, and from 7.9 to 2.3 at work or sports, and the mean disabilities of the arm, shoulder and hand scores improved from 42.2 to 23.5. These results suggest that this technique can be effective in treating patients with medial epicondylitis and coexistent ulnar nerve symptoms.

Analysis of adrenal masses by 18F-FDG positron emission tomography scanning.

This study aimed to analyse the characteristics of adrenal masses visible in the computerised tomography (CT) scans which have been also evaluated by 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET), and to characterise the features of 18F-FDG PET scans associated with various adrenal endocrine tumours, especially benign functional tumours. 18F-FDG PET scans of 105 patients with adrenal masses on the CT scan were analysed. Positive uptakes in the 18F-FDG PET scans were seen in 60 malignant tumours (54 metastasic lesions, six primary adrenal cancers) and seven benign tumours. The positive predictive value of 18F-FDG PET imaging to characterise an adrenal mass as a malignant tumour was 90%; the corresponding negative predictive value to rule out malignancy was also 90%. Benign adrenal tumours were smaller than that of malignant lesions (p<0.05). The mean standardised uptake value max (SUVmax) of the metastatic lesions [8.4+/-6.5 (microCi/g)/microCi/kg] was significantly higher than that of the benign adrenal tumours [2.4+/-1.2 (microCi/g)/microCi/kg, p<0.001]. Examination of only the primary adrenal lesions revealed that all adrenocortical carcinomas, two of three cases of pheochromocytomas, three of five neuroblastomas and two of four cases of primary aldosteronism showed positive 18F-FDG uptake. In conclusion, for patients presenting adrenal masses with a high probability of malignancy, 18F-FDG PET can be used to differentiate malignant from benign adrenal lesions. However, the 18F-FDG PET uptake did not show an always consistent pattern for endocrine tumours, which was probably due to the variability inherent in 18F-FDG uptake. This study suggests that 18F-FDG PET scanning can offer supporting data to localise and characterise adrenal tumours.

Phorbol ester up-regulates aldose reductase expression in A549 cells: a potential role for aldose reductase in cell cycle modulation.

Over-expression of aldose reductase (AR) has been observed in many cancer cells. To clarify the role of AR in tumor cells, we investigated the pathways mediating expression of the AR gene induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent tumor promoter. In A549 human lung adenocarcinoma cells, TPA elicited a dose- and time-dependent increase in AR mRNA level with an elevated enzyme activity. The TPA-induced increase in mRNA level and promoter activity of the AR gene was significantly attenuated in the presence of an inhibitor of protein kinase C, tyrosine kinase, or nuclear factor kappaB (NF-kappaB). TPA augmented the NF-kappaB-dependent gene transcription, indicating the involvement of NF-kappaB in this regulation. Accumulation of TPA-treated cells in S phase was almost completely abolished in the presence of ethyl 1-benzyl-3-hydroxy-2(5H)-oxopyrrole-4-carboxylate, an AR inhibitor. Taken together, TPA augmented the promoter activity of the AR gene via the activation of protein kinase and NF-kappaB. The inhibition of AR may assist in the chemotherapy of malignant tumors by suppressing the rapid growth of cancer cells.

Finger reconstruction with a free neurovascular wrap-around flap from the big toe.

From 1983 to 1998, 16 cases of finger reconstruction with a free neurovascular wrap-around flap from the big toe were treated. Fourteen cases were successful, and two cases failed. The authors reviewed these cases on the average of about 38 months after surgery. Pinch power was 51 percent of the unaffected normal hand, and two-point discrimination was 7.6 mm. The mean resorption of the grafted bone was 13 percent in width and 9 percent in length. There were no complications such as fracture of the grafted bone, nonunion, and pulp dislodgement. This procedure provided length, stability, and adequate sensibility for a functional pinch and grasp. Sensory return to the wrap-around flap on the thumb was often greater than for the same area on the opposite foot. The donor site of the wrap-around flap was acceptable, both aesthetically and functionally, and allowed the wearing of open-toed shoes by young women. Finger reconstruction with a wrap-around flap from the big toe yielded excellent cosmetic and functional results in cases involving amputation at the level of the metacarpophalangealjoints or distal to it. In addition, this procedure was an excellent choice for treatment in cases involving avulsion injuries of the fingers and reconstruction of soft-tissue defects after tumor excision.

Complications of operative treatment for mallet fractures of the distal phalanx.

Twenty-four of 59 (41%) surgically treated mallet fractures developed postoperative complications. The most common complication was marginal skin necrosis on the dorsal aspect of the distal phalanx, but recurrent extension lag, permanent nail deformities, transient infections along the Kirschner wires and pull-out steel wires and osteomyelitis were also observed.

Schwannomas of the upper extremity.

This study presented the clinical characteristics, MRI features and postoperative results of 20 schwannomas in the arms of 13 patients. Twelve tumours had a positive Tinel's sign, one caused weakness of the wrist and another in Guyon's canal caused hypothenar muscle atrophy. Of the nine cases which underwent magnetic resonance imaging preoperatively, six were correctly diagnosed as schwannomas. All masses were excised using microsurgical techniques and two transient neurological complications occurred.

Endoscopic carpal tunnel release in patients receiving long-term hemodialysis.

This study evaluated the clinical results of endoscopic carpal tunnel release in carpal tunnel syndrome caused by long-term hemodialysis and compared the results with that of idiopathic carpal tunnel syndrome. Operations were done in 32 patients (60 hands) with idiopathic carpal tunnel syndrome and in eight patients (15 hands) with carpal tunnel syndrome resulting from long-term hemodialysis. There was no significant difference in findings of preoperative evaluations and postoperative clinical results between the two groups, except for a difference with the patient satisfaction score with surgery on a visual analogue scale. The mean satisfaction score was 9.0 at 6 months, 9.3 at 1 year, and 9.5 at the 2-year followup in the group of patients with idiopathic carpal tunnel syndrome. However, in the group of patients with carpal tunnel syndrome resulting from long-term hemodialysis, the mean satisfaction score was 8.5 at 6 months, 8.2 at 1 year, and 6.5 at the 2-year followup. The score began to decrease at an average of 17.2 months after surgery. Long-term hemodialysis related carpal tunnel syndrome showed satisfactory short-term clinical results until approximately 1.5 years after the operation. After that time, the symptoms tended to deteriorate in 50% of the patients who received hemodialysis continuously.

The role of radiotherapy in the treatment of aggressive fibromatosis.

Aggressive fibromatosis is a rare benign soft tissue tumor that is difficult to cure because of its infiltrative nature and high tendency to recur locally. The authors retrospectively analyzed 20 patients with histologically-confirmed fibromatosis. All patients underwent surgery with a wide or marginal margin. Five (25%) cases with histologically-negative margins had recurred. External beam radiotherapy was administered to patients whose margins were positive or who had local recurrence. However, out of concern for safety, radiotherapy was not given to two babies and a reproductive-aged woman. The average dose was 5,020 cGy. During the follow-up (mean 32.6 months), all the patients undergoing radiotherapy showed no evidence of local recurrence. A wide local excision has traditionally been the treatment of choice. However, postoperative radiotherapy could be an effective measure for preventing local recurrence in patients with a histologically-positive surgical margin and recurrence independent of any signs of relapse.