Inhibitory effect of octyl-phenol and bisphenol A on calcium signaling in cardiomyocyte differentiation of mouse embryonic stem cells.

Endocrine-disrupting chemicals (EDCs) have structures similar to steroid hormones and can interfere with hormone synthesis and normal physiological functions of reproductive organs. For example, sex steroid hormones influence calcium signaling of the cardiac muscle in early embryo development. To confirm the effect of progesterone (P4), octyl-phenol (OP), and bisphenol A (BPA) on early differentiation of mouse embryonic stem cells (mESCs) into cardiomyocytes, mESCs were treated with P4, OP, and BPA two days after attachment and media were replaced every two days. In addition, cells were treated with mifepristone (RU486), a synthetic steroid that has an affinity for progesterone receptor (Pgr), for one day starting on day 11. Beating ratio was decreased with P4, OP, and BPA treatment. The Pgr mRNA level was significantly increased in the P4-, OP- and BPA-treated groups. However, the mRNA level of the calcium channel gene (Trpv2), contraction-related genes (Ryr2, Cam2, and Mylk3) and cardiac development and morphogenesis genes (Rbp4, Ly6e, and Gata4) were significantly decreased in the P4-, OP-, and BPA-treated groups. Interestingly, treatment with RU486 rescued the altered calcium channel gene, contraction-related genes, and cardiac development and morphogenesis genes. P4, OP, and BPA treatments reduced the intracellular calcium level. Taken together, these results indicate that EDCs (OP and BPA) has a structure similar to that of endogenous steroid hormones such as progesterone and estrogen, and OP and BPA act like progesterone to inhibit and disrupt cardiomyocyte differentiation of mESCs.

Regulatory effect of dexamethasone on tracheal calcium processing proteins and mucosal secretion.

Dexamethasone inhibits mucin secretion considering the primary option for treating acute asthma exacerbation. However, the mechanism underlying dexamethasone-induced decreased in mucosecretion is unclear. Recent studies have reported that dexamethasone exerts an inhibitory effect on mucosecretion in the lung by modulating the expression of calcium processing genes. However, the expression of the calcium processing genes in the trachea is not examined yet. Thus, the present study is the first to report the localization of calcium processing proteins such as transient receptor potential vanilloid-4 (Trpv4), transient receptor potential vanilloid-6 (Trpv6), calbindin-D9k (CaBP-9k) and plasma membrane Ca2+-ATPase 1 (Pmca1) in the mouse trachea and their glucocorticoid-induced response. In this study, mice were subcutaneously injected with dexamethasone for 5 days, and their tracheal samples were collected by dividing the trachea into the cervical, and thoracic sections based on its anatomical structure. The localization of TRPV4, TRPV6, CaBP-9k, and PMCA1 proteins was detected in the tracheal epithelium, submucosal glands, cartilages and muscles. Dexamethasone treatment downregulated the mRNA expression of the four calcium processing genes and mucin producing genes. The dexamethasone-induced decrease in the secretion of mucosubstances in the trachea was determined by performing Alcian blue-periodic acid-Schiff staining. Thus, the findings of the present study suggest that glucocorticoids simultaneously can regulate the expression of calcium processing genes and tracheal mucosecretion.

Clonorchis sinensis omega-class glutathione transferases are reliable biomarkers for serodiagnosis of clonorchiasis and opisthorchiasis.

OBJECTIVES: To determine the potential for immunodiagnostic application of two recombinant forms of Clonorchis sinensis omega-class glutathione transferases (rCsGSTo1 and rCsGSTo2) against human small liver-fluke C. sinensis and Opisthorchis viverrini infections. METHODS: Specific antibody levels against rCsGSTo1 and rCsGSTo2 in patients' sera of egg-positive opisthorchiasis (n = 87) and clonorchiasis (n = 120), as well as those in sera from patients with other helminthic infections (n = 252) and healthy controls (n = 40) were retrospectively analysed by ELISA. RESULTS: We observed highly positive correlation coefficients between specific antibody levels against rCsGSTo1 and rCsGSTo2 and egg counts per gramme of faeces (EPG) of patients with opisthorchiasis (n = 87; r = 0.88 for rCsGSTo1 and r = 0.90 for rCsGSTo2). Sera from opisthorchiasis patients whose EPG counts >100 (n = 43) revealed high antibody titres against both antigens. Patients' sera with low EPG counts (<100, n = 44) also exhibited reliable sensitivities of 93.2% and 97.7% for rCsGSTo1 and rCsGSTo2, respectively. Sera from clonorchiasis patients showed sensitivities of 90% (108/120 samples) and 89.2% (107/120 sera) for rCsGSTo1 and rCsGSTo2. Overall diagnostic sensitivities for liver-fluke infections were 92.3% for rCsGSTo1 (191/207 samples) and 93.2% for rCsGSTo2 (193/207 samples). Specificities were 89.7% (rCsGSTo1) and 97.6% (rCsGSTo2). CONCLUSIONS: Detection of specific antibody levels against rCsGSTo1 or rCsGSTo2 might be promising for the serodiagnosis of patients infected with these two phylogenetically close carcinogenic liver-flukes.

MRA of the skin: mapping for advanced breast reconstructive surgery.

Autologous breast reconstruction using muscle-sparing free flaps are becoming increasingly popular, although microvascular free flap reconstruction has been utilised for autologous breast reconstructions for >20 years. This innovative microsurgical technique involves meticulous dissection of artery-vein bundle (perforators) responsible for perfusion of the subcutaneous fat and skin of the flap; however, due to unpredictable anatomical variations, preoperative imaging of the donor site to select appropriate perforators has become routine. Preoperative imaging also reduces operating time and enhances the surgeon's confidence in choosing the appropriate donor site for harvesting flaps. Although computed tomography angiography has been widely used for preoperative imaging, concerns over excessive exposure to ionising radiation and poor iodinated contrast agent enhancement of the intramuscular perforator course has made magnetic resonance angiography, the first choice imaging modality in our centre. Magnetic resonance angiography with specific post-processing of the images has established itself as a reliable method for mapping tiny perforator vessels. Multiple donor sites can be imaged in a single setting without concern for ionising radiation exposure. This provides anatomical information of more reconstruction donor site options, so that a surgeon can design a flap of tissue centralised around the best perforator, as well as a back-up perforator, and even a back-up flap option located on a different region of the body. This information is especially helpful in patients with a history of scar tissue from previous surgeries, where the primary choice perforator is found to be damaged or unsuitable intraoperatively. In addition, chest magnetic resonance angiography evaluates recipient site blood vessel suitability including vessel diameters, course, and branching patterns. In this article we provide a broad overview of various skin flaps, clinical indications, advantages and disadvantages of each of these flaps, basic imaging technique, along with advanced sequences for visualising tiny arteries in the groin and in the chest. Post-processing techniques, structure of the report and how automation of the reporting system improves workflow is described. We also describe applications of magnetic resonance angiography in postoperative imaging.

VDJ Gene Usage of B Cell Receptors in Peripheral Blood of ABO-incompatible Kidney Transplantation Patients.

INTRODUCTION: B cell subtypes and immunoglobulin variable (V), diversity (D), joining (J) gene segment usage of B cell receptors in ABO-incompatible (ABOi) kidney transplantation (KT) in comparison to ABO-compatible KT have not been studied. The aims of this study were to analyze the VDJ gene segment usages of B cell receptors in peripheral blood of ABOi KT recipients. METHODS: Eighteen ABOi KT patients with accommodation (ABOiA), 10 ABO-compatible stable KT patients (ABOcS), and 10 ABOi KT patients with biopsy-proven acute antibody-mediated rejection (ABOiR) at day 10 after transplantation were selected. Complete transcriptomes of their peripheral blood samples were sequenced and analyzed through RNA sequencing. RESULTS: By family, immunoglobulin heavy chain variable 3 (IGHV3), immunoglobulin light kappa chain variable 1 (IGKV1), immunoglobulin light lambda chain variable 2 (IGLV2), and immunoglobulin light lambda chain joining 3 (IGLJ3) gene segments were most frequently used in all groups, and their usage was not statistically different among the three groups except for IGHV3 and IGKV1. IGKV1 was more frequently used in the ABOiA group than in the ABOcS group. According to individual gene segments, IGHV3-7, IGHV3-15, IGHV4-59, IGKV3-11, IGLV1-44, IGLV2-14, IGLV4-69, and IGLV7-46 were more frequently used in the ABOcS group than other groups, and IGKV3-7 was more frequently used in the ABOiR group than other groups. IGLV5-52 and IGLV7-43 were more frequently used in the ABOiA group than in ABOcS group. CONCLUSIONS: Our findings suggest that RNA sequencing transcriptomic analyses of peripheral blood can provide information on the VDJ gene usage of B cell receptors and the mechanisms of accommodation and immune reaction in ABOi KT.

Red Blood Cell Distribution Width Is Associated with Carotid Atherosclerosis in People with Type 2 Diabetes.

AIMS: Red cell distribution width (RDW) has been shown to be associated with cardiovascular diseases (CVD). The relationship between RDW and carotid intima-media thickness (C-IMT), a marker of subclinical atherosclerosis, has been inconsistent in subjects with cardiovascular risk factors. In this study, we investigated the relationship between RDW and carotid atherosclerosis in people with type 2 diabetes. METHODS: Four hundred sixty-nine people with type 2 diabetes without history of cardiovascular or cerebrovascular diseases were enrolled. Anthropometric measures and various biochemical parameters including RDW were assessed. Ultrasonographic measurement of carotid intima-media thickness was used to evaluate subclinical atherosclerosis. RESULTS: The participants were stratified into 3 groups according to RDW. The C-IMT increased gradually according to RDW tertiles (lowest, second, highest RDW tertiles; 0.740 ± 0.120, 0.772 ± 0.138, and 0.795 ± 0.139, respectively; p < 0.01). Multiple regression analysis and multivariate logistic regression analysis revealed that RDW was associated with C-IMT in people with type 2 diabetes, and it remained significant after control for various cardiovascular risk factors including body mass index, blood pressure, insulin resistance, and smoking status in multivariate logistic regression analysis. CONCLUSION: RDW is associated with subclinical atherosclerosis assessed by carotid IMT after control of various covariates in people with type 2 diabetes without cardiovascular or cerebrovascular diseases.

Anti-asthmatic effects of volatile organic compounds from Chamaecyparis obtusa, Pinus densiflora, Pinus koraiensis, or Larix kaempferi wood panels.

Asthma is a common chronic inflammatory disease in which lung airways narrow and produce extra mucus. Numerous medications, such as steroids, are used to prevent or control asthmatic symptoms, but side effects are associated with those medications. There are reports of anti-inflammatory, antibacterial, and antiparasitic effects of terpene, a volatile organic compound (VOC) in conifers. VOCs easily enter a gaseous form, and wood products are good sources of VOCs. However, only a few studies have been conducted on the effect on asthma of VOCs emitted by wood. In this study, we examined the effects of VOCs diffused from wood panels on ovoalbumin (OVA)-induced asthma in a mouse model. The mice were intraperitoneally sensitized with 10 µg of OVA with aluminum hydroxide on days 0, 7, and 14. From day 21 to day 26, the mice were challenged with 2% OVA intranasally for 30 min. For VOC treatment, asthma model mice were placed in polyacrylamide chambers containing wood panels of Chamaecyparis obtusa, Pinus densiflora, Pinus koraiensis, or Larix kaempferi. On day 27, serum, lung tissue, and bronchoalveolar lavage fluids were prepared for H&E staining, qRT-PCR, ELISA, and Diff-Quik staining, as appropriate. OVA treatment induced hypertrophy of the bronchiolar wall. The budesonide group and all four of the wood panel-exposed groups showed less thickening of the bronchiolar wall and downregulated transcriptional expressions of cytokines such as interleukin-4 (IL-4) and interleukin-13 (IL-13). The serum tumor necrosis factor-α (TNF-α) mRNA expression level was significantly decreased only in the C. obtusa group, but the serum IL-4 levels were decreased in all wood panel treatment groups. Diff-Quik staining of bronchoalveolar lavage fluids revealed a decrease in the number of granulocytes in all wood panel treatment groups. The results suggest that VOCs from C. obtusa, P. densiflora, P. koraiensis and L. kaempferi produce antiasthmatic effects by regulating the production of IL-4, IL-9, IL-13, TNF-α.

Acute Graft-vs-Host Disease After Liver Transplantation: Experience at a High-volume Liver Transplantation Center in Korea.

BACKGROUND: Acute graft-vs-host disease (GVHD) is a rare but life-threatening complication of orthotopic liver transplantation (OLT). We present 6 cases of GVHD after OLT. METHODS: Among our 4294 OLT recipients, we identified 6 patients (0.14%) who were diagnosed with GVHD. Their medical records were reviewed retrospectively. RESULTS: Liver graft types included deceased donor whole liver graft (n = 3) and right liver graft from son (n = 3). Mean recipient and donor ages were 57.2 ± 6.6 years and 32.7 ± 10.8 years, respectively. Onset of GVHD symptoms occurred 14 to 32 days after OLT, and initial symptoms were skin rash (n = 5) and fever (n = 1). GVHD was pathologically confirmed by skin or rectal biopsy. Chimerism of donor lymphocytes was identified in all 3 patients who underwent the short tandem repeat polymerase chain reaction assay. Attempts were made to treat the GVHD in all 6 patients by corticosteroids with or without low-dose calcineurin inhibitor, but we had to stop early or reduce these agents due to aggravation of pancytopenia and septic complications. Ultimately, 5 patients died 6 to 106 days after the onset of GVHD, and only 1 patient recovered. This surviving patient was diagnosed earlier and had been administered the recommended dosage of corticosteroid for a longer period with aggressive infection prophylaxis compared to the other cases. CONCLUSIONS: Because of very poor outcomes of GVHD after OLT, early diagnosis and vigorous treatment should be emphasized, although no effective treatment modality has been established yet. We strongly suggest performing aggressive infection prophylaxis during GVHD treatment.

Survival Benefit of Early Cancer Detection Through Regular Endoscopic Screening for De Novo Gastric and Colorectal Cancers in Korean Liver Transplant Recipients.

BACKGROUND: De novo malignancy is not uncommon after liver transplantation (LT). Gastric cancer is one of the most common malignancies in both the Korean general population and LT recipients, and colorectal cancer prevalence is gradually increasing. METHODS: Among 3690 adult recipients who underwent LT from January 1999 and December 2013, the screening patterns and prognosis of 26 cases of gastric cancer and 22 cases of colorectal cancer were analyzed. RESULTS: For gastric cancer, the mean patient age was 54.6 ± 6.2 years at LT and 59.5 ± 6.7 years at cancer diagnosis, with a post-transplant interval of 60.2 ± 29.8 months. Patients were divided into regular (n = 18) and non-regular (n = 8) screening groups, with early cancer found in 14 and 0 patients; their 2-year survival rates after cancer diagnosis were 93.1% and 33.3% (P = .006), respectively. Endoscopic resection was successfully performed in 8 patients, all in the regular screening group. For colorectal cancer, the mean patient age was 53.3 ± 6.1 years at LT and 58.1 ± 6.7 years at cancer diagnosis, with a post-transplant interval of 54.3 ± 38.0 months. Patients were divided into regular (n = 19) and non-regular (n = 3) screening groups, with early cancer found in 12 and 0 patients; their 2-year survival rates after cancer diagnosis of 92.3% and 33.3% (P = .003), respectively. Endoscopic resection was successfully performed in 6 patients, all in the regular screening group. CONCLUSIONS: LT recipients are strongly advised to undergo regular screening studies for various de novo malignancies, especially cancers common in the general population. Regular endoscopic screening contributes to the timely detection of gastric and colorectal cancers, improving post-treatment survival outcomes.

The Introduction of Human Heme Oxygenase-1 and Soluble Tumor Necrosis Factor-α Receptor Type I With Human IgG1 Fc in Porcine Islets Prolongs Islet Xenograft Survival in Humanized Mice.

Apoptosis during engraftment and inflammation induce poor islet xenograft survival. We aimed to determine whether overexpression of human heme oxygenase-1 (HO-1) or soluble tumor necrosis factor-α receptor type I with human IgG1 Fc (sTNF-αR-Fc) in porcine islets could improve islet xenograft survival. Adult porcine islets were transduced with adenovirus containing human HO-1, sTNF-αR-Fc, sTNF-αR-Fc/HO-1 or green fluorescent protein (control). Humanized mice were generated by injecting human cord blood-derived CD34(+) stem cells into NOD-scid-IL-2Rγ(null) mice. Both HO-1 and sTNF-αR-Fc reduced islet apoptosis under in vitro hypoxia or cytokine stimuli and suppressed RANTES induction without compromising insulin secretion. Introduction of either gene into islets prolonged islet xenograft survival in pig-to-humanized mice transplantation. The sTNF-αR-Fc/HO-1 group showed the best glucose tolerance. Target genes were successfully expressed in islet xenografts. Perigraft infiltration of macrophages and T cells was suppressed with decreased expression of RANTES, tumor necrosis factor-α and IL-6 in treatment groups; however, frequency of pig-specific interferon-γ-producing T cells was not decreased, and humoral response was not significant in any group. Early apoptosis of islet cells was suppressed in the treatment groups. In conclusion, overexpression of HO-1 or sTNF-αR-Fc in porcine islets improved islet xenograft survival by suppressing both apoptosis and inflammation. HO-1 or sTNF-αR-Fc transgenic pigs have potential for islet xenotransplantation.

Liver transplantation in Korea: past, present, and future.

PURPOSE: This study reviewed the past and present status of liver transplantation (LT) and outlooks for the future of LT in Korea. METHOD: The first LT in Korea was successfully performed using a deceased donor graft in 1988. Pediatric and adult living donor liver transplantations (LDLTs) were initiated in 1994 and 1997, respectively. From 1988 to 2013, 10,581 LTs were performed at 40 centers, whereas LDLT accounted for 76.5% of all LTs. RESULTS: In the early 1990s, the deceased organ donation rate was less than 1.5 per million population (PMP) per year, but it increased to 5 PMP beginning in 2008. Despite the increasing number of deceased donor liver transplantations (DDLTs), high prevalence of hepatitis B virus (HBV)-induced cirrhosis and hepatocellular carcinoma (HCC) has provoked persistent performance of adult LDLT with technical advancement including middle hepatic vein (MHV) reconstruction of right lobe graft and dual graft LDLT with 1 nationwide donor mortality. CONCLUSION: The number of LTs in Korea in 2010 was 23.2 PMP (1042 LTs/45 million population), lower than 23.5 PMP of Spain, but higher than 20 PMP of the United States. However, future LT numbers may decrease because of lowering the HBV carrier rate (neonatal HBV universal vaccination began in 1992), new potent anti-HBV agents, and lowest birth rate (1.22 children per family) with a decrease of potential live donors.

Hepatic differentiation of porcine embryonic stem cells for translational research of hepatocyte transplantation.

Porcine embryonic stem cells (ES) are considered attractive preclinical research tools for human liver diseases. Although several studies previously reported generation of porcine ES, none of these studies has described hepatic differentiation from porcine ES. The aim of this study was to generate hepatocytes from porcine ES and analyze their characteristics. We optimized conditions for definitive endoderm induction and developed a 4-step hepatic differentiation protocol. A brief serum-free condition with activin A efficiently induced definitive endoderm differentiation from porcine ES. The porcine ES-derived hepatocyte-like cells highly expressed hepatic markers including albumin and α-fetoprotein, and displayed liver characteristics such as glycogen storage, lipid production, and low-density lipoprotein uptake. For the first time, we describe a highly efficient protocol for hepatic differentiation from porcine ES. Our findings provide valuable information for translational liver research using porcine models, including hepatic regeneration and transplant studies, drug screening, and toxicology.

Molecular and biochemical characterization of Paragonimus westermani tyrosinase.

Trematode tyrosinases (TYRs) play a major role in the tanning process during eggshell formation. We investigated the molecular and biochemical features of Paragonimus westermani TYR (PwTYR). The PwTYR cDNA was composed of 1568-bp encompassing a 1422-bp-long open reading frame (474-amino acid polypeptide). A strong phylogenetic relationship with Platyhelminthes and Deuterostomian orthologues was evident. The recombinant PwTYR expressed in prokaryotic cells promptly oxidized diphenol substrates, with a preferential affinity toward ortho-positioned hydroxyl groups. It demonstrated fairly weak activity for monophenol compounds. Diphenol oxidase activity was augmented with an increase of pH from 5.0 to 8.0, while monophenol oxidase activity was highest at an acidic pH and gradually decreased as pH increased. Transcription profile of PwTYR was temporally upregulated along with worm development. PwTYR was specifically localized in vitellocytes and eggs. The results suggested that conversion of tyrosine to L-dihydroxyphenylalanine by PwTYR monophenol oxidase activity might be rate-limiting step during the sclerotization process of P. westermani eggs. The pH-dependent pattern of monophenol and diphenol oxidase activity further proposes that the initial hydroxylation might slowly but steadily progress in acidic secreted vesicles of vitellocytes and the second oxidation process might be rapidly accelerated by neural or weak alkaline pH environments within the ootype.

Effects of xenoestrogens on streptozotocin-induced diabetic mice.

In diabetic mellitus, apoptotic or necrotic deaths of pancreatic ß-cells lead to insulin deficiency because plasma insulin is synthesized and released from pancreatic ß-cells and involved with blood glucose homeostasis. Since estrogen receptors have been related with glucose metabolis, estrogen-like chemicals (xenoestrogens) including bisphenol A (BPA) and octylphenol (OP) alter the endocrine system, and cause adverse health consequences such as obesity and diabetes. In the current study, levels of plasma glucose were evaluated after administration of BPA and OP using biochemical analysis, and were investigated in insulin and insulin synthesis-related genes in the pancreas and liver of streptozotocin (STZ)-induced insulin-deficient mice. Although the STZ-induced insulin-deficient groups showed an increase in blood glucose compared with control groups, the induced blood glucose level dropped to that of baseline after administration of xenoestrogens. When insulin level and mRNA expression of insulin transcriptional regulators (Pdx1, Mafa, and Neurod1) in pancreatic ß-cells were decreased in STZ-induced insulin-deficient groups, they were significantly restored by administration of xenoestrogens. The latter observation is also related to NF-κB activation for anti-apoptosis effects in pancreatic ß-cells. In addition, we observed a complementary convergence in regulation of gluconeogenesis for determination of blood glucose levels. Therefore, the current study may be particularly important for assessment of xenoestrogens under condition of diabetic mellitus or metabolic disorder.

Long-term survival analysis of liver transplantation for hepatocellular carcinoma with bile duct tumor thrombus.

BACKGROUND: Long-term prognosis of liver transplantation (LT) for hepatocellular carcinoma (HCC) with macroscopic bile duct tumor thrombus (BDTT) has not been well assessed. This study intended to analyze the post-transplantation outcomes in patients who had HCC with macroscopic BDTT. METHODS: A retrospective study was performed with 14 patients who underwent LT for HCC with BDTT (0.7%) after selection from an institutional database of 2052 adult LT cases. RESULTS: Types of LT were living donor LT in 13 and deceased donor LT in 1. The extents of BDTT were Ueda type 1 in 4, type 2 in 3, and type 3 in 7. Milan criteria were met in 8 (57.1%). Concurrent bile duct resection was performed in 7 (50%). Mean model for end-stage liver disease score was 18.7 ± 4.9. Mean graft-recipient weight ratio was 1.2 ± 0.3. There was one case of perioperative mortality and one case of HCC-unrelated late mortality. Cumulative HCC recurrence rates were 15.4% at 1 year, 46.2% at 3 years, and 46.2% at 5 years. Overall patient survival rates were 92.9% at 1 year, 57.1% at 3 years, and 50% at 5 years. Univariate risk factor analyses revealed that only macrovascular invasion was a significant risk factor for HCC recurrence (P = .019). CONCLUSIONS: The results of this study revealed that LT for HCC with macroscopic BDTT has a high risk of post-transplantation HCC recurrence; therefore, further large-volume studies are necessary to elucidate the risk factors.

Complications analysis of polytetrafluoroethylene grafts used for middle hepatic vein reconstruction in living-donor liver transplantation.

BACKGROUND: We previously showed that ringed polytetrafluoroethylene (PTFE) grafts combined with small allograft patches showed high patency rates similar to those of iliac vein grafts and therefore that they can be used for middle hepatic vein (MHV) reconstruction. Although such use of PTFE graft showed high patency rates, its long-term safety regarding infection and other types of complications were not presented. In this study, we investigated the actual risk of complications directly associated with PTFE graft interposition for MHV reconstruction. METHODS: During the study period of 30 months, we performed 215 cases of adult living-donor liver transplantation with modified right lobe graft and PTFE grafts. We classified the potential complications directly associated with PTFE graft interposition as infectious and surgical complications. The medical records of study patients were retrospectively reviewed. RESULTS: MHV graft patency rate was 76.3% at 6 months and 36.7% at 12 months. Their 1-year graft and patient survival rates were 92.6% and 93.5%, respectively. The 1-year actual incidences of infectious complication and surgical complication were near zero and 1 case (0.5%), respectively. In 1 recipient, the PTFE graft penetrated into the stomach wall 6 months after transplantation, but the patient did not complain of any specific symptoms. The PTFE graft was removed with the use of laparotomy, and the patient recovered uneventfully. CONCLUSIONS: Although the incidence of PTFE graft-associated complication rate is very low, we suggest that it is necessary to closely monitor the PTFE graft, because unexpected complications can happen during long-term follow-up.

Expression pattern analysis of hepatocellular carcinoma tumor markers in viral hepatitis B and C patients undergoing liver transplantation and resection.

BACKGROUND: This study was conducted to compare the expression patterns of serum alpha-fetoprotein (AFP) and proteins induced by vitamin K absence or antagonist-II (PIVKA-II) in hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT) and resection at a high-volume single institution. METHODS: First, 663 liver transplant recipients with HCC were selected. They were divided into hepatitis B virus (HBV) (n = 628) and hepatitis C virus (HCV) groups (n = 35). Their medical records were retrospectively reviewed. Second, another cohort of 2709 patients who underwent HCC resection included 2258 HBV, 143 HCV, and 308 non-HBV non-HCV (NBNC) patients. RESULTS: In the transplantation group, pretransplantation AFP level >20 ng/mL was observed in 42.5% of HBV patients and 60% of HCV patients (P = .042). PIVKA-II level >40 mAU/mL was observed in 30.6% of HBV patients and 42.9% of HCV patients (P = .127). In the resection group, a preoperative AFP level >20 ng/mL was observed in 51.7% of HBV patients and 43.3% of HCV patients (P = .052). PIVKA-II level >40 mAU/mL was observed in 59.7% of HBV patients and 56.6% of HCV patients (P = .47). Preoperative AFP level >20 ng/mL and PIVKA-II level >40 mAU/mL were observed in 35.7% and 61% of NBNC patients, respectively. Receiver-operator characteristic curve analyses revealed that the expression pattern of PIVKA-II in patients with elevated AFP level was not predictable and vice versa, regardless of background liver diseases. CONCLUSIONS: This study indicates that serum AFP and PIVKA-II may be expressed variably regardless of the types of background liver disease. Further large-volume multicenter studies are needed to evaluate the possibility of the etiology-dependent expression of tumor markers.

Effects of newly developed chemotherapy regimens, comorbidities, chemotherapy-related toxicities on the changing patterns of the leading causes of death in elderly patients with colorectal cancer.

BACKGROUND: Abundant evidences have shown that newly developed chemotherapy regimens improved 5-year survival rate of colorectal cancer (CRC) patients over the past two decades. However, their impact on risk of death from leading causes among elderly patients is still poorly understood. PATIENTS AND METHODS: A retrospective cohort study of 69 718 elderly CRC patients with their first primary tumors in 1992-2009, identified from the 12 areas of Surveillance, Epidemiology, and End Results-Medicare linked database with their Medicare claims up to 2010. Multivariate Cox regression models were used to assess the effect of newly developed chemotherapy regimens, comorbidities, and chemotherapy related toxicities on cause-specific death and their temporal patterns among elderly CRC patients. RESULTS: The leading causes of death among CRC patients were CRC, circulation disorders, and secondary cancers, which accounted for 51.4%, 25%, and 4.6% of all-cause death, respectively. Patients diagnosed in more recent diagnostic time periods were significantly less likely to die of CRC [period 2: 5-year hazard ratio = 0.94, 95% confidence interval (CI) 0.90-0.97; period 3: 0.86, 0.83-0.90], circulation disorders (period 2: 0.94, 0.88-1.00; period 3: 0.80, 0.75-0.87), and more likely to die of secondary cancer (period 3: 1.42, 1.20-1.68) compared with those diagnosed in period 1. Charlson comorbidities index and the selected pre-existing comorbidities were significantly associated with increased 5-year risk of death from all three leading causes. Both hematological and gastric toxicity were associated with reduced risk of death from CRC and circulation disorders. The association between diagnostic time period and risk reduction in death from CRC depended on chemotherapy treatment (P < 0.0001). Subgroup analyses showed that the chemotherapy-dependent significant risk reduction was seen in patients with stage II-III CRC, patients without comorbidities, and patients without toxicities (P < 0.0001 for all). CONCLUSION: The newly developed chemotherapy regimens were associated with the decreased risk of mortality from CRC.

Utility of QuantiFERON-TB assay for prediction of tuberculosis development in kidney transplant patients in an intermediate-tuberculosis-burden country: lack of evidence for enhanced prediction for short-term tuberculosis development.

INTRODUCTION: Although a latent tuberculosis (TB) infection is a risk factor for active TB, the diagnosis of latent TB infection is difficult in end-stage renal disease patients. PATIENTS AND METHODS: We retrospectively compared the results of the QuantiFERON-TB (QFT) test and the tuberculin skin test in patients on the waiting list for kidney transplantation (KT), and investigated whether the QFT test can predict TB development in KT recipients in an intermediate-TB-burden country. RESULTS: The incidence of post-KT TB was 283 cases/100,000 patient-years among 1274 KT recipients at the Seoul National University Hospital. The overall standardized incidence ratio of TB was 4.358 compared with the general population. A past history of TB infection, smoking history, myocardial infarction after KT, and pneumocystis infection were significant predictors of subsequent TB development (adjusted odds ratios were 3.618, 2.959, 9.993, and 5.708, respectively). Among the 129 recipients who had the QFT test, 42 patients (32.5%) had positive a QFT. At a median follow-up of 8.4 ± 6.8 months, 1 patient with positive QFT results developed TB after KT, and 1 of the 87 patients with negative QFT results developed TB after KT. In both of these 2 cases, active TB developed despite isoniazid prophylaxis. Among 272 patients on the waiting list for KT, the tuberculin skin test and QFT were positive in 22.8% and 35.3%, respectively. The degree of agreement between the 2 tests was poor (κ = 0.352). CONCLUSIONS: The QFT test did not predict subsequent short-term TB development. Furthermore, a long-term and larger-scale study is needed to confirm our results.