Single-Center Experience Using Marginal Liver Grafts in Korea.

BACKGROUND: Liver transplantation (LT) is an established therapeutic modality for patients with end-stage liver disease. The use of marginal donors has become more common worldwide due to the sharp increase in recipients, with a consequent shortage of suitable organs. We analyzed our single-center experience over the last 8 years in LT to evaluate the outcomes of using so-called "marginal donors." METHODS: We retrospectively analyzed the database of all LTs performed at our institution from 2009 to 2017. Only patients undergoing deceased-donor LTs were analyzed. Marginal grafts were defined as livers from donors >60 years of age, livers from donors with serum sodium levels >155 mEq, graft steatosis >30%, livers with cold ischemia time ≥12 hours, livers from donors who were hepatitis B or C virus positive, livers recovered from donation after cardiac death, and livers split between 2 recipients. Patients receiving marginal grafts (marginal group) were compared with patients receiving standard grafts (standard group). RESULTS: A total of 106 patients underwent deceased-donor LT. There were 55 patients in the standard group and 51 patients in the marginal group. There were no significant differences in terms of age, sex, Model for End-Stage Liver Disease score, underlying liver disease, presence of hepatocellular carcinoma, and hospital stay between the 2 groups. Although the incidence of acute cellular rejection, cytomegalovirus infection, and postoperative complications was similar between the 2 groups, the incidence of early allograft dysfunction was higher in the marginal group. With a median follow-up of 26 months, the 1-, 3-, and 5-year overall and graft (death-censored) survivals in the marginal group were 85.5%, 75%, and 69.2% and 85.9%, 83.6%, and 77.2%, respectively. Patient overall survival and graft survival (death-censored) were significantly lower in the marginal group (P = .023 and P = .048, respectively). On multivariate analysis, receiving a marginal graft (hazard ratio [HR], 4.862 [95% confidence interval (CI), 1.233-19.171]; P = .024) and occurrence of postoperative complications (HR, 4.547 [95% CI, 1.279-16.168]; P = .019) were significantly associated with worse patient overall survival. Also, when factors associated with marginal graft were analyzed separately, graft steatosis >30% was independently associated with survival (HR, 5.947 [95% CI, 1.481-23.886]; P = .012). CONCLUSIONS: Patients receiving marginal grafts showed lower but acceptable overall survival and graft survival. However, because graft steatosis >30% was independently associated with worse survival, caution must be exercised when using this type of marginal graft by weighing the risk and benefits.

EMP2 is a novel therapeutic target for endometrial cancer stem cells.

Previous studies have suggested that overexpression of the oncogenic protein epithelial membrane protein-2 (EMP2) correlates with endometrial carcinoma progression and ultimately poor survival from disease. To understand the role of EMP2 in the etiology of disease, gene analysis was performed to show transcripts that are reciprocally regulated by EMP2 levels. In particular, EMP2 expression correlates with and helps regulate the expression of several cancer stem cell associated markers including aldehyde dehydrogenase 1 (ALDH1). ALDH expression significantly promotes tumor initiation and correlates with the levels of EMP2 expression in both patient samples and tumor cell lines. As therapy against cancer stem cells in endometrial cancer is lacking, the ability of anti-EMP2 IgG1 therapy to reduce primary and secondary tumor formation using xenograft HEC1A models was determined. Anti-EMP2 IgG1 reduced the expression and activity of ALDH and correspondingly reduced both primary and secondary tumor load. Our results collectively suggest that anti-EMP2 therapy may be a novel method of reducing endometrial cancer stem cells.

A New Practical Desensitization Protocol for Oxaliplatin-Induced Immediate Hypersensitivity Reactions: A Necessary and Useful Approach.

BACKGROUND AND OBJECTIVE: Desensitization protocols for patients with immediate hypersensitivity reactions (IHSRs) have proven to be effective, but they are not widely used in clinical practice because of impracticalities such as high cost, long procedure duration, and a lack of trained personnel. We aimed to determine the clinical characteristics of oxaliplatin-induced IHSRs and assess measures to protect against these reactions and to validate a new practical desensitization protocol. METHODS: We retrospectively reviewed 2640 cases of oxaliplatin IHSRs in 271 oxaliplatin users and prospectively used a newly designed desensitization protocol 32 times in 12 patients with hypersensitivity to platinum-based chemotherapy. The protocol consisted of increases in infusion rate every 15 minutes, regardless of the concentration of the chemotherapy agent in the infusion bags. RESULTS: Of the 271 patients administered oxaliplatin, 45 (16.6%) experienced IHSRs. Of 39 patients who experienced an IHSR but needed to continue oxaliplatin, 6 (15.4%) stopped treatment due to the reaction, and 33 (84.6%) continued despite the risk of further reactions. The new desensitization protocol was successfully completed in 12 patients (100%), but it was ineffective in 3 patients (all with a negative skin prick test), who experienced fever without urticaria. CONCLUSIONS: Many patients who experience oxaliplatin-induced IHSRs are required to stop first-line oxaliplatin-based chemotherapy or to continue without desensitization, with the associated risks. Our new desensitization protocol is practical and easy to use in clinical practice.

The C/EBPδ protein is stabilized by estrogen receptor α activity, inhibits SNAI2 expression and associates with good prognosis in breast cancer.

Hypoxia and inflammatory cytokines like interleukin-6 (IL-6, IL6) are strongly linked to cancer progression, and signal in part through the transcription factor Ccaat/enhancer-binding protein δ (C/EBPδ, CEBPD), which has been shown to promote mesenchymal features and malignant progression of glioblastoma. Here we report a different role for C/EBPδ in breast cancer. We found that the C/EBPδ protein is expressed in normal breast epithelial cells and in low-grade cancers. C/EBPδ protein (but not mRNA) expression correlates with estrogen receptor (ER+) and progesterone receptor (PGR) expression and longer progression-free survival of breast cancer patients. Specifically in ER+ breast cancers, CEBPD-but not the related CEBPB-mRNA in combination with IL6 correlated with lower risk of progression. Functional studies in cell lines showed that ERα promotes C/EBPδ expression at the level of protein stability by inhibition of the FBXW7 pathway. Furthermore, we found that C/EBPδ attenuates cell growth, motility and invasiveness by inhibiting expression of the SNAI2 (Slug) transcriptional repressor, which leads to expression of the cyclin-dependent kinase inhibitor CDKN1A (p21CIP1/WAF1). These findings identify a molecular mechanism by which ERα signaling reduces the aggressiveness of cancer cells, and demonstrate that C/EBPδ can have different functions in different types of cancer. Furthermore, our results support a potentially beneficial role for the IL-6 pathway specifically in ER+ breast cancer and call for further evaluation of the role of intra-tumoral IL-6 expression and of which cancers might benefit from current attempts to target the IL-6 pathway as a therapeutic strategy.

Five-year decreased incidence of surgical site infections following gastrectomy and prosthetic joint replacement surgery through active surveillance by the Korean Nosocomial Infection Surveillance System.

BACKGROUND: Surveillance of healthcare-associated infection has been associated with a reduction in surgical site infection (SSI). AIM: To evaluate the Korean Nosocomial Infection Surveillance System (KONIS) in order to assess its effects on SSI since it was introduced. METHODS: SSI data after gastrectomy, total hip arthroplasty (THA), and total knee arthroplasty (TKA) between 2008 and 2012 were analysed. The pooled incidence of SSI was calculated for each year; the same analyses were also conducted from hospitals that had participated in KONIS for at least three consecutive years. Standardized SSI rates for each year were calculated by adjusting for SSI risk factors. SSI trends were analysed using the Cochran-Armitage test. FINDINGS: The SSI rate following gastrectomy was 3.12% (522/16,918). There was a significant trend of decreased crude SSI rates over five years. This trend was also evident in analysis of hospitals that had participated for more than three years. The SSI rate for THA was 2.05% (157/7656), which decreased significantly from 2008 to 2012. The risk factors for SSI after THA included the National Nosocomial Infections Surveillance risk index, trauma, reoperation, and age (60-69 years). The SSI rate for TKA was 1.90% (152/7648), which also decreased significantly during a period of five years. However, the risk-adjusted analysis of SSI did not show a significant decrease for all surgical procedures. CONCLUSION: The SSI incidence of gastrectomy and prosthetic joint replacement declined over five years as a result of active surveillance by KONIS.

Mesenteric vasculitis after G-CSF administration in a severe neutropenic patient with systemic lupus erythematosus.

Granulocyte colony-stimulating factor (G-CSF) is commonly used with neutropenic patients to accelerate recovery. G-CSF is a hematopoietic cytokine that regulates the proliferation and differentiation of neutrophil precursors, and is known as a safe and effective treatment for chemotherapy-induced neutropenia. However, we encountered a case in which a patient with systemic lupus erythematosus (SLE) developed mesenteric vasculitis after G-CSF administration. The patient was a 36-year-old female admitted with fever, arthralgia, and generalized erythematous rash. Despite symptomatic improvement with a high-dose steroid, severe neutropenia persisted for three weeks, precipitating a decision to use G-CSF to enhance recovery. Mesenteric vasculitis developed 15 hours after administration of G-CSF injection. Because the response of immune cells such as neutrophils and T cells is uncontrolled and dysfunctional in patients with lupus, G-CSF therapy should be used with caution.

NLRP3 inflammasome activation by mitochondrial ROS in bronchial epithelial cells is required for allergic inflammation.

Abnormality in mitochondria has been suggested to be associated with development of allergic airway disorders. In this study, to evaluate the relationship between mitochondrial reactive oxygen species (ROS) and NLRP3 inflammasome activation in allergic asthma, we used a newly developed mitochondrial ROS inhibitor, NecroX-5. NecroX-5 reduced the increase of mitochondrial ROS generation in airway inflammatory cells, as well as bronchial epithelial cells, NLRP3 inflammasome activation, the nuclear translocation of nuclear factor-κB, increased expression of various inflammatory mediators and pathophysiological features of allergic asthma in mice. Finally, blockade of IL-1ß substantially reduced airway inflammation and hyperresponsiveness in the asthmatic mice. These findings suggest that mitochondrial ROS have a critical role in the pathogenesis of allergic airway inflammation through the modulation of NLRP3 inflammasome activation, providing a novel role of airway epithelial cells expressing NLRP3 inflammasome as an immune responder.

A possible role of serum uric acid as a marker of metabolic syndrome.

BACKGROUND/AIMS: The association between serum uric acid (SUA) levels and metabolic syndrome (MetS) has recently been reported in several cross-sectional and longitudinal studies. We investigated SUA as a biomarker to predict future development of MetS in healthy Korean men without diabetes or hypertension and determined the optimal cut-off levels of SUA. METHODS: A retrospective cohort study was conducted using data from healthy men who received a general health check-up in 2003. A total of 1809 participants free of MetS, diabetes and hypertension was enrolled. Participants were classified into three groups based on SUA levels: group 1 (<5.5 mg/dL), group 2 (5.5-6.9 mg/dL) and group 3 (≥7.0 mg/dL). RESULTS: During 13,802 person-years of follow up, 127 participants developed MetS. After adjusting for multiple associated parameters, SUA was significantly associated with incident MetS (hazard ratios comparing groups 2 and 3 vs group 1, 2.45 and 3.47 respectively; P < 0.001). In receiver operating characteristic curve analysis, the optimal cut-off level for SUA to predict the development of MetS was 6.5 mg/dL. CONCLUSION: Our results indicate that an increased level of SUA, even within the normal range, is associated with future development of MetS in healthy middle-aged men.

Comparison of clinical outcomes after conservative and surgical treatment of isolated anastomotic leaks after esophagectomy for esophageal cancer.

The clinical course and outcome of isolated anastomotic leaks (IALs) after esophagectomy are significantly different from those of necrotic leaks. The purpose of this study was to investigate the clinical features, diagnosis, treatment, and long-term outcome in patients with IALs after esophagectomy with reconstruction for esophageal cancer. A total of 663 patients underwent esophagectomy with esophageal reconstruction because of esophageal cancer between 2000 and 2010 at the Seoul Asan Medical Center. IALs occurred in 23 patients (3.5%). All patients with IAL were male, with a median age of 61 years. Patients with IAL were divided into three groups based on their clinical course. group A comprised patients who had definite clinical symptoms and/or signs indicating mediastinal contamination or leak before routine contrast esophagography was performed. Groups B and C comprised patients who had no definite clinical symptoms and/or signs of leaks before the routine contrast examination. Furthermore, group B contained those patients who resumed oral intake because no leak was found in the routine contrast examination and was diagnosed some days after resuming oral intake. Group C contained those patients who kept fasting because the leak was found in the routine contrast examination. The median follow-up period was 30 months. The mean time to closure of the IAL was 70.1 ± 96.0 days (range 4-364). There was a 72.7% overall closure rate within 60 days. By univariate analysis, the mean time to closure of the IAL was found to be significantly longer for group A patients or in cases where the patients had an uncontained leak, leukocytosis, or empyema. However, there was no statistically significant differences in age, neoadjuvant treatment, site of anastomosis (cervical vs. thoracic), fever, or treatment of the leak. By multivariate analysis, group A was found to be an independent predictive factor for the time to closure of the IAL. Repeat contrast studies revealed no anastomotic leaks in 18 patients and the formation of contained fistula in four cases (excluding one patient who died in hospital). The four patients with a contained fistula showed no clinical symptoms or signs, and tolerated resumed oral intake. IALs were resolved in most cases with low leak-related mortality, and resolution of the leaks occurred within 2 months in the majority of patients.

Long-term results of thoracoscopic thymectomy for thymoma without myasthenia gravis.

OBJECTIVE: To compare the feasibility and safety of thoracoscopic thymectomy with conventional sternotomy thymectomy for thymoma without myasthenia gravis. METHODS: Data from 70 patients diagnosed with thymoma, who underwent thoracoscopic thymectomy (n = 25, Group T) or sternotomy thymectomy (n = 45, Group S) between March 2002 and March 2008, were retrospectively evaluated. RESULTS: Mean follow-up durations were 78.0 ± 21.9 months and 70.0 ± 23.6 months in Groups T and S, respectively. No deaths occurred in Group T; seven deaths occurred in Group S, all > 1 month post follow-up. Durations of chest intubation and hospitalization were significantly shorter in Group T than in Group S. No significant between-group difference in the incidence of operative complications was observed. Tumour recurrence-free rates at 5 and 7 years postsurgery were 96% (both years) in Group T and 95% (both years) in Group S. CONCLUSIONS: Long-term follow-up indicates that thoracoscopic thymectomy for thymoma without myasthenia gravis is effective and is well tolerated, and associated with low rates of operative complications and recurrence.

Additional effects of bisphenol A and paraben on the induction of calbindin-D(9K) and progesterone receptor via an estrogen receptor pathway in rat pituitary GH3 cells.

There are concerns about the combined estrogenic effects of chemicals since mixtures of these chemicals exist in our environment. This study investigated potential additional interactions between bisphenol A (BPA) and isobutylparaben (IBP), which are major xenoestrogens used in the manufacture of plastics, cosmetics, drugs, and other products. The combined effects of these two chemicals were analyzed by measuring the expression of calbindin-D(9k) (CaBP-9k) in rat pituitary cancer GH3 cells. GH3 cells were treated with single and combination doses of both chemicals (BPA single doses: 10(-7), 10(-6) and 10(-5) M; IBP single doses: 10(-7), 10(-6) and 10(-5) M, and each of the BPA and IBP doses combined). Prior to treatment, cells were temporarily transfected with a plasmid containing an ERE-luciferase reporter gene. Luciferase activity was measured as an indicator of ER activation by 17ß-estradiol (E2), BPA, and IBP. BPA (10(-5) M) combined with IBP (10(-7) M and 10(-6) M) induced a significant increase in the luciferase activity. Twenty-four hours after treatment, dose-dependent effects were observed in both single and combined dose groups, and several combination doses induced significant increases in the expression of CaBP-9k and progesterone receptor (PR) at both transcriptional and translational levels. Pre-treatment with ICI 182,780, a pure estrogen antagonist, significantly reversed BPA- and IBP-induced CaBP-9k and PR upregulation in GH3 cells. Taken together, these results indicate that BPA and IBP may have additionally increased estrogenic potency via an estrogen receptor-mediated pathway.

Recombinant IGFBP-3 inhibits allergic lung inflammation, VEGF production, and vascular leak in a mouse model of asthma.

BACKGROUND: Vascular endothelial growth factor (VEGF) plays a pro-inflammatory mediator as well as a vascular permeability factor in bronchial asthma. Insulin-like growth factor (IGF)-I is also involved in the inflammatory process associated with bronchial asthma and stimulates VEGF expression. The IGF-binding proteins (IGFBPs), especially IGFBP-3, display distinctive properties and can interfere with various biological processes. METHODS: In this study, an ovalbumin (OVA)-induced murine model of allergic airway disease was used to investigate which mechanism is implicated in the preventive and therapeutic actions of IGFBP-3 administered exogenously on allergen-induced bronchial inflammation and airway hyper-responsiveness, in particular focusing on the regulation of VEGF expression. RESULTS: Administration of recombinant human IGFBP-3 to OVA-inhaled mice substantially attenuated the increases in hypoxia-inducible factor (HIF)-α activity, IGF-I production, and VEGF protein levels in the lung. In addition, the blockade of IGF-I action decreased the OVA-induced VEGF expression, airway inflammation, and bronchial hyper-responsiveness. The administration of recombinant human IGFBP-3 or CBO-P11 also reduced significantly increases in inflammatory cells, airway hyper-responsiveness, levels of IL-4, IL-5, IL-13, and vascular permeability in the lung of OVA-inhaled mice. Moreover, when recombinant human IGFBP-3 was administered after the completion of OVA inhalation, these therapeutic effects of IGFBP-3 were also observed. CONCLUSIONS: These results indicate that IGFBP-3 administered exogenously may attenuate antigen-induced airway inflammation and hyper-responsiveness through the modulation of vascular leakage and VEGF expression mediated by HIF-1α/HIF-2α signaling as well as IGF-I action in allergic airway disease of mice.

Monitoring of viruses in chum salmon (Oncorhynchus keta) migrating to Korea.

It is important to investigate the prevalence of salmonid pathogens because they can affect the amount of release of salmonid fry and the migration rate of adult salmonids. In this study, routine surveys were conducted for investigating virus distribution in migrating chum salmon spawners (Oncorhynchus keta) and their offsprings at the Namdae River, Yangyang, Korea, during 2006-2008. Anterior kidneys were removed from chum salmon spawner individuals, homogenized with minimal essential medium, and centrifuged to make supernatants for conducting RT-PCR. Five offspring were pooled to for conducting RT-PCR. Infectious pancreatic necrosis virus (IPNV), infectious hematopoietic necrosis virus (IHNV) and viral hemorrhagic septicemia virus (VHSV) were the target viruses for monitoring. In 2006, only spawners were investigated, and 27.5% of fish (22/80) were found to be IHNV-positive by nested PCR. In 2007, 65.6% of pooled fry (21/32) were IHNV-positive, and 9.4% (3/32) were IPNV-positive by one-step PCR. When nested PCR was conducted, 84.4% (27/32) were IHNV-positive, and 28.1% (9/32) were IPNV-positive. However, only 1.3% of spawners (1/80) were IHNV-positive by nested PCR. In 2008, 25% (8/32) of pooled fry were IHNV-positive by one-step PCR, but 59.4% (19/32) were IHNV-positive and 12.5% (4/32) were IPNV-positive by nested PCR. All of the samples tested were VHSV-negative. Although all viruses detected in this study were from chum salmon, phylogenetic analysis showed that they possibly originated from rainbow trout or clustered with the rainbow trout isolates. More extensive long-term studies are needed to clarify the origins of these viruses and their potential effects on chum salmon migration in Korea.

Homozygous CDA*3 is a major cause of life-threatening toxicities in gemcitabine-treated Japanese cancer patients.

Among 242 Japanese pancreatic cancer patients, three patients (1.2%) encountered life-threatening toxicities, including myelosuppression, after gemcitabine-based chemotherapies. Two of them carried homozygous CDA*3 (CDA208G>A [Ala70Thr]), and showed extremely low plasma cytidine deaminase activity and gemcitabine clearance. Our results suggest that homozygous *3 is a major factor causing gemcitabine-mediated severe adverse reactions among the Japanese population.

The relationship between adipokines, metabolic parameters and insulin resistance in patients with metabolic syndrome and type 2 diabetes.

This study was designed to investigate the relationship between adipokines in metabolic syndrome and insulin resistance. Sixty male and female subjects with or without metabolic syndrome and type 2 diabetes were included. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Compared with lean control subjects, patients with metabolic syndrome and type 2 diabetes had lower circulating levels of total adiponectin and high molecular weight (HMW) adiponectin, and higher levels of leptin and interleukin-6 (IL-6). Total and HMW adiponectin and the adiponectin/leptin (A/L) ratio were negatively correlated with HOMA-IR. After adjusting for age and sex, leptin, IL-6 and tumour necrosis factor-alpha (TNF-alpha) were positively correlated with HOMA-IR. After also adjusting for body mass index, HOMA-IR was found to be independently associated with leptin, A/L ratio and TNF-alpha levels. In conclusion, decreased total adiponectin and HMW adiponectin and increased leptin and IL-6 levels are characteristic of patients with metabolic syndrome and type 2 diabetes.

Inhibition of VEGF blocks TGF-beta1 production through a PI3K/Akt signalling pathway.

Vascular endothelial growth factor (VEGF) is a mediator of airway inflammation and remodelling in asthma. Transforming growth factor (TGF)-beta(1) plays pivotal roles in diverse biological processes, including tissue remodelling and repair in a number of chronic lung diseases. However, there are few studies elucidating the interactions between VEGF and TGF-beta(1) in allergic airway disease. A murine model of allergic airway disease was used to define the mechanism by which VEGF induces subepithelial fibrosis and to investigate a potential relationship between VEGF and TGF-beta(1) and the mechanisms by which VEGF signalling regulates TGF-beta(1) expression in allergic airway disease. The ovalbumin (OVA)-inhaled murine model revealed the following typical pathophysiological features of allergic airway disease in the lungs: increased numbers of inflammatory cells of the airways, airway hyperresponsiveness, increased peribronchial fibrosis, and increased levels of VEGF and TGF-beta(1). Administration of VEGF inhibitors reduced the pathophysiological signs of allergic airway disease and decreased the increased TGF-beta(1) levels and peribronchial fibrosis, including phosphoinositide 3-kinase (PI3K) activity after OVA inhalation. In addition, the increased TGF-beta(1) levels and collagen deposition after OVA inhalation were decreased by administration of PI3K inhibitors. These results suggest that inhibition of vascular endothelial growth factor attenuates peribronchial fibrosis, at least when mediated by regulation of transforming growth factor-beta(1) expression through phosphoinositide 3-kinase/Akt pathway in a murine model of allergic airway disease.

Pad - a new self-collection device for human papillomavirus.

This study was designed to determine the accuracy and agreement of a self-collection method using pad for human papillomavirus (HPV) DNA. One hundred and thirty-four patients at university hospitals voluntarily participated in the accuracy study, and 314 volunteers participated in the agreement study at local clinics. DNA was extracted and amplified using HPV L1 consensus primers designed for the direct sequencing. In the accuracy study, all samples were probed via histological examinations. With regard to the detection of squamous intraepithelial lesion (SIL), self-collection pad sampling displays sensitivity, of 76.9%, and specificity, of 93.3%. Three hundred and fourteen self-collection pad samples and the concurrent physicians' samples showed a 97.8% agreement, with a Kappa value of 0.9200. A new self-collection pad for the detection of HPV DNA appears to constitute an easy, rapid, and convenient alternative method for the cervical cancer screening of many women with the virtue of being incredible readily accessible.

Development of hepatocellular carcinoma in patients with chronic hepatitis C who had a sustained virological response to interferon therapy: a multicenter, retrospective cohort study of 1124 patients.

BACKGROUND: Interferon (IFN) improves hepatic inflammation/fibrosis and reduces the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CH-C). However, HCC develops in some patients who have a sustained virological response (SVR) to IFN therapy. We designed this study to establish a follow-up protocol for patients with CH-C who have SVR to IFN therapy. METHODS: We retrospectively studied 1124 patients with CH-C who received IFN. RESULTS: HCC developed in 3.5% of patients with SVR to IFN. As compared with SVR patients without HCC, SVR patients with HCC were predominantly male (P=0.003), older at the initiation of IFN therapy (P=0.002), and at a more advanced histologic stage of disease (P<0.001). However, three of the 13 SVR HCC patients had mild fibrosis. The mean interval from IFN therapy to the detection of HCC in SVR HCC patients was 5.8 years and did not differ significantly from that in non-SVR HCC patients (P=0.304). Although most patients with HCC received curative therapy, the prognosis of some SVR HCC patients was poor, probably because of insufficient follow-up, resulting in delayed detection of HCC. CONCLUSIONS: SVR patients with CH-C who are elderly, male, or have an advanced histologic stage are at a high risk for the development of HCC after IFN therapy. We recommend that SVR patients should be observed carefully for more than 10 years after the completion of IFN therapy, even if they only have early fibrosis.

Four-dimensional ultrasound guidance of prenatal invasive procedures.

OBJECTIVE: Technological advances in ultrasonography have revolutionized prenatal diagnosis and treatment. Here we evaluate the effectiveness of using four-dimensional (4D) ultrasonography to guide prenatal invasive procedures. PATIENTS AND METHODS: Prenatal invasive procedures using 4D ultrasound were recorded prospectively in 93 cases: 10 amnioinfusions, 50 amniocenteses, 8 chorionic villus samplings (CVS) and 25 cordocenteses. The needle target site was first identified using the two-dimensional (2D) mode, and was then confirmed using the three-dimensional (3D) mode. The needle was inserted under 4D ultrasound guidance. After selecting the needle target site, the true position of the needle was determined in three planes ('real-time 3D targeting'). RESULTS: Using 4D ultrasound guidance, most procedures were performed within 5 min and with a 100% success rate, even in cases involving severe oligohydramnios (amniocentesis), thin placentas (CVS) or narrow umbilical veins (cordocentesis). Moreover, there were no serious complications during or after any procedure. CONCLUSIONS: 4D ultrasonography can be used to guide various prenatal invasive procedures offering clear information in all three planes. It is likely that such imaging will reduce the time taken to complete the procedures and reduce the risks associated with them. Published by John Wiley & Sons, Ltd.

Identification and molecular characterization of a prophenoloxidase involved in Aedes aegypti chorion melanization.

Chorion melanization is a vital biochemical event for the survival of mosquito eggs in the environment. This study describes the identification and molecular characterization of a prophenoloxidase (proPO) involved in chorion melanization in Aedes aegypti by various biochemical and molecular techniques. Results revealed that transcription of the chorion proPO occurs only in adults, blood feeding greatly stimulated its transcription and haemocytes are responsible for its transcription. Our study provides a solid basis for suggesting an essential role of the isolated proPO in chorion melanization during chorion hardening and also raises fundamental questions regarding its transportation and distribution in the chorion. This study should serve as a useful reference towards functional elucidation of other proPOs in mosquitoes.