Weaning of Veno-venous Bypass in Liver Transplantation: A Single Center Experience.

BACKGROUND: Veno-venous bypass (VVB) has been used in liver transplantation (LT) to minimize hemodynamic instability during caval anastomosis of anhepatic phase. With the introduction of the piggyback (PB) technique, which is a caval-sparing technique, the use of VVB progressively decreased over the world. The aim of this study was to introduce our experience using VVB with the focus on its weaning process. METHODS: A total of 300 consecutive LT cases from May 1996 to November 2003 were examined. Except for pediatric LT, 242 LT cases were investigated to evaluate the trends in VVB use, surgical technique, the amount of transfusion requirements, and durations of operation and anhepatic phase. RESULTS: For the early 100 LT cases, VVB was used in 97.5% of recipients, especially in all the recipients of deceased donor LT (DDLT). Then, the frequency of VVB use was decreased, and VVB was not used after the 268th recipient. In DDLT, the PB technique was first introduced in the 58th recipient and became a routine procedure of the DDLT since the 191th recipient. Living donor LT was increased, and the amount of transfusion requirement, duration of operation, and duration of anhepatic phase was reduced over time. CONCLUSIONS: The increasing experience and sophisticated surgical and anesthetic techniques were important factors responsible for the weaning of VVB. The advancement of the PB technique used in living donor LT might be a main factor of its weaning.

Association of Platelet Count and Platelet Transfusion With Serotonin Level During Living Donor Liver Transplantation: Possible Connection to Graft Regeneration.

BACKGROUND: We recently showed that platelet counts and the amount of platelet transfusion during liver transplantation are positively associated with early graft regeneration. It was hypothesized that platelet-derived serotonin mediates liver regeneration. OBJECTIVES: This study aimed to evaluate the association between intraoperative platelet count, platelet transfusion, and serum serotonin level. METHODS: Thirty-two recipients undergoing living-donor liver transplantation were enrolled into this prospective observational study. Serum platelet counts and serotonin levels were measured at the following times: anesthetic induction, start of the anhepatic phase, before graft reperfusion, 5 minutes/1 hour/3 hours/5 hours after graft reperfusion, and before/after platelet transfusion. Serotonin was measured by using a liquid chromatography tandem mass spectrometry. RESULTS: Serotonin level at the anesthetic induction was 24.5 µg/mL (interquartile range, 14.6 to 38.1 µg/mL). During surgery, serial changes in platelet counts and serotonin levels showed a similar trend: they decreased during the anhepatic phase, increased during the first hour after graft reperfusion, and thereafter gradually decreased. Serotonin level was positively correlated with platelet counts (correlation coefficient = 0.620, P < .001). Allogeneic platelet transfusion significantly increased platelet count from 22 (19-31) × 109/L to 53 (50-81) × 109/L (P = .008) and it also increased serum serotonin from 11.04 (6.41-15.34) µg/mL to 34.26 (25.86-41.94) µg/mL (P = .008). CONCLUSIONS: Our findings indicate that allogeneic platelets could act as effector cells deriving serotonins. Also, our findings support the hypothesis that the association between platelets and post-transplantation graft regeneration is mediated by serotonin. Further studies are warranted regarding the respective role of serotonin and other platelet-derived molecules mediating liver regeneration.

Ischemic Preconditioning Produces Comparable Protection Against Hepatic Ischemia/Reperfusion Injury Under Isoflurane and Sevoflurane Anesthesia in Rats.

BACKGROUND: Various volatile anesthetics and ischemic preconditioning (IP) have been demonstrated to exert protective effect against ischemia/reperfusion (I/R) injury in liver. We aimed to determine whether application of IP under isoflurane and sevoflurane anesthesia would confer protection against hepatic I/R injury in rats. METHODS: Thirty-eight rats weighing 270 to 300 grams were randomly divided into 2 groups: isoflurane (1.5%) and sevoflurane (2.5%) anesthesia groups. Each group was subdivided into sham (n = 3), non-IP (n = 8; 45 minutes of hepatic ischemia), and IP (n = 8, IP consisting of 10-minute ischemia plus 15-minute reperfusion before prolonged ischemia) groups. The degree of hepatic injury and expressions of B-cell lymphoma 2 (Bcl-2) and caspase 3 were compared at 2 hours after reperfusion. RESULTS: Hepatic ischemia induced significant degree of I/R injuries in both isoflurane and sevoflurane non-IP groups. In both anesthetic groups, introduction of IP dramatically attenuated I/R injuries as marked by significantly lower aspartate aminotransferase and aminotransferase levels and better histologic grades compared with corresponding non-IP groups. There were 2.3- and 1.7-fold increases in Bcl-2 mRNA levels in isoflurane and sevoflurane IP groups, respectively, compared with corresponding non-IP groups (both P < .05). Caspase 3 level was significantly high in the isoflurane non-IP group compared with the sham group; however, there were no differences among the sevoflurane groups. CONCLUSIONS: The degree of hepatic I/R injury was significantly high in both isoflurane and sevoflurane groups in rats. However, application of IP significantly protected against I/R injury in both volatile anesthetic groups to similar degrees, and upregulation of Bcl-2 might be an important mechanism.

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.

Risk factors for inadvertent hypothermia during adult living-donor liver transplantation.

BACKGROUND: Hypothermia (core temperature <35°C) causes multiple physiologic disturbances, including coagulopathy and cardiac dysfunction. Patients undergoing liver transplantation are at risk of inadvertent hypothermia and might be more vulnerable to its adverse effects. We sought to identify the factors contributing to hypothermia during living-donor liver transplantation (LDLT), which have not yet been studied in depth. METHODS: Medical records of 134 recipients who underwent adult-to-adult LDLT were reviewed. Core temperature at the following time points were taken: anesthetic induction, skin incision, start and end of the anhepatic phase, and hourly after hepatic reperfusion. RESULTS: Of 134 recipients, 29 (21.6%) developed hypothermia during surgery. Four independent risk factors for hypothermia were identified: small body weight-to-body surface area ratio, acute hepatic failure, high Model for End-Stage Liver Disease (MELD) score, and low graft-to-recipient weight ratio. The amount of core temperature drop was positively correlated with the number of involved risk factors. Each risk factor had a respective contribution according to the operative phases: body weight-to-body surface area ratio and the MELD score for the preanhepatic phase, acute deterioration of hepatic failure for the anhepatic phase, and graft-to-recipient weight ratio was for the postreperfusion phase. CONCLUSIONS: Hypothermia was independently associated with the recipient's morphometric characteristics, emergency of end-stage liver disease, MELD score, and graft volume. These factors showed a cumulative effect, and the role of each factor was different according to the operative phase. These results should aid in the development of an optimal thermal strategy during LDLT.

Analysis of predictors for lactate elimination after reperfusion in recipients of living-donor liver transplantation.

BACKGROUND: Graft-recipient weight ratio (GRWR) is the only documented predictor that influences the lactate elimination after reperfusion in living-donor liver transplantation (LDLT). This study was performed to investigate the predictors of lactate elimination after reperfusion in recipients of adult LDLT. METHODS: The medical records of 159 patients who underwent LDLT were analyzed. Lactate level (mmol/L) was measured from just before the initiation of surgery (P0) and 5, 60, and 120 minutes after reperfusion of graft (R0, R1, and R2, respectively). The change of lactate level after reperfusion was defined as difference between lactate level measured at R0 and R2. Patients were divided into accumulation and elimination groups. Donor and recipient factors were compared between the 2 groups. RESULTS: Lactate accumulation occurred in 80 of 159 recipients (50.3%), and elimination occurred in 79 (49.7%). GRWR and Model for End-Stage Liver Disease (MELD) score were higher in the elimination group. Lactate at R0 was lower in the elimination group. CONCLUSIONS: Higher GRWR and MELD score and lower lactate level immediate after reperfusion of graft were predictors of lactate elimination after reperfusion during adult LDLT.

Expanded criteria for liver transplantation in patients with hepatocellular carcinoma.

Liver transplantation (LT) is one of the few effective treatment options for hepatocellular carcinoma (HCC). Our aim in this study was to evaluate the risk factors for HCC recurrence and propose new criteria for LT based on pretransplantation findings. One hundred eighty patients who underwent LT for HCC between 2002 and 2008 were reviewed retrospectively. Outcome measures included maximal tumor size and number of tumors revealed by radiological studies before transplantation, demographics, and tumor recurrence. Maximal tumor size >6 cm, >7 tumors, and alpha-fetoprotein (AFP) levels >1000 ng/mL were identified as independent prognostic factors of HCC recurrence in univariate and multivariate analysis. Disease-free survival rate in patients with a maximal tumor size ≤6 cm, ≤7 tumors, and/or AFP levels ≤1000 ng/mL at 1, 3, and 5 years was 97.9%, 91.5%, and 90.0%, respectively, but the 1-, 3-, and 5-year disease-free survival rate of patients who had a maximal tumor size >6 cm, >7 tumors, and/or AFP levels >1000 ng/mL was 61.9%, 47.6%, and 47.6%, respectively (P < .001). In conclusion, LT can improve the survival of patients with advanced HCC if they have a maximal tumor size ≤6 cm, tumor number ≤7, and/or AFP levels ≤1000 ng/mL.

Liver transplantation in lymphoma patients with hepatitis B virus reactivation.

BACKGROUND: Acute-on-chronic liver failure (AoCLF) occurs in lymphoma patients because of hepatitis B virus (HBV) reactivation. We aimed to identify characteristics of patients who underwent liver transplantation (OLT) because of AoCLF that occurred due to HBV reactivation in the setting of lymphoma and to compare these patients with AoCLF patients who did not have lymphoma. METHODS: Twenty patients underwent OLT due to AoCLF between February 2009 and June 2011. Among these patients, five were diagnosed with lymphoma before OLT and assigned to group 1. The remaining patients (n = 15) were assigned to group 2. RESULTS: Hospitalization after transplantation in group 2 was longer than in group 1 (P = .014). However, there were no differences in other variables between the two groups. The overall survival rate of group 1 was lower than that of group 2, but there was no difference between the two groups (P = .134). With the exception of one patient, the median time from complete remission to liver transplantation in group 1 was 4.5 months (range, 1-15) in group 1. Lymphoma recurrence occurred in one patient 8 months after transplantation. CONCLUSION: Our study revealed that OLT is a feasible and effective approach in AoCLF due to HBV reactivation in select lymphoma patients.

The protective effect of ischemic preconditioning against hepatic ischemic-reperfusion injury under isoflurane anesthesia in rats.

PURPOSE: Apoptosis is a central mechanism of ischemic-reperfusion injury (IRI) to the liver. Among the methods to reduce IRI, ischemic preconditioning (IP) has been shown to confer protection. Therefore, the aim of this study was to determine if IP conferred protection against hepatic IRI under isoflurane anesthesia in rats and to investigate underlying protective mechanisms. MATERIALS AND METHODS: Twenty-three rats weighing 270 to 300 grams were randomly divided into three groups: (1) the sham operated group (n = 5); (2) the non-IP group (n = 9; 45 minutes of hepatic ischemia followed by 2 hours of reperfusion); and (3) the IP group (n = 9); IP induced by 10 minutes of hepatic ischemia followed by 15 minutes of reperfusion before 45 minutes of prolonged hepatic ischemia). Anesthesia was maintained with isoflurane (1.5%). We compared the degrees of hepatic injury and expressions of B cell lymphoma 2 (Bcl-2) and caspase 3 and 8 mRNAs. RESULTS: The IP group showed significantly lower levels of aspartate transaminase and alanine transaminase as well as reduced histological grades of hepatocyte injury compared with the non-IP group at 2 hours after reperfusion. At the corresponding time, the Bcl-2 mRNA level was 2-fold higher in the IP group. Caspase 3 mRNA levels were highest in the non-IP group significantly compared with the sham cohort. Similarly, caspase 8 mRNA levels were highest in the Non_IP group albeit not significancely. CONCLUSION: IP protected against hepatic IRI under isoflurane anesthesia in rats. The mechanism of protection appeared to involve upregulation of Bcl-2 expression resulting in inhibited apoptosis.

Comparison of mixed venous oxygen saturation after in vitro calibration of pulmonary artery catheter with that of pulmonary arterial blood in patients undergoing living donor liver transplantation.

INTRODUCTION: Mixed venous saturation (SvO2) reflects the balance between oxygen delivery and consumption throughout the body. A multifunction pulmonary artery catheter (PAC) can monitor continuous SvO2 after in vitro calibration (CSvO2), obviating the need for in vivo calibration with pulmonary arterial blood. In critically ill patients CSvO2 has shown a good correlation with measured SvO2 of pulmonary arterial blood using co-oximetry (MSvO2). The aim of this study was to compare CSvO2 and MSvO2 in liver transplantation (OLT) recipients. METHODS: We enrolled 44 OLT recipients for comparison with 24 coronary artery bypass graft (CABG) controls free of end-stage liver disease. After anesthetic induction, the PAC was inserted after in vitro calibration and CSvO2 and MSvO2 simultaneously measured. In OLT recipients, additional measurements of CSvO2 and MSvO2 were performed at anhepatic and postreperfusion phases. Pearson's correlation analysis was used to evaluate the correlation between the 2 measurements. A Bland-Altman analysis was used to determine precision of and bias between the 2 measurements. With ±3% regarded to be interchangeable. RESULTS: Cardiac output and intrapulmonary shunt in CABG patients were lower than among OLT recipients. OLT recipients, showed a significant correlation between CSvO2 and MSvO2, but the coefficients were different during the three phases of OLT (r = 0.597, 0.753, and 0.756). In addition, bias values between the two measurements were 6.0%, 6.4%, and 2.9% for the preanhepatic, anhepatic, and postreperfusion phases, respectively, with 29.5%, 31.8%, and 50% of them being interchangeable. In contrast CABG patients showed bias in -0.17% with 75% of measurements interchangeable. CONCLUSION: While in vitro calibration of the PAC can be used in CABG patients, MSvO2 is higher than CSvO2 in OLT recipients. Therefore, in vivo calibration with pulmonary arterial blood is necessary for accurate monitoring of SvO2 in OLT recipients.

Afamin stimulates osteoclastogenesis and bone resorption via Gi-coupled receptor and Ca2+/calmodulin-dependent protein kinase (CaMK) pathways.

BACKGROUND: Afamin was recently identified as a novel osteoclast-derived coupling factor that can stimulate the in vitro and in vivo migration of preosteoblasts. AIM: In order to understand in more detail the biological roles of afamin in bone metabolism, we investigated its effects on osteoclastic differentiation and bone resorption. METHODS: Osteoclasts were differentiated from mouse bone marrow cells. Tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells were considered as osteoclasts, and the resorption area was determined by incubating the cells on dentine discs. The intracellular cAMP level was determined using a direct enzyme immunoassay. Signaling pathways were investigated using western blot and RT-PCR. Recombinant afamin was administered exogenously to bone cell cultures. RESULTS: Afamin stimulated both osteoclastogenesis and in vitro bone resorption. Consistently, the expressions of osteoclast differentiation markers were significantly increased by afamin. Although afamin mainly affected the late-differentiation stages of osteoclastogenesis, the expression levels of receptor activator of nuclear factor-κB ligand (RANKL)-dependent signals were not changed. Afamin markedly decreased the levels of intracellular cAMP with reversal by pretreatment with pertussis toxin (PTX), a specific inhibitor of Gi-coupled receptor signaling. In addition, PTX almost completely blocked afamin-stimulated osteoclastogenesis. Furthermore, pretreatment with KN93 and STO609 - Ca2+/cal - mo dulin-dependent protein kinase (CaMK) and CaMK kinase inhibitors, respectively - significantly prevented decreases in the intracellular cAMP level by afamin while attenuating afamin-stimulated osteoclastogenesis. CONCLUSION: Afamin enhances osteoclastogenesis by decreasing intracellular cAMP levels via Gi-coupled receptor and CaMK pathways.

Higher serum uric acid is associated with higher bone mass, lower bone turnover, and lower prevalence of vertebral fracture in healthy postmenopausal women.

UNLABELLED: Higher serum uric acid (UA) was associated with higher bone mass, lower bone turnover, and lower prevalence of vertebral fracture in postmenopausal women. Furthermore, UA suppressed osteoclastogenesis and decreased production of reactive oxygen species in osteoclast precursors, indicating UA may have beneficial effects on bone metabolism as an antioxidant. INTRODUCTION: UA is known to play a physiological role as an antioxidant, and oxidative stress has detrimental effects on bone metabolism. In the present study, we investigated the association of serum UA level with the osteoporosis-related phenotypes and its direct effect on bone-resorbing osteoclasts using in vitro systems. METHODS: This is a large cross-sectional study, including 7,502 healthy postmenopausal women. Bone mineral density (BMD) and serum UA concentrations were obtained from all subjects. Data on bone turnover markers and lateral thoracolumbar radiographs were available for 1,023 and 6,918 subjects, respectively. An in vitro study investigated osteoclastogenesis and reactive oxygen species (ROS) levels according to UA treatment. RESULTS: After adjusting for multiple confounders, serum UA levels were positively associated with BMD at all sites (all p < 0.001). Compared with the participants in the highest UA quartile, the odds for osteoporosis were 40 % higher in those in the lowest quartile. The serum UA levels were inversely related to both serum C-terminal telopeptide of type I collagen and osteocalcin levels (p < 0.001 and p = 0.004, respectively). Consistently, subjects with vertebral fracture had lower serum UA levels, compared with those without it (p = 0.009). An in vitro study showed that UA decreased osteoclastogenesis in a dose-dependent manner and reduced the production of ROS in osteoclast precursors. CONCLUSION: These results provide epidemiological and experimental evidence that serum UA may have a beneficial effect on bone metabolism as an antioxidant in postmenopausal women.

Arthroscopic shoulder surgery under general anesthesia with brachial plexus block: postoperative respiratory dysfunction of combined obstructive and restrictive pathology.

OBJECTIVE: Changes in respiratory parameters and pulmonary function tests were evaluated after shoulder arthroscopic surgery with brachial plexus block (BPB). The purpose of this study was to identify the mechanism of respiratory dysfunction after this type of surgery. METHODS: Patients undergoing arthroscopic rotator cuff repair under general anesthesia (GA) with BPB were enrolled in the arthroscopy group (n = 30) while those undergoing open reduction of a clavicle or humerus fracture under GA were enrolled in the control group (n = 30). Forced vital capacity (FVC) and forced expiratory volume 1 s (FEV(1)) were measured at the outpatient clinic stage (#1) before (#2) and 20 min after BPB (#3) and 1 h after extubation (#4). Respiratory variable measurements along with the cuff leak test were performed 5 min after surgical positioning (T1) and at the start of skin closure (T2). Respiratory discomfort was evaluated after extubation. The upper airway diameters and soft tissue depth of chest wall were also measured by ultrasonography at stages #3 and #4. RESULTS: Static compliance decreased significantly at T2 in the arthroscopy group (50 ± 11 at T1 vs. 44 ± 9 ml/cm H(2)O at T2, p =0.035) but not in the control group. The incidence of positive cuff leak tests at T2 was significantly higher in the arthroscopy group than in the control group (47% in the arthroscopy group vs. 17% in controls, p =0.010). While FEV(1) and FVC remained stable at stages #1 and #2, FVC and FEV(1) decreased at stages #3 and #4 only in the arthroscopy group (FVC in arthroscopy group, #2: 3.26 ± 0.77 l; #3: 2.55 ± 0.63 l, p =0.015 vs. #2; #4: 2.66 ± 0.41 l, p =0.040 vs. #2). The subglottic diameter decreased at #4 in the arthroscopy group, while no changes occurred in the control group (0.70 ± 0.21 cm vs. 0.85 ± 0.23 cm in the arthroscopy and control groups, respectively, p =0.011). Depth of skin to pleura increased at both intercostal spaces 1-2 and 3-4 in the arthroscopy group. There were three cases of hypoxia (S(p)O(2) < 95%) with room air in the arthroscopy group while none occurred in the controls. CONCLUSION: Shoulder arthroscopic surgery under GA with BPB induced both restrictive and obstructive pathologies. It is important to maintain a high level of awareness for the potential negative respiratory effects of this surgery especially for subjects with pre-existing cardiopulmonary disease. The measurements in this study would be useful to monitor the risk of respiratory dysfunction in these patients.

Effect of active airway warming on body core temperature during adult liver transplantation.

INTRODUCTION: Active inspired gas humidification (AH) preserves body heat and maintains normothermia intraoperatively. However, it is unclear whether AH shows comparable influences during liver transplantation (OLT), which may be affected by both large internal heat loss and external heat supply. Thus, the aim of this study was to evaluate the effect of AH compared with passive humidification (PH) on body temperature in OLT. MATERIALS AND METHODS: Thirty-four adult patients undergoing living donor OLT were randomly enrolled into two groups: those given AH using a heated humidifier (HH group, n = 17) and those using a heat-and-moisture exchanger (HME group, n = 17). Both core and skin temperatures (Tc and Ts), as well as respiratory parameters, including static/dynamic lung compliances and PaO(2), were recorded at predetermined times. RESULTS: Both Tc and Ts were consistently higher among the HH versus the HME group after 2 hours of anesthesia. Differences in Tc and Ts between the two groups increased gradually over time. The overall Tc during surgery was higher among the HH than the HME group (P = .023). The incidences of hypothermia were lower in the HH group at 3 hours of anesthesia, 1 and 3 hours of reperfusion, and at the end of surgery (P = .037, 0.024, 0.005, and 0.010 respectively). The duration of hypothermia was lower in the HH than the HME group (3.9 ± 3.5 hours versus 6.7 ± 3.3 hours, P = .025). Both groups showed no significant intraoperative changes in respiratory parameters; there were no postoperative respiratory complications. CONCLUSION: Active humidification warms the patient's body effectively, lessening the incidence and duration of hypothermia during OLT with no respiratory risks.

Hormonal differences between female kidney transplant recipients and healthy women with the same gynecologic conditions.

BACKGROUND: End-stage renal disease is associated with severe abnormalities in reproductive function. However, the abnormalities are reversed by successful kidney transplantation. The aim of the present study was to compare hormonal levels between recipients with successful kidney transplantations and healthy women with the same gynecologic conditions. METHODS: The study group consisted of 31 women of reproductive age with end-stage renal disease who underwent successful kidney transplantation. The ratio of the control group, composed of healthy woman, to the study group was 3:1 matched for age and symptoms. RESULTS: Abnormal bleeding (n = 14) and infertility were the most common gynecologic conditions in kidney transplant recipients. The levels of estrogen (E2) and follicle-stimulating hormone (FSH) in the study group were higher than in the control group, but the levels of progesterone (P4) and luteinizing hormone (LH) were lower in the study group than in the control group. There were no significant differences in prolactin and thyroid-stimulating hormone between the two groups. The incidence of infertility in patients who receive steroid was higher than those with no steroid use (P = .007). CONCLUSIONS: Compared with healthy age- and symptom-matched women, female kidney transplant recipients have increased levels of E2 and FSH and decreased levels of P4 and LH. These differences in hormone profiles may predispose kidney transplant recipients to increased risk of gynecologic pathologies.

Effectiveness of locoregional therapy before living donor liver transplantation in patients with hepatocellular carcinoma who meet the Milan criteria.

BACKGROUND: Many patients are diagnosed with hepatocellular carcinoma (HCC) within the Milan criteria. In Korea, these patients are preferentially treated with locoregional therapy (LRT) instead of living donor liver transplantation. We investigated the effectiveness of LRT in liver transplant recipients who met the Milan criteria at the time of HCC diagnosis and investigated risk factors for HCC recurrence. METHODS: We retrospectively reviewed the medical records of patients diagnosed with HCC who met the Milan criteria between 2002 and 2008. RESULTS: We performed 101 liver transplants for HCC during the study period. Seventy-one patients (70%) underwent pretransplant LRT. The disease-free survival rates at 1, 3, and 5 years in patients who received LRT were 96.6%, 93.1%, and 93.1%, and in those who did not receive LRT, 94.2%, 83.4%, and 83.4%, respectively. There were no differences between the 2 groups. Multivariate analysis showed that a low Model for End-Stage Liver Disease (MELD) score and microvascular invasion were independent predictors of HCC recurrence after transplantation. The MELD scores and rate of microvascular invasion were not statistically different in patients with or without previous LRT. CONCLUSION: Pretransplant LRT for patients with HCC who met the Milan criteria at the time of diagnosis did not provide a clear benefit with respect to HCC recurrence after transplantation. If patients have suitable living donors, those who meet the Milan criteria should undergo a liver transplantation as soon as possible.

Long-term treatment with raloxifene, but not bisphosphonates, reduces circulating sclerostin levels in postmenopausal women.

UNLABELLED: We determined whether suppression of sclerostin levels by estrogen treatment was mediated by anti-resorptive effect. Raloxifene, but not bisphosphonates, suppressed circulating sclerostin concentration, suggesting that sclerostin may mediate the action of estrogen on bone metabolism, independently of their anti-resorptive effects. INTRODUCTION: Circulating sclerostin concentrations are higher in postmenopausal than in premenopausal women, and estrogen treatment suppresses sclerostin levels in both men and women. We determined whether anti-resorptives may suppress the circulating sclerostin levels. METHODS: We conducted a retrospective observational study. Eighty postmenopausal women were treated with raloxifene for 19.4 ± 7.7 months (n = 16), bisphosphonates for 19.2 ± 6.7 months (n = 32), or were untreated (n = 32) for 17.1 ± 4.6 months. Plasma sclerostin concentrations were measured before and after treatment. RESULTS: Plasma sclerostin levels after treatment were significantly lower in the raloxifene than in the control group (55.8 ± 23.4 pmol/l vs. 92.1 ± 50.4 pmol/l, p = 0.046), but were similar between the bisphosphonate and control groups. Relative to baseline, raloxifene treatment markedly reduced plasma sclerostin concentration (-40.7 ± 22.8%, p < 0.001), with respect to both control (-7.5 ± 29.1%) and bisphosphonate (-3.1 ± 35.2%) groups. Changes in bone-specific alkaline phosphatase and osteocalcin levels showed reverse associations with sclerostin concentration changes in the raloxifene (γ = -0.505, p = 0.017) and control (γ = -0.410, p = 0.020) groups. CONCLUSIONS: Raloxifene, but not bisphosphonates, significantly suppressed circulating sclerostin concentration, suggesting that sclerostin may mediate the action of estrogen on bone metabolism, independently of their anti-resorptive effects.

Efficacy and safety of bazedoxifene in postmenopausal Asian women.

UNLABELLED: This 6-month study examined the efficacy and safety of bazedoxifene 20 mg in postmenopausal Asian women. Bazedoxifene showed statistically significant improvements over placebo in bone mineral density at all skeletal sites evaluated. Bazedoxifene significantly reduced bone turnover and had favorable effects on lipid parameters. Bazedoxifene was safe and well tolerated. INTRODUCTION: This 6-month, randomized, double-blind, placebo-controlled phase 3 study conducted in China, Korea, and Taiwan evaluated the efficacy and safety of bazedoxifene in postmenopausal Asian women. METHODS: Generally, healthy postmenopausal Asian women (N=487; mean age, 57.2 years; mean lumbar spine bone mineral density [BMD], -1.1) were randomized to daily therapy with bazedoxifene 20 mg or placebo; all subjects received daily supplemental calcium carbonate 600 mg. The changes from baseline in BMD at the lumbar spine (primary end point) and at other skeletal sites, bone turnover markers, and lipid parameters were evaluated at 6 months. Safety assessments included adverse event (AE) reporting and physical/gynecologic examination. RESULTS: At 6 months, women who received bazedoxifene 20 mg had significantly greater BMD compared with those receiving placebo at the lumbar spine (0.41% vs -0.32%, P<0.01), femoral neck (-0.08% vs -0.69%, P=0.014), trochanter (0.50% vs -0.23%, P=0.010), and total hip (-0.03% vs -0.77%, P<0.001), respectively. Bazedoxifene 20 mg was also associated with significant differences from placebo in median percent reductions from baseline in serum C-telopeptide (-21.8%, P<0.001) and osteocalcin (-12.9%, P<0.001) levels and total (-5.0%, P<0.001) and low-density lipoprotein cholesterol (-9.5%, P<0.001) levels. The incidence of AEs was not different between subjects treated with bazedoxifene and those who received placebo. CONCLUSION: Bazedoxifene was generally safe and effective in preventing bone loss in this short-term study of postmenopausal Asian women.

The association between serum osteocalcin levels and metabolic syndrome in Koreans.

UNLABELLED: The association between serum osteocalcin levels and metabolic syndrome (MS) in Korean individuals was investigated. Serum osteocalcin levels are significantly lower in subjects with MS than in those without the disease, regardless of glucose metabolism. INTRODUCTION: Osteocalcin was recently shown to affect energy metabolism. In the present study, we investigated the possible association between serum osteocalcin concentrations and MS. METHODS: A cross-sectional community-based survey was conducted. Serum osteocalcin, type 1 collagen C-telopeptide (CTX) and total alkaline phosphatase (ALP) concentrations were determined in 567 subjects. MS was defined according to NCEP-ATP III criteria. RESULTS: Serum osteocalcin concentrations were significantly lower in subjects with MS than those without MS in postmenopausal women (18.923 ± 7.685 vs 22.513 ± 7.344 ng/ml, P<0.001) and marginally lower in subjects with MS than those without MS in men (14.550 ± 5.090 vs 16.125 ± 4.749 ng/ml, P=0.086) after adjustment for age and BMI. Further controlling with CTX or ALP did not affect this association in postmenopausal women; however, controlling with osteocalcin abolished the association between CTX and MS. Significant differences in serum osteocalcin levels by MS status were noted in subjects with normal glucose tolerance as well as those with abnormal glucose tolerance (P=0.032 and P<0.001, respectively). Compared with subjects with the highest quartile of osteocalcin, those in the lower quartile groups (Q1-Q3) had significantly increased risks of MS (ORs=5.18, CIs=1.15-23.42) in men. In postmenopausal women, the ORs for MS were significantly higher in the lowest quartile than in the highest quartile (ORs=5.25, CIs=2.42-11.36). CONCLUSIONS: These findings suggest that osteocalcin is associated with MS, independently of glucose metabolism.

Predictors of high intraoperative blood loss derived by simple and objective method in adult living donor liver transplantation.

We conducted a risk factor analysis for high intraoperative blood loss (IBL) in 555 living donor liver transplantation (LDLT) cases with a simple and objective method of IBL estimation based on the concept of red cell mass (RCM): Lost RCM (mL) = patient's estimated blood volume (mL) × (preoperative hematocrit in % - postoperative hematocrit in %) + (transfused leukocyte-depleted red blood cell in units × 213 × 70%) + (transfused Cell Saver blood in mL × 55%). Analysis of 33 preoperative variables revealed that Model for End-stage Liver Disease (MELD) score, albumin, the presence of ascites, and previous abdominal surgery were correlated with high IBL (lost RCM > 1000 mL) in multivariate logistical regression analysis. In conclusion, we found that MELD score, albumin, the presence of ascites, and previous abdominal surgery were significantly correlated with high IBL during adult LDLT.