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BACKGROUND AND AIMS Despite frequent cirrhotic cardiomyopathy or subclinical heart failure (HF), the prognostic value of peri-liver transplant (LT) B-type natriuretic peptide (BNP) has been poorly studied in advanced liver disease. We examined the association between BNP and mortality in a large cohort of LT patients and identified risk factors for peri-LT BNP increase. APPROACH AND RESULTS Using prospectively collected data from the Asan LT Registry between 2008 and 2019, 3,811 patients who measured serial pretransplant BNP (preBNP) and peak BNP levels within the first 3 posttransplant days (postBNPPOD3 ) were analyzed. Thirty-day all-cause mortality predicted by adding preBNP and/or postBNPPOD3 to the traditional Revised Cardiac Risk Index (RCRI) was evaluated. PreBNP > 400 pg/mL (known cutoff of acute HF) was found in 298 (7.8%); however, postBNPPOD3 > 400 pg/mL was identified in 961 (25.2%) patients, specifically in 40.4% (531/1,315) of those with a Model for End-Liver Disease score (MELDs) > 20. Strong predictors of postBNPPOD3 > 400 pg/mL were preBNP, hyponatremia, and MELDs, whereas those of preBNP > 400 pg/mL were MELDs, kidney failure, and respiratory failure. Among 100 (2.6%) post-LT patients who died within 30 days, patients with postBNPPOD3 ≤ 150 pg/mL (43.1%, reference group), 150-400 pg/mL (31.7%), 400-1,000 pg/mL (18.5%), 1,000-2,000 pg/mL (4.7%), and >2,000 pg/mL (2.0%) had 30-day mortalities of 0.9%, 2.2%, 4.0%, 7.7%, and 22.4%, respectively. Adding preBNP, postBNPPOD3 , and both BNP to RCRI improved net reclassification index to 22.5%, 29.5%, and 33.1% of 30-day mortality, respectively. CONCLUSIONS PostBNPPOD3 > 400 pg/mL after LT was markedly prevalent in advanced liver disease and mainly linked to elevated preBNP. Routine monitoring of peri-LT BNP provides incremental prognostic information; therefore, it could help risk stratification for mortality as a practical and useful biomarker in LT.

Background: Given the severe shortage of donor liver grafts, coupled with growing proportion of cardiovascular death after liver transplantation (LT), precise cardiovascular risk assessment is pivotal for selecting recipients who gain the greatest survival benefit from LT surgery. We aimed to determine the prognostic value of pre-LT combined measurement of B-type natriuretic peptide (BNP) and high-sensitivity troponin I (hsTnI) in predicting early post-LT mortality. Methods: We retrospectively evaluated 2,490 consecutive adult LT patients between 2010 and 2018. Cut-off values of BNP and hsTnI for predicting post-LT 90-day mortality were calculated. According to the derived cut-off values of two cardiac biomarkers, alone and in combination, adjusted hazard ratios (aHR) of post-LT 90-day mortality were determined using multivariate Cox regression analysis.Results: Mortality rate after 90 days was 2.9% (72/2,490). Rounded cut-off values for post-LT 90-day mortality were 400 pg/ml for BNP (aHR 2.02 [1.15, 3.52], P = 0.014) and 60 ng/L for hsTnI (aHR 2.65 [1.48, 4.74], P = 0.001), respectively. Among 273 patients with BNP ≥ 400 pg/ml, 50.9% of patients were further stratified into having hsTnI ≥ 60 ng/L. Combined use of pre-LT cardiac biomarkers predicted post-LT 90-day mortality rate; both non-elevated: 1.0% (21/2,084), either one is elevated: 9.0% (24/267), and both elevated: 19.4% (27/139, log-rank P < 0.001; aHR vs non-elevated 4.23 [1.98, 9.03], P < 0.001).Conclusions: Concomitant elevation of both cardiac biomarkers posed significantly higher risk of 90-day mortality after LT. Pre-LT assessment cardiac strain and myocardial injury, represented by BNP and hsTnI values, would contribute to prioritization of LT candidates and help administer target therapies that could modify early mortality.

Introduction Early allograft dysfunction (EAD) is known to be a prototype of graft failure and ultimately influences long-term graft failure or death. We hypothesized that pretransplant thrombogenicity evaluated by procoagulant and anticoagulant, von Willebrand factor (vWF), factor Ⅷ (FⅧ), protein C (PC) and their imbalance ratio of vWF-to-PC (vWFPCR) and FVIII-to-PC (FⅧPCR), is associated with EAD and 90-day graft failure after living-related liver transplantation (LDLT) and contributes to further exacerbation of graft dysfunction when coexists with systemic inflammation. Material and methods Of 1199 prospectively registered LDLT patients, 698 with measurements of each thrombogenicity parameters were analyzed. Risk factors for EAD development were searched and subsequent best cut-offs was calculated according to the receiver operator characteristic curve analysis. When comparing the outcome, multivariable regression analysis and inverse probability of treatment weighting (IPTW) of the propensity score were performed. Results The prevalence of EAD was 10.7% (n = 75/698) after LDLT. Of parameters, vWFPCR had highest predictivity potential of EAD with the best cut-off of 8.06. The relationship between vWFPCR≥8.06 showed significant association with EAD development (OR [95%CI], 2.55[1.28–5.09], P = 0.008) and 90-day graft failure (HR [95%CI], 2.24 [1–4.98], P = 0.043) after IPTW-adjustment. Furthermore, risk of EAD increased proportionally with increasing C-reactive protein as a continuous metric of systemic inflammation, and more steeply in those with higher thrombogenicity (i.e., higher vWFPCR). Adding vWFPCR to MELD score improved EAD risk prediction by 21.9%. Conclusions Pretransplant thrombogenicity assessed by imbalance of pro- and anticoagulant, was significantly associated with EAD and 90-day graft failure after LDLT and this association was worsened by systemic inflammation.

Background and aim The proportional increase of corrected QT interval (QTc) along end-stage liver disease (ESLD) severity may lead to inconsistent outcome reporting if based on conventional threshold of prolonged QTc. We investigated the comprehensive QTc distribution among ESLD patients and assessed the association between QTc > 500 ms, a criterion for diagnosing severe long-QT syndrome, and the 30-day major adverse cardiovascular event (MACE) after liver transplantation (LT) and identified the risk factors for developing QTc > 500 ms. Methods Data were collected prospectively from the Asan LT Registry between 2011 and 2018, and outcomes were retrospectively reviewed. Multivariable analysis and propensity score-weighted adjusted odds ratios (ORs) were calculated. Thirty-day MACEs were defined as the composite of cardiovascular mortality, arrhythmias, myocardial infarction, pulmonary thromboembolism, and/or stroke. Results Of 2579 patients, 194 (7.5%) had QTc > 500 ms (QTc500_Group), and 1105 (42.8%) had prolonged QTc (QTcP_Group), defined as QTc > 470 ms for women and >450 ms for men. The 30-day MACE occurred in 336 (13%) patients. QTc500_Group showed higher 30-day MACE than did those without (20.1% vs 12.5%, P = 0.003), with corresponding adjusted OR of 1.24 (95% CI: 1.06-1.46, P = 0.007). However, QTcP_Group showed comparable 30-day MACE (13.3% vs 12.8% without prolonged QTc, P = 0.764). Significant risk factors for QTc > 500 ms development were advanced liver disease, female sex, hypokalemia, hypocalcemia, high left ventricular end-diastolic volume, and tachycardia. Conclusion Our results revealed that, among ESLD patients, a novel threshold of QTc > 500 ms was associated with post-LT 30-day MACE but not with conventional threshold, indicating that a longer QTc threshold should be considered for this unique patient population.

This study aimed to assess the effects of remote ischemic preconditioning (RIPC) on liver function in donors and recipients after living donor liver transplantation (LDLT).Ischemia reperfusion injury (IRI) is known to be associated with graft dysfunction after liver transplantation. RIPC is used to lessen the harmful effects of IRI.A total of 148 donors were randomly assigned to RIPC (n = 75) and control (n = 73) groups. RIPC involves 3 cycles of 5-minute inflation of a blood pressure cuff to 200 mm Hg to the upper arm, followed by 5-minute reperfusion with cuff deflation. The primary aim was to assess postoperative liver function in donors and recipients and the incidence of early allograft dysfunction and graft failure in recipients.RIPC was not associated with any differences in postoperative aspartate aminotransferase (AST) and alanine aminotransferase levels after living donor hepatectomy, and it did not decrease the incidence of delayed graft hepatic function (6.7% vs 0.0%, P = 0.074) in donors. AST level on postoperative day 1 [217.0 (158.0, 288.0) vs 259.5 (182.0, 340.0), P = 0.033] and maximal AST level within 7 postoperative days [244.0 (167.0, 334.0) vs 296.0 (206.0, 395.5), P = 0.029) were significantly lower in recipients who received a preconditioned graft. No differences were found in the incidence of early allograft dysfunction (4.1% vs 5.6%, P = 0.955) or graft failure (1.4% vs 5.6%, P = 0.346) among recipients.RIPC did not improve liver function in living donor hepatectomy. However, RIPC performed in liver donors may be beneficial for postoperative liver function in recipients after living donor liver transplantation.

Background Although, living donor liver transplantation (LDLT) is the standard treatment option for patients with end-stage liver disease, it always entails ethical concerns about the risk of living donors. Recent studies have reported a correlation between sarcopenia and surgical prognosis in recipients. However, there are few studies of donor sarcopenia and the surgical prognosis of donors. This study investigated the association between sarcopenia and postoperative acute kidney injury in liver donors. Methods This retrospective study analyzed 2,892 donors who underwent donor hepatectomy for LDLT between January 2008 and January 2018. Sarcopenia was classified into pre-sarcopenia and severe sarcopenia, which were determined to be -1 standard deviation (SD), and -2 SD from the mean baseline of the skeletal muscle index, respectively. Multivariate regression analysis was performed to evaluate the association between donor sarcopenia and postoperative AKI. Additionally, we assessed the association between donor sarcopenia and delayed recovery of liver function (DRHF). Results In the multivariate analysis, donor sarcopenia was significantly associated a higher incidence of postoperative AKI (adjusted odds ratio [OR]: 2.65, 95% confidence interval [CI]: 1.15-6.11, P=0.022 in pre-sarcopenia, OR: 5.59, 95% CI: 1.11-28.15, P=0.037 in severe sarcopenia, respectively). Additionally, hypertension, and synthetic colloid use were significantly associated with postoperative AKI. In the multivariate analysis, risk factors of DRHF were male gender, indocyanine green retention rate at 15 minutes, and graft type, however, donor sarcopenia was not a risk factor. Conclusions Donor sarcopenia is associated with postoperative AKI following donor hepatectomy.

We aimed to determine if the severity of computed tomographic coronary angiography (CTCA)-diagnosed coronary artery disease (CAD) is associated with postliver transplantation (LT) myocardial infarction (MI) within 30 days and early mortality. We retrospectively evaluated 2118 consecutive patients who underwent CAD screening using CTCA. Post-LT type-2 MI, elicited by oxygen supply-and-demand mismatch within a month after LT, was assessed according to the severity of CTCA-diagnosed CAD. Obstructive CAD (>50% narrowing, 9.2% prevalence) was identified in 21.7% of patients with 3 or more known CAD risk factors of the American Heart Association. Post-LT MI occurred in 60 (2.8%) of total patients in whom 90-day mortality rate was 16.7%. Rates of post-LT MI were 2.1%, 3.1%, 3.4%, 4.3%, and 21.4% for normal, nonobstructive CAD, and 1-, 2-, and 3-vessel obstructive CAD, respectively. Two-vessel or 3-vessel obstructive CAD showed a 4.9-fold higher post-LT MI risk compared to normal coronary vessels. The sensitivity and negative predictive value of obstructive CAD in detecting post-LT MI were, respectively, 20% and 97.5%. In conclusion, negative CTCA finding in suspected patients can successfully exclude post-LT MI, whereas proceeding with invasive angiography is needed to further risk-stratify in patients with significant CTCA-diagnosed CAD. Prognostic role of CTCA in predicting post-LT MI needs further research.

Background: PNI is significantly associated with surgical outcomes, however, the association between PNI and intraoperative transfusions is unknown. Methods: This study retrospectively analyzed 1065 patients who underwent hepatectomy. We divided patients into two groups according to the PNI (&lt, 44 and &gt, 44) and compared their transfusion rates and surgical outcomes. We performed multivariate logistic and Cox regression analysis to determine risk factors for transfusion and the 5-year survival. Additionally, we found the net reclassification index (NRI) to validate the discriminatory power of PNI. Results: The PNI &lt, 44 group had higher transfusion rates (adjusted odds ratio [OR]: 2.20, 95%CI: 1.06–4.60, p = 0.035) and poor surgical outcomes, such as post hepatectomy liver failure (adjusted [OR]: 3.02, 95%CI: 1.87–4.87, p &lt, 0.001), and low 5-year survival (adjusted OR: 1.68, 95%CI: 1.17–2.24, p &lt, 0.001). On multivariate analysis, PNI &lt, 44, age, hemoglobin, operation time, synthetic colloid use, and laparoscopic surgery were risk factors for intraoperative transfusion. On Cox regression analysis, PNI &lt, 44, MELD score, TNM staging, synthetic colloid use, and transfusion were associated with poorer 5-year survival. NRI analysis showed significant improvement in the predictive power of PNI for transfusion (p = 0.002) and 5-year survival (p = 0.004). Conclusions: Preoperative PNI &lt, 44 was significantly associated with higher transfusion rates and surgical outcomes.

Various biological indicators are reportedly associated with postoperative acute kidney injury (AKI) in the surgical treatment of hepatocellular carcinoma (HCC). However, only a few studies have evaluated the association between the preoperative prognostic nutritional index (PNI) and postoperative AKI. This study evaluated the association of the preoperative PNI and postoperative AKI in HCC patients. We retrospectively analyzed 817 patients who underwent open hepatectomy between December 2007 and December 2015. Multivariate regression analysis was performed to evaluate the association between the PNI and postoperative AKI. Additionally, we evaluated the association between the PNI and outcomes such as postoperative renal replacement therapy (RRT) and mortality. Cox regression analysis was performed to assess the risk factors for one-year and five-year mortality. In the multivariate analysis, high preoperative PNI was significantly associated with a lower incidence of postoperative AKI (odds ratio (OR): 0.92, 95% confidence interval (CI): 0.85 to 0.99, p = 0.021). Additionally, diabetes mellitus and the use of synthetic colloids were significantly associated with postoperative AKI. PNI was associated with postoperative RRT (OR: 0.76, 95% CI: 0.60 to 0.98, p = 0.032) even after adjusting for other potential confounding variables. In the Cox regression analysis, high PNI was significantly associated with low one-year mortality (Hazard ratio (HR): 0.87, 95% CI: 0.81 to 0.94, p &lt, 0.001), and five-year mortality (HR: 0.93, 95% CI: 0.90–0.97, p &lt, 0.001). High preoperative PNI was significantly associated with a lower incidence of postoperative AKI and low mortality. These results suggest that the preoperative PNI might be a predictor of postoperative AKI and surgical prognosis in HCC patients undergoing open hepatectomy.

Postoperative hemorrhagic stroke (HS) is a rare yet devastating complication after liver transplantation (LT). Unruptured intracranial aneurysm (UIA) may contribute to HS, however, related data are limited. We investigated UIA prevalence and aneurysmal subarachnoid hemorrhage (SAH) and HS incidence post-LT. We identified risk factors for 1-year HS and constructed a prediction model. This study included 3544 patients who underwent LT from January 2008 to February 2019. Primary outcomes were incidence of SAH, HS, and mortality within 1-year post-LT. Propensity score matching (PSM) analysis and Cox proportional hazard analysis were performed. The prevalence of UIAs was 4.63% (n = 164, 95% confidence interval (CI), 3.95–5.39%). The 1-year SAH incidence was 0.68% (95% CI, 0.02–3.79%) in patients with UIA. SAH and HS incidence and mortality were not different between those with and without UIA before and after PSM. Cirrhosis severity, thrombocytopenia, inflammation, and history of SAH were identified as risk factors for 1-year HS. UIA presence was not a risk factor for SAH, HS, or mortality in cirrhotic patients post-LT. Given the fatal impact of HS, a simple scoring system was constructed to predict 1-year HS risk. These results enable clinical risk stratification of LT recipients with UIA and help assess perioperative HS risk before LT.

Pleural effusion and hypoalbuminaemia frequently occur after hepatectomy. Despite the emphasis on the safety of donors, little is known about the impact of postoperative albumin level on pleural effusion in liver donors. We retrospectively assessed 2316 consecutive liver donors from 2004 to 2014. The analysis of donors from 2004 to 2012 showed that postoperative pleural effusion occurred in 47.4% (970/2046), and serum albumin levels decreased until postoperative day 2 (POD2) and increased thereafter. In multivariable analysis, the lowest albumin level within POD2 (POD2ALB) was inversely associated with pleural effusion (OR 0.28, 95% CI 0.20–0.38; P P P P = 0.024), compared with synthetic colloid infusion after PS matching (193 pairs). In conclusion, our data showed that POD2ALB is inversely associated with pleural effusion, and that intraoperative albumin infusion is associated with a lower incidence of pleural effusion when compared to synthetic colloid infusion in liver donors.

Although the revised cardiac risk index (RCRI) is a useful tool for estimating the risk of postoperative cardiac events, whether it improves the prediction of cardiac events in patients undergoing liver transplantation (LT) has not been sufficiently demonstrated.We retrospectively analyzed 1429 patients who underwent LT. Cardiac events were defined as myocardial infarction, death, or combined events within 30 days after surgery. The RCRI was defined as the number of independent predictors including high-risk surgery, ischemic heart disease, congestive heart failure, cerebrovascular disease, insulin treatment, and creatinine level2 mg/dL. Multivariate logistic regression analysis was performed to identify factors independently associated with cardiac events. The additive predictability of RCRI for the Model for End-Stage Liver Disease (MELD) score was assessed using receiver operating characteristic curve analysis.Forty-four (3.1%) cardiac events occurred within 30 days after surgery. Both the MELD score (adjusted odds ratio [aOR], 1.05; P = .005) and RCRI (aOR, 4.35; P .001 for RCRI score 2; aOR, 6.27; P = .009 for RCRI score 3 compared with RCRI score 1) independently predicted postoperative 30-day cardiac events. The model with MELD score plus RCRI was significantly more predictive for postoperative 30-day cardiac events than the model with MELD score alone (C-statistics 0.800 vs 0.757; P = .030).For preoperative risk stratification, RCRI showed additive value to MELD score in predicting postoperative 30-day cardiac events after LT.

Background Antiphospholipid antibodies (aPL), including anticardiolipin (aCL), anti-β2-glycoprotein I (anti-β2GPI), and lupus anticoagulant (LA) antibodies, are frequently found in liver cirrhosis and associated with splanchnic vein thrombosis. Although the risk factors of early allograft dysfunction (EAD) are known, the association between EAD and aPL has been poorly investigated. We hypothesized that LA, potent aPL with thrombotic potential, may be associated with EAD development after living donor liver transplantation (LDLT). Methods Data of 719 patients who underwent LDLT from February 2014 to June 2016 at our center were retrospectively collected and analyzed. Patients were divided into 2 groups according to the positivity of LA screening test (LA group [n = 148] vs no-LA group [n = 571]). Risk factors for EAD were investigated using multivariable regression analysis and inverse probability of treatment weighting (IPTW) of propensity scores. Results The prevalence of LA screening positivity, confirmatory test positivity, and EAD was 20.6%, 1.1%, and 11.3%, respectively. aCL positivity rate was 7.5% and anti-β2GPI positivity rate was 7.0%. The EAD prevalence in LA and no-LA group was 25.7% and 7.5%, respectively. However, multivariable and IPTW analyses showed no association between EAD and LA screening positivity (P = .263 and P = .825, respectively), although a significant association was found in univariate analysis (odds ratio, 4.242; P Conclusion A positive LA screening test result was associated with EAD only in the univariate analysis. Inflammation, based on C-reactive protein level, was more important for EAD development.

BACKGROUND As end-stage liver disease progresses, renal blood flow linearly correlates with mean arterial blood pressure (MBP) due to impaired autoregulation. We investigated whether the lower degree of postoperative MBP would predict the occurrence of postoperative acute kidney injury (AKI) after liver transplantation. MATERIAL AND METHODS This retrospective study enrolled 1,136 recipients with normal preoperative kidney function. Patients were categorized into two groups according to the averaged postoperative MBP

Introduction: Perioperative anesthetic management in cases of severe airway obstruction with positional symptoms can be associated with difficulties in ventilation or intubation, with a risk of acute respiratory decompensation at every stage of anesthesia. Patient concerns: Here we describe the anesthetic management of a 67-year-old man with a massive intrathoracic goiter causing severe tracheal obstruction with positional symptoms. The patient presented with progressive dyspnea that was aggravated in the supine position and was scheduled for total thyroidectomy. Diagnosis: Preoperative computed tomography showed a large goiter extending into the thoracic cavity, with diffuse segmental tracheal narrowing for 6 cm. The diameter at the narrowest portion of the trachea was 4.29 mm. Interventions: Before the induction of general anesthesia, we applied extracorporeal membrane oxygenation (ECMO) in preparation for potential difficulties in securing the airway during general anesthesia. Subsequently, anesthesia was successfully induced and maintained. Outcomes: After the surgical procedure, fiberoptic bronchoscopy and chest radiography showed resolution of the tracheal narrowing. ECMO was weaned 2 hours after the surgery, and the patient was extubated on the first postoperative day. He was discharged without any complication. Conclusion: The findings from this case suggest that the use of ECMO before the induction of general anesthesia is a safe method for maintaining oxygenation in patients with severe tracheal obstruction.

Fluid overload (FO) has been shown to adversely affect multiple organs and survival in critically ill patients. Liver transplantation (LT) carries the risk of massive transfusion, which frequently results in FO. We investigated the association of postoperative weight gain with graft failure, early allograft dysfunction (EAD), and overall mortality in LT. 1833 living donor LT (LDLT) recipients were retrospectively analysed. Patients were divided into 2 groups according to postoperative weight gain (P = 0.001). When postoperative weight change was used as a continuous variable, the aHR for each 1% increase in postoperative weight was 1.045 (95% CI, 1.009–1.082; P = 0.015). In addition, the ≥3% group was associated with EAD (adjusted OR [aOR], 1.553; 95% CI, 1.024–2.356; P = 0.038) and overall mortality (aHR, 1.731; 95% CI, 1.182–2.535; P = 0.005). In conclusion, postoperative weight gain may be independently associated with increased risk of graft failure, EAD, and mortality in LDLT recipients.

Background This study aims to investigate the noninferiority of Enhanced Recovery After Surgery (ERAS) for pancreaticoduodenectomy (PD). Methods In this single-center trial, we randomly assigned 276 adult patients who underwent open PD into ERAS and conventional groups with 138 patients in each, from 2015 through 2017. The primary endpoint was the incidence of overall morbidity until postoperative 3 months. The secondary endpoints were in-hospital or 30-day mortality, postoperative length of stay (LOS), nutritional status and overall hospital costs. Results Overall morbidity was reported in 64 patients (52.0%, ERAS group) and in 68 patients (54.8%, conventional group) (risk difference [RD] -2.81 percentage points (pp); 90% two-sided confidence interval -13.24 to 7.63). Mortality did not occur in any patients. The two groups did not differ significantly in median postoperative LOS (both 11 days; RD -8.46 pp), body mass index (22.4 ± 2.75 vs. 22.4 ± 2.65 kg/m2 ; RD -3.48 pp), Patient-Generated Subjective Global Assessment score over 4 (45 [40.5%] vs. 50 [43.1%] patients; RD -2.56 pp), and median overall hospital cost (15.61 vs. 16.04, ×106 KRW; RD -6.08 pp). Conclusions Even in PD, modified ERAS protocol was not inferior to conventional protocol, while reducing treatment burden.

We aimed to determine the association between the preoperative antithrombin III (ATIII) level and postoperative acute kidney injury (AKI) after LT (post-LT AKI). We retrospectively evaluated 2395 LT recipients between 2010 and 2018 whose data of perioperative ATIII levels were available. Patients were divided into two groups based on the preoperative level of ATIII (ATIII &lt, 50% vs. ATIII ≥ 50%). Multivariable regression analysis was performed to assess the risk factors for post-LT AKI. The mean preoperative ATIII levels were 30.2 ± 11.8% in the ATIII &lt, 50% group and 67.2 ± 13.2% in the ATIII ≥ 50% group. The incidence of post-LT AKI was significantly lower in the ATIII ≥ 50% group compared to that in the ATIII &lt, 50% group (54.7% vs. 75.5%, p &lt, 0.001), odds ratio (OR, per 10% increase in ATIII level) 0.86, 95% confidence interval (CI) 0.81–0.92, p &lt, 0.001. After a backward stepwise regression model, female sex, high body mass index, low albumin, deceased donor LT, longer duration of surgery, and high red blood cell transfusion remained significantly associated with post-LT AKI. A low preoperative ATIII level is associated with post-LT AKI, suggesting that preoperative ATIII might be a prognostic factor for predicting post-LT AKI.

Background & Aims Ventriculo-arterial coupling (VAC) reflects the interaction between ventricular performance and effective arterial load. Current criteria for cirrhotic cardiomyopathy focus only on cardiac function without addressing the effect of hyperdynamic, low-resistance circulation. We investigated alterations in VAC in cirrhotic patients and their associations with post-liver transplant all-cause mortality. Methods In this single institution cohort study, cirrhotic patients who underwent liver transplantation (LT) (n=914) were retrospectively compared with healthy matched controls using noninvasively measured end-systolic ventricular elastance (Ees), arterial elastance (Ea), and VAC (Ea/Ees). All-cause mortality based on VAC values were investigated using a Cox hazard model with the inverse probability treatment weighting (IPTW) of propensity score. Results Cirrhotic patients had significantly lower Ees, Ea and VAC values than controls. Over a median of 30months, 96 patients died after LT. In patients with a high model for end-stage liver disease score (⩾25), VAC of >0.61 (highest tertile) had poorer survival outcomes than patients with VAC of ⩽0.50 (lowest tertile) (66.0% vs. 91.8%; Log-rank p =0.001), and was independently associated with risk of mortality (hazard ratio, 2.44; 95% CI, 1.10–5.39; p =0.028) compared with VAC of ⩽0.61 after IPTW adjustment. Conclusions In cirrhotic patients, ventricular elastance and VAC values are lower than those in controls. However, in advanced cirrhotic patients, an increase in VAC value is associated with all-cause mortality after LT, suggesting that this non-invasive estimation of ventriculo-arterial uncoupling is an additional novel prognosticator in cirrhotic cardiovascular disorders. Lay summary In cirrhotic patients, cardiac dysfunction is latent and only manifests under stressful conditions because of arterial vasodilation. In this study, based on the pressure-volume curve of cardiac function, we investigated characteristics of the ventricular-arterial coupling in cirrhotic patients and further found that disparities in the ventriculo-arterial relationship are associated with graft failure and all-cause mortality after liver transplantation.

Although left ventricular diastolic dysfunction (LVDD) is a pronounced feature of adult cirrhotic cardiomyopathy and a major predictor of poor outcomes following liver transplantation (LT), little is known about if pretransplant cardiac dysfunction affects perioperative outcomes in pediatric LT.We retrospectively evaluated pretransplant clinical and Doppler echocardiographic data for 45 consecutive pediatric LT recipients who were treated between 2007 and 2013 (median age = 15 months; interquartile range = 9 to 78 months). LVDD was defined according to the cirrhotic cardiomyopathy criteria, and the myocardial performance index (MPI) was measured using tissue Doppler imaging. Intraoperative data and hospitalization days following LT were compared.LVDD and MPI ≥0.5 (defined as a z score ≥2) were observed in 13% and 27% of patients, respectively. Patients with an MPI ≥0.5 demonstrated the increased accumulation of lactate at the end of their LT operation (mean = 2.48 vs 0.82; P = .026) compared with patients with an MPI 0.5. The hospital stay was longer in patients with LVDD (median = 46 days vs 30 days; P = .041) and patients with an MPI ≥0.5 (median = 38 days vs 29 days; P = .014) compared with patients without LVDD and MPI 0.5, respectively.LVDD might be less prevalent (13%) in pediatric patients compared with adults. However, pretransplant cardiac dysfunction in patients with LVDD and an MPI ≥0.5 adversely affects perioperative outcomes, necessitating that such pediatric LT recipients be cautiously observed perioperatively.

Background Repeated administration of morphine leads to characteristic tolerance. We tested the effects of intrathecal oxcarbazepine (OXC) on spinal morphine tolerance in rats using the tail flick test. Methods Sprague-Dawley rats received intrathecal injections of 10 microliter saline alone, or 10 microliter of solutions containing 100 microgram OXC, 15 microgram morphine, or OXC + morphine for 7 days. Different groups of rats received OXC on days 1-7, 1-3, or 5-7. The tail-flick assay was used to measure acute and chronic nociception. The nociceptive stimulus consisted of dipping the distal 5 cm of the tail into warm water before and 30 min after drug injection. On day 8, an antinociceptive dose-response curve was plotted, and the 50% effective dose for morphine (given alone) was determined for all groups. Results Morphine or OXC both produced acute antinociception; OXC + morphine resulted in a significantly larger response than obtained with morphine alone. Morphine tolerance was produced by intrathecal injection of morphine over 7 days. Co-administration of morphine and OXC completely blocked morphine tolerance, but tolerance developed when OXC injection was stopped, and morphine potency was partially restored by co-administration of OXC in tolerant rats. Conclusions The antinociceptive effect of both acute and chronic morphine therapy is increased with intrathecal OXC, and antinociceptive morphine tolerance is attenuated in rats.

Donor safety is the major concern in living donor liver transplantation, although hepatic resection may be associated with postoperative coagulopathy. Recently, the use of sugammadex has been gradually increased, but sugammadex is known to prolong prothrombin time (PT) and activated partial thromboplastin time (aPTT). We compared the postoperative coagulation profiles and outcomes of sugammadex versus pyridostigmine group in donors receiving living donor hepatectomy. Consecutive donor hepatectomy performed between September 2013 and August 2016 was retrospectively analyzed. For reversal of rocuronium-induced neuromuscular blockade, donors received sugammadex 4 mg/kg or pyridostigmine 0.25 mg/kg. The primary end-points were laboratory findings (PT, aPTT, hemoglobin, platelet count) and clinically evaluated postoperative bleeding (relaparotomy for bleeding, cumulative volume collected in drains). Secondary outcomes were anesthesia time, postoperative hospital day. Of 992 donors, 383 treated with sugammadex and 609 treated with pyridostigmine for the reversal of neuromuscular blockade. There were no significant differences between both groups for drop in hemoglobin and platelet, prolongation in PT, aPTT, and the amount of 24-h drain volume. Bleeding events within 24 h were reported in 2 (0.3%) for pyridostigmine group and 0 (0%) for sugammadex group (P = .262). Anesthesia time was significantly longer in pyridostigmine group than that in sugammadex group (438.8 ± 71.4 vs. 421.3 ± 62.3, P

Cerebral air embolism is a rare but potentially life-threatening complication. We experienced a living-donor liver transplant recipient who presented with unexpected cerebral air embolism and transient neurologic abnormalities that subsequently developed just after the removal of the pulmonary artery catheter from the central venous access device. One day after the initial event, the patient's neurologic status gradually improved. The patient was discharged 30 days after liver transplantation without neurologic sequelae.

Background: Acute aortic dissection (AD) is a lethal cardiovascular disease with severe inflammatory complications. Considering the proinflammatory properties of plasma mitochondrial DNA (mtDNA), we postulate that plasma mtDNA from activated platelets may be responsible for post-acute AD inflammatory responses. Methods: We consecutively enrolled 68 patients with acute AD as well as matched hypertensive and healthy participants. Blood samples were collected on admission for blood routine tests, mtDNA assay, and inflammatory cytokine analysis. A computed tomography scan was used to evaluate the extent of dissections. Results: Our results demonstrate that plasma mtDNA, platelet activation, and inflammatory levels were remarkably higher in acute AD patients than in hypertensive or healthy participants. These parameters were also higher in the Stanford A group than in the Stanford B group (p < 0.05). Bivariate correlation analysis demonstrated positive associations between mtDNA and inflammatory levels (tumor necrosis factor-α: r = 0.577; interleukin-6: r = 0.632), mtDNA and platelet activation (r = 0.642), and platelet activation and the extent of dissection (r = 0.635). Conclusion: Our study suggests that acute AD-induced tunica media exposure causes platelet activation, which leads to the initiation of inflammatory responses via the release of mtDNA into the circulation. Our study provides a novel fundamental basis and a potential therapeutic target for the prevention and treatment of post-AD inflammatory responses.

Reducing blood loss is beneficial in living liver donor hepatectomy. Although it has been suggested that maintaining a low central venous pressure is important, it is known that low stroke volume variation may be associated with increased blood loss. Therefore, we compared the effect on blood loss of 40 patients randomly assigned to a high stroke volume variation group (maintaining 10-20% of stroke volume variation) vs 38 patients in a control group (maintaining < 10% stroke volume variation) during living-donor right hepatectomy. Mean (SD) blood loss during donor hepatectomy was significantly lower in the high stroke volume variation group than in the control group: 476 (131) ml vs 836 (341) ml, respectively (p < 0.001). Blood pressure and peri-operative laboratory values did not differ between the two groups. However, in the high stroke volume variation group, central venous pressure values were also significantly lower. We were unable to disentangle the effects of stroke volume variation and central venous pressure, but our results confirm that the two together appear beneficial.

BACKGROUND Enhanced Recovery After Surgery (ERAS) program is a standardized, multimodal perioperative management plan that integrates various evidence-based interventions. We aimed to investigate the noninferiority of ERAS for pancreaticoduodenectomy (PD), one of the most complex abdominal surgeries. METHODS In this single-center trial, we randomly assigned 276 adult patients who underwent open pancreaticoduodenectomy into ERAS and conventional groups with 138 patients in each, from Mar 2, 2015 through January 11, 2017. In ERAS group, the modified ERAS Guidelines were applied, and the conventional group received the conventional perioperative management of our center. The primary endpoint was the incidence of overall operation-related morbidity until postoperative 3 months, with a noninferiority margin of 15*0 percentage points (pp). The secondary endpoints were in-hospital or 30-day mortality, postoperative length of stay, nutritional status and overall hospital costs. FINDINGS Overall morbidity was reported in 64 patients (52*0%, ERAS group) and in 68 patients (54*8%, conventional group) (risk difference (RD), -2*81 pp; 90% two-sided confidence interval, -13*24 to 7*63). Mortality did not occur in any patients. The two groups did not differ significantly in terms of median postoperative length of stay (both 11 days; RD, -8*46 pp), body mass index (22*4 ± 2*75 vs. 22*4 ± 2*65 kg/m2; RD, -3*48 pp), albumin level (2*6 ± 0*34 vs. 2*6 ± 0*33 g/dl; RD, 1*27 pp), Patient-Generated Subjective Global Assessment score over 4 (45 (40*5%) vs. 50 (43*1%) patients; RD, -2*56 pp), and median overall hospital cost (15*61 versus 16*04, x 106 KRW; RD, -6*08 pp). INTERPRETATION Even in pancreaticoduodenectomy, the modified ERAS protocol was not inferior to the conventional protocol regarding the postoperative morbidity, mortality, postoperative length of stay and hospital cost, while reducing treatment burden. Trial Registration Number: ClinicalTrials.gov number NCT02372331 Funding: Funded by the Asan Institute for Life Sciences (2014-0961). Declaration of Interest: We declare no competing interests Ethical Approval: The protocol was approved by the institutional review board of the Asan Medical Center (2014-0961).

BACKGROUND Although desflurane and sevoflurane, the most commonly used inhalational anesthetics, have been linked to postoperative liver injury, their impact on liver regeneration remains unclear. We compared the influence of these anesthetics on the postoperative liver regeneration index (LRI) after living donor hepatectomy (LDH). METHODS We conducted a retrospective chart review of 1629 living donors who underwent right hepatectomy for LDH between January 2008 and August 2016. The patients were divided into sevoflurane (n = 1206) and desflurane (n = 423) groups. Factors associated with LRI were investigated using multivariable logistic regression analysis. Propensity score matching analysis compared early (1 postoperative week) and late (within 1-2 months) LRIs and delayed recovery of hepatic function between the 2 groups. RESULTS The mean early and late LRIs in the 1629 patients were 63.3% ± 41.5% and 93.7% ± 48.1%, respectively. After propensity score matching (n = 403 pairs), there were no significant differences in early and late LRIs between the sevoflurane and desflurane groups (early LRI: 61.2% ± 41.5% vs 58.9% ± 42.4%, P = .438; late LRI: 88.3% ± 44.3% vs 94.6% ± 52.4%, P = .168). Male sex (regression coefficient [β], 4.6; confidence interval, 1.6-7.6; P = .003) and remnant liver volume (β, -4.92; confidence interval, -5.2 to -4.7; P < .001) were associated with LRI. The incidence of delayed recovery of hepatic function was 3.6% (n = 29) with no significant difference between the 2 groups (3.0% vs 4.2%, P = .375) after LDH. CONCLUSIONS Both sevoflurane and desflurane can be safely used without affecting liver regeneration and delaying liver function recovery after LDH.

The connection between renal dysfunction and cardiovascular dysfunction has been consistently shown. In patients with liver cirrhosis, renal dysfunction shows a tight correlation with prognosis after liver transplantation (LT); therefore, precise renal assessment is mandatory. Cystatin C, a sensitive biomarker for assessing renal function, has shown superiority in detecting mild renal dysfunction compared to classical biomarker creatinine. In this study, we aimed to compare cystatin C and creatinine in predicting 30-day major cardiovascular events (MACE) and all-cause mortality in LT recipients with normal serum creatinine levels.Between May 2010 and October 2015, 1181 LT recipients (mean Model for End-stage Liver Disease score 12.1) with pretransplantation creatinine level ≤1.4 mg/dL were divided into tertiles according to each renal biomarker. The 30-day MACE was a composite of troponin I0.2 ng/mL, arrhythmia, congestive heart failure, death, and cerebrovascular events.The highest tertile of cystatin C (≥0.95 mg/L) was associated with a higher risk for a 30-day MACE event (odds ratio: 1.62; 95% confidence interval: 1.07 to 2.48) and higher risk of death (hazard ratio: 1.96; 95% confidence interval: 1.04 to 3.67) than the lowest tertile (0.74 mg/L) after multivariate adjustments. However, the highest tertile of creatinine level showed neither increasing MACE event rate nor worse survival rate compared with the lowest tertile (both insignificant after multivariate adjustment).Pretransplantation cystatin C is superior in risk prediction of MACE and all-cause mortality in LT recipients with normal creatinine, compared to creatinine. It would assist further risk stratification which may not be detected with creatinine.

Background Measuring activated clotting time (ACT) is widely performed to monitor heparin therapy. Regardless of anticoagulant use, ACT is affected by coagulopathies such as coagulation factor deficiency and thrombocytopenia. However, its use in end-stage liver disease (ESLD) with complex coagulopathy is not well characterized. We evaluated whether ACT could be used to detect innate coagulopathy in ESLD patients. Methods We retrospectively assessed Hemochron (International Technidyne, Edison, NJ, USA) ACT (FTCA 510, normal range 105–167 seconds) and INTEM clotting time (CT) of rotational thromboelastometry (ROTEM; ROTEM delta, Pentapharm GmbH, Munich, Germany) (100–240 seconds) in 366 liver transplantation (LT) recipients, simultaneously measured before anesthetic induction for LT. Multiple linear regression analyses helped identify the factors related to ACT in ESLD patients. The relationship between ACT and INTEM CT was evaluated by Spearman rank correlation analysis and receiver operating characteristic curve. Results Median ACT was 143 seconds (range 73–295 seconds), and 60 patients (16.4%) had ACTs of >167 seconds. Multiple regression analyses revealed that prolonged prothrombin time, activated partial thromboplastin time, low antithrombin III, and young age were associated with high ACT levels. INTEM CT was associated with ACT independent of liver disease severity, while EXTEM CT was not. ACT was moderately correlated with INTEM CT ( r = 0.535), and the optimal cutoff value of ACT for predicting INTEM CT >240 seconds was 151 seconds (area under the curve = 0.787). Conclusions In ESLD patients, ACT is effective in detecting prolonged INTEM CT. Therefore, ACT may be used to predict intrinsic pathway defects with a cutoff value of 151 seconds, suggesting feasibility when ROTEM is unavailable.

Background The importance of heart rate (HR) measurement as a prognostic factor has been recognized in many clinical conditions, such as hypertension, coronary artery disease, or heart failure. Patients with liver cirrhosis tend to have increased resting HR as consequence of hyperdynamic circulation. In the current study, we examined whether pretransplant resting increased HR is associated with overall mortality in cirrhotic patients following liver transplantation (LT). Patients and Methods We retrospectively collected and analyzed the data of 881 liver recipients who underwent LT surgery between October 2009 and September 2012. Patients were categorized into 3 groups by tertile of resting HR as follows: tertile 1 group, HR ≤ 65 beats per minute (bpm); tertile 2 group, HR 66 to 80 bpm; and tertile 3 group, HR > 80 bpm. Results Kaplan-Meier analysis showed that the all-cause mortality rate was significantly different according to tertiles of HR ( P = .016, log-rank test). The multivariate Cox regression analysis showed that tertile 3 group was significantly associated with higher risk for all-cause mortality (hazard ratio 1.83, 95% confidence interval, 1.10–3.07; P = .021) compared with tertile 1 group, after adjusting for clinically significant variables in univariate analysis. Conclusions Our results demonstrate that pretransplant resting tachycardia can identify patients at high risk of death in cirrhotic patients following LT, suggesting that further study will be need to clarify relationship between HR burden and sympathetic cardiac neuropathy.

Purpose Lamotrigine, a novel anticonvulsant, is a sodium channel blocker that is efficacious in certain forms of neuropathic pain. Recently, microglial and astrocytic activation has been implicated in the development of nerve injury-induced neuropathic pain. We have assessed the effects of continuous intrathecal administration of lamotrigine on the development of neuropathic pain and glial activation induced by L5/6 spinal-nerve ligation in rats. Materials and Methods Following left L5/6 spinal nerve ligation (SNL), Sprague-Dawley male rats were intrathecally administered lamotrigine (24, 72, or 240 µg/day) or saline continuously for 7 days. Mechanical allodynia of the left hind paw to von Frey filament stimuli was determined before surgery (baseline) and once daily for 7 days postoperatively. On day 7, spinal activation of microglia and astrocytes was evaluated immunohistochemically, using antibodies to the microglial marker OX-42 and the astrocyte marker glial fibrillary acidic protein (GFAP). Results Spinal-nerve ligation induced mechanical allodynia in saline-treated rats, with OX-42 and GFAP immunoreactivity being significantly increased on the ipsilateral side of the spinal cord. Continuously administered intrathecal lamotrigine (240 µg/day) prevented the development of mechanical allodynia, and lower dose of lamotrigine (72 µg/day) ameliorated allodynia. Intrathecal lamotrigine (72 and 240 µg/day) inhibited nerve ligation-induced microglial and astrocytic activation, as evidenced by reduced numbers of cells positive for OX-42 and GFAP. Conclusion Continuously administered intrathecal lamotrigine blocked the development of mechanical allodynia induced by SNL with suppression of microglial and astrocytic activation. Continuous intrathecal administration of lamotrigine may be a promising therapeutic intervention to prevent neuropathy.

Background Regional oxygen saturation (rSO2) is a sensitive marker of cerebral hypoperfusion during liver transplantation. However, bilirubin absorbs near-infrared light, resulting in falsely low rSO2 values. We sought to determine whether rSO2 values vary in response to bilirubin concentrations during liver transplantation and to assess whether rSO2 changes were associated with factors reflecting cerebral oxygen delivery in patients with hyperbilirubinemia. Methods Measurements of rSO2 values continuous cardiac output (CO), mean arterial pressure, central venous pressure, body temperature, arterial blood gas analysis, and laboratory parameters were simultaneously performed at 1 hour after the surgical incision (baseline) and at 3 predetermined times during the anhepatic and neohepatic phases in 95 end-stage liver disease patients including 67 males of Child A/B/C/29/29/37 categories respectively. Relationships between changes in parameters were evaluated by correlation and multivariate regression analyses. Results The 273 measurements revealed changes in rSO2 (range, −18% to 40%) to correlate significantly with alterations in hemoglobin (Hb), serum glucose, lactate, prothrombin time, pH, partial arterial CO2 pressure (PaCO2), and CO, but not with serum total bilirubin (TB). Multivariate linear regression analysis revealed that changes in Hb, CO, PaCO2, and pH were independent of rSO2 changes during liver transplantation. Conclusions Our findings showed that rSO2 changes were independently associated with factors reflecting cerebral oxygen delivery, such as Hb, CO, PaCO2, and pH, whereas rSO2 values did not correlate with changes in bilirubin concentrations, indicating that rSO2 changes reveal cerebral oxygen balance regardless of TB levels among patients undergoing liver transplantation.

The anti-CD20 monoclonal antibody rituximab has significantly decreased the prevalence of antibody-mediated rejection of ABO-incompatible (ABOi) living donor liver transplantation (LDLT). However, little is known about acute kidney injury (AKI) following ABOi LDLT. The aim of this study was to identify the incidence of AKI in ABOi LDLT and compare it with that of ABO-compatible (ABOc) LDLT. We retrospectively collected and analyzed the data of 1617 patients who underwent liver transplant surgery from November 2008 to December 2014. Risk factors for AKI were investigated using multivariate regression analysis. In 271 ABOi LDLTs, AKI occurred in 184 (67.9%) according to Kidney Disease: Improving Global Outcomes criteria. After propensity score matching, the incidence of AKI was significantly higher after ABOi LDLT than after ABOc LDLT (67.0% versus 48.2%; P 0.001). Furthermore, the intensive care unit stay (P = 0.01) was significantly prolonged, but there were no significant differences in mortality (P = 0.74), graft failure (P = 0.32), and postoperative dialysis (P = 0.74) between the 2 groups. Hemoglobin level and operation time were independent risk factors for AKI following ABOi LDLT. In conclusion, the incidence of AKI is higher in ABOi LDLT than ABOc LDLT. However, the impact of AKI on postoperative outcomes was not marked in our study. Therefore, ABOi LDLT in selected patients is promising with apparent good graft and survival outcomes. Liver Transplantation 22 1656-1665 2016 AASLD.

Background Hepatic resection may be associated with postoperative coagulopathy. However, there is limited information about the predictors affecting coagulopathy after donor hepatectomy. We evaluated the contributors of maximal changes in prothrombin time (PT), activated thromboplastin time (aPTT), and platelet count in the development of postoperative coagulopathy. Methods We retrospectively analyzed 864 living donors, all of whom received general anesthesia using desflurane, isoflurane, or sevoflurane. A coagulation derangement was defined as one or more of the following events postoperatively: peak PT >1.5 international normalized ratio (INR; highest quartile of PT), peak aPTT >46 seconds (highest quartile of aPTT), or nadir platelet count 9 /L. Factors were evaluated by univariate and multivariate logistic regression analysis to identify predictors of coagulopathy. Results Mean postoperative peak PT, peak aPTT, and nadir platelet count were 1.4 ± 0.2 INR, 43.8 ± 23.7 seconds, and 155.9 ± 37.3 × 10 9 /L, respectively, with 39.4% of donors being at the risk for coagulation derangement. Multivariate logistic regression analysis revealed that predictors of such derangement included anesthesia duration, remnant liver volume, and body mass index (BMI). However, coagulation derangement was not independently associated with age, gender, volatile anesthetics, central venous pressure, fatty change in the liver, estimated blood loss, or intraoperative hypotensive episodes. Conclusion We found that long anesthesia duration, low BMI, and small remnant liver volume were predictors of coagulation derangement. These results provide a better understanding of risk factors affecting changes in coagulation profiles after living donor hepatectomy.

Laparoscopic pylorus-preserving pancreaticoduodenectomy is being performed more frequently because of improved surgical techniques. Although several studies have demonstrated safety and favourable outcomes of laparoscopic pylorus-preserving pancreaticoduodenectomy compared to open pylorus-preserving pancreaticoduodenectomy, few studies have focused on the development of postoperative acute kidney injury. This retrospective study compared the prevalence and risk factors of acute kidney injury following laparoscopic and open pylorus-preserving pancreaticoduodenectomy. Data from 809 patients who underwent pylorus-preserving pancreaticoduodenectomy between February 2012 and September 2016 were analysed. Patients were divided into two groups according to the surgical procedure (open pylorus-preserving pancreaticoduodenectomy [n = 632] vs laparoscopic pylorus-preserving pancreaticoduodenectomy [n = 177]). The Kidney Disease: Improving Global Outcomes criteria were used to define postoperative acute kidney injury and risk factors were investigated using multivariable logistic regression analysis with propensity score matching analysis and standardized mortality ratio weighting to compare outcomes. No significant differences were found in the occurrence of postoperative acute kidney injury and incidence of postoperative ICU admission between open and laparoscopic pylorus-preserving pancreaticoduodenectomy groups after propensity score matching (p = 1.000, p = 0.999, respectivelyand standardized mortality ratio weighted analysis (p = 0.619, p = 0.982, respectively). Hospital stay was significantly shorter in the laparoscopic pylorus-preserving pancreaticoduodenectomy group (propensity matched set, mean [SD], 16.7 [10.0] vs. 18.7 [9.6] days, p = 0.004; standardized mortality ratio, 16.6 [9.9] vs. 18.1 [8.8] days, p = 0.001). There was no significant difference in postoperative acute kidney injury incidence between both groups. Laparoscopic pylorus-preserving pancreaticoduodenectomy is promising with comparable postoperative outcomes to open pylorus-preserving pancreaticoduodenectomy and has the advantage of shorter hospital stay.

Purpose: Patients with relapsed mantle-cell lymphoma have poor prognosis and short survival. Our aim was to determine the efficacy of nonablative allogeneic stem-cell transplantation in patients with relapsed mantle-cell lymphoma. Patients and Methods: Eighteen patients were treated in one of two consecutive trials. Thirteen patients underwent a conditioning regimen of fludarabine (30 mg/m2 daily for 3 days), cyclophosphamide (750 mg/m2 daily for 3 days), and high-dose rituximab. For the remaining five patients, the conditioning regimen consisted of cisplatin (25 mg/m2 daily for 4 days), fludarabine (30 mg/m2 daily for 2 days), and cytarabine (1,000 mg/m2 daily for 2 days). Tacrolimus and methotrexate were used for graft-versus-host disease prophylaxis. Results: The median age was 56.5 years. Patients underwent a median of three prior chemotherapy regimens. Prior autologous transplantation failed in five (28%) patients and 16 (89%) had chemosensitive disease. Donor cell engraftment occurred in all patients. Eight patients (44%) required no platelet or RBC transfusion, and acute graft-versus-host disease of greater than grade 2 did not develop in any patient. The day-100 mortality was 0%. Complete remission (CR) occurred in 17 patients. Three patients progressed, and one was reinduced into continuous CR with donor lymphocyte infusion. With a median follow-up period of 26 months, the actuarial probability of current-event-free-survival at 3 years was 82% (95% CI, 65% to 99%). Conclusion:Our data suggest that nonablative allogeneic transplantation is a safe and potentially effective strategy for patients with relapsed and chemosensitive mantle-cell lymphoma.

Subclavian central venous catheterization is a common procedure for which misplacement of the central venous catheter (CVC) is a frequent complication that can potentially be fatal. The carina is located in the mid-zone of the superior vena cava (SVC) and is considered a reliable landmark for CVC placement in chest radiographs. The C-length, defined as the distance from the edge of the right transverse process of the first thoracic spine to the carina, can be measured in posteroanterior chest radiographs using a picture archiving and communication system. To evaluate the placement of the tip of the CVC in subclavian central venous catheterizations using the C-length, we reviewed the medical records and chest radiographs of 122 adult patients in whom CVC catheterization was performed (from January 2012 to December 2014) via the right subclavian vein using the C-length. The tips of all subclavian CVCs were placed in the SVC using the C-length. No subclavian CVC entered the right atrium. Tip placement was not affected by demographic characteristics such as age, sex, height, weight, and body mass index. The evidence indicates that the C-length on chest radiographs can be used to determine the available insertion length and place the right subclavian CVC tip into the SVC.

Low-dose metronomic (LDM) chemotherapy with cytotoxic agents, aimed at disrupting tumor endothelial cells, is an alternative method to maximum tolerated dose chemotherapy targeting proliferating tumor cells in clinical practice. However, even in the LDM schedule, cytotoxic agents still exhibit serious side effects due to non-distribution and high accumulated doses in the body. Nanocarriers can maximize the efficacy of the encapsulated drug by adjusting the pharmacokinetics and bio-distribution pattern, and minimize excessive toxic side effects. In the present study, we prepared polyethylene glycol (PEG)-coated stealth nanoparticles containing paclitaxel (PTX-NP) in order to evaluate their accumulation in tumor and their anti-tumor activity following LDM administration. PTX-NPs were prepared by a modified emulsification/solvent diffusion method with methoxy PEG–poly(lactide). The in vitro viability, migration, and tube formation of primary human umbilical vein endothelial cells, in addition to thrombospondin-1 positive expression and microvessel density in vivo, confirmed the anti-angiogenic activity of PTX-NP. The cellular uptake and retention study, in addition to pharmacokinetics in Sprague–Dawley rats demonstrated sustained circulation of PTX-NP. The in vivo tumor accumulation of PTX-NP was monitored using the Xenogen IVIS 200 non-invasive optical imaging system. The anti-tumor activity of LDM PTX-NP was studied in B16 melanoma cancer-bearing mice in vivo. In conclusion, PTX-NP improved tumor accumulation and anti-tumor efficacy following LDM administration.

Background Early detection of coagulopathy is important to prevent bleeding during liver transplantation (LT). Rotation thromboelastometry (ROTEM ® ) provides the earliest parameter of clot amplitudes at 5 min (A5). We evaluated whether A5 correlates with platelet count (PLT) and fibrinogen concentration (Fib) and can predict thrombocytopenia and hypofibrinogenaemia in hypocoagulable patients undergoing living-donor LT (LDLT). Methods A total of 3446 retrospective ROTEM ® measurements, including 1139 EXTEM, 1182 INTEM, and 1125 FIBTEM, with simultaneously measured PLT and Fib, were analysed during LDLT in 239 patients. The correlations between A5 and maximum clot firmness (MCF) index, PLT, and Fib were calculated. Receiver operating characteristic analysis with area under the curve (AUC) was used to assess A5 thresholds predictive of PLT and Fib. Results The median PLT was 47 000 mm −3 and the median Fib was 100 mg dl −1 during LDLT. The A5 parameters of EXTEM (A5 EXTEM ) and INTEM (A5 INTEM ) were highly correlated with MCF ( r =0.96 and r =0.95, respectively), PLT ( r =0.76 and r =0.77, respectively), and Fib ( r =0.63 and r =0.64, respectively). A5 of FIBTEM (A5 FIBTEM ) was also correlated with MCF ( r =0.91) and Fib ( r =0.75). A5 EXTEM thresholds of 15 and 19 mm predicted PLT −3 (AUC=0.90) and −3 (AUC=0.87), respectively, whereas A5 FIBTEM 4 mm predicted Fib −1 (AUC=0.86). Biases from A5 EXTEM and A5 FIBTEM to their MCFs were 16.4 and 1.3 mm, respectively. Conclusions A5 as an early variable of clot firmness is effective in detecting critically low PLT and Fib. A5 can therefore be a reliable fast index guiding transfusion therapy in hypocoagulable patients undergoing LDLT.

BACKGROUND The safety of healthy living donors undergoing hepatic resection for living-donor liver transplantation is of paramount concern. Although blood transfusions have been associated with morbidity and mortality after hepatectomy, there is limited information about the risk factors associated with blood transfusion in living liver donors. METHODS We retrospectively analyzed 2344 donors who underwent a hepatectomy for living-donor liver transplantation. Logistic regression analysis was performed to determine blood transfusion predictors in living-donor hepatectomy. RESULTS Of these donors, 48 (2.0%) and 97 (4.1%) were transfused with packed red blood cell (PRBC) and fresh-frozen plasma (FFP), respectively. The amount of PRBC and FFP administered to donors transfused with blood products were 1.9±0.8 and 3.7±2.5 units, respectively. In multivariate logistic regression analysis, a low preoperative hemoglobin level was found to be an independent predictor of PRBC transfusion in donor hepatectomy (odds ratio=0.585; 95% confidence interval=0.451-0.758; P

A 55-year-old man with end-stage renal disease had severe left ventricular dysfunction and a history of deep vein thrombosis. He underwent renal transplantation, during which a central venous catheter was inserted into the right jugular vein. The central venous pressure (CVP) exceeded 20 mmHg throughout the operation but there was no other adverse event. After surgery, although the left ventricular dysfunction improved, the CVP remained high. On postoperative day 10, the patient presented with cyanosis of the arms and redness of the face and was diagnosed with superior vena cava (SVC) syndrome, for which he underwent emergency thrombectomy and SVC reconstruction. The clinical course of this patient suggests that his end-stage renal disease-associated hypercoagulable state may have promoted thrombus formation. Moreover, placing the central venous catheter tip too deep may have encouraged thrombus formation. Repositioning the tip may have prevented this complication.

Background Although stroke volume variation (SVV) is a valuable index of preload responsiveness, there is limited information about the association between low SVV and increased hepatectomy-related bleeding. We therefore evaluated whether SVV predicts blood loss during living donor hepatectomy. Methods We evaluated 93 adult liver donors undergoing right hepatectomy for transplantation. Arterial blood pressure, heart rate, body temperature, central venous pressure, SVV, cardiac output, and systemic vascular resistance were measured. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to determine independent factors and optimal cutoff values of hemodynamic parameters for predicting intraoperative blood loss ≥ 700 mL. Results Of these 93 donors, 36 (38.7%) had blood loss ≥ 700 mL. Univariate logistic regression analysis showed that factors associated with blood loss ≥ 700 mL included heart rate, SVV, cardiac output, and systemic vascular resistance. Multivariate logistic regression analysis revealed that only SVV was an independent predictor of blood loss ≥ 700 mL. ROC curve analysis showed that the optimal cutoff value for SVV predicting blood loss ≥ 700 mL was 6% (area under the curve = 0.64). Conclusions SVV is a significant independent predictor of blood loss ≥ 700 mL during donor hepatectomy, suggesting that low SVV may provide useful information on intraoperative bleeding in donors undergoing right hepatectomy.

Background Stroke volume variation (SVV) is being increasingly used to predict fluid responsiveness. Since radial arterial pressure (RAP) and femoral arterial pressure (FAP) frequently showing discrepancies during liver transplantation (LT), we sought to investigate the effect of differing arterial waveforms on SVV and cardiac output (CO) derived from the Vigileo device, by comparing SVV and CO values derived from RAP (SVV RAP , CO RAP ) and FAP (SVV FAP , CO FAP ) during LT. Methods The linear associations and agreements between SVV RAP and SVV FAP and between CO RAP and CO FAP were assessed during LT. Hemodynamic variables were measured at nine predefined time points in all 32 recipients, resulting in 288 data pairs. Results Correlations were observed between SVV RAP and SVV FAP ( r = .961) and between CO RAP and CO FAP ( r = .848) at all time points. These correlations between SVV RAP and SVV FAP ( r = .923) and between CO RAP and CO FAP ( r = .902) existed even during the period when mean RAP and FAP values differed (10 minutes after reperfusion). Bland-Altman analysis for SVV RAP versus SVV FAP and for CO RAP versus CO FAP showed weak biases (−0.2% and −0.5 L/min) and reasonable limits of agreement (−2.2 to 1.8% and −1.9 to 0.9 L/min). The percentage errors for SVV and CO values were 27.0% and 22.2%. Conclusions There was no significant difference between SVV RAP and SVV FAP when measured using the Vigileo device during LT. This finding indicated that SVV obtained using the Vigileo device offered relatively consistent information regardless of the catheterization site.

Background: Although low central venous pressure (CVP) anesthesia has been used to minimize blood loss during hepatectomy, the efficacy of this technique remains controversial. We therefore assessed the association between blood loss and CVP during hepatic resection, and examined significant determinants associated with intraoperative hemorrhage during hepatectomy in living donors. Methods: Between April 2004 and April 2008, 984 living donors who underwent a hepatic resection were assessed retrospectively. Univariate and multivariate analyses were performed to explore the relationships between intraoperative blood loss and several variables including CVP. Results: The mean intraoperative blood loss was 691.3 ± 365.5 ml. Only four donors required packed red blood cell transfusions (mean, 1.5 U). The mean duration of hepatic resection was 92.1 ± 26.3 min. The mean, maximum, and minimum values of CVP measured during hepatectomy were 4.6 ± 1.7, 5.3 ± 1.8, and 4.0 ± 1.8 mmHg, respectively, and were not significantly correlated with intraoperative blood loss. On multivariate analysis, predictors of hemorrhage were liver fatty change, gender, and body weight, but none of the mean CVP, surgeons, anesthesiologists, anesthesia duration, resected liver volume, hepatectomy type, systolic blood pressure, heart rate, or body temperature were significant. Conclusions: CVP during hepatic resection was not associated with intraoperative blood loss in living liver donors, suggesting that CVP may not be an important factor in predicting blood loss during hepatectomy in healthy subjects.

Optimal fluid management to reduce blood loss during donor hepatectomy is important for maximizing donor safety. Mannitol can induce osmotic diuresis, helping prevent increased intravascular volume status. We therefore evaluated the effect of high stroke volume variation (SVV) method by mannitol administration and fluid restriction on blood loss during donor hepatectomy. In this prospective study, 64 donors scheduled for donor right hepatectomy were included and allocated into 2 groups. In group A, the SVV value of each patient was maintained at 10% to 20% during hepatic resection with 0.5 g/kg mannitol administration and fluid restriction at a rate of 2 to 4 mL/kg/h. In group B, the SVV value was maintained at

In pediatric patients, dynamic preload indices to predict fluid responsiveness have conflicting results in comparison with adults. A recent study demonstrated that pulse pressure variation (PPV) ≥16% has provided an accurate method for predicting fluid responsiveness in pediatric congenital heart surgery. We aimed to compare PPV and respiratory systolic, diastolic and pulse transit time interval variation (STV, DTV and PTTV, respectively) as predictors of fluid responsiveness during pediatric liver transplantation.

Background Chronic administration of morphine leads to the development of tolerance. We investigated the effects of intrathecal lamotrigine on the spinal morphine tolerance in rats that are undergoing tail flick tests. Methods Sprague-Dawley rats were given intrathecal injections of saline 10 microl, lamotrigine 300 microg, morphine 15 microg or lamotrigine plus morphine combinations for 7 days (lamotrigine was given for days 1-7, days 1-3 or days 5-7). The acute and chronic nociceptive sensitivities were assessed using a tail flick test in which the distal 5 cm of the tail was dipped into warm water before and 30 minutes after the drug injection. With successive injections of morphine on day 8, a cumulative antinociceptive dose-response curve was constructed and the 50% effective dose (ED50) was calculated for each study group. Results The coinjection group of lamotrigine with morphine blocked the development of tolerance, as was shown by the preservation of morphine antinociception over 7 days and the concomitant decrease in the ED50 values on day 8, as compared with the morphine-alone group. Coinjection of lamotrigine blocked the development of morphine tolerance, as shown by the preservation of morphine antinociception over 7 days and the concomitant decrease in the ED50 values on day 8, as compared with the morphine-alone group. Conclusions This study suggests that lamotrigine augments the antinociceptive action of both acute and chronic morphine therapy, and it also attenuates the antinociceptive morphine tolerance in rats.

Analgesic tolerance to opioids has been described in both experimental and clinical conditions, which may limit their clinical utility. This study investigated the effects of intrathecal adenosine A1 receptor agonist (R-PIA) on spinal morphine tolerance. Methods: SD rats were given intrathecal injections of saline 10μl, R-PIA 10μg, morphine 10μg, or R-PIA plus morphine combinations for 7 days (R-PIA given for days 1-7; days 1-3; or days 5-7). Antiallodynic testing using von Frey filaments was carried out before and 30 minutes after the drug injection. On day 8, an antiallodynic dose-response curve was constructed and the 50% effective dose (ED50) for morphine (given alone) was calculated for each study group. Results: The coinjection group of R-PIA with morphine blocked the development of tolerance, as shown by the preservation of morphine antiallodynia over 7 days the concomitant decrease in the ED50 values on day 8, compared with the morphine-alone group. Although additive analgesia over days 1-7 cannot be ruled out, the reductions of the ED50 in the R-PIA and morphine combination group suggest some suppression of tolerance. Conclusions: These results suggest that intrathecal R-PIA prevents the development of spinal opioid tolerance. Future studies will be needed to examine the respective roles of supraspinal and peripheral sites of R-PIA and morphine interaction, and to investigate the mechanisms underlying the action of R-PIA on opioid tolerance.

Lesch-Nyhan syndrome (LNS) is a rare, X-linked recessive inherited disorder caused by a deficiency of the enzyme hypoxanthine-guanine-phophoribosyltransferase, leading to excessive purine production and elevation of uric acid. Clinical manifestations include mental retardation, spasticity, choreathetosis, compulsive self-mutilation, renal calculi followed by obstructive nephropathy, and arthritis. Patient with LNS may have increased risk of aspiration pneumonia, acute renal failure and unexpected sudden death. We accomplished successful general anesthesia in a case of LNS requiring percutaneous nephrolithotomy due to