Stroke risk related to intentional discontinuation of antithrombotic therapy for invasive procedures.

OBJECTIVE: Antithrombotic medications pose a challenge for conducting surgical or invasive procedures, because their discontinuation is required to avoid postprocedural hemorrhagic complications but potentially increases the ischemic risk for the patient. This study aimed to estimate the increased risk of developing cerebral ischemic events during hospitalization requiring discontinuation of antithrombotic therapy. METHODS: This investigation was a single-center retrospective observational study. Clinical data in patients scheduled for admission between January 1, 2021, and December 31, 2022, were collected. Patients requiring discontinuation of antithrombotic therapy were identified by referring to the admission database. Patients who developed cerebral ischemia were identified by referring to the institution's stroke center database. RESULTS: Seven hundred ninety-six patients scheduled for nonneurosurgical procedures and 39 scheduled for neurosurgical procedures underwent discontinuation of antithrombotic therapy. Anticoagulation therapy was prescribed in 40.0%, and antiplatelet therapy was prescribed in 69.1% of the patients. A total of 9.2% of the entire cohort of patients were receiving both anticoagulation and antiplatelet therapy. Bridging therapy was administered in 20.9% of nonneurosurgical patients. No ischemic event was observed in the patients undergoing neurosurgical procedures. Among the entire cohort, 3 patients encountered some kind of thrombotic event-2 of which were cerebral ischemia-accounting for an incidence of 0.24%, which was significantly higher than incidental in-hospital stroke unrelated to discontinuation of antithrombotic therapy (p = 0.04). Patients undergoing both anticoagulation and antiplatelet therapy harbored a significantly higher risk for cerebral ischemia related to discontinuation of antithrombotic therapy (p < 0.0001). CONCLUSIONS: Discontinuing antithrombotic therapy during hospitalization for elective invasive procedures-including neurosurgical procedures-entailed a relatively small risk of developing cerebral ischemic events, but the risk was significantly higher compared to hospitalized patients without discontinuation of antithrombotic therapy.

Machine perfusion preservation with hemoglobin based oxygen vesicles alleviate ultrastructural damages in porcine liver donated after cardiac death.

Midthermic machine perfusion (MMP) of post-circulatory arrest donor liver grafts has the advantage of preserving the functional ultrastructure of hepatocytes in donor grafts. It was reported that oxygenation during MMP reduces portal venous resistance and increases bile production. The MMP with hemoglobin-based oxygen vesicles (HbV) keeps the lower aspartate aminotransferase level (an indicator of liver injury) and maintains the functional ultrastructure of mitochondria in the hepatocytes. To evaluated differences of ultrastructural damages in donor livers between the MMP with and without HbV, porcine liver grafts after 60 min of warm ischemia were perfused at 22°C for 4 h with or without HbV, and a part of liver grafts were analyzed by transmission electron microscopy (TEM) and osmium-maceration scanning electron microscopy (OM-SEM). The remaining grafts were perfused with autologous blood at 38°C for 2 h in an isolated liver reperfusion model (IRM) that mimics the inside of the body after transplantation, and then analyzed by TEM and OM-SEM. Hepatocytes after MMP had small round mitochondria with rod-shaped cristae and reticulovesicular rough endoplasmic reticulum (rER) in both HbV(+) and HbV(-) livers. After IRM of HbV(+) livers, the well-developed lamellar rER was often found in hepatocytes. Liver sinusoidal endothelial cells (LSECs) after MMP contained some large vacuolar structures containing amorphous garbage in the cytoplasm, and their size along with appearance frequency were smaller and lower, respectively, in HbV(+) livers than HbV(-). Oxygenation during the MMP by using HbV suppressed the ultrastructural damages in donor livers, in particular for the LSECs. RESEARCH HIGHLIGHTS: Liver sinusoidal endothelial cells after midthermic machine perfusion had large vacuolar organelles with amorphous garbage. Oxygenation during the perfusion made them less and smaller, ultrastructurally supporting its utility.

Synthesis and properties of a novel modified nucleic acid, 2'-N-methanesulfonyl-2'-amino-locked nucleic acid.

2'-Amino-locked nucleic acid has a functionalizable nitrogen atom at the 2'-position of its furanose ring that can provide desired properties to a nucleic acid as a scaffold. In this study, we synthesized a novel nucleic acid, 2'-N-methanesulfonyl-2'-amino-locked nucleic acid (ALNA[Ms]) and conducted comparative studies on the physical and pharmacological properties of the ALNA[Ms] and on conventional nucleic acids, such as 2'-methylamino-LNA (ALNA[Me]), which is a classical 2'-amino-LNA derivative, and also on 2',4'-BNA/LNA (LNA). ALNA[Ms] oligomers exhibited binding affinities for the complementary RNA strand that are similar to those of conventional nucleic acids. Four types of ALNA[Ms] nucleosides exhibited no genotoxicity in bacterial reverse mutation assays. The knockdown abilities of Malat1 RNA using the Matat1 antisense oligonucleotide (ASO) containing ALNA[Ms] were higher than those of ALNA[Me] and were closer to those of LNA. Furthermore, the ASO containing ALNA[Ms] showed different tissue tropism from that containing LNA. ALNA[Ms] exhibited biological activities that were distinct from conventional constrained nucleic acids, suggesting the possibility that ALNA[Ms] can serve as novel modified nucleic acids in oligonucleotide therapeutics.

2'-N-Alkylaminocarbonyl-2'-amino-LNA: Synthesis, duplex stability, nuclease resistance, and in vitro anti-microRNA activity.

2'-Amino-LNA has the potential to acquire various functions through chemical modification at the 2'-nitrogen atom. This study focused on 2'-N-alkylaminocarbonyl 2'-amino-LNA, which is a derivative of 2'-amino-LNA. We evaluated its practical usefulness as a chemical modification of anti-miRNA oligonucleotide. The synthesis of phosphoramidites of 2'-N-alkylaminocarbonyl substituted 2'-amino-LNA bearing thymine and 5-methylcytosine proceeded in good yields. Incorporating the 2'-N-alkylaminocarbonyl-2'-amino-LNA monomers into oligonucleotides improved the duplex stability for complementary RNA strands and robust nuclease resistance. Moreover, 2'-N-alkylaminocarbonyl-2'-amino-LNA is a promising scaffold that significantly increases the potency of anti-miRNA oligonucleotides.

Parallel synthesis of oligonucleotides containing N-acyl amino-LNA and their therapeutic effects as anti-microRNAs.

2'-Amino-locked nucleic acid (ALNA), maintains excellent duplex stability, and the nitrogen at the 2'-position is an attractive scaffold for functionalization. Herein, a facile and efficient method for the synthesis of various 2'-N-acyl amino-LNA derivatives by direct acylation of the 2'-amino moiety contained in the synthesized oligonucleotides and its fundamental properties are described. The introduction of the acylated amino-LNA enhances the potency of the molecules as therapeutic anti-microRNA oligonucleotides.

Allograft liver failure awaiting liver transplantation in Japan.

BACKGROUND: Following liver transplantation (LT), allograft liver failure can be developed by various causes and requires re-LT. Hence, this study aimed to clarify the characteristics and prognostic factors of patients with allograft liver failure awaiting deceased donor LT (DDLT) in Japan. METHODS: Of the 2686 DDLT candidates in Japan between 2007 and 2016, 192 adult patients listed for re-LT were retrospectively enrolled in this study. Factors associated with waitlist mortality were assessed using the Cox proportional hazards model. The transplant-free survival probabilities were evaluated using the Kaplan-Meier analysis and log-rank test. RESULTS: The median period from the previous LT to listing for re-LT was 1548 days (range, 4-8449 days). Primary sclerosing cholangitis (PSC), which was a primary indication, showed a higher listing probability for re-LT as compared with other primary etiologies. Recurrent liver disease was a leading cause of allograft failure and was more frequently observed in the primary indication of hepatitis C virus (HCV) infection and PSC in contrast with other etiologies. Multivariate analysis identified the following independent risk factors associated with waitlist mortality: age, Child-Turcotte-Pugh (CTP) score, mode for end-stage liver disease (MELD) score, alanine aminotransferase (ALT), and causes of allograft failure. CONCLUSIONS: Recurrent HCV and PSC were major causes of allograft liver failure in Japan. In addition to CTP and MELD scores, either serum ALT levels or causes of allograft failure should be considered as graft liver allocation measures.

No impact of donor sex on the recurrence of hepatocellular carcinoma after liver transplantation.

BACKGROUND/PURPOSE: We aimed to verify a recent theory that female donors reduced the risk of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). METHODS: A total of 1118 recipients registered in the Japanese Liver Transplantation Society database were evaluated for HCC, of whom 446 received a graft from female donors (F-D group) and 672 from male donors (M-D group). RESULTS: Between the groups, donor age, recipient age and sex, positivity of hepatitis viruses, and graft type were different, whereas tumor-related factors were all comparable. The 5-year overall recurrence rates were 14% and 16% in the F-D and M-D groups, respectively (P = 0.59). The 5-year graft recurrence rate was also comparable between the groups (4% and 6%, respectively, P = 0.17). Neither univariate nor multivariate analysis identified donor sex as a significant risk factor for recurrence. Propensity score matching showed similar 5-year overall recurrence rates (15% in the F-D group and 14% in the M-D group, P = 0.63) and graft recurrence rates (5% and 5%, respectively, P = 0.94) between the groups. CONCLUSION: Donor sex did not affect post-LT recurrence of HCC in the Japanese cohort and should not be considered in the process of donor selection or organ allocation.

Beneficial effects of end-ischemic oxygenated machine perfusion preservation for split-liver transplantation in recovering graft function and reducing ischemia-reperfusion injury.

This study examined the efficacy of end-ischemic hypothermic oxygenated machine perfusion preservation (HOPE) using an originally developed machine perfusion system for split-liver transplantation. Porcine split-liver grafts were created via 75% liver resection after 10 min of warm ischemia. In Group 1, grafts were preserved by simple cold storage (CS) for 8 h (CS group; n = 4). In Group 2, grafts were preserved by simple CS for 6 h and end-ischemic HOPE for 2 h (HOPE group; n = 5). All grafts were evaluated using an isolated ex vivo reperfusion model with autologous blood for 2 h. Biochemical markers (aspartate aminotransferase and lactate dehydrogenase levels) were significantly better immediately after reperfusion in the HOPE group than in the CS group. Furthermore, the HOPE group had a better histological score. The levels of inflammatory cytokines (tumor necrosis factor-α, interferon-γ, interleukin-1ß, and interleukin-10) were significantly lower after reperfusion in the HOPE group. Therefore, we concluded that end-ischemic HOPE for split-liver transplantation can aid in recovering the graft function and reducing ischemia-reperfusion injury. HOPE, using our originally developed machine perfusion system, is safe and can improve graft function while attenuating liver injury due to preservation.

Severe liver injury with traumatic cardiac arrest successfully treated by damage control surgery and transcatheter arterial embolization in the hybrid operating room: a case report.

BACKGROUND: The damage control approach is known to reduce the mortality rate in severely injured patients and has now become a common practice. Transcatheter arterial embolization (TAE) has been shown to be useful with combining with damage control laparotomy in identifying and controlling active arterial hemorrhage. Hybrid operating room (OR) allows both damaged control surgery and TAE in the same location in minimal time. We report a case of a patient with three cardiac arrests who was saved by early intervention using damage control surgery (DCS) with interventional radiology (IVR) in the hybrid OR. CASE PRESENTATION: A 46-year-old woman was injured in a collision with a tree while snowboarding. She was eventually transported to hybrid operating room in our hospital with the diagnosis of significant liver laceration and hemorrhagic shock. Damage control surgery was performed with perihepatic packing (PHP) and TAE was conducted to stop active bleeding from right hepatic artery. She experienced 3 times of cardiopulmonary arrest, which was successfully resuscitated on each occasion. Although she had total of 3 times of laparotomy but tolerated well. She was discharged on day 82 of hospitalization and showed no neurological sequelae. CONCLUSION: Saving the life of a patient with severe trauma requires a multidisciplinary approach with cooperation and early information sharing among trauma team members. Sharing treatment strategy with the trauma team and early intervention using DCS with IVR in the hybrid operating room could save the patient's life.

Decreased Portal Circulation Augments Fibrosis and Ductular Reaction in Nonalcoholic Fatty Liver Disease in Mice.

Nonalcoholic fatty liver disease often progresses to cirrhosis and causes liver cancer, but mechanisms of its progression are yet to be elucidated. Although nonalcoholic fatty liver disease is often associated with abnormal portal circulation, there have not been any experimental studies to test its pathogenic role. Here, whether decreased portal circulation affected the pathology of nonalcoholic steatohepatitis (NASH) was examined using congenital portosystemic shunt (PSS) in C57BL/6J mice. Whereas PSS significantly attenuated free radical-mediated carbon tetrachloride injury, it augmented pericellular fibrosis in the centrilobular area induced by a 0.1% methionine choline-deficient l-amino acid-defined high-fat diet (CDAHFD). PSS aggravated ductular reaction and increased the expression of connective tissue growth factor. Pimonidazole immunohistochemistry of the liver revealed that the centrilobular area of PSS-harboring mice was more hypoxic than that of control mice. Although tissue hypoxia was observed in the fibrotic area in CDAHFD-induced NASH in both control and PSS-harboring mice, it was more profound in the latter, which was associated with higher carbonic anhydrase 9 and vascular endothelial growth factor expression and neovascularization in the fibrotic area. Furthermore, partial ligation of the portal vein also augmented pericellular fibrosis and ductular reaction induced by a CDAHFD. These results demonstrate that decreased portal circulation, which induces hypoxia due to disrupted intralobular perfusion, is an important aggravating factor of liver fibrosis in NASH.

A comparison of laparoscopic procedures performed by novice medical students using 8K ultra-high-definition/two-dimensional and 2K high-definition/three-dimensional monitors.

PURPOSE: 8K Ultra-high-definition (UHD) imaging has been developed in accordance with the progression of imaging technologies. We evaluated laparoscopic procedures performed by novice medical students using 2K/two-dimensional (2D), 2K/three-dimensional (3D) and 8K/2D monitors, with a particular focus on depth perception. METHODS: Nine medical students were enrolled. They performed two tasks using 2K/2D, 2K/3D and 8K/2D monitors. In Task 1, they were asked to grasp three metal rods with forceps using each hand. In Task 2, they were asked to grasp a metal rod with forceps held in the right hand, pass the metal rod through a metal ring and transfer it to their left hand. RESULTS: In Task 1, when performed with the dominant hand, the procedures performed using 2K/3D took a significantly shorter time than those performed using 8K/2D (P = 0.04). However, there was no significant difference among the three groups in the time required for procedures performed by the non-dominant hand. In Task 2, the procedure time with 2K/2D was significantly longer than that with 2K/3D or 8K/2D (P = 0.02). CONCLUSION: 2K/3D showed superior utility to 8K/2D for performing forceps procedures using the dominant hand. However, when the movement of both hands was coordinated ("bi-hand coordination"), the laparoscopic procedures were performed almost as deftly with 8K/2D and 2K/3D.

Incidental intrahepatic cholangiocarcinoma in patients undergoing liver transplantation: A multi-center study in Japan.

BACKGROUND: Intrahepatic cholangiocarcinoma had been considered a contraindication for liver transplantation because of poorer outcomes. However, incidental intrahepatic cholangiocarcinoma in the explanted liver has been reported because of the difficulty of obtaining an accurate diagnosis in cirrhotic livers on preoperative imaging. METHODS: We conducted a nationwide survey to analyze the incidence of incidental intrahepatic cholangiocarcinoma and outcomes after liver transplantation, in Japan. RESULTS: Forty-five of 64 institutions (70%) responded to our initial investigation. Between January 2001 and December 2015, 6627 liver transplantations were performed in these 45 institutions, with 19 cases (0.3%) of incidental intrahepatic cholangiocarcinoma reported from 12 transplant centers. Six cases were diagnosed as hepatocellular carcinoma preoperatively. The 1-, 3-, and 5-year recurrence-free survival rates were 79%, 45%, and 45%, respectively. Tumor recurrence after liver transplantation was found in 10 patients (53%). The 1-, 3-, and 5-year overall survival rates were 79%, 63%, and 46%, respectively. CONCLUSIONS: Intrahepatic cholangiocarcinoma at liver transplantation is associated with a high risk of recurrence and poor prognosis, even these tumors are detected incidentally in the explanted liver.

A Novel Preservation Solution Containing Quercetin and Sucrose for Porcine Kidney Transplantation.

In organ transplantation, the University of Wisconsin (UW) solution has been the gold standard for organ preservation. Quercetin (Que) has numerous antioxidant and anti-inflammatory activities, and sucrose (Suc) may be effective for cold storage (CS). This study aimed to investigate the in vitro protective effect of Que and Suc on cold injury to the kidney and to determine whether Que + Suc could improve ischemia-reperfusion injury during CS and hypothermic oxygenated perfusion (HOPE) in autologous transplantation models. METHODS: BHK-21 cells were stored at 4°C for 3 days in UW solution for CS/machine perfusion (CS/MP-UW) with Que (33.1 µM, 3.3 µM, 0.33 µM) and Suc (0.1 M). In a porcine model of renal autologous transplantation, left kidney grafts were preserved under 3 conditions: group 1, CS preservation for 24 hours; group 2, CS preservation for 22 hours and HOPE with CS/MP-UW solution for 2 hours; and group 3, identical preservation as group 2, with Que and Suc added to the solution. Animals were euthanized on day 7 after autologous transplantation. RESULTS: After 3 days of CS preservation, the CS/MP-UW solution with Que (33.1 µM, 3.3 µM) and Suc showed significant cell protection against cold injury. In the porcine model of renal autologous transplantation, the last blood Cre level and the blood lipid hydroperoxide on posttransplantation day 2 were significantly different between group 1 and group 3. Moreover, the total endothelial, glomerular, tubular, interstitial (EGTI) histology score in the kidney tissue was also significantly different. Regarding the change in renal resistance in HOPE, the decrease observed in group 3 was significantly larger than that in group 2. CONCLUSIONS: Our results suggest that the addition of Que and Suc to a UW solution can improve kidney preservation and could potentially enhance the outcome of kidney transplantation.

Outcome of patients with acute liver failure awaiting liver transplantation in Japan.

AIM: To clarify the outcome and predictive factors in patients with acute liver failure (ALF) awaiting deceased donor liver transplantation (DDLT) in Japan. METHODS: Of the DDLT candidates in Japan between 2007 and 2016, 264 adult patients with ALF were retrospectively enrolled in this study. Factors associated with DDLT and waiting-list mortality were assessed using the Cox proportional hazard model. The DDLT and transplant-free survival probabilities were evaluated using Kaplan-Meier analysis and the log-rank test. RESULTS: The waiting-list registration year after the Transplant Law revision in 2010 was a significant factor associated with DDLT. The adjusted hazard ratio indicated that DDLT probability after 2010 was four times higher than that before, and the 28-day cumulative DDLT probability was more than 35%. The median survival time of the entire cohort was 40 days. Multivariate analysis identified the following three factors associated with waiting-list mortality: age, coma grade, and international normalized ratio. The transplant-free survival probabilities were significantly stratified by the number of risks, and patients with all three risks showed extremely poor short-term prognosis (median survival time = 23 days). CONCLUSIONS: The DDLT probability of ALF patients increased after the law revision in 2010; however, patients at high risk of short-term waiting-list mortality might need emergent living donor transplantation.

Rapid Detection of Microbial Contamination in Intravenous Fluids by ATP-Based Monitoring System.

In this study, we investigated four clinical cases of microbial contamination of in-use intravenous infusion fluid, detected by measuring "Adenosine triphosphate (ATP) + adenosine monophosphate (AMP)" ("ATP+AMP") levels. High "ATP+AMP" values correlate with microbial contamination, and by utilizing these values as indicator for microbial contamination possibility, we were able to rapidly detect the contamination and recommend replacement of catheters and administration sets. In three out of four cases, changing the infusion fluid led to improvement in the condition of the patients. "ATP+AMP" levels can be used to confirm microbial contamination of in-use intravenous infusion fluids, as it is fast (several minites) and convenient to measure them.

Phosphorylated vimentin as an immunotherapeutic target against metastatic colorectal cancer.

Colorectal cancer (CRC) patients with metastatic lesions have low 5-year survival rates. During metastasis, cancer cells often obtain unique characteristics such as epithelial-mesenchymal transition (EMT). Vimentin a biomarker contributes to EMT by changing cell shape and motility. Since abnormal phosphorylation is a hallmark of malignancy, targeting phosphorylated vimentin is a feasible approach for the treatment of metastatic tumors while sparing non-tumor cells. Recent evidence has revealed that both CD8 cytotoxic T lymphocytes (CTLs) and also CD4 helper T lymphocytes (HTLs) can distinguish post-translationally modified antigens from normal antigens. Here, we showed that the expression of phosphorylated vimentin was upregulated in metastatic sites of CRC. We also showed that a chemotherapeutic reagent augmented the expression of phosphorylated vimentin. The novel phosphorylated helper peptide epitopes from vimentin could elicit a sufficient T cell response. Notably, precursor lymphocytes that specifically reacted to these phosphorylated vimentin-derived peptides were detected in CRC patients. These results suggest that immunotherapy targeting phosphorylated vimentin could be promising for metastatic CRC patients.

Applicability of Hypothermic Oxygenate Machine Perfusion Preservation for Split-Liver Transplantation in a Porcine Model: An Experimental Study.

BACKGROUND Split-liver transplantation can be useful in situations of limited donor resources. However, novel preservation methods are required to help the recipient recover from severe ischemic reperfusion injury incurred due to receiving a relatively small liver graft. MATERIAL AND METHODS Our experiment was performed using porcine livers without warm ischemia time, assuming a brain-dead organ. We made porcine split-liver grafts by 75% liver resection at the back table and divided the specimens into 4 groups. Group 1 was preserved with simple cold storage after splitting (CS; n=3), Group 2 was preserved with hypothermic perfusion preservation (HMP) after splitting (SBP; n=3), Group 3 was preserved with HMP after splitting under perfusion preservation (SDP; n=4), and Group 4 had the whole liver perfused as control grafts (Whole Liver; n=3). To assess potential methods of preservation and their effects, all grafts were evaluated by an ex vivo isolated liver reperfusion model using diluted autologous blood. RESULTS Portal vein pressure resistances during reperfusion were low in Group3 (SDP). Hepatic artery pressure resistances during reperfusion were markedly higher in Group 1(CS) than in the other groups. The levels of AST and LDH were high and increased at 2 h after reperfusion in Group 1 (CS). The histological findings show that the liver cell structure was irregular in Group 1 (CS) but remained regular in Groups 2 (SBP) and 3 (SDP). Histological Suzuki scores were also significantly better in Groups 2 (SBP) and 3 (SDP) compared with Group 1 (CS). CONCLUSIONS Splitting the liver under machine perfusion preservation may help restore the function and reduce ischemia-reperfusion injury.

Successful hepatic resection for recurrent hepatocellular carcinoma after lenvatinib treatment: A case report.

BACKGROUND: Lenvatinib has been shown to be noninferior to sorafenib regarding prognosis and recurrence rate in patients with unresectable hepatocellular carcinoma (HCC) who have not received prior systemic chemotherapy. In patients treated with lenvatinib, 40% of cases achieved sufficient tumor reduction to make potential surgery possible. However, the outcomes of such surgery are unknown. We report a successful case of hepatic resection for recurrent HCC after lenvatinib treatment. CASE SUMMARY: A 69-year-old man underwent right anterior sectionectomy for HCC in segment 8 of the liver. Ten months later, he was found to have an intrahepatic HCC recurrence that grew rapidly to 10 cm in diameter with sternal bone metastases. After confirming partial response to lenvatinib administration for 2 mo, a second hepatectomy was performed. Pathological examination showed that 80% of the tumor was necrotic. The patient did not develop any adverse effects under lenvatinib treatment. He was discharged at 25 d after surgery. Radiation therapy for bone metastases continued to be given under lenvatinib, and the patient has remained alive for 1 year after the second hepatectomy. CONCLUSION: The prognosis of patients with recurrent HCC may be improved by liver resection combined with prior lenvatinib therapy.

Initial perfusate purification during subnormothermic machine perfusion for porcine liver donated after cardiac death.

Improvement of machine perfusion (MP) technologies is required to enhance organ quality for donor after cardiac death (DCD) grafts. Installing a dialyzer or a filter into the perfusion circuit to maintain the perfusate condition has some advantages. However, the consequences of purification perfusate during subnormothermic machine perfusion (SNMP) remain unexplained. In this study, the effects of initial purification perfusate with simple method of replacing the first 0.5-L perfusate during SNMP were investigated to consider installation effect of the filter or the dialyzer. Porcine liver grafts, which have 60-min warm ischemia time, were procured to imitate the DCD graft condition. Purified SNMP (PSNMP) results were compared with simple cold storage and conventional SNMP. In PSNMP, initial perfusate of 0.5 L was removed to substitute for purification. After preservation process, the preserved grafts were reperfused with diluted autologous blood for 2 h under normothermic machine perfusion condition to evaluate the liver function using an isolated reperfusion model. The vascular pressures, enzyme release rates and the metabolic indexes during reperfusion were analyzed. The pressures in the hepatic artery after reperfusion 60 min were significantly lower in PSNMP group compared with cold storage (CS) and SNMP groups. In addition, lactate dehydrogenase and alkaline phosphatase were significantly lower after PSNMP than after the CS or SNMP. Also, the metabolic indexes of hyaluronic acid and lactate were significantly decreased by purifying the perfusate in MP preservation than in CS or SNMP. The effectiveness of initial purification perfusate during SNMP was investigated.

A Multicenter Japanese Survey Assessing the Long-term Outcomes of Liver Retransplantation Using Living Donor Grafts.

BACKGROUND: Liver transplantation is the most suitable treatment option available for end-stage liver disease. However, some patients require retransplantation, despite medical advances that have led to improved survival. We aimed to compile a definitive, nationwide resource of liver retransplantation data in Japan, seeking to identify the predictors of patient survival posttransplantation. METHODS: Questionnaires were sent to 32 institutions that had conducted 281 retransplantations before 2015. RESULTS: Among the 265 patients included in this study (142 pediatric cases), the average age at primary transplantation was 23 years, and retransplantation was performed after an average of 1468 days. The main indication for retransplantation was graft rejection (95 patients). Living-donor liver transplantation accounted for 94.7% of primary transplantations and 73.2% of retransplantations. Patient survival at 1, 3, or 5 years did not differ by type of transplantation but was better for pediatric (70.8%, 68.3%, and 60.1%, respectively) than for adult (57.2%, 50.4%, and 45.2%, respectively) recipients (P = 0.0003). Small-for-size syndrome, retransplantation within 365 days, and inpatient status at retransplantation were significant predictors of poor survival in pediatric cases. Retransplantation within 365 days and conditions warranting retransplantation were significant predictors of poor survival in adult patients. CONCLUSIONS: In Japan, where >70% of retransplantations are performed using living donors, the indications and timing are different from those in previous reports from other countries, while maintaining comparable survival rates. Considering technical challenges, graft failure within 365 days should be thoroughly restricted to justify the use of living donor.