Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND The management and fate of liver transplant (LT) recipients with preformed donor-specific antibodies (pDSA) remain controversial. The aim of this study was to evaluate the clinical impact of rituximab desensitization on pDSA in LT recipients. MATERIAL AND METHODS This retrospective observational study enrolled 120 LT patients aged ≥18 years. Patients with pDSA were administered 500 mg/body rituximab 1-21 days before LT, except for those who had an active infection or had insufficient time to receive rituximab. We allocated patients to groups with or without pDSA, and then divided patients with pDSA into rituximab (+) and rituximab (-) groups for further analysis. RESULTS Twenty-three patients (19.2%) with pDSA were identified. Of these, 18 received rituximab and 5 did not receive rituximab. No patients developed adverse events related to rituximab. In both groups, the levels of pDSA class I in all patients were decreased immediately after LT, whereas those of pDSA class II decreased slowly. There were no significant differences in pathology findings and overall survival between patients with pDSA who were rituximab (+) or rituximab (-), and between patients with or without pDSA. CONCLUSIONS Rituximab desensitization for LT patients with pDSA was managed successfully without significant complications. Due to the small sample size, we could not demonstrate the benefit of rituximab desensitization for LT patients compared with the rituximab (-) group. Additionally, clinical outcomes in patients with pDSA, with or without rituximab, were similar to those without pDSA. Rituximab desensitization might be not essential for LT.

DOI： 10.12659/AOT.941456

Open Access

Scopus

PubMed

Language：English   Publisher：Medicine (United States)  

Rationale: The purpose of this case report is to describe a case of successful early rehabilitation intervention for simultaneous liver and kidney transplantation (SLKT). Patient concerns: A 51-year-old Japanese man was diagnosed with Caroli disease 27 years ago. Hemodialysis was introduced due to end-stage renal disease 17 years ago. Diagnoses: After successful SLKT, the patient was extubated on postoperative day (POD) 1, liberated from dialysis on POD 4, and discharged from the intensive care unit on POD 9. Interventions: Supervised rehabilitation was started on POD 2, and the patient was able to walk 100 m on POD 9. Electrical muscle stimulation therapy was started to improve muscle weakness in both legs on POD 16, and aerobic exercise using a cycle-ergometer was started on POD 24. Outcomes: The 6-minute walking distance improved from 324 m on POD 14 to 501 m on POD 28. The patient could walk 4000 to 5000 steps per day at hospital discharge, and was discharged home on POD 32. There were no adverse events, including worsening hepatic or renal function, during the rehabilitation period. One month after discharge, the patient was able to perform 30 to 40 minutes of aerobic exercise every day, and returned to work 5 months after discharge. Lessons: This case shows that early rehabilitation intervention immediately after SLKT safely and rapidly improved physical performance without adverse events. The results in the present case suggest that regular physical assessment and appropriate interventions with a variety of exercise modalities can contribute to improved physical performance in SLKT patients.

DOI： 10.1097/MD.0000000000035324

Open Access

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Neuroblastoma is the most common extracranial solid tumor in childhood. Stage 4S neuroblastoma is a unique subset of neuroblastoma characterized by a favorable course and potentially low malignancy with a high rate of spontaneous tumor regression. However, recent reports have shown that there is a subgroup of patients with stage 4S neuroblastoma characterized by MYCN amplification, chromosomal aberrations, age of < 2 months at diagnosis, and significantly poorer outcomes. CASE PRESENTATION: A 1-month-old male infant with a huge abdominal tumor was transferred to our hospital and diagnosed with stage 4S neuroblastoma. The patient showed respiratory distress due to abdominal compartment syndrome secondary to massive hepatic invasion, and he required a silo operation and mechanical ventilation. After chemotherapy using carboplatin and etoposide, the infiltrative massive hepatic invasion was resolved and the abdominal compartment syndrome gradually improved; however, liver dysfunction as evidenced by hyperbilirubinemia, coagulopathy, and hyperammonemia continued. At the age of 3 months, living-donor liver transplantation was performed for treatment of sustained liver failure using a reduced lateral segment graft from the patient's father. Post-transplant liver function recovered immediately. Examination of the explanted liver demonstrated that the majority of liver tissue had been replaced by fibroblastic cells after massive hepatocyte dropout. There were only small areas of residual neuroblastoma cells in the liver specimen. The patient was discharged from the hospital 5 months after transplantation with home intermittent respiratory support. At the time of this writing (23 months after liver transplantation), he was in good condition with no signs of recurrence of neuroblastoma. CONCLUSIONS: We have herein presented a case of successful pediatric living-donor liver transplantation for sustained liver failure even after resolution of infiltrative massive hepatic invasion of stage 4S neuroblastoma. Our case clearly shows that liver transplantation can be added as an appropriate extended treatment option for liver failure after resolution of stage 4S neuroblastoma.

DOI： 10.1186/s40792-023-01681-0

PubMed

Publisher：金原出版  

DOI： 10.18888/op.0000003117

CiNii Research

Language：English   Publisher：The Pharmaceutical Society of Japan  

<p>Lenvatinib has been approved for treating various cancers; however, it exerts numerous adverse effects. Hochuekkito, a Japanese Kampo medicine, can alleviate these adverse effects. Here, we aimed to evaluate the effect of Hochuekkito on lenvatinib-induced chronic fatigue in a murine model. BALB/C mice were fed a control diet or a diet supplemented with 1.5% Hochuekkito for six weeks. On days 15–42, the mice were intraperitoneally injected with dimethyl sulfoxide or lenvatinib. Accordingly, the mice were divided into control/dimethyl sulfoxide, control/lenvatinib, 1.5% Hochuekkito/dimethyl sulfoxide, and 1.5% Hochuekkito/lenvatinib groups. Body weight and food intake were recorded daily. Nesting tests were performed once a week, and the serum interleukin-6 (IL-6) concentration was measured. Liver drug-metabolizing enzyme, CYP3A4, breast cancer resistance protein (BCRP), and P-glycoprotein (P-gp) levels were determined. The serum lenvatinib concentration and CYP3A4, BCRP, and P-gp levels did not differ significantly between the control/lenvatinib and 1.5% Hochuekkito/lenvatinib groups. The usage rate of nesting material on day 42 was higher in the 1.5% Hochuekkito/lenvatinib group than in the control/lenvatinib group (p < 0.05). The serum IL-6 level was lower in the control/dimethyl sulfoxide and 1.5% Hochuekkito/lenvatinib groups than in the control/lenvatinib group (p < 0.05). Overall, Hochuekkito may alleviate lenvatinib-induced fatigue through IL-6 inhibition.</p>

DOI： 10.1248/bpbreports.6.1_1

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

AIM: This study evaluated the relationship between the relative dose intensity (RDI) and the prognosis to assess the optimal duration of adjuvant chemotherapy for pancreatic cancer. PATIENTS AND METHODS: From 2013 to 2018, 119 patients with pancreatic cancer underwent radical surgery. After excluding five patients who underwent R2 resection, three with stage IV disease, and two with adjuvant chemotherapy other than S-1, 109 cases were evaluated. They were classified into four groups based on the RDI for the total dosage of S-1: group 1: <50%, group 2: 50% to <80%, group 3: 80% to ≤125%, and group 4: >125%. RESULTS: The number of patients in each group were 48, 20, 30 and 11, with median ages of 74, 73, 66 and 74, respectively. Median estimated glomerular filtration rate was 75, 72, 89 and 77 ml/min/1.73 m2, respectively, demonstrating statistically significant differences. The corresponding median and 5-year overall survival rates were: 378 days and 17.9%; 1,011 days and 35.1%; 1,246 days and 41.6%; 1,389 days and 10.6%. Using group 1 as a reference, the adjusted hazard ratio was 0.39 for group 2, 0.36 for group 3, and 0.30 for group 4; all were statistically significant. CONCLUSION: The higher the RDI of S-1 in adjuvant chemotherapy, the better the overall survival. Therefore, 1 year of adjuvant chemotherapy with S-1 in pancreatic cancer may be preferable to 6 months.

DOI： 10.21873/cdp.10258

Scopus

PubMed

Language：English  

DOI： 10.1016/j.surg.2022.02.010

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: This study assessed the significance of measuring liver stiffness using virtual touch quantification before hepatectomy to predict posthepatectomy refractory ascites. METHODS: A total of 267 patients with hepatocellular carcinoma who underwent hepatectomy were prospectively analyzed. Liver stiffness was defined as the median value of the virtual touch quantification (Vs; m/s) by acoustic radio-force-impulse-based virtual touch. RESULTS: A multivariate analysis showed that Vs and the aspartate aminotransferase-to-platelet ratio index were independent risk factors for postoperative refractory ascites (odds ratio = 3.27 and 3.08, respectively). The cutoff value for Vs was 1.52 m/s (sensitivity: 59.5%, specificity: 88.6%) as determined by the analysis of the receiver-operating characteristic curve, and the area under the receiver-operating characteristic curve was 0.79. The cutoff value for the aspartate aminotransferase-to-platelet ratio was 0.952 (sensitivity: 65.5%, specificity: 82.9%), and the area under the receiver-operating characteristic curve was 0.75. CONCLUSIONS: Vs is an independent risk factor for refractory ascites after hepatectomy. The measurement of liver stiffness by virtual touch quantification before hepatectomy can help estimate the risk of postoperative refractory ascites. Nonsurgical treatments should be considered for the management of patients who are at high risk for refractory ascites.

DOI： 10.1007/s00595-021-02392-5

PubMed

Language：Japanese   Publisher：(株)アークメディア  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Informa UK Limited  

The success of islet transplantation in both basic research and clinical settings has proven that cell therapy has the potential to cure diabetes. Islets intended for transplantation are inevitably subjected to damage from a number of sources, including ischemic injury during removal and delivery of the donor pancreas, enzymatic digestion during islet isolation, and reperfusion injury after transplantation in the recipient. Here, we found that protein factors secreted by porcine adipose-tissue mesenchymal stem cells (AT-MSCs) were capable of activating preserved porcine islets. A conditioned medium was prepared from the supernatant obtained by culturing porcine AT-MSCs for 2 days in serum-free medium. Islets were preserved at 4°C in University of Wisconsin solution during transportation and then incubated at 37°C in RPMI-1620 medium with fractions of various molecular weights prepared from the conditioned medium. After treatment with certain fractions of the AT-MSC secretions, the intracellular ATP levels of the activated islets had increased to over 160% of their initial values after 4 days of incubation. Our novel system may be able to restore the condition of isolated islets after transportation or preservation and may help to improve the long-term outcome of islet transplantation.Abbreviations: AT-MSC, adipose-tissue mesenchymal stem cell; Cas-3, caspase-3; DAPI, 4,6-diamidino-2-phenylindole; DTZ, dithizone; ES cell, embryonic stem cell; FITC, fluorescein isothiocyanate; IEQ, islet equivalent; INS, insulin; iPS cell, induced pluripotent stem cell; Luc-Tg rat, luciferase-transgenic rat; PCNA, proliferating cell nuclear antigen; PDX1, pancreatic and duodenal homeobox protein-1; UW, University of Wisconsin; ZO1, zona occludens 1.

DOI： 10.1080/19382014.2021.2022423

PubMed

Language：Japanese   Publisher：金原出版(株)  

Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J00620&link_issn=&doc_id=20220114040014&doc_link_id=10.18888%2Fop.0000002583&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fop.0000002583&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

<title>Abstract</title>Polyamines are important to the survival and activation of organs and tissues via a homeostatic cell-metabolic process, and the polyamine content in cytoplasm decreases with aging. Decreases in cellular polyamine have been known to augment mutagenesis and cell death. Thus, supplementary polyamine in food is important to the prevention of aging. Here we show the anti-aging effects of oral intake of polyamine using luciferase-transgenic rats. Healthy rats, 10–12 weeks old, were given foods containing 0.01% and 0.1% (w/w) of polyamine, as compared a control food without polyamine, for 4 weeks. Using a bioimaging system, the photon intensities seen in the whole bodies and livers of rats consuming 0.1% of polyamine in food were stronger than those in rats consuming 0.01% and 0% of polyamine. However, there were no differences between groups in other characteristics, such as liver damage and body weight. In conclusion, we found that polyamine intake can activate cells throughout the whole body, providing an anti-aging effect.

DOI： 10.1007/s00726-021-03079-4

PubMed

Other Link： https://link.springer.com/article/10.1007/s00726-021-03079-4/fulltext.html

Publisher：(株)東京医学社  

DOI： 10.24479/j00645.2021229962

Language：Japanese   Publisher：(株)南江堂  

＜文献概要＞切除不能大腸癌肝転移に対して化学療法を行い,腫瘍の縮小により肝切除を可能とすることをconversion療法と呼ぶ.技術的切除不能肝転移に対する前向き臨床試験でのconversion率は23～77%である.Conversion肝切除が行われた症例の予後は,非切除例と比較して有意に良好であることから,肝外転移のない,もしくはコントロールされている症例においてはconversion肝切除を行うことが治療の第一目標である.Conversion肝切除後の再発率は高率であるが,再発巣の切除を繰り返すことで長期生存が得られる.

Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J00393&link_issn=&doc_id=20210618060007&doc_link_id=issn%3D0016-593X%26volume%3D83%26issue%3D6%26spage%3D686&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0016-593X%26volume%3D83%26issue%3D6%26spage%3D686&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

Language：Japanese   Publisher：金原出版(株)  

Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J00620&link_issn=&doc_id=20210311060003&doc_link_id=10.18888%2Fop.0000002092&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fop.0000002092&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

DOI： 10.11477/mf.1407213186

CiNii Books

Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I030715379

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The purpose of this study was to examine the impact of pretreatments on outcomes after living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC). METHODS: From February 1999 to March 2015, 223 patients underwent LDLT for HCC. Until December 2006, there was no restriction in patient selection criteria regarding the number and size of tumors, following which we implemented the Kyoto criteria (tumor number ≤10, maximal diameter ≤5 cm, and des-gamma-carboxy prothrombin ≤400 mAU/ml) since January 2007. RESULTS: Of 223 patients, 156 had a history of pretreatments. Among 101 patients meeting the Milan criteria at the initial diagnosis, 38 progressed to beyond the criteria at liver transplantation (LT). Twenty-two out of 38 met the Kyoto criteria, and their survival and recurrence rates were significantly better than those of patients exceeding the Kyoto criteria (P = 0.004 and 0.035, respectively). Regarding the number of pretreatments (0 vs. 1-4 vs. ≥5), recurrence rate was significantly higher in the ≥5 pretreatments group than the 0 group. However, for patients meeting the Kyoto criteria, there were no significant differences in recurrence rates between these three groups. CONCLUSION: Better outcomes will be achieved by performing LT for HCCs meeting the Kyoto criteria even after repeated pretreatments.

DOI： 10.1002/jhbp.602

Web of Science

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: It was demonstrated that polyamines ameliorate ischemia-reperfusion injury (IRI) and promote regeneration in the liver. An optimal protocol of polyamine treatment remains unknown in the clinical setting. We examined 2 types of administration methods using rat models. METHODS: Experiment 1: evaluation of pharmacokinetics of polyamines. Experiment 2: for 3 days preoperatively and 5 days postoperatively, polyamines were given to male Lewis rats in the following three groups: the control group, no polyamine administration; the chow group, 0.05% polyamines mixed in chow; the bolus group, polyamines (200 μmol/kg) given by gastric tube once a day. All rats received 70% hepatectomy after 40 min of warm IRI. Postoperatively, IRI and regeneration were evaluated with assessment of serum levels of hepatic enzymes, histology and immunohistochemistry of liver tissue, and measurement of remnant liver weight. RESULTS: The blood concentrations of polyamines in the portal vein increased at 1 h of bolus administration, while they did not increase without the bolus. The bolus group was significantly associated with lower serum levels of aspartate/alanine aminotransferases (p < 0.05), decreased hepatocyte congestion, vacuolization and necrosis in histopathological scoring (p < 0.05), a lower number of TUNEL-positive hepatocytes (p < 0.05), higher remnant liver weight at 24, 48, and 168 h (p < 0.05), and a higher Ki-67 labeling index (24 h, p < 0.01) compared with the chow group. CONCLUSION: The bolus administration of polyamines was more effective in ameliorating IRI and promoting regeneration than chow administration. Perioperative bolus administration of polyamines might be an optimal treatment, when clinically applied.

DOI： 10.1159/000497434

Web of Science

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Accurate preoperative estimation of graft weight is essential for improving outcomes in living donor liver transplantation. METHODS: This retrospective study sought to identify factors associated with graft weight overestimation. From April 2006 to August 2015, 340 living donors were assigned to no-overestimate (n = 284) or overestimate (n = 56) groups. We defined graft weight overestimation as a discrepancy ≥15% between estimated graft volume and actual graft weight. Donor data were compared, and associated factors for graft weight overestimation were analyzed. Recipient outcomes were compared between the groups according to identified factors. RESULTS: Donors were significantly younger in the overestimate group than in the no-overestimate group (35.0 vs. 46.0 years; p < 0.001). Multivariate analysis identified donor age <45 years as an independent risk factor for graft weight overestimation (odds ratio 2.068; 95% confidence interval 1.114-3.839; p = 0.021). Among recipients with donors <45 years (n = 168), incidence of small-for-size dysfunction (SFSD) was significantly higher in the overestimate group than in the no-overestimate group (7/37 patients vs. 7/131 patients; p = 0.016); no significant difference was observed among recipients with donors ≥45 years (n = 172). First-year mortality was lower in SFSD recipients with donors <45 years (14.3 vs. 60.9%, p = 0.007). Among recipients with younger donors, graft survival was not significantly different between overestimate and no-overestimate groups. CONCLUSIONS: Younger donor age was an independent risk factor for graft weight overestimation leading to SFSD in recipients, but did not impair graft survival.

DOI： 10.1007/s00268-017-4140-2

Web of Science

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Although minimally invasive living donor surgery has been increasingly accepted, its safety remains to be fully clarified in a large-scale study. This study evaluated the safety and effectiveness of our laparoscopy-assisted hybrid living donor surgery (LAHDS) procedure with an upper median incision in comparison with conventional open donor hepatectomy (ODH). METHODS: From 2011 to 2016, 153 adult living donors [right lobe (RL) graft: 80 donors; left lobe (LL) graft: 73 donors] were enrolled and divided into LAHDS (n = 76) and ODH (n = 77) groups. Donor characteristics, surgical outcomes, and postoperative complications were compared between the 2 groups in each graft subgroup. Postoperative liver function tests (LFTs), inflammatory markers, pain parameters, incision-related symptoms, and recipient outcomes were compared between the 2 groups in all donors. RESULTS: In RL donors, operative blood loss was significantly lower in the LAHDS group than in the ODH group (201 vs. 313 g; p = 0.034). In LL donors, duration of surgery was significantly longer in the LAHDS group than in the ODH group (459 vs. 403 min; p = 0.034). The incidence of complications, length of hospital stay, and postoperative changes in both LFTs and inflammatory markers were comparable. The incidence of postoperative scar discomfort or tightness was significantly lower in the LAHDS group than in the ODH group (2.6 vs. 31.2%; p < 0.001), whereas postoperative pain parameters were comparable. The incidence of wound problems and abdominal wall numbness tended to be lower, but not significantly so, in the LAHDS group. CONCLUSIONS: This large consecutive case series demonstrates that our LAHDS procedure can be performed as safely as ODH, and it can improve quality of life without impaired donor and recipient outcomes.

DOI： 10.1007/s00464-017-5575-0

Web of Science

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

The outcomes of liver transplantation (LT) from donation after cardiac death (DCD) donors remain poor due to severe warm ischemia injury. Perfluorocarbon (PFC) is a novel compound with high oxygen carrying capacity. In the present study, a rat model simulating DCD LT was used, and the impact of improved graft oxygenation provided by PFC addition on liver ischemia/reperfusion injury (IRI) and survival after DCD LT was investigated. Orthotopic liver transplants were performed in male Lewis rats, using DCD liver grafts preserved with cold University of Wisconsin (UW) solution in the control group and preserved with cold oxygenated UW solution with addition of 20% PFC in the PFC group. For experiment I, in a 30-minute donor warm ischemia model, postoperative graft injury was analyzed at 3 and 6 hours after transplantation. For experiment II, in a 50-minute donor warm ischemia model, the postoperative survival was assessed. For experiment I, the levels of serum aspartate aminotransferase, alanine aminotransferase, hyaluronic acid, malondialdehyde, and several inflammatory cytokines were significantly lower in the PFC group. The hepatic expression levels of tumor necrosis factor α and interleukin 6 were significantly lower, and the expression level of heme oxygenase 1 was significantly higher in the PFC group. Histological analysis showed significantly less necrosis and apoptosis in the PFC group. Sinusoidal endothelial cells and microvilli of the bile canaliculi were well preserved in the PFC group. For experiment II, the postoperative survival rate was significantly improved in the PFC group. In conclusion, graft preservation with PFC attenuated liver IRI and improved postoperative survival. This graft preservation protocol might be a new therapeutic option to improve the outcomes of DCD LT. Liver Transplantation 23 1171-1185 2017 AASLD.

DOI： 10.1002/lt.24806

Web of Science

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

AIM: Liver transplantation is the only curative treatment for hepatorenal syndrome (HRS); however, the influence of HRS on the patient and renal outcome after living donor liver transplantation (LDLT) is still unclear. The aim of the present study was to evaluate the influence of HRS on the outcome of LDLT. METHODS: We retrospectively analyzed 357 consecutive adult patients who underwent primary LDLT between January 2005 and March 2013 at Kyoto University Hospital. The outcome of the patients with HRS was compared with those without HRS. RESULTS: A total of 29 patients (8%) were diagnosed as HRS (Group-HRS) preoperatively, and the other 328 patients (92%) were not diagnosed as HRS (Group-Non-HRS). Group-HRS showed a significantly lower preoperative estimated glomerular filtration rate (22.1 vs 78.3 mL/min/1.73m2 , P < 0.001) and higher Child-Pugh-Turcotte score (13 vs 10, P < 0.001) than Group-non-HRS. After a median follow up of 60 months, the 1-, 3- and 5-year recipients' survival were 60.7%, 57.1% and 57.1% in Group-HRS, and 83.7%, 79.4% and 76.2% in Group-Non-HRS, respectively (P = 0.030). Concomitant HRS significantly elongated postoperative hospital stays (75 vs 50 days, P = 0.003), as well as predisposed patients to higher in-hospital mortality (41% vs 18%, P = 0.005). Multivariate analysis showed that preoperative renal dysfunction (estimated glomerular filtration rate on admission <40 mL/min/1.73m2 , OR 2.106, P = 0.03) was an independent risk factor for 1-year recipients' survival after LDLT, in addition to donor age ≥38 years (OR 3.114, P < 0.001), Child-Pugh-Turcotte score ≥13 (OR 2.929, P < 0.001) and left lobe graft (OR 2.225, P = 0.004). CONCLUSION: Coincidence of HRS is associated with significantly worse outcome after LDLT, especially in the early post-transplant period.

DOI： 10.1111/hepr.12764

Web of Science

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Decrease in skeletal muscle mass and function, known as sarcopenia, is associated with poor prognosis. Visceral fat accumulation also is related to mortality. This study investigated the impact of preoperative skeletal muscle mass, muscle quality, and visceral adiposity on outcomes in patients undergoing resection of intrahepatic cholangiocarcinoma (ICC). METHODS: A retrospective analysis was performed of 109 patients undergoing resections of ICC between January 2004 and April 2015. Skeletal muscle mass [skeletal muscle index (SMI)], skeletal muscle quality [muscle attenuation (MA)], and visceral adiposity [visceral to subcutaneous adipose tissue area ratio (VSR)] were measured on preoperative computed tomography images. The impacts of these parameters on outcomes after ICC resections were analyzed. RESULTS: The overall survival rates were significantly lower in patients with low SMI (P = 0.002), low MA (P = 0.032), and high VSR (P = 0.026) compared with patients with high SMI, high MA, and low VSR, respectively. With multivariate analyses, in patients with stage I-III, low SMI (hazard ratio (HR) 3.29, P = 0.003) and low MA (HR 2.86, P = 0.010) were revealed as independent significant risk factors for mortality. In patients with stage IV, none of these parameters was identified as risk factors, with only the absence of adjuvant chemotherapy identified as an independent risk factor for mortality (HR 5.92, P = 0.001). CONCLUSIONS: Although stage was the most important factor, low skeletal muscle mass and quality were closely related to mortality after resection of ICC in patients with stage I-III.

DOI： 10.1245/s10434-016-5668-3

Web of Science

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

The role of liver transplantation (LT) in acute liver failure (ALF) complicated by severe acute pancreatitis is still unclear. We here report a case of deceased-donor LT for idiopathic ALF accompanied by severe acute pancreatitis. A 58-year-old man with no history of liver disease presented with idiopathic ALF and acute pancreatitis. After careful consideration, he received a liver from a deceased donor. Following surgery, the patient's liver function rapidly reverted to normal level and the acute pancreatitis simultaneously subsided. The patient later developed a pancreatic pseudocyst, which was treated successfully with combination interventional radiology. LT can be considered for ALF associated with severe acute pancreatitis if there is no clinical evidence of an absolute contraindication for organ transplantation, such as systemic or local infection. Moreover, we recommend a close follow-up by ultrasonography to allow early detection and treatment of pancreatic pseudocysts following surgery.

DOI： 10.1136/bcr-2016-215959

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Polyamines are essential for cell growth and differentiation. They play important roles in protection from liver damage and promotion of liver regeneration. However, little is known about the effect of oral exogenous polyamine administration on liver damage and regeneration. This study investigated the impact of polyamines (spermidine and spermine) on ischemia/reperfusion injury (IRI) and liver regeneration. We used a rat model in which a 70% hepatectomy after 40 minutes of ischemia was performed to mimic the clinical condition of living donor partial liver transplantation (LT). Male Lewis rats were separated into 2 groups: a polyamine group given polyamines before and after operation as treatment and a vehicle group given distilled water as placebo. The levels of serum aspartate aminotransferase and alanine aminotransferase at 6, 24, and 48 hours after reperfusion were significantly lower in the polyamine group compared with those in the vehicle group. Polyamine treatment reduced the expression of several proinflammatory cytokines and chemokines at 6 hours after reperfusion. Histological analysis showed significantly less necrosis and apoptosis in the polyamine group at 6 hours after reperfusion. Sinusoidal endothelial cells were also well preserved in the polyamine group. In addition, the regeneration of the remnant liver at 24, 48, and 168 hours after reperfusion was significantly accelerated, and the Ki-67 labeling index and the expressions of proliferating cell nuclear antigen and phosphorylated retinoblastoma protein at 24 hours after reperfusion were significantly higher in the polyamine group compared with those in the vehicle group. In conclusion, perioperative oral polyamine administration attenuates liver IRI and promotes liver regeneration. It might be a new therapeutic option to improve the outcomes of partial LT. Liver Transplantation 22 1231-1244 2016 AASLD.

DOI： 10.1002/lt.24471

Web of Science

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Skeletal muscle depletion, referred to as sarcopenia, has been shown to be an independent predictor of lower disease-free and overall survivals in various kinds of diseases. The quality of skeletal muscle has recently attracted much attention as a new parameter of sarcopenia, but its impact on surgical complications is still unknown. METHODS: A retrospective analysis of 492 patients undergoing hepatectomy for hepatocellular carcinoma (HCC) in our institution between April 2005 and December 2014 was performed. The quality of skeletal muscle was evaluated by intramuscular adipose tissue content (IMAC) using preoperative CT imaging at the umbilical level. The impact of sarcopenia on postoperative complications and the predictors of surgical complications after hepatectomy for HCC were analyzed. RESULTS: Patients with high IMAC were older and had higher body mass index, higher indocyanine green retention test at 15 min, and more operative blood loss. Among 492 patients, 108 (22 %) patients had major postoperative complications (Clavien grade ≥ III), and infectious complications were found in 74 (15 %) patients. Twelve (2 %) patients died from postoperative complications. On multivariate analysis, preoperative high IMAC was an independent risk factor for increased major postoperative complications [odds ratio (OR) 1.580; P = 0.049] and infectious complications (OR 1.903; P = 0.021). CONCLUSIONS: Preoperative muscle steatosis evaluated with IMAC was closely correlated with increased postoperative complications, especially infectious complications. The preoperative nutritional intervention and rehabilitation might lead to the improvement of postoperative outcomes after hepatectomy for HCC.

DOI： 10.1007/s00268-016-3504-3

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AIM: The FIB-4 index has been proposed as a simple, non-invasive surrogate marker of liver fibrosis in patients with hepatitis C virus (HCV). However, the utility of FIB-4 in HCV positive patients after living donor liver transplantation (LDLT) has not been assessed. The aim of this study was to evaluate the efficacy of FIB-4 in the detection of significant liver graft fibrosis caused by recurrent HCV infection after LDLT compared with other simple fibrosis markers. METHODS: A total of 259 liver biopsies (LB) with evidence of recurrent HCV were taken from 110 HCV positive LDLT patients who had undergone concomitant splenectomy before administration of antiviral therapy. In LB performed at 3 months or later after LT (n = 202, subject group), FIB-4 was compared between fibrosis stages and the accuracy of FIB-4 in predicting significant fibrosis (METAVIR, F ≥ 2) was assessed compared with aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio, age-platelet index, and AST to platelet ratio index (APRI). RESULTS: FIB-4 was significantly different between all fibrosis stages (F0 and F1-F4, P = 0.022; F0/1 and F2-F4, P < 0.0005; and F0-F2 and F3F4, P = 0.034) and provided the best area under the receiver-operator curve (AUROC) compared with other markers (FIB-4, 0.711; APRI, 0.693; age-platelet index, 0.663; and AST to ALT ratio, 0.562). The optimal cut-off value to identify significant fibrosis was 2.20 with 65% sensitivity and 69% specificity. CONCLUSION: FIB-4 is a more reliable marker for diagnosing significant liver fibrosis than APRI, age-platelet index, and AST to ALT ratio in LDLT patients with HCV.

DOI： 10.1111/hepr.12617

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

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BACKGROUND: Smaller size grafts for living donor liver transplantation (LDLT) can enhance donor safety and expand donor availability. We previously reported that modulation of portal venous pressure (PVP) was key for successful LDLT with small grafts, and that it actively lowered graft-to-recipient weight ratio (GRWR) for adult-to-adult LDLT. This retrospective study investigated the outcome of LDLT using small grafts with PVP modulation. METHOD: This study analyzed 221 adult LDLT patients between March 2008 and December 2013 and divided them into 3 groups based on GRWR: large (L), GRWR ≥ 0.8% (n = 154), medium (M), ≥ 0.7% GRWR < 0.8% (n = 38); and small (S) GRWR < 0.7% (n = 29). Donor and recipient factors, PVP, pressure gradient between PVP and central venous pressure (CVP), occurrence of small for size syndrome (SFSS), ascites, and posttransplant laboratory data were compared across the 3 groups. Patient and graft survival were compared using Kaplan-Meier methods. RESULTS: There was no difference in patient or graft survival between the 3 groups. Amount of posttransplant ascites and posttransplant International Normalized Ratio were similar, but the S and M groups had more prolonged cholestasis. SFSS was identified in 17%, 13%, and 13% in the S, M, and L groups, respectively (P = NS). Patients with a final PVP of ≤15 mmHg had better survival than patients with a final PVP of >15 mmHg (P < .001). Multivariate analysis showed that donor age >40 years old, final PVP of >15 mmHg, and pressure gradient of PVP-CVP >5 mmHg were risk factors for inferior patient survival. CONCLUSION: We achieved satisfactory outcomes in LDLT with GRWR as low as 0.6% using PVP modulation. Thus, we currently set a lower limit of GRWR at 0.6% while protecting donor safety and expanding donor availability.

DOI： 10.1016/j.surg.2016.01.009

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Hepatic venous outflow obstruction (HVOO) is a critical complication after living donor liver transplantation (LDLT). This study aimed to evaluate the incidence of HVOO and the risk factors for HVOO in adults. From 2005 to 2015, 430 adult LDLT patients (right lobe [RL] graft, 270 patients; left lobe [LL] graft, 160 patients) were enrolled and divided into no HVOO (n = 413) and HVOO (n = 17) groups. Patient demographics and surgical data were compared, and risk factors for HVOO were analyzed. Furthermore, the longterm outcomes of percutaneous interventions as treatment for HVOO were assessed. HVOO occurred in 17 (4.0%) patients. The incidence of HVOO in patients receiving a LL graft was significantly higher than in those receiving a RL graft (8.1% versus 1.5%; P = 0.001). The body weight and caliber of hepatic vein anastomosis in the HVOO group were significantly lower compared with the no HVOO group (P = 0.02 and P = 0.008, respectively). Multivariate analysis revealed that only LL graft was an independent risk factor for HVOO (OR, 4.782; 95% CI, 1.387-16.488; P = 0.01). Among 17 patients with HVOO, 7 patients were treated with single balloon angioplasty, and 9 patients who developed recurrence were treated with repeated interventions. Overall, 6 patients underwent stent placement: 1 at the initial procedure, 3 at the second procedure for early recurrence, and 2 following repeated balloon angioplasty (≥3 interventions). These 6 patients experienced no recurrence. Overall graft survival was not significantly different between the HVOO and no HVOO groups (P = 0.99). In conclusion, the use of a LL graft was associated with HVOO, and percutaneous interventions were effective for treating adult HVOO after LDLT. Liver Transplantation 22 785-795 2016 AASLD.

DOI： 10.1002/lt.24399

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BACKGROUND: Little is known as to whether the interleukin4 (IL4) gene polymorphisms in recipients or donors affect the incidence of acute cellular rejection (ACR) following living donor liver transplantation (LDLT). Therefore, we determined the effect of IL4 T-33C polymorphisms in recipients and donors on ACR in a large cohort of patients that underwent LDLT. METHODS: We examined 155 LDLT cases treated at Nagoya University or Kyoto University, Japan, between 2004 and 2009. IL4 T-33C polymorphisms were analyzed in recipients and donors. RESULTS: Forty-seven recipients (30.3%) developed early ACR. The genotype frequency of IL4 T-33C in the recipients was associated with ACR incidence (P=0.008, P<0.0125 considered significant). Patients with the IL4-33C carrier genotype (C/C or C/T) were significantly associated with a higher incidence of ACR relative to those with the T/T genotype (OR=3.27, 95% CI: 1.56-6.88, P=0.002). The genotype frequencies of IL4 T-33C in the donors were not associated with rejection incidence. In addition, there was no significant effect of IL4 T-33C genotype combinations on ACR incidence in donors and recipients. CONCLUSIONS: Genotyping of IL4 T-33C in recipients might be useful to stratify the liver transplant recipients according to their risk of ACR.

DOI： 10.1016/j.clinre.2015.06.019

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DOI： 10.1111/cei.12740

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BACKGROUND: Skeletal muscle depletion, referred to as sarcopenia, predicts mortality after major surgery. This study investigated the impact of preoperative skeletal muscle quantity and quality on outcomes in patients undergoing resection of extrahepatic biliary cancer. METHODS: We performed a retrospective analysis of 207 patients undergoing resection for biliary cancer between 2004 and 2013. The quantity and quality of skeletal muscle, indicated by the psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC), were measured on preoperative images of computed tomography. Overall survival (OS) and recurrence-free survival (RFS) rates were compared by PMI and IMAC, and prognostic factors after operation were assessed. RESULTS: The OS and RFS rates were less in patients with low PMI (low muscle quantity) than in those with normal PMI (P < .001 and P < .001; 5-year OS, 15.7 vs 53.5%). The OS and RFS rates were also less in patients with high IMAC (low muscle quality) than in those with normal IMAC (P < .001 and P < .001; 5-year OS, 23.8 vs 55.9%). Low PMI and high IMAC were independent factors predictive of poor OS (hazard ratio [HR], 2.921 [95% CI, 1.920-4.470; P < .001] and HR, 1.725 [95% CI, 1.159-2.590; P = .007]) and RFS (HR, 2.141 [95% CI, 1.464-3.129, P < .001] and HR, 1.492 [95% CI, 1.032-2.166, P = .034]). CONCLUSION: Preoperative sarcopenia, indicating a low quantity and quality of skeletal muscle, is related closely to mortality after resection of biliary cancer.

DOI： 10.1016/j.surg.2015.08.047

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PURPOSE: To investigate the outcomes of living donor liver transplantation for advanced hepatocellular carcinoma in Child-Pugh A/B patients and the usefulness of our expanded selection criteria, the Kyoto criteria. METHODS: A total of 82 recipients with a Child-Pugh class A (n = 27) or B (n = 55) status having either multiple hepatic nodules or solitary tumors ≥5 cm in size treated between February 1999 and August 2012 were enrolled in this study. RESULTS: The overall recurrence rate was significantly less for the Child-Pugh B patients than for the Child-Pugh A patients (P = 0.042), while the survival rates did not differ. In the Child-Pugh A and B patients, the survival rate was significantly greater, while the recurrence rate was lower among the patients meeting the Kyoto criteria than those exceeding these criteria (P = 0.006, P = 0.001, P = 0.032 and P < 0.001, respectively). In the Child-Pugh B patients, the overall survival and recurrence rates did not differ between the patients treated with and without pretreatment for hepatocellular carcinoma. In the Child-Pugh B patients treated with pretreatment, the overall survival rate was significantly greater, while the recurrence rate was lower among the patients meeting the Kyoto criteria than those exceeding these criteria (P < 0.001, P < 0.001, respectively). CONCLUSIONS: Living donor liver transplantation performed within the Kyoto criteria achieves excellent overall survival and recurrence rates, especially for Child-Pugh B patients, even those with advanced hepatocellular carcinoma.

DOI： 10.1007/s00595-015-1142-2

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Invasive fungal infection (IFI) in liver transplant recipients is associated with poor outcomes. Targeted antifungal prophylaxis is recommended for high-risk populations; however, the epidemiology of IFI has changed, and the risk criteria remain unclear. In addition, the risk factors for late-onset invasive aspergillosis (IA) have not been fully characterized. We examined 279 recipients over 16 years of age to uncover their IFI epidemiology, clinical characteristics and outcomes. In addition, a case-control study was performed to identify the risk factors of late-onset IA. Of the 279 recipients, 96.1% underwent living donor liver transplantation. Antifungal prophylaxis was administered to 80.6% of the recipients. IFI occurred in 15 patients, among which 8 cases were early-onset (≤90 days after liver transplantation) and 7 cases were late-onset (>90 days after liver transplantation). Five of the late-onset cases were invasive pulmonary aspergillosis, and 2 were fungemia cases. The mortality rate of late-onset IA was 80.0%. According to a multivariate analysis, steroid use before liver transplantation, bloodstream infection within 90 days after liver transplantation and reoperation within 90 days after liver transplantation were significant risk factors for late-onset IA after liver transplantation. The prevalence of IFI was low in our population given that over 80% of liver recipients received antifungal prophylaxis. The prognosis of late-onset IA remains poor, and predictors associated with late-onset IA, such as steroid use before liver transplantation, bloodstream infection and reoperation after liver transplantation, may help clinicians to optimize prevention measures for these devastating infections.

DOI： 10.1016/j.jiac.2015.11.005

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Language：English   Publisher：WILEY-BLACKWELL  

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Language：English   Publisher：WILEY-BLACKWELL  

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DOI： 10.1111/tid.12425

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We report the first case of initially unresectable advanced hepatocellular carcinoma (HCC) with portal vein and hepatic venous tumor thrombosis and multiple lung metastases that allowed for curative hepatectomy after multidisciplinary treatment including sorafenib. A 54-year-old male presented with a large HCC in the right liver with tumor thrombosis of the left portal vein and middle hepatic vein (MHV) as well as multiple lung metastases. His serum alpha-fetoprotein level was elevated at 52,347 ng/mL and palliative treatment with sorafenib was initiated. One month later, a significant reduction in the serum AFP level, decrease in the tumor size with recanalization of the portal vein and the absence of lung metastases were noted. Three months after the start of sorafenib treatment, external-beam radiotherapy was performed to treat enlargement of the area of MHV thrombosis, and the thrombosis regressed. Five months after the initiation of sorafenib treatment, central bisegmentectomy associated with removal of the tumor thrombus in the inferior vena cava was performed. A microscopic examination revealed complete necrosis of the tumor. Sorafenib treatment may be a bridge to curative resection in selected patients with initially unresectable advanced HCC, even in cases involving multiple extrahepatic metastases.

DOI： 10.1007/s12328-015-0594-7

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Language：Japanese   Publisher：(一社)日本移植学会  

Language：English   Publishing type：Research paper (scientific journal)  

Surgical site infections (SSIs) are a major threat for liver transplant recipients. We prospectively studied SSIs after living donor liver transplantation (LDLT) at Kyoto University Hospital from April 2001 to March 2002 (1st period) and from January 2011 to June 2012 (2nd period). We investigated the epidemiology of SSIs after LDLT and determined the differences between the two periods. A total of 129 adult recipients (66 during the 1st period and 63 during the 2nd period) and 72 pediatric recipients (39 and 33) were included in this study. The SSI rates for each period were 30.3% (1st period) and 41.3% (2nd period) among the adult recipients and 25.6% and 30.3% among the pediatric recipients. The overall rates of 30-day mortality among adult transplant recipients with SSIs were 10.0% (1st period) and 3.9% (2nd period). No pediatric recipient died from SSIs after LDLT in either period. The incidence of Enterococcus faecium increased from 5.0% to 26.9% in the adults and from 10.0% to 40.0% in the pediatric patients. Extended-spectrum β-lactamase-producing Enterobacteriaceae were emerging important isolates during the 2nd period. For this period, a univariate analysis showed that ABO incompatibility (P = 0.02), total operation duration (P = 0.01), graft-to-recipient body weight ratio (GRWR [P = 0.04]), and Roux-en-Y biliary reconstruction (P<0.01) in the adults and age (P = 0.01) and NHSN risk index (P = 0.02) in the children were associated with SSI development. In a multivariate analysis, lower GRWR (P = 0.02) and Roux-en-Y biliary reconstruction (P<0.01) in the adults and older age (P = 0.01) in the children were independent risk factors for SSIs during the 2nd period. In conclusion, SSIs caused by antibiotic resistant bacteria may become a major concern. Lower GRWR and Roux-en-Y biliary reconstruction among adult LDLT recipients and older age among pediatric LDLT recipients increased the risk of developing SSIs after LDLT.

DOI： 10.1371/journal.pone.0136559

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DOI： 10.1111/cei.12588

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Skeletal muscle depletion, referred to as sarcopenia, is predictive of mortality in patients undergoing digestive operations. The impact of muscle quality on outcomes, however, is unclear. This retrospective study investigated the impact of preoperative skeletal muscle quantity and quality on survival in patients undergoing resection of pancreatic cancer. METHODS: We investigated 230 patients who underwent resection of pancreatic cancer between 2004 and 2013. The quantity and quality of skeletal muscle, indicated by psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC), were measured in preoperative computed tomography images. Overall survival (OS) and recurrence-free survival (RFS) rates were compared according to PMI and IMAC, and prognostic factors after pancreatic resection were assessed. RESULTS: The OS and RFS rates in patients with low PMI were lesser than in those with normal/high PMI (P < .001, P < .001), with a mean survival time of 17.7 and 33.2 months, respectively. The OS and RFS rates in patients with high IMAC also were less than in those with normal/low IMAC (P < .001, P = .003) (mean survival time = 21.5 and 56.5 months, respectively). Low PMI (low muscle mass) and high IMAC (low muscle quality) were independent prognostic factors of poor OS (hazard ratio [HR] = 1.999, P < .001; HR = 2.527, P < .001) and RFS (HR = 1.607, P = .007; HR = 1.640, P = .004), respectively. CONCLUSION: Preoperative sarcopenia, indicating low quality and quantity of skeletal muscle, is closely related to mortality after resection of pancreatic cancer.

DOI： 10.1016/j.surg.2015.02.002

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BACKGROUND: Liver transplantation (LT) used to be contraindicated in patients with portal vein thrombosis (PVT). In comparison to deceased donor LT, living donor LT (LDLT) still presents additional difficulties in determining appropriate vein grafts and overcoming small-for-size syndrome. Here, we introduce our LDLT strategies and assess their outcomes in adult patients with pre-existing PVT. METHODS: We performed 282 consecutive adult LDLTs between April 2006 and December 2011. Forty-eight patients (17%) had pre-existing PVT (grade I; 15, II; 20, III; 12, IV; 1). RESULTS: Our preferred treatments for PVT were thrombectomies/thromboendovenectomies in 30 patients, replaced grafts in seven, jump grafts in seven, renoportal anastomosis in one and no surgical intervention owing to minimal thrombosis in three. Post-transplant portal vein complications occurred in eight of 48 (17%) cases, which were treated by surgery, anticoagulation therapy, and/or interventional radiology. Post-transplant survival rates of patients with preexisting PVT at 1 year and 5 years were comparable to a PVT-free cohort (1 year; 81% vs. 77%, 5 years; 81% vs. 73%). CONCLUSIONS: The excellent survival rates in patients with PVT who underwent LDLT could be attributed to our strategies, which included surgical techniques and timely treatment of postoperative complications.

DOI： 10.1002/jhbp.235

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Language：Japanese   Publisher：(一社)日本肝胆膵外科学会  

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Sarcopenia has been shown to be an independent predictor of lower disease-free and overall survival in various kinds of diseases. The quality of skeletal muscle has recently attracted much attention as a new parameter of sarcopenia. METHODS: We performed a retrospective analysis of 477 patients undergoing hepatectomy for hepatocellular carcinoma (HCC) between April 2005 and August 2014. The quality of skeletal muscle was evaluated by intramuscular adipose tissue content (IMAC) using preoperative computed tomography (CT) imaging. The impact of IMAC on outcomes after hepatectomy for HCC was analyzed. RESULTS: Patients with high IMAC showed older age, higher body mass index, higher indocyanine green retention test at 15 min, and more operative blood loss. The overall and recurrence-free survival rates were significantly lower in patients with high IMAC than in patients with normal IMAC (P < 0.0001, P = 0.0012, respectively). Multivariate analysis showed that high IMAC was the significant risk factor for death (hazard ratio [HR] = 2.942; P < 0.0001) and for HCC recurrence (HR = 1.529; P = 0.0007) after hepatectomy. CONCLUSIONS: Preoperative quality of skeletal muscle was closely correlated with postoperative mortality and HCC recurrence. IMAC could be incorporated into new selection criteria for hepatectomy for HCC.

DOI： 10.1002/jhbp.236

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Language：English   Publisher：WILEY-BLACKWELL  

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Elderly donor grafts for liver transplantation (LT) are recognized to be marginal grafts. The present study investigated the impact of using elderly donors for LT. Between June 1990 and August 2012, 1631 patients received LT at Kyoto University Hospital. Out of 1631 patients, 1597 patients received living donor liver transplantation (LDLT), whereas the other 34 patients underwent deceased donor liver transplantation (DDLT). Seventy-five grafts that were used came from individuals who were ≥60 years old. We retrospectively analyzed the recipients' survival rates according to donor age. The overall survival rates of the recipients of all LDLT (P < 0.001), adult-to-adult LDLT (P = 0.007), all DDLT (P = 0.026), and adult-to-adult DDLT (P = 0.011) were significantly lower for the elderly donor group versus the younger group and especially for those who were hepatitis C-positive. A multivariate analysis revealed that donor age, ABO incompatibility, and preoperative intensive care unit stay were independent risk factors for poor patient survival in adult-to-adult LDLT. However, no significant differences existed between the 2 groups among those who received adult-to-adult LDLT in and after April 2006. No significant association was found between donor age and incidence of acute cellular rejection. In conclusion, donor age was closely related to the survival rate for LDLT and DDLT, although the impact of donor age was not shown in the recent cases.

DOI： 10.1002/lt.24086

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Language：Japanese   Publisher：日本外科系連合学会  

Language：Japanese   Publisher：(一社)日本医療安全学会  

当院では2011年11月に脳死肝移植後患者の死亡事故があり、その一因として「スタッフ間のコミュニケーションの不備」があったと考えられた。外部委員を加えた調査委員会では、事故の背景要因となった病院の管理体制について検討を行い、外部委員は安全への意識が向上するまでは肝移植を中断するよう勧告し、当院は成人肝移植を約半年間中断した。肝移植チームでは移植再開を目指し、コミュニケーション向上を目的とした以下の活動を行い、成果が得られたので、その詳細を報告した。1)コミュニケーション上の課題の抽出。2)肝移植領域医師のコミュニケーション技能・態度を評価するための質問紙調査(自己評価と看護師による他者評価)。3)調査結果のフィードバック。4)医師からのインシデント報告の分析。

Language：Japanese   Publisher：(一社)日本外科学会  

Language：English   Publishing type：Research paper (scientific journal)  

Bile duct injury is one of the known serious complications of laparoscopic fenestration for nonparasitic liver cysts. Herein, we report the case of a huge liver cyst for which we performed laparoscopic fenestration using intraoperative fluorescent cholangiography with indocyanine green. A 71-year-old woman with abdominal distention was referred to our hospital. CT demonstrated a 17 × 11.5-cm simple cyst replacing the right lobe of the liver, so laparoscopic fenestration was performed. Although the biliary duct could not be detected because of compression by the huge cyst, fluorescent cholangiography with indocyanine green through endoscopic naso-biliary drainage tube clearly delineated the intrahepatic bile duct in the remaining cystic wall. The patient had no complications at 3 months after surgery. Fluorescent cholangiography using indocyanine green is a safe and effective procedure to avoid bile duct injury during laparoscopic fenestration, especially in patients with a huge liver cyst.

DOI： 10.1111/ases.12137

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During a prospective surveillance using PCR for the detection of plasmid-mediated AmpC β-lactamase (pAmpC)-producing Enterobacteriaceae, outbreaks due to pAmpC-producing Klebsiella pneumoniae (pAmpC-Kp) occurred in an adult liver transplantation unit (aLTU) and a paediatric liver transplantation unit (pLTU), with carbapenem-resistant (CR) variants. Between April 2010 and March 2012, a total of 32 patients infected with pAmpC-Kp were found by prospective surveillance using PCR detection at a Japanese university hospital. Multilocus sequence typing, analysis of outer membrane proteins, and detection of carbapenemases were performed. Clinical courses of patients with bloodstream infection (BSI) were reviewed. Of 32 pAmpC-Kp isolates from each patient, 20 (18 from aLTU patients) were DHA-1-producing sequence type 11 (DHA-1-ST11), 9 were CMY-2-ST45/778 (all from pLTU patients) and the other 3 isolates had different sequence types. CR variants were isolated from 8 aLTU patients with DHA-1-ST11 and from 1 pLTU patient with CMY-2-ST45. All of the pAmpC-Kp isolates, including CR variants, were negative for carbapenemases. All of the DHA-1-ST11 and CMY-2-ST45 isolates lacked OmpK35, and seven CR variants also lacked OmpK36. BSIs due to DHA-1-ST11 isolates, including CR variants, occurred in six aLTU patients, four of whom died. The outbreaks were controlled after application of intensified infection control measures. During pAmpC-Kp outbreaks involving 27 liver transplants, CR variants with porin loss developed in nine patients, and DHA-1-ST11 K. pneumoniae caused BSIs with high mortality.

DOI： 10.1016/j.ijantimicag.2014.08.015

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Language：English   Publisher：Springer  

In liver transplantation, prolonged ischemia and/or a relatively small graft (living, split, reduced) are the risk factors for liver dysfunction. Novel measures to enhance liver function with a smaller graft can be a clue for safe partial or living-donor liver transplantation or safe hepatectomy for malignant disease. The therapeutic potential and immunomodulatory effects of mesenchymal stem cells (MSCs) have been reported. In this chapter, recent finding on the positive effect of MSCs for liver transplantation and hepatectomy are discussed. Our rat experiment revealed that introduction of MSCs provides trophic support to the I/R-injured liver by inhibiting hepatocellular apoptosis and by stimulating regeneration, which is shown with the pig model as well. In the rat liver transplantation model, portal transfusion of the MSCs ameliorates the injury of the liver graft after prolonged cold preservation and transplantation. Those findings together suggest a potential advantage with partial or living-donor liver transplantation. The most severe complication with cell therapy is embolus formation due to cell aggregation. However, with modification of the solution, we can keep cells in a suspended form for several hours, which secures safe administration of MSCs.

DOI： 10.1007/978-4-431-55651-0

PubMed

Language：Japanese   Publisher：Japanese Society for Parenteral and Enteral Nutrition  

<b>Objectives:</b> Postoperative steatosis is sometimes found in patients undergoing liver transplantation (LT). However, the nutritional significance is unclear. Therefore, we investigated nutritional significance and risk factor for postoperative steatosis in the early period after LT.<br><b>Methods:</b> We retrospectively analyzed 117 patients who underwent adult living donor LT in our center between May 2010 and September 2012. Sixty-two of 117 patients underwent liver biopsy due to liver dysfunction during hospitalization. We compared various nutritional parameters including daily calorie intake per ideal body weight, ratio of non-protein calorie-to-nitrogen, and route of calorie intake between steatosis group (histologically diagnosed steatosis equal or more than 5%, n=41) and non-steatosis group (steatosis less than 5%, n=21). Moreover, the change of fatty acid level before and after the diagnosis of steatosis and risk factor for posttransplant steatosis were analyzed.<br><b>Results:</b> Calorie intake, ratio of non-protein calorie-to-nitrogen, and bloodchemical data just before diagnosis did not differ between steatosis group and non-steatosis group. Interestingly, distribution of 2 peaks characteristics in calorie intake, namely calorie over and calorie shortage, was found in the steatosis group. Calorie over or calorie shortage was a risk factor for posttransplant steatosis. Route of calorie intake was significantly different between patients with calorie over and calorie shortage. The ratio of eicosapentaenoic acid to arachidonic acid significantly decreased after the diagnosis of steatosis.<br><b>Conclusions:</b> Posttransplant steatosis was closely involved with calorie over or calorie shortage. Decrease in the ratio of eicosapentaenoic acid to arachidonic acid would be useful as a surrogate marker of posttransplant steatosis.

DOI： 10.11244/jspen.30.697

CiNii Research

Language：Japanese   Publisher：The Japan Society for Portal Hypertension  

DOI： 10.11423/jsph.21.229

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

Solid pseudopapillary neoplasm (SPN) is a rare tumor of the pancreas. Laparoscopic distal pancreatectomy (DP) is a feasible and safe procedure, and successful spleen preservation rates are higher using a laparoscopic approach. We hypothesized that certain patients with SPN would be good candidates for laparoscopic surgery; however, few surgeons have reported laparoscopic DP for SPN. We discuss the preoperative assessment and surgical simulation for two SPN cases. A simulation was designed because we consider that a thorough preoperative understanding of the procedure based on three-dimensional image analysis is important for successful laparoscopic DP. We also discuss the details of the actual laparoscopic DP with or without splenic preservation that we performed for our two SPN cases. It is critical to use appropriate instruments at appropriate points in the procedure; surgical instruments are numerous and varied, and surgeons should maximize the use of each instrument. Finally, we discuss the key techniques and surgical pitfalls in laparoscopic DP with or without splenic preservation. We conclude that experience alone is inadequate for successful laparoscopic surgery.

DOI： 10.1155/2015/487639

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Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: Uncontrollable hepatic hydrothorax and massive ascites (H&MA) requiring preoperative drainage are sometimes encountered in liver transplantation (LT). We retrospectively analyzed the characteristics of such patients and the impact of H&MA on the postoperative course. METHODS: We evaluated 237 adult patients who underwent LT in our institute between April 2006 and October 2010. RESULTS: Recipients with uncontrollable H&MA (group HA: n = 36) had more intraoperative bleeding, higher Child-Pugh scores, lower serum albumin concentrations and higher blood urea nitrogen concentrations than those without uncontrollable H&MA (group C: n = 201). They were also more likely to have preoperative hepatorenal syndrome and infections. The incidence of postoperative bacteremia was higher (55.6 vs. 46.7%, P = 0.008) and the 1- and 3-year survival rates were lower (1 year: 58.9 vs. 82.9%; 3 years: 58.9 vs. 77.7%; P = 0.003) in group HA than in group C. The multivariate proportional regression analyses revealed that uncontrollable H&MA and the Child-Pugh score were independent risk factors for the postoperative prognosis. CONCLUSIONS: Postoperative infection control may be an important means of improving the outcome for patients with uncontrollable H&MA undergoing LT, and clinicians should strive to perform surgery before H&MA becomes uncontrollable.

DOI： 10.1007/s00595-014-0839-y

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Language：English   Publishing type：Research paper (scientific journal)  

Derangements of various serum biochemical nutritional/metabolic parameters are common in patients with end-stage liver disease who undergo liver transplantation (LT). The aim of this study was to explain the benefit of LT with respect to parameter changes and to examine the impact of the graft-to-recipient weight ratio (GRWR) on such changes. We investigated each parameter's course in 208 adult recipients for 1 year after living donor LT and analyzed changes in the parameters with a GRWR of 0.8% as the cutoff point. Bonferroni corrections were applied to account for multiple testing. Liver disease-induced high pretransplant ammonia and tyrosine levels and low branched-chain amino acids to tyrosine ratio (BTR) and zinc levels normalized within 2 weeks after transplantation, and the total lymphocyte count (TLC) normalized within 2 months, whereas low pretransplant prealbumin levels took 1 year to normalize. Branched-chain amino acids (BCAA), zinc, and TLC levels transiently dropped shortly after transplantation and then were corrected later. An accelerated recovery of ammonia and tyrosine levels and the BTR were found with larger grafts, especially early after transplantation, whereas zinc, prealbumin, BCAA, and TLC levels recovered regardless of the graft size. In conclusion, graft size had little effect on the recovery of nutritional/metabolic parameters except for ammonia and tyrosine levels.

DOI： 10.1002/lt.23992

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PubMed

Language：Japanese   Publisher：(株)へるす出版  

Language：English   Publishing type：Research paper (scientific journal)  

Intramuscular fat accumulation has come to be associated with loss of muscle strength and function, one of the components of sarcopenia. However, the impact of preoperative quality of skeletal muscle on outcomes after living donor liver transplantation (LDLT) is unclear. The present study evaluated the intramuscular adipose tissue content (IMAC) and psoas muscle mass index (PMI) in 200 adult patients undergoing LDLT at our institution between January 2008 and October 2013. Correlations of IMAC with other factors, overall survival rates in patients classified according to IMAC or PMI, and risk factors for poor survival after LDLT were analyzed. IMAC was significantly correlated with age (r = 0.229, P = 0.03) and PMI (r = -0.236, P = 0.02) in males and with age (r = 0.349, P < 0.001) and branched-chain amino acid (BCAA)-to-tyrosine ratio (r = -0.250, P = 0.01) in females. The overall survival rates in patients with high IMAC or low PMI were significantly lower than those for patients with normal IMAC or PMI (P < 0.001, P < 0.001, respectively). Multivariate analysis showed that high IMAC [odds ratio (OR) = 3.898, 95% confidence interval (CI) = 2.025-7.757, P < 0.001] and low PMI (OR = 3.635, 95% CI = 1.896-7.174, P < 0.001) were independent risk factors for death after LDLT. In conclusion, high IMAC and low PMI were closely involved with posttransplant mortality. Preoperative quality and quantity of skeletal muscle could be incorporated into new selection criteria for LDLT. Perioperative nutritional therapy and rehabilitation could be important for good outcomes after LDLT.

DOI： 10.1002/lt.23970

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Language：English   Publishing type：Research paper (scientific journal)  

This study investigated adequate liver graft selection for donor safety by comparing postoperative donor liver function and morbidity between the right and left hemilivers (RL and LL, respectively) of living donors. Between April 2006 and March 2012, RL (n = 168) and LL (n = 140) donor operations were performed for liver transplantation at Kyoto University Hospital. Postoperative hyperbilirubinemia and coagulopathy persisted in RL donors, whereas the liver function of LL donors normalized more rapidly. The overall complication rate of the RL donors was significantly higher than that of the LL donors (59.5% vs. 30.7%; P < 0.001). There were no significant differences in severe complications worse than Clavien grade IIIa or in biliary complication rates between the two donor groups. In April 2006, we introduced an innovative surgical procedure: hilar dissection preserving the blood supply to the bile duct during donor hepatectomy. Compared with our previous outcomes (1990-2006), the biliary complication rate of the RL donors decreased from 12.2% to 7.2%, and the severity of these complications was significantly lower. In conclusion, LL donors demonstrated good recovery in postoperative liver function and lower morbidity, and our surgical innovations reduced the severity of biliary complications in living donors.

DOI： 10.1111/tri.12414

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PubMed

Language：Japanese   Publisher：(一社)日本外科感染症学会  

Language：Japanese   Publisher：日本アフェレシス学会  

CiNii Books

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

Tacrolimus is widely used as an immunosuppressant in liver transplantation, and tacrolimus-induced acute kidney injury (AKI) is a serious complication of liver transplantation. For early detection of AKI, various urinary biomarkers such as monocyte chemotactic protein-1, liver-type fatty acid-binding protein, interleukin-18, osteopontin, cystatin C, clusterin and neutrophil gelatinase-associated lipocalin (NGAL) have been identified. Here, we attempt to identify urinary biomarkers for the early detection of tacrolimus-induced AKI in liver transplant patients. Urine samples were collected from 31 patients after living-donor liver transplantation (LDLT). Twenty recipients developed tacrolimus-induced AKI. After the initiation of tacrolimus therapy, urine samples were collected on postoperative days 7, 14, and 21. In patients who experienced AKI during postoperative day 21, additional spot urine samples were collected on postoperative days 28, 35, 42, 49, and 58. The 8 healthy volunteers, whose renal and liver functions were normal, were asked to collect their blood and spot urine samples. The urinary levels of NGAL, monocyte chemotactic protein-1 and liver-type fatty acid-binding protein were significantly higher in patients with AKI than in those without, while those of interleukin-18, osteopontin, cystatin C and clusterin did not differ between the 2 groups. The area under the receiver operating characteristics curve of urinary NGAL was 0.876 (95% confidence interval, 0.800-0.951; P<0.0001), which was better than those of the other six urinary biomarkers. In addition, the urinary levels of NGAL at postoperative day 1 (p = 0.0446) and day 7 (p = 0.0006) can be a good predictive marker for tacrolimus-induced AKI within next 6 days, respectively. In conclusion, urinary NGAL is a sensitive biomarker for tacrolimus-induced AKI, and may help predict renal event caused by tacrolimus therapy in liver transplant patients.

DOI： 10.1371/journal.pone.0110527

Open Access

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Language：English  

DOI： 10.1111/tid.12282

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PubMed

Language：Japanese   Publisher：(一社)日本移植学会  

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: We investigated whether the cytochrome P450 3A5*3 (CYP3A5*3) genotype affects tacrolimus pharmacokinetics and the risk of acute cellular rejection in living-donor liver transplant patients in Japan. MATERIALS AND METHODS: Between July 2004 and June 2011, we enrolled 410 living-donor liver transplant patients receiving tacrolimus. Biopsy specimens of intestinal mucosa and graft liver at surgery were obtained to examine the mRNA expression of CYP3A subfamilies as well as the genotyping of CYP3A5*3 polymorphism. RESULTS: The CYP3A5 genotype in the native intestine had no significant effect on the occurrence of acute cellular rejection between postoperative days 14 and 23 in cases with identical or compatible ABO blood types (11.5% for the CYP3A5*1 allele vs. 7.4% for CYP3A5*3/*3; P=0.2643), although the concentration/dose ratio of tacrolimus was significantly higher in patients with the intestinal CYP3A5*3/*3 genotype than in those with the CYP3A5*1 allele for 5 post-transplant weeks. However, patients who received a graft liver with the CYP3A5*1 allele showed a higher rate of acute cellular rejection than those who received a graft liver with the CYP3A5*3/*3 genotype (14.5 vs. 5.7%; P=0.0134). The relative risk for acute cellular rejection associated with the CYP3A5*1 liver allele was 2.629 (P=0.018, Cox regression model). Consequently, graft liver CYP3A5*1 genotype might increase the risk for acute cellular rejection after living-donor liver transplantation, possibly by associating with the local hepatic tacrolimus concentration. CONCLUSIONS: The target level of tacrolimus may be affected by the CYP3A5*3 genotype of the liver, rather than by that of the small intestine, after postoperative day 14.

DOI： 10.1097/FPC.0000000000000060

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

Language：Japanese   Publisher：(一社)日本消化器外科学会  

Language：Japanese  

DOI： 10.11477/mf.4426101093

CiNii Research

J-GLOBAL

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1097/TP.0000000000000060

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Liver transplant outcomes using grafts donated after cardiac death (DCD) remain poor. METHODS: We investigated the effects of ex vivo reconditioning of DCD grafts with venous systemic oxygen persufflation using nitric oxide gas (VSOP-NO) in rat liver transplants. Orthotopic liver transplants were performed in Lewis rats, using DCD grafts prepared using static cold storage alone (group-control) or reconditioning using VSOP-NO during cold storage (group-VSOP-NO). Experiment I: In a 30-min warm ischemia model, graft damage and hepatic expression of inflammatory cytokines, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and endothelin-1 (ET-1) were examined, and histologic analysis was performed 2, 6, 24, and 72 hr after transplantation. Experiment II: In a 60-min warm ischemia model, grafts were evaluated 2 hr after transplantation (6 rats/group), and survival was assessed (7 rats/group). RESULTS: Experiment I: Group-VSOP-NO had lower alanine aminotransferase (ALT) (P<0.001), hyaluronic acid (P<0.05), and malondialdehyde (MDA) (P<0.001), hepatic interleukin-6 expression (IL-6) (P<0.05), and hepatic tumor necrosis factor-alpha (TNF-α) expression (P<0.001). Hepatic eNOS expression (P<0.001) was upregulated, whereas hepatic iNOS (P<0.01) and ET-1 (P<0.001) expressions were downregulated. The damage of hepatocyte and sinusoidal endothelial cells (SECs) were lower in group-VSOP-NO.Experiment II: VSOP-NO decreased ET-1 and 8-hydroxy-2'deoxyguanosine (8-OHdG) expression and improved survival after transplantation by 71.4% (P<0.01). CONCLUSION: These results suggest that VSOP-NO effectively reconditions warm ischemia-damaged grafts, presumably by decreasing ET-1 upregulation and oxidative damage.

DOI： 10.1097/TP.0000000000000025

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Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：English   Publisher：Japan Surgical Society (JSS)  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：English   Publisher：Japan Surgical Society (JSS)  

CiNii Research

Language：English   Publisher：Japan Surgical Society (JSS)  

CiNii Research

Language：Japanese   Publisher：(一社)日本外科学会  

Language：Japanese   Publisher：(一社)日本外科学会  

J-GLOBAL

Language：Japanese   Publisher：(一社)日本外科学会  

Language：Japanese   Publisher：(一社)日本外科学会  

Language：Japanese   Publisher：(一社)日本外科学会  

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Chronic rejection (CR) has been reported to be associated with antiviral therapy for recurrent hepatitis C in liver transplant (LT) recipients. The aims of this study were to clarify the details of antiviral therapy-associated CR after living-donor liver transplantation (LDLT) and to identify the factors associated with CR. METHODS: A retrospective chart review was performed on 125 recipients who had received antiviral therapy for recurrent hepatitis C after LDLT between January 2001 and September 2012. The characteristics of patients who developed CR during or within 6 months after antiviral therapy were compared with those of 76 patients who did not develop CR despite receiving antiviral therapy for more than 1 year. RESULTS: Seven of 125 (6%) patients developed CR during or within 6 months after the end of antiviral therapy. CR was diagnosed after a median (range) of 9 (1-16) months of antiviral therapy. In five patients, rejection progressed rapidly and resulted in death within 3 months after diagnosis. Analysis revealed two significant factors associated with CR: reduction of the immunosuppressant dose during antiviral therapy and a low fibrosis score as the indication for antiviral therapy. CONCLUSIONS: CR developed in association with antiviral therapy for recurrent hepatitis C after LDLT. This complication may be prevented by ensuring that the immunosuppressant dose is not reduced during antiviral therapy.

DOI： 10.1097/01.TP.0000435702.61642.0a

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.transproceed.2013.07.077

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Japanese Society for the Study of Xenobiotics  

  We retrospectively examined whether cytochrome P450 (CYP) 3A5 genotypes are associated with high-dose steroid pulse treatment-induced functional gain of tacrolimus biotransformation in living-donor liver transplant patients. Concentrations of tacrolimus and its 3 primary metabolites, 13-<i>O</i>-demethyl tacrolimus (M-I), 31-<i>O</i>-demethyl tacrolimus (M-II), and 15-<i>O</i>-demethyl tacrolimus (M-III), were measured in trough blood samples from 18 liver transplant patients, by liquid chromatography–tandem mass spectrometry/mass spectrometry (LC-MS/MS). In patients engrafted with a <i>CYP3A5*1</i>-carrying liver but not with a <i>CYP3A5*3/*3</i>-carrying liver, the concentration/dose ratio of tacrolimus significantly fell after therapy, while ratios of M-I/tacrolimus, M-II/tacrolimus, and M-III/tacrolimus were significantly higher after therapy than before (p = 0.032, p = 0.023, and p = 0.0078, respectively). After steroid pulse therapy, the concentration of tacrolimus measured by immunoassay was significantly higher than that measured by LC-MS/MS in patients engrafted with a <i>CYP3A5*1</i>-carrying liver, but not those engrafted with a <i>CYP3A5*3/*3</i>-carrying liver. This suggests that the increased ratio of tacrolimus metabolites/tacrolimus can be explained by induction of CYP3A5 <i>via</i> high-dose steroid pulse therapy. Further, the concentrations of tacrolimus measured by the immunoassays were overestimated, partly because of cross-reactivity of the monoclonal antibody they incorporated to detect tacrolimus, with the increased metabolites in patients with a <i>CYP3A5*1</i>-carrying graft liver.<br>

DOI： 10.2133/dmpk.dmpk-13-rg-060

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Pharmaceutical Society of Japan  

Telaprevir (TVR) is a protease inhibitor used in combination with pegylated interferon alfa-2b and ribavirin for hepatitis C, and TVR strongly inhibits CYP3A4 and CYP3A5. We reported successful TVR treatment of liver transplant patients with recurrence of hepatitis C during receiving immunosuppressive therapy. Before initiation of triple therapy, all patients switched from tacrolimus to cyclosporine, which has a lower inhibitory effect on CYP3A4 and CYP3A5 than tacrolimus. To avoid graft failure, we measured the cyclosporine blood concentrations at 0, 2, and 6 h after administration to maintain the target level (150–200 ng/mL) within 1 week after initiation of TVR and adjusted the dose of cyclosporine. The dose of cyclosporine was decreased 0.24–0.40 fold in all patients after initiation of TVR treatment. In 3 patients, the dose of TVR was decreased two-thirds of starting dose because of adverse effects, including anorexia and skin rash. However, the HCV RNA level rapidly decreased to undetectable levels within 1 month. Furthermore, all patients completed the TVR therapy in 12 weeks and did not experience liver graft rejection. In addition, we found the rapid elimination of inhibitory effect of TVR on the disposition of cyclospirne in the all four cases and therefore, rapid increase in the dosage of cyclosporine would be required immediately after the end of TVR administration. These results suggest that frequent measurement of cyclosporine levels was important for successful TVR triple therapy and prevention of rejection.

DOI： 10.1248/bpb.b13-00769

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CiNii Research

Language：Japanese   Publisher：Japan Surgical Association  

A 49-year-old woman developed high fever and increases in white blood cell count and C-reactive protein (CRP) with after chemotherapy for acute myelocytic leukemia. She was diagnosed with multiple liver abscesses by PET/CT. Ultrasound-guided percutaneous fine-needle biopsy of the hepatic lesion was performed, but no causative microorganism was identified. The clinical course supported the diagnosis of fungal liver abscess, and antifungal medical treatment was started. However, CRP remained positive, and PET/CT revealed progression of the liver abscess. Laparoscopic partial resection of three lesions was performed for identification of causative microorganism and susceptibility testing.<BR>Histopathological findings indicated epithelioid cell granuloma with caseation necrosis, and Ziehl-Neelsen staining detected mycobacterium. Although the QuantiFERON<SUP>®</SUP>-TB Gold In-Tube test was negative, the causative microorganism could not be identified from laboratory culture ; therefore, the patient received four-agent combination therapy for atypical mycobacterial disease. She received allo-peripheral blood stem cell transplantation 4 months after the operation, and her condition has been stable.<BR>Identification of causative microorganisms by ultrasound-guided percutaneous fine-needle liver biopsy is difficult and may not provide a definitive diagnosis. Alternatively, laparoscopic partial liver resection can be useful in making an etiological diagnosis and treatment.

DOI： 10.3919/jjsa.75.179

CiNii Research

J-GLOBAL

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

Pancreatic islet transplantation has received widespread attention as a promising treatment for type 1 diabetes. However, islets for transplantation are subject to damage from a number of sources, including ischemic injury during removal and delivery of the donor pancreas, enzymatic digestion during islet isolation, and reperfusion injury after transplantation in the recipient. Here we found that protein fractions secreted by mesenchymal stem cells (MSCs) were capable of activating preserved islets. A conditioned medium from the supernatant obtained by culturing adipose tissue MSCs (derived from wild-type Lewis rats) was prepared for 2 days in serum-free medium. Luc-Tg rat islets to which an organ preservation solution was added were then incubated at 4°C with fractions of various molecular weights prepared from the conditioned medium. Under the treatment with some of the fractions, by 4 days the relative luminescence intensities (representative of the ATP levels of the cold-preserved islets) had increased to over 150% of their initial values. Our novel system may be able to restore isolated islets to the condition they were in before transport, culture, and transplantation.

DOI： 10.3727/215517913X666477

PubMed

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Language：English   Publisher：WILEY-BLACKWELL  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Previously, we proposed expanded selection criteria for liver transplantation (LT) for hepatocellular carcinoma (HCC), the Kyoto criteria, involving a combination of tumor number ≤10, maximal diameter of each tumor ≤5 cm, and serum des-gamma-carboxy prothrombin levels ≤400 mAU/mL, and we have used these criteria since January 2007. In the present study, the usefulness of the criteria was validated prospectively as well as retrospectively. METHODS: One hundred ninety-eight patients with HCC who underwent living donor LT (LDLT) from February 1999 through December 2011 were enrolled in this study. Overall survival and recurrence rates were investigated in patients classified according to the Kyoto criteria, the Milan criteria, or previous treatments for HCC. Tumor biological aggressiveness, including microvascular invasion and histologic differentiation, according to selection criteria was also examined. RESULTS: The 5-year overall survival for patients within the Kyoto criteria (n = 147; 82%) was greater than that for the 49 patients exceeding them (n = 49; 42%; P < .001). The 5-year recurrence rate for patients within the Kyoto criteria (4.4%) was less than that for patients exceeding them (51%; P < .001). Intention-to-treat analysis of the 62 patients who underwent LDLT after implementation of the Kyoto criteria showed that the 5-year overall survival rate and the recurrence rate were 82% and 7%, respectively. Tumor biology was significantly less aggressive in patients within the Kyoto criteria. CONCLUSION: The Kyoto criteria are useful expanded criteria for LDLT for HCC and could help to achieve favorable outcomes.

DOI： 10.1016/j.surg.2013.04.056

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Language：English   Publisher：WILEY-BLACKWELL  

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Language：English   Publisher：WILEY-BLACKWELL  

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Language：English   Publisher：WILEY-BLACKWELL  

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Language：English   Publishing type：Research paper (scientific journal)  

Background/Aims: We investigated the efficacy of endoscope guided transabdominal ultrasonography (EGTUS) for the evaluating the depth of colorectal cancer invasion. Methodology: The subjects were 52 patients with colon cancer and 30 patients with rectal cancer who underwent transabdominal US and curative surgery. During endoscopy, we applied transabdominal US by filling the area around the tumor with de-gassed water. The accuracy of depth invasion assessment using EGTUS was compared with that using endoscopic, computed tomography (CT), surgical or histological findings. Results: The tumor detection rate was 75.6% (62/82), 88.5% (46/52) for colon cancer and 53.3% (16/30) for rectal cancer. The diagnostic accuracies of EGTUS, endoscopic, CT and surgical findings were 87.1% (54/62), 73.2% (60/82), 66.7% (46/69), 65.9% (54/82), respectively. The diagnostic accuracy of EGTUS was 100% (2/2), 66.7% (4/6), and 90.0% (44/49) for T1, T2 and T3 cancer, respectively. Conclusion: The results suggest that EGTUS is useful for evaluating preoperative T staging of colorectal cancer. © H.G.E. Update Medical Publishing S.A.

DOI： 10.5754/hge11298

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PubMed

Language：Hungarian   Publishing type：Research paper (scientific journal)   Publisher：AKADEMIAI KIADO RT  

Introduction: Due to the limited number of cadaver donors, adult living liver donor transplantation became an alternative for liver transplantation. During living liver donor transplantation, the safety and uncomplicated recovery of the donor are as important as the appropriate volume and weight of the donated graft. The middle hepatic vein causes a significant dilemma, due to the special anatomical position. The reconstruction of the middle hepatic vein branches supplying S5, S8 is suggested when the anatomically right liver lobe is transplanted. Aim: The aim of the present study was to investigate the requirements of the reconstruction of middle hepatic vein and to give an accurate description about the discrepancy between the portal vein in-and outflow. Method: The authors analyzed the liver anatomic characteristics of 130 donors undergoing living liver donor transplantation with the use of MeVis software. The so-called porto-hepatic disparity index (shift) was introduced. Results: The right hepatic vein was dominant in 64.6% of all cases, while the left hepatic vein was never observed to be dominant. The territories of V5 and V8 were responsible for the 33.2 +/- 8.9% of the right hepatic lobe area. The correlation between portal venous territory and vein dominancy were as follows: R-2 = 0.7811 in the left liver lobe; R-2 = 0.5463 in the area of middle hepatic vein and R-2 = 0.5843 in the case of the right hepatic vein. The average value of the shift was 28.2%. Conclusions: The differences among the pattern of portal in-and hepatic outflow is an important issue that should be taken into consideration when deciding the necessity for reconstruction of the middle hepatic vein.

DOI： 10.1556/OH.2013.29698

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Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: Despite improvements in immunosuppressive therapy, acute cellular rejection (ACR) remains an important cause of graft loss in patients undergoing liver transplantation. Recently, associations between cytokine gene polymorphisms in recipients and the occurrence of ACR have been reported. However, most studies did not investigate gene polymorphisms in donors or were limited by the number of cases investigated. METHODS: We examined 155 living donor liver transplantation (LDLT) patients treated at Nagoya University or Kyoto University from 2004 to 2009. The following gene polymorphisms in recipients and donors were analyzed: tumor necrosis factor A (TNF-A) T-1031C, interleukin 2 (IL-2) T-330G, IL-10C-819T, IL-13C-1111T, and transforming growth factor B (TGF-B) T29C. RESULTS: Forty-seven recipients (30.3 %) developed early ACR. Of the investigated gene polymorphisms, the IL-13 -1111C/C genotype in recipients was significantly associated with a higher incidence of ACR relative to the other two genotypes (OR = 2.64, 95 % CI 1.19-5.86, p = 0.017), while we showed the lack of association between investigated gene polymorphisms in donors and ACR incidence. CONCLUSION: The IL-13 -1111C/C genotype in recipients might be a risk factor for ACR in LDLT, and this might contribute to individualized immunosuppression strategies for recipients. On the other hand, the current study showed no associations of cytokine gene polymorphisms in donors with ACR incidence.

DOI： 10.1007/s12072-013-9443-2

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Language：Japanese   Publisher：(株)東京医学社  

Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.transproceed.2013.02.117

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Skeletal muscle depletion, referred to as sarcopenia, predicts morbidity and mortality in patients undergoing digestive surgery. However, the impact on liver transplantation is unclear. The present study investigated the impact of sarcopenia on patients undergoing living donor liver transplantation (LDLT). Sarcopenia was assessed by a body composition analyzer in 124 adult patients undergoing LDLT between February 2008 and April 2012. The correlation of sarcopenia with other patient factors and the impact of sarcopenia on survival after LDLT were analyzed. The median ratio of preoperative skeletal muscle mass was 92% (range, 67-130%) of the standard mass. Preoperative skeletal muscle mass was significantly correlated with the branched-chain amino acids to tyrosine ratio (r=-0.254, p=0.005) and body cell mass (r=0.636, p&lt;0.001). The overall survival rate in patients with low skeletal muscle mass was significantly lower than in patients with normal/high skeletal muscle mass (p&lt;0.001). Perioperative nutritional therapy significantly increased overall survival in patients with low skeletal muscle mass (p=0.009). Multivariate analysis showed that low skeletal muscle mass was an independent risk factor for death after transplantation. In conclusion, sarcopenia was closely involved with posttransplant mortality in patients undergoing LDLT. Perioperative nutritional therapy significantly improved overall survival in patients with sarcopenia.

DOI： 10.1111/ajt.12221

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Language：English   Publisher：WILEY-BLACKWELL  

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00383-013-3281-0

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Given the limited efficacy and high adverse event rate associated with treatment of recurrent hepatitis C after liver transplantation, an individualized treatment strategy should be considered. The aim of this study was to identify predictors of response to antiviral therapy for hepatitis C after living donor liver transplantation (LDLT) and to study the associated adverse events. METHODS: A retrospective chart review was performed on 125 hepatitis C virus (HCV)-positive LDLT recipients who received interferon plus ribavirin and/or peginterferon plus ribavirin therapy at Kyoto University between January 2001 and June 2011. RESULTS: Serum HCV RNA reached undetectable levels within 48 weeks in 77 (62%) of 125 patients, and these patients were defined as showing virological response (VR). Of 117 patients, 50 (43%) achieved sustained VR (SVR). Predictive factors associated with both VR and SVR by univariate analysis included low pretransplant serum HCV RNA levels, a non-1 HCV genotype, and low pretreatment serum HCV RNA levels. In addition, LDLT from ABO-mismatched donors was significantly associated with VR, and white cell and neutrophil counts before interferon therapy were associated with SVR. Multivariate analysis showed that 2 variables-pretransplant serum HCV RNA level less than 500 kIU/mL and a non-1 HCV genotype-remained in models of both VR and SVR and that an ABO mismatch was associated with VR. No variables with a significant effect on treatment withdrawal were found. CONCLUSIONS: Virological response to antiviral therapy in patients with hepatitis C recurring after LDLT can be predicted prior to transplant, based on pretransplant serum HCV-RNA levels and HCV genotype. LDLT from ABO-mismatched donors may contribute to more efficacious interferon therapy. TRIAL REGISTRATION: UMIN-CTR UMIN000003286.

DOI： 10.1371/journal.pone.0058380

Open Access

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Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: Generation of human livers in pigs might improve the serious shortage of grafts for human liver transplantation, and enable liver transplantation without the need for deceased or living donors. We developed a chimeric liver (CL) by repopulation of rat hepatocytes in a mouse and successfully transplanted it into a rat recipient with vessel reconstruction. This study was designed to investigate the feasibility of CL for supporting the recipient after auxiliary liver grafting. METHODS: Hepatocytes from luciferase transgenic or luciferase/LacZ double-transgenic rats were transplanted into 20- to 30-day-old urokinase-type plasminogen activator/severe-combined immunodeficiency (uPA/SCID) mice (n = 40) to create CLs with rat-origin hepatocytes. After replacement of mouse hepatocytes with those from rats, the CLs were transplanted into wild-type Lewis (n = 30) and analbuminemia (n = 10) rats, followed by immunosuppression using tacrolimus (TAC) with/without cyclophosphamide (CPA) or no immunosuppression. Organ viability was traced by in vivo bioimaging and Doppler ultrasonography in the recipient rats for 4 to 6 months. Rat albumin production was also evaluated in the analbuminemia rats for 4 months. In addition, histological analyses including Ki67 proliferation staining were performed in some recipients. RESULTS: Both immunosuppressive protocols significantly improved graft survival and histological rejection of CLs as compared to the nonimmunosuppressed group. Although rat albumin production was maintained in the recipients for 4 months after transplantation, ultrasonography revealed patent circulation in the grafts for 6 months. Ki67 staining analysis also revealed the regenerative potential of CLs after a hepatectomy of the host native liver, whereas immune reactions still remained in the mouse-origin structures. CONCLUSIONS: This is the first report showing that engineered CLs have potential as alternative grafts to replace the use of grafts from human donors.

DOI： 10.1097/SLA.0b013e31825c5349

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PubMed

Language：Japanese   Publisher：(一社)日本外科学会  

Language：Japanese   Publisher：(一社)日本外科学会  

J-GLOBAL

Language：English   Publishing type：Research paper (scientific journal)  

Acute rejection of a small-bowel transplant is often difficult to diagnose due to complicated immune responses. The present study aimed to elucidate the specific immune responses involved in intestinal transplant rejection. We correlated immunohistologic findings with an increase in crypt apoptosis, which has been commonly accepted as a criterion for the diagnosis of acute cellular rejection (ACR). Of 8 patients who received an intestinal allograft at Kyoto University Hospital, biopsy specimens from 7 patients were assessed immunohistologically with antibodies against 20 types of lymphocytic antigens including CD3, CD4, CD8, CD79a, CD20, IgG, and T-cell receptor, along with assessment of the patients' clinical courses. It was revealed that, in addition to apoptotic crypts, T-lymphocyte apoptosis and phagocytosis of apoptotic bodies in the lamina propria of villi were findings of ACR; both were observed in all cases. Immunostaining of the Fas ligand, one of the apoptosis-inducing molecules, was useful for the identification of the apoptotic bodies in the lamina propria of villi. Apoptotic body phagocytosis may be a surrogate diagnostic finding of grafts undergoing ACR.

DOI： 10.1097/PAS.0b013e31826393fe

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Language：English   Publishing type：Research paper (scientific journal)  

It has previously been demonstrated that glutathione S-transferase T1 (GSTT1) genetic mismatch between recipient and donor is a risk factor for developing immune-mediated hepatitis following liver transplantation and for antibody-mediated rejection in renal transplantation. Little is known whether the GSTT1 gene polymorphism affects the incidence of acute cellular rejection (ACR) following living donor liver transplantation (LDLT). Patients underwent LDLT at Nagoya University or Kyoto University, Japan, between 2004 and 2009. Genotyping of GSTT1 genes (null or present genotype) was conducted in recipients and donors. A total of 155 LDLT cases were examined. Forty-seven recipients (30.3%) developed early ACR. There was no association of recipient GSTT1 genotype with ACR incidence. However, ACR incidence was significantly higher in recipients transplanted from GSTT1 present genotype donors than in those transplanted from GSTT1 null genotype donors [odds ratio (OR)=2.64, 95% confidence interval (CI)=1.12-5.83, p=0.016]. Moreover, GSTT1 recipient/donor genotype mismatch (present/null or null/present) was significantly associated with ACR development (OR=2.28, 95% CI=1.12-4.61, p=0.022). The genotyping of GSTT1 in recipients and donors might be useful to stratify the liver transplant recipients according to risk of ACR.

DOI： 10.1016/j.trim.2012.11.002

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Pharmaceutical Society of Japan  

Association between cytochrome P450 (CYP) <i>3A4*1G</i> genotype of donors (<i>n</i>=412) and/or recipients (<i>n</i>=410), and the pharmacokinetics of tacrolimus and the risk of acute cellular rejection was examined in Japanese living-donor liver transplant patients between 2004 and 2011. The concentration/dose (C/D) ratio of tacrolimus in patients carrying graft liver with <i>CYP3A4*1/*1</i> was significantly higher during 7 d after surgery than in that with <i>CYP3A4*1/*1G</i> (214 <i>vs.</i> 157 [ng/mL]/[mg/kg/day], <i>p</i><0.01). After postoperative day 8, no significant difference was observed among <i>CYP3A4*1G</i> genotypes in the graft liver. However, the C/D ratio in <i>CYP3A4*1/*1</i> of the intestine was significantly higher than that in <i>CYP3A4*1G/*1G</i> for 5 weeks after surgery (postoperative days 1–14; <i>p</i><0.001, postoperative days 15–35; <i>p</i><0.01). During postoperative days 14 and 26, acute cellular rejection incidences tended to be lower in the patients with graft liver carrying the <i>CYP3A4*1</i>/*<i>1</i> allele than in the patients carrying <i>CYP3A4*1G</i> allele (8.7% <i>vs.</i> 14.6%, <i>p</i>=0.0973). However, <i>CYP3A4*1G</i> in the intestine had almost no effect on the incidence of rejection (9.9% in <i>CYP3A4*1/*1</i> <i>vs.</i> 12.5% in <i>CYP3A4*1G</i> allele, <i>p</i>=0.4824). <i>CYP3A4*1G</i> was significantly related to mRNA expression of CYP3A5 rather than of CYP3A4 in the graft liver and intestine and was strongly linked with the <i>CYP3A5*1</i>. Thus, we elucidated that <i>CYP3A4*1G</i> genotype in the intestine was an important indicator of the pharmacokinetics of tacrolimus, whereas this genotype in the graft liver tended to influence the frequency of acute cellular rejection after transplantation.

DOI： 10.1248/bpb.b13-00509

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CiNii Research

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Few studies have examined the long-term outcomes and prognostic factors associated with pediatric living living-donor liver transplantation (LDLT) using reduced and hyper-reduced left lateral segment grafts. We conducted a retrospective, single-center assessment of the outcomes of this procedure, as well as clinical factors that influenced graft and patient survival. Between September 2000 and December 2009, 49 patients (median age: 7 months, weight: 5.45 kg) underwent LDLT using reduced (partial left lateral segment; n = 5, monosegment; n = 26), or hyper-reduced (reduced monosegment grafts; n = 18) left lateral segment grafts. In all cases, the estimated graft-to-recipient body weight ratio of the left lateral segment was more than 4%, as assessed by preoperative computed tomography volumetry, and therefore further reduction was required. A hepatic artery thrombosis occurred in two patients (4.1%). Portal venous complications occurred in eight patients (16.3%). The overall patient survival rate at 1, 3 and 10 years after LDLT were 83.7%, 81.4% and 78.9%, respectively. Multivariate analysis revealed that recipient age of less than 2 months and warm ischemic time of more than 40 min affected patient survival. Pediatric LDLT using reduced and hyper-reduced left lateral segment grafts appears to be a feasible option with acceptable graft survival and vascular complication rates.

DOI： 10.1111/j.1600-6143.2012.04268.x

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Language：Japanese   Publisher：(一社)日本臓器保存生物医学会  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Early diagnosis and treatment of acute cellular rejection (ACR) after intestinal transplantation (ITx) is challenging. We report the outcome of three patients: two presented mild ACR improved with steroids. One presented steroid-resistant severe rejection, improved after rabbit anti-thymocyte globulin (r-ATG), but unfortunately died for encephalitis caused by opportunistic infections.

DOI： 10.1007/s00383-012-3110-x

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J-GLOBAL

Language：Japanese   Publisher：(一社)日本消化器外科学会  

Language：Japanese   Publisher：(一社)日本小児外科学会  

Other Link： https://search.jamas.or.jp/default/link?pub_year=2012&ichushi_jid=J01113&link_issn=&doc_id=20120703080087&doc_link_id=10.11164%2Fjjsps.48.4_810_3&url=https%3A%2F%2Fdoi.org%2F10.11164%2Fjjsps.48.4_810_3&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：English   Publisher：WILEY-BLACKWELL  

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Language：English   Publishing type：Research paper (scientific journal)  

Immunological responses in human intestinal allografts are poorly understood and accurate diagnosis of acute cellular rejection remains difficult. Here, human intestinal allografts were analyzed by multi-color quantitative fluorescent immunohistochemical morphometry in order to monitor the clinical course of rejection. Morphometry gave two-dimensional plots based on size and circularity, and identified phenotypes of individual cells infiltrating the allograft by fluorescent staining. Using this method, invariant TCRVα24(+) NKT (iNKT) cells were observed in the intestinal allograft during rejection. Because these were not identified in the normal donor intestine before surgery, this finding was considered to be a signature of acute cellular rejection of the intestinal allograft. Infiltrating iNKT cells released IL-4 and IL-5, Th2-related cytokines that antagonize the Th1 responses that induce acute cellular rejection. Histological observation suggested eosinophilic enteritis in the mucosa with elevation of IL-4 and IL-5. In conclusion, iNKT cells were recruited to the intestine; however, because higher levels of IL-4 and IL-5 may contribute to eosinophilic enteritis, timely steroid administration is recommended for allograft injury due to enteritis, as well as acute cellular rejection.

DOI： 10.1111/j.1432-2277.2012.01450.x

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Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Publisher：南江堂  

DOI： 10.15106/j00393.2012100116

CiNii Research

Language：Japanese   Publisher：(株)南江堂  

肝尾状葉切除にはさまざまな術式が存在する。肝機能因子と腫瘍因子を考慮して肝切除範囲を決定する。助手は、肝尾状葉の立体的イメージと尾状葉枝の解剖を術前によく理解しておく。術中は「場」の確保、確実な結紮、十分なコミュニケーションに留意する。手術助手には、術者になったつもりで次の手を考えながら、術者をサポートしてほしい。(著者抄録)

Language：Japanese   Publisher：特定非営利活動法人 日本小児外科学会  

DOI： 10.11164/jjsps.48.4_810_3

CiNii Research

Language：Japanese   Publisher：(一社)日本移植学会  

Language：Japanese   Publisher：(一社)日本移植学会  

Language：Japanese   Publisher：(一社)日本移植学会  

Language：Japanese   Publisher：(一社)日本移植学会  

Language：Japanese   Publisher：(一社)日本臓器保存生物医学会  

Language：Japanese   Publisher：(一社)日本移植学会  

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：(一社)日本外科学会  

Language：Japanese   Publisher：(一社)日本外科学会  

Language：Japanese   Publisher：日本外科系連合学会  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS INC  

The development of organ preservation solutions and associated technology has been a major effort in tissue transplantation recently. However, this research takes a great deal of time and resources. In this study, a novel method for the evaluation of preservation solutions was established by using islet cells. Primary islets were obtained by hand-picking method from the luciferase transgenic (Luc-Tg) rat pancreas. The viability rate and living condition of islets preserved with several solutions were evaluated by relative photon intensity. Preserved islets were transplanted to the renal capsule of streptozotocin (STZ)-induced type 1 diabetic NOD-scid mouse, and the intraperitoneal glucose tolerance test (IPGTT) and histology were analyzed. The Luc-Tg rat islet viability was increased in a relative photon intensity-dependent manner. In the recipients of ET-Kyoto (ET-K) or University of Wisconsin (UW) solution preserved Luc-Tg rat islet at 1 day, hyperglycemia induced by glucose injection declined to the normal range. In conclusion, this study demonstrates that the ET-K preservation method allowed tissue ATP synthesis and amelioration of cold ischemic tissues damage during extended 24 h isolated-islet preservation. This simple method will be adapted easily to the clinical setting and used to maximize the utilization of islet transplantation as well as for pancreas sharing with remote centers.

DOI： 10.4161/isl.3.3.15626

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Ischemia-reperfusion (I/R) injury associated with living donor liver transplantation impairs liver graft regeneration. Mesenchymal stem cells (MSCs) are potential cell therapeutic targets for liver disease. In this study, we demonstrate the impact of MSCs against hepatic I/R injury and hepatectomy. METHODOLOGY/PRINCIPAL FINDINGS: We used a new rat model in which major hepatectomy with I/R injury was performed. Male Lewis rats were separated into two groups: an MSC group given MSCs after reperfusion as treatment, and a Control group given phosphate-buffered saline after reperfusion as placebo. The results of liver function tests, pathologic changes in the liver, and the remnant liver regeneration rate were assessed. The fate of transplanted MSCs in the luciferase-expressing rats was examined by in vivo luminescent imaging. The MSC group showed peak luciferase activity of transplanted MSCs in the remnant liver 24 h after reperfusion, after which luciferase activity gradually declined. The elevation of serum alanine transaminase levels was significantly reduced by MSC injection. Histopathological findings showed that vacuolar change was lower in the MSC group compared to the Control group. In addition, a significantly lower percentage of TUNEL-positive cells was observed in the MSC group compared with the controls. Remnant liver regeneration rate was accelerated in the MSC group. CONCLUSIONS/SIGNIFICANCE: These data suggest that MSC transplantation provides trophic support to the I/R-injured liver by inhibiting hepatocellular apoptosis and by stimulating regeneration.

DOI： 10.1371/journal.pone.0019195

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Language：Japanese   Publisher：(一社)日本移植学会  

J-GLOBAL

Language：Japanese   Publisher：(株)臨床評価刊行会  

Language：English   Publisher：Clinical Transplantation  

Living donor liver transplantation (LDLT) has evolved based on the premise that donor safety is most important. In 2005, we encountered a donor who developed a pulmonary embolism during the early post-operative period. As it is important for donors to be healthy, most risk factors related to perioperative thrombosis, such as obesity, age, and malignancy are used as exclusion criteria during the evaluation process. We speculated that thrombophilia not detected by conventional laboratory examinations may cause post-operative thrombotic complications and should be investigated by application of additional parameters, including protein S, protein C, antithrombin III, anti-β2-glycoprotein I antibodies (anti-β2GPI), and lupus anticoagulant. From July 2005 to June 2007, we evaluated 44 donor candidates for LDLT using our novel algorithm for screening of thrombophilia, which revealed two suspected candidates (one with low protein S, one with low protein C, and positive anti-β2GPI findings), who were subsequently excluded from the donor pool. Thereafter, all donor hepatectomies, which included two borderline donors given anticoagulants perioperatively, were performed without complications. Four donors (two suspected, two borderline) would not have been recognized without additional screening. In conclusion, we were able to detect thrombophilia and avoid donor thrombosis using additional screening criteria and our novel algorithm. © 2010 John Wiley & Sons A/S.

DOI： 10.1111/j.1399-0012.2010.01216.x

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Language：Japanese   Publisher：(株)学研メディカル秀潤社  

J-GLOBAL

Language：Japanese   Publisher：(一社)日本移植学会  

Language：Japanese   Publisher：(一社)日本移植学会  

Language：Japanese   Publisher：(一社)日本臓器保存生物医学会  

Language：Japanese   Publisher：(一社)日本移植学会  

Language：Japanese   Publisher：(一社)日本消化器外科学会  

Language：Japanese   Publisher：日本組織移植学会  

Language：English   Publisher：WILEY-BLACKWELL PUBLISHING, INC  

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Language：Japanese   Publishing type：Research paper (scientific journal)  

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

The transjugular portosystemic shunt, widely used to treat portal hypertension today, may increase the risk of encephalopathy and reduce effective hepatic flow. To address these issues, a strategy to produce a portocaval shunt (PCS) with hepatic function using intestinal grafts was conceived, and rat models were developed. We transplanted ileal grafts from wild-type and luciferase transgenic Lewis rats to wild-type Lewis rats, anastomosing the graft mesenteric artery (SMA) and portal vein (PV) to the recipient PV trunk and inferior vena cava, respectively. Recipient survival was significantly longer in the partial PCS model, in which the graft SMA was anastomosed to the recipient PV trunk in an end-to-side fashion, than in the total PCS model, with the end-to-end anastomosis. In the partial PCS model, histological and luminescence analyses showed graft survival for 1 month. These results suggest that intestinal grafts can be maintained in the particular conditions required for our strategy.

DOI： 10.1002/micr.20751

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It is thought that the small intestine may provide a scaffold for pancreas regeneration. Herein, we investigated whether fetal pancreatic tissue could be transplanted into the segmental intestine in rats. Fetal pancreases from firefly luciferase transgenic Lewis rat embryos (embryonic day 14.5 and 15.5) were transplanted into streptozotocin (STZ)-induced diabetic wild-type Lewis rats. As a scaffold for pancreatic development, rat small intestinal segments were utilized after the removal of mucosa, and fetal pancreases were grafted into the luminal surface through the stoma. We also transplanted fetal pancreases into the omentum. The survival of transplanted fetal pancreases was monitored by luciferase-derived photons and blood glucose levels. Transplanted fetal pancreas-derived photons were stable for 28 days, suggesting that transplanted fetal pancreatic tissues survived and that their intestinal blood supply was maintained.

DOI： 10.1002/micr.20771

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Language：English   Publisher：Transplantation Proceedings  

Respiratory complications often develop in liver transplant recipients, and appropriate respiratory management is crucial to improve patient outcome. To evaluate the clinical usefulness of noninvasive positive pressure ventilation (NPPV) in liver transplant recipients, we established application criteria for NPPV in respiratory management in these patients, as follows: (1) arterial oxygen tension to fraction of inspired oxygen ratio less than 300 and arterial carbon dioxide tension greater than 45 mm Hg; (2) arterial oxygen tension to fraction of inspired oxygen ratio less than 200; (3) respiratory rate greater than 25/min; and (4) presence of severe atelectasis or pulmonary edema. A bilevel positive airway pressure ventilator was used with the pressure level adjusted to minimize patient discomfort. In patients who were not able to tolerate NPPV, it was discontinued. However, it was continued until patients no longer had dyspnea without NPPV or to resolution of the initial indication for NPPV such as hypoxemia, hypercapnia, or atelectasis. Of 36 patients who underwent liver transplantation between 2005 and 2007, NPPV was administered in 6 according to our criteria. After extubation, recipients demonstrated hypoxemia, hypercapnia, tachypnea, severe atelectasis, or pulmonary edema. After treatment, these conditions improved without apparent problems related to treatment with NPPV. In 1 patient, reintubation was required because of deterioration of respiratory function due to systemic infection. In conclusion, NPPV was useful in liver transplant recipients after extubation to prevent respiratory deterioration. For successful NPPV, settings must be individualized for each patient. © 2009 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.transproceed.2009.06.218

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Language：English   Publisher：British Journal of Surgery  

Background: The aim of this study was to evaluate the effects of mild macrovesicular steatosis on the outcome of living liver donors following right hepatectomy. Methods: The medical records of 46 living liver donors who underwent right hepatectomy were studied. Ten donors had mild macrovesicular steatosis (5-10 per cent in seven and 11-20 per cent in three patients). Five donors with other liver pathology were excluded. Outcome in these ten donors (group 1) was compared with that in the remaining 31 donors with normal liver histology (group 2). Results: The median duration until normalization of total bilirubin levels was 14 and 5 days in groups 1 and 2 respectively (P = 0·028). The peak total bilirubin level was significantly higher in group 1 than in group 2 (80·4 versus 49·6 μmol/l; P = 0·033).Multivariable analysis showed mild macrovesicular steatosis to be an independent risk factor for hyperbilirubinaemia (odds ratio 7·94 (95 per cent confidence interval 1·17 to 54·03); P = 0·034). Conclusion: Mild macrovesicular steatosis may be related to adverse outcome in living liver donors who undergo right hepatectomy and, in terms of donor safety, is of potential concern in donor selection. © 2009 British Journal of Surgery Society Ltd.

DOI： 10.1002/bjs.6479

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Abstract:  A central venous catheter (CVC) is commonly used for intraoperative management by anesthetists and surgeons during major operations, including donor operations for living donor liver transplantation (LDLT), in which donor safety is of utmost importance. Reasons for use of CVC for donors include measurement of central venous pressure and drug infusion when necessary. A potentially serious complication of a major operation is pulmonary thromboembolism. We report two cases of LDLT donors complicated by catheter related thrombosis (CRT) of the jugular vein, who were eventually discharged without long‐term complications. To the best of our knowledge, there has been no report of CRT among LDLT donor population. In this report, in order to minimize the risks related to CRT in LDLT donors, we propose thorough screening for thrombophilic disorders, use of a silicone or polyurethane double‐lumen CVC as thin as possible, placement of the tip of the CVC at the superior vena cava via the right jugular vein using ultrasonography as a guide for puncture, and removal of the catheter at the end of the operation based on our experience of CRT among LDLT donors.

DOI： 10.1111/j.1399-0012.2008.00939.x

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Language：Japanese   Publisher：一般社団法人日本消化器外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本消化器外科学会  

CiNii Research

Language：English  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Consideration of the prognosis of patients with liver cirrhosis is important when determining the appropriate timing of liver transplantation. Especially in Japan, where 99% of liver transplants are from living donors, timing is very important not only for the patient but also for the family, who need time to consider the various factors involved in living donations. METHODS: To clarify the applicability of the Model for End-Stage Liver Disease (MELD) score in Japanese patients with cirrhosis, changes in the MELD score over 24 months were reviewed in 79 patients with cirrhosis who subsequently died of liver failure (n=33) or who survived 24 months (n=46). All patients had Child class B or C cirrhosis at the start of follow-up. We also compared their survival with that of 30 patients treated by living donor liver transplantation (LDLT) in our institute to determine the proper timing of transplantation in patients with cirrhosis. RESULTS: Significant stratification of survival curves was observed for MELD scores of <12, 12-15, 15-18, and >18 (P=0.0018). A significant survival benefit of LDLT was observed in patients with MELD score >or=15 (P=0.0181), and significantly more risk with transplantation was observed in those with MELD score <15 compared with that of patients in whom the disease followed its natural course (P=0.0168). CONCLUSIONS: MELD score is useful for predicting 1-year survival in Japanese patients with cirrhosis. MELD scores of 15 had discriminatory value for indicating a survival benefit to be gained by liver transplantation and thus can be used to help patients and their families by identifying patients who would benefit from LDLT.

DOI： 10.1007/s00535-008-2168-7

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Language：English   Publishing type：Research paper (scientific journal)  

Addition of the middle hepatic vein (MHV) or reconstruction of its tributaries to increase noncongestive graft volume is expected to improve graft function in right liver living donor liver transplantation (LDLT). However, the relationship between noncongestive graft volume and graft function after transplantation has not been clarified and definitive criteria for the reconstruction of MHV tributaries have yet to be established. We analyzed 29 right liver LDLT cases. The noncongestive graft weight was calculated as the total weight of the graft regions drained by hepatic veins reconstructed without postoperative occlusion. We calculated the noncongestive graft-to-recipient weight ratio (ncGRWR) by comparing it to the GRWR. Indocyanine green (ICG) clearance results on days 1 and 3 were significantly correlated with ncGRWR, but not with GRWR. Patients were then divided into 2 groups based on ncGRWR: lower than the median (L-ncGRWR group) and above the median (H-ncGRWR group). ICG clearance in the H-ncGRWR group was significantly better on days 1 and 3. For a different analysis, the patients were again divided into 2 groups, those with and without prolonged cholestasis after transplantation. ncGRWR was significantly lower in patients with prolonged cholestasis, and 7 of 9 patients with an ncGRWR value lower than 0.65 suffered from prolonged cholestasis. Our results demonstrated that the noncongestive volume of a right liver graft has a significant association with early graft function. Further, ncGRWR can play a key role in preoperative determination for additional vein reconstruction of MHV tributaries. When the estimated ncGRWR value with reconstruction of only the right hepatic vein (RHV) (+ inferior right hepatic vein [IRHV]) is)ess than 0.65, additional vein reconstruction of MHV tributaries should be planned. © 2007 AASLD.

DOI： 10.1002/lt.21231

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Language：Japanese   Publisher：一般社団法人日本消化器外科学会  

CiNii Research

Language：English   Publisher：American Journal of Transplantation  

A major concern in adult-to-adult living donor liver transplantation is the selection of graft type; that is, is it is better to use the right lobe with or without the middle hepatic vein (MHV)? This choice has a considerable impact on donor safety, vascular reconstruction and graft function in the recipient. To facilitate making an appropriate choice, on the basis of a preliminary study (n = 17), we herein propose a graft selection algorithm using three parameters: graft-to-recipient body weight ratio (GRWR), percentage remnant liver volume (%RLV) and estimated congestion ratio (ECR). The algorithm was evaluated with 50 consecutive cases with respect to postoperative liver function of donors and recipients and survival of recipients. Postoperative recovery was comparable between the two groups (p = NS). The overall cumulative 18-month survival rate was 86.7% for the 'with MHV graft group', and 76.1% for the gwithout MHV graft grouph (p = NS). For 41 cases (82%), graft types were chosen according to the algorithm, whereas the remaining 9 cases (18%) needed detailed discussion of donor, recipient and operative factors. In conclusion, we constructed a graft selection algorithm based on congestion volume, which will contribute to objective graft-type selection in adult-to-adult LDLT. © 2007 The Authors.

DOI： 10.1111/j.1600-6143.2007.01849.x

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Language：Japanese  

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

Invasive aspergillosis (IA) is a severe complication of liver transplantation. Risk factors for IA after deceased donor liver transplantation (DDLT) have been presented in several reports, but are not well established for living donor liver transplant recipients. Here, a retrospective case-control study was performed. Five cases with IA were investigated after living donor liver transplantation (LDLT) between January 1999 and December 2002 at Kyoto University Hospital. For comparison, living donor liver transplant recipients without IA were taken as controls. These patients had undergone LDLT 1 month before or after each IA case and had the same survival times as the latter. We evaluated the clinical and laboratory findings for both groups up until their demise. Patients with IA after LDLT had a very poor prognosis. By univariate analysis, risk factors for IA were preoperative intensive care unit stay (P = 0.02) and preoperative steroid administration (P = 0.02). Preoperative steroid administration for fulminant hepatitis possibly predisposed to the development of IA after LDLT.

DOI： 10.1002/lt.21099

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Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：English   Publisher：BLACKWELL PUBLISHING  

Tuberculosis remains one of the most serious infections after organ transplantation. Isoniazid prophylaxis for liver transplant recipients with a history of tuberculosis is generally recommended. However, its benefit is controversial because of potential hepatotoxicity of isoniazid. It is crucial to determine appropriate post-transplant managements for the recipients with a history of tuberculosis. The purpose of this study was to investigate the necessity of isoniazid prophylaxis for liver transplant recipients who had a history of tuberculosis. The medical records of 1116 liver transplant recipients were studied, of whom seven had a history of tuberculosis (0.63%). One who underwent living-donor liver transplantation for fulminant hepatic failure was excluded from evaluation because of early death, caused by bacterial sepsis two months after transplantation, although reactivation of tuberculosis was not observed. The median observation period after transplantation was 25.5 months (range 12-82). Reactivation of tuberculosis did not occur in any of these six patients. In conclusion, we could not find rationale for isoniazid prophylaxis in liver transplant recipients with past diagnosis of tuberculosis, when the disease is considered to be inactive. Tuberculosis should be considered as cause of post-transplant infections, and careful post-transplant observations are essential for an early diagnosis.

DOI： 10.1111/j.1399-0012.2006.00630.x

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BACKGROUND: In 2003, we encountered the first donor death for living donor liver transplantation in Japan, which was related to nonalcoholic steatohepatitis (NASH). The aim of this study was to retrospectively investigate the prevalence of NASH among a living donor liver transplantation donor population and to analyze the postoperative course for both donors and recipients of NASH grafts to minimize risk for donors. METHODS: The study population comprised 263 donors who donated the right lobe of the liver between February 1998 and April 2003. Their zero-hour biopsy specimens were screened retrospectively. Regarding severe steatosis or NASH, long-term follow-up results for laboratory data from donors were investigated along with changes in graft histologic findings in recipients. RESULTS: NASH was diagnosed histopathologically in three cases (1.1%). Pathologic examination showed that a donor who died in 2003 had the most severe NASH among the three cases. The remaining two NASH donors had uneventful postoperative courses without complications. All grafts showed improvement with respect to the steatosis and histologic findings of NASH. CONCLUSIONS: Donor safety is a top priority in living donor liver transplantation. To exclude patients with NASH from potential donor lists, careful evaluation, including selective preoperative liver biopsy, should be carried out.

DOI： 10.1097/01.tp.0000250671.06456.3f

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING  

Hepatitis C virus reinfection after liver transplantation is universal and more severe than in nontransplant patients. Rejection episodes and immunosuppressive agents are considered risk factors for deterioration of recurrent hepatitis C. We report 2 cases of living donor liver transplantation for patients with hepatitis C-related cirrhosis who received right-lobe grafts from an identical twin. Thanks to genetic identity, no immunosuppressive drugs were administered during or after transplantation without rejection. Hepatitis C virus RNA kinetics showed a rapid increase following transplantation and liver biopsies 1 month after transplantation showed acute lobular hepatitis in both cases. Antiviral therapy using interferon alpha and ribavirin was started immediately, and both cases showed virological and histological response. In conclusion, avoidance of immunosuppression did not delay hepatitis C recurrence following transplantation, while early antiviral therapy without risk of rejection or immunosuppression led to successful viral eradication.

DOI： 10.1111/j.1600-6143.2006.01531.x

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DOI： 10.1111/j.1432-2277.2006.00386.x

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This report concerns the long-term outcome of living donor liver transplantation (LDLT) for pediatric patients at a single center. Between June 1990 and December 2003, a total of 600 LDLTs, including 568 primary transplantations and 32 retransplantations, were performed for pediatric patients, who were immunosuppressed with FK506 and low-dose corticosteroids. Patient survival at 1, 5, and 10 years were 84.6%, 82.4%, and 77.2%, respectively, and the corresponding findings for graft survivals were 84.1%, 80.9%, and 74.5%. Multivariate analysis demonstrated that fulminant hepatic failure (FHF), a graft vs. body weight (GBWR) ratio of <0.8, and ABO-incompatible transplants were independently associated with both patient and graft survival. The retransplantation rate was 6%, and 55 patients (9.7%) have been completely weaned off immunosuppressants. Long-term patient and graft survival after pediatric LDLT for a large cohort of children at our hospital were found to be as good as those for cadaveric liver transplantation, although this series includes 13% liver transplantations with ABO-incompatible donors, which are obviously inferior in patient and graft survival. To obtain better outcomes for patients with FHF and for patients with ABO-incompatible transplants, immunosuppressive therapy needs to be improved.

DOI： 10.1002/lt.20826

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Language：Japanese   Publisher：一般社団法人日本消化器外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本消化器外科学会  

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

The primed status of T cells is markedly different among liver transplant recipients, due to a lifetime of antigen exposure and reduced thymopoiesis by aging, and diseases. This study aims to characterize the preoperative immunological status of CD8+ T cell subpopulations and relate it to the outcome for liver transplant recipients. We classified 112 liver transplant recipients into 5 groups, based on hierarchical clustering of the CD8+CD45 isoform proportion of T cells. In Groups I and II (pediatric), the naive T cell proportion was more than 50%. In adult recipients, Group III was characterized by a naive T cell proportion of 50%, Group IV had the greatest effector/memory T cells (EM), and Group V had the greatest proportion of effector T cells. In Groups IV and V, the effector T cell proportion was considerably higher, and was accompanied by marked downregulation of the CD27+CD28+ subsets and upregulation of interferon gamma (IFN)-gamma, tumor necrosis factor-alpha, and perforin expression. Group V recipients tended to be complicated postoperatively, with a significantly reduced survival rate (1 yr, 66.8%) and markedly reduced Eastern Cooperative Oncology Group performance status.

DOI： 10.1002/lt.20705

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This study examined the decision-making processes of donors in adult-to-adult living donor liver transplantation. Twenty-two donors were interviewed using a semi-structured format. Interview contents were transcribed verbatim and analyzed qualitatively using grounded theory. A decision-making model was developed consisting of 5 stages: (1) recognition, (2) digestion, (3) decision-making, (4) reinforcement, and (5) resolution. The second and the third stages described donors' experiences of "reaching a decision"; the fourth and fifth stages described those of "facing transplantation." The central theme of this model was "having no choice," which consisted of 4 codes: (1) priority of life, (2) only LDLT, (3) for family, and (4) only me. In conclusion, this model can help health care professionals to understand the donor experience and, based on that understanding, to provide sufficient support to the donor.

DOI： 10.1002/lt.20689

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CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

Complement C4d deposition in graft capillaries has been reported to be associated with antibody-mediated rejection in kidney and other solid organ transplantation. The correlation of C4d deposits and humoral rejection in liver transplants, however, is not well understood. We investigated the C4d immunostaining pattern in 34 patients whose liver biopsy was taken within the first 3 postoperative weeks for suspected acute rejection after ABO blood type-incompatible liver transplantation. The staining pattern was classified as positive (portal stromal staining), indeterminate (endothelial staining only), and negative (no staining). Positive C4d immunostaining was seen in 17 (50%) patients and was significantly associated with high (x64 or more) postoperative antidonor A/B antibody (immunoglobulin M (IgM)) titers (88 vs. 35%, P = 0.002) and poorer overall survival rate (41 vs. 88%, P = 0.007). Ten of 11 (91%) cases with histological acute humoral rejection (periportal edema and necrosis (PEN) or portal hemorrhagic edema) were positive for C4d, all of which showed high postoperative antibody titers. The other histologies associated with C4d positivity was purulent cholangitis (n = 4), coagulative hepatocyte necrosis (n = 1), acute cellular rejection (n = 1), and hepatocanalicular cholestasis (n = 1). Full clinical recovery was observed in only 6 of 17 (35%) C4d-positive patients, and tended to be associated with a lower rejection activity index (RAI). In conclusion, our study indicates that C4d deposits in the portal stroma can be a hallmark of acute humoral rejection in ABO-incompatible liver transplantation, and allograft damage can be reversible in a minority of cases.

DOI： 10.1002/lt.20652

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Graft-versus-host disease (GVHD) is an uncommon but potentially devastating complication following liver transplantation. Recently, it was shown that use of a human leukocyte antigen (HLA)-homozygous donor leading to one-way HLA matching significantly increases the risk of GVHD after living donor liver transplantation (LDLT). However, the precise impact of HLA matching between donor and recipient on the risk of GVHD is not yet clear. We surveyed instances of fatal GVHD following LDLT in Japan and reviewed all 8 cases in detail, especially with respect to HLA matching. Serological typing showed that 7 of those cases had donor-dominant one-way HLA matching in the 3 loci of HLA-A, -B, and -DR, while one had donor-dominant one-way HLA matching in the 2 loci of HLA-A and -DR and identical alleles in the B locus. However, DNA typing revealed that the latter case had 1-way HLA matching in the 3 loci. Further, we analyzed HLA typing of 906 donor-recipient pairs who underwent LDLT. There were 5 cases with donor-dominant one-way matching in 2 loci and 2 with donor-dominant one-way matching in 1 locus. All of those cases except 1, who died from an unrelated cause, are alive without an obvious presentation of GVHD. In conclusion, our results suggest that the total number of loci with donor-dominant one-way HLA matching is important for determining the risk of fatal GVHD following LDLT, and that DNA typing of HLA alleles is indispensable in some cases to identify the true risk of donor-dominant 1-way HLA matching. © 2005 AASLD.

DOI： 10.1002/lt.20573

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DOI： 10.11477/mf.1407100245

CiNii Research

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Living-donor liver transplantation (LDLT) has become an established technique to treat children with end-stage liver disease. Biliary atresia (BA), one of the most common indications for liver transplantation in children, can be associated with situs inversus (SI). In the past, the presence of SI has been considered to be an absolute contraindication for liver transplantation because of the technical difficulties. Recently, some reports of successful diseased-donor liver transplantation in patients with BA complicated by SI have been published; however, few reports of that with LDLT exist. The technical difficulties involved with LDLT for such cases have not been described. Herein, we present 4 successful cases of LDLT for BA with SI. Complex anomalies associated with SI, such as a hepatic artery arising from the supraceliac aorta, a preduodenal portal vein, and absence of the retrohepatic inferior vena cava, increase the technical difficulties involved with the operation. Additional caution is required in LDLT because a living-donor graft has short vessels and the availability of vascular grafts from the donor is limited. In conclusion, LDLT for BA complicated by SI can be managed successfully with technical modifications and scrupulous attention. This series represents the largest reported group of patients with BA complicated by SI who underwent a successful LDLT procedure.

DOI： 10.1002/lt.20584

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Language：English   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Background. Prolonged T-cell depletion after liver transplantation leads to life-threatening infections. Members of the anti-apoptotic Bcl-2 gene family can maintain T-cell viability. T-cell numbers and their Bcl-2 expression following living donor liver transplantation (LDLT) were analyzed in 108 surviving and 13 deceased recipients.
Materials and methods. Bcl-2 mRNA levels and phenotypic changes of T-cells were examined by quantitative PCR and by measuring expression of CD45RO and CCR7.
Results. Based on the restoration of peripheral T-cell numbers, the 108 surviving recipients were classified into three groups. All recipients showed T-cell depletion, down to approximately 30% of pretransplant levels within 3 h of graft reperfusion. In Group 1, the T-cell numbers were rapidly restored to pretransplant levels, within 5 days, with a rapid decrease in Bcl-2 mRNA levels immediately after LDLT. In Group 11, the T-cell numbers were restored to normal levels by 19 days, with down-regulation of Bcl-2 mRNA. In Group III, the T-cell numbers were maintained at low levels for much longer, with high levels of Bcl-2 mRNA. In all three groups of recipients, there was statistically significant (r = -0.78) inverse correlation between T-cell numbers and Bcl-2 mRNA.
Conclusions. For successful transplantation, homeostatic restoration of T-cells must occur as soon as possible. Evaluation of peripheral T-cell numbers and of Bcl-2 expression may have therapeutic potential in identifying those transplant patients who face increased risk of infection. (c) 2005 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.jss.2005.03.008

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Language：Japanese   Publisher：一般社団法人日本消化器外科学会  

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Technical improvements in adult-to-adult living-donor liver transplantation (LDLT) have led to the use of right-lobe grafts to overcome the problems encountered with 'small-for-size grafts'. The major controversy remains that the venous drainage from anterior segment substantially depends on tributaries of the middle hepatic vein (MHV), and deprivation of such tributaries may critically influence the postoperative graft function. Right-lobe grafts with MHV could resolve the potential problem of congestion in anterior segment. From December 2000 to January 2004, we performed 217 right-lobe LDLTs for adult patients. Of these, 40 patients received a right lobe with MHV graft (18.4%). The overall cumulative 3-year graft survival rate of a right lobe with (n = 40) and without MHV (n = 177) was 86.2% and 74.8% (p = NS). The proximal side of the MHV and the drainage vein of segment IV to the MHV (the left medial superior vein) were preserved in 24 patients. All of them needed venous interposition graft for anastomosis. All patients had a patent right hepatic vein (RHV) and MHV anastomosis during the follow-up period. We adopted the right lobe with MHV graft in 40 LDLT cases. Vein graft is essential for safe MHV anastomosis in cases which preserve proximal side of the MHV.

DOI： 10.1111/j.1600-6143.2005.00817.x

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Language：Japanese   Publisher：一般社団法人日本外科学会  

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Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1097/01.TP.0000146241.67033.21

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Auxiliary partial orthotopic liver transplantation (APOLT) was initially indicated as a potentially reversible fulminant hepatic failure and non-cirrhotic metabolic liver disease to compensate for enzyme deficiency without complete removal of the native liver. We expand our indication of APOLT for small-for-size grafts to support the function of implanted grafts during the early post-operative period, and for ABO-incompatibility to sustain a patient's life if the patient has a graft failure. We retrospectively reviewed 31 patients undergoing APOLT from living donor. The indication of APOLT was fulminant hepatic failure in 6, non-cirrhotic metabolic liver disease in 6, small-for-size grafts in 13 and ABO-incompatible cases in 6. The cumulative survival rate for APOLT at 1 and 5 years was 57.9% and 50.6%, and 78.8% and 73.8% for standard LDLT. None of the patients who underwent transplantation with APOLT for fulminant hepatic failure had long-term patient survival. The incidence of acute cellular rejection was higher in APOLT (58.1%) than standard LDLT (35.0%). Biliary complication was higher and the need for retransplantation was greater in APOLT than standard LDLT (p < 0.01). The results suggest that the indications of APOLT should be reconsidered in view of the risk for complications and retransplantation.

DOI： 10.1111/j.1600-6143.2005.00717.x

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Two cases of living-donor liver transplantation performed in patients with situs inversus are reported. The authors discuss the operative management for a situs inversus recipient to undergo liver transplantation.

DOI： 10.1016/j.jpedsurg.2004.11.013

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：Elsevier USA  

The frequency and the outcome of patients with portal vein (PV) complications in the long-term course after pediatric living donor liver transplantation (LDLT) have rarely been reported. Between June 1990 and September 2003, 527 pediatric patients underwent primary LDLT with left lobe grafts, among which 479 patients with functioning grafts at 3 months after LDLT were included in this analysis. The ages ranged from 29 days to 17 years, 3 months (median: 1 year, 9 months) and body weight from 3.1 kg to 62.4 kg (median: 9.6 kg). Biliary cirrhosis was the most common cause for LDLT (81%). The PV was anastomosed with or without a vein graft. Thirty-nine patients (8%) showed a PV complication (stenosis: 16
obstruction: 17
thrombus: 2
twist: 3). Their ages ranged from 4 months to 17 years, 3 months (median: 1 year) and their body weight from 3.8 kg to 44.8 kg (median: 8.5 kg) at operation. PV complications were detected between 4 and 116 months (median: 14 months) after the transplant. Splenomegaly and decreased platelet counts were observed in more than 90% of the patients with a PV complication. In 27 patients (71%), interventional venoplasty was successful. Eleven patients had obstruction of the PV (2.3%) including three who showed cirrhosis
one with severe pulmonary hypertension
one death after retransplantation
and one alive after retransplantation. Moderate fibrosis was found in two patients at 3 and 2 years after the procedure, one of whom had the complication of a moderate intrapulmonary shunt. Early detection of PV stenosis with these two markers can lead to successful angioplasty and avoid graft loss. © 2005 by Elsevier Inc. All rights reserved.

DOI： 10.1016/j.transproceed.2005.01.044

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Language：Japanese   Publisher：(一社)日本移植学会  

7歳男児.帝王切開で出生後,臍帯ヘルニア・先天性腸閉鎖の診断で小腸切除術を受け,短腸症候群となり高カロリー輸液(TPN)管理されていた.長期TPN管理によるカテーテル感染を繰り返し,中心静脈カテーテル留置のための静脈経路確保が困難なため,3歳9ヵ月で小腸移植適応となった.術後免疫抑制剤はFK506,ステロイド,cyclophsohamide,抗CD25抗体を使用した.術後拒絶反応を2回認めたが,ステロイドパルス療法で軽快した.術後2年10ヵ月で人工肛門を閉鎖した.1ヵ月後に発熱,下痢を訴え,内視鏡検査で小腸グラフト盲端部に多発潰瘍を確認した.EBVによる小腸グラフト腸炎・潰瘍性病変と診断した.抗ウイルス剤投与で臨床症状・病変部内視鏡所見の改善がみられなかったため,グラフト盲端部切除術を施行した.術後12日目で軽快退院した

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CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

Pulmonary complications are an important cause of the mortality associated with liver transplantation. The efficacy of noninvasive ventilation (NIV) in pediatric patients following transplantation is unknown. The purpose of this retrospective study is to investigate the effects of NIV for pediatric patients undergoing liver transplantation. Of 102 pediatric patients who underwent liver transplantation, 15 patients (aged 73 months; range 2.5-179) were supported by NIV because of atelectasis, hypercapnia, hypoxemia, pneumonia, massive effusion, or postextubation ventilatory support. Of 15 patients, 5 were under the age of 1 year (range 2.5-12 months). Of the 15 patients, 7 had required multiple intubations before NIV treatment because of pulmonary complications. NIV treatment was administered to 6 patients because of hypercapnia. Partial pressure of arterial carbon dioxide (PaCO(2)) levels improved from 56.9 (95% confidence interval [CI]: 48.4-65.4) to 41.5 (95% CI: 36.8-46.2) mmHg (P = .028) within 2 days. NIV treatment was very effective for patients with atelectasis with and without other pulmonary complications. Mean inspiratory positive pressure (IPAP) was 7.2 (95% CI: 6.0-8.3) cm H(2)O and expiratory positive pressure (EPAP) was 3.5 (95% CI: 3.2-3.9) cm of H(2)O. Mean duration of NIV was 18.5 (95% CI: 8.6-28.4) days. IPAP and EPAP levels were closely and significantly correlated with height (IPAP: r = .65, P = .016; EPAP: r = .77, P = .004). A total of 13 patients recovered and 2 patients died. However, no patient died of respiratory complications. In conclusion, NIV is effective in pediatric patients undergoing liver transplantation with subsequent pulmonary complications. The IPAP and EPAP levels may be predicted by the height of the patient.

DOI： 10.1002/lt.20297

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Background. Bolus steroids are usually administered prior to graft reperfusion in an attempt to provide protection against ischemia reperfusion injury (IRI). However, the anti-IRI properties of steroids have not been established. Living donor liver transplantation (LDLT) between identical twins provides a unique opportunity to study the natural production of cytokines during transplantation without the confounding influences of the alloimmune response or of immunosuppression in particular steroids.
Methods. A 38-year-old male with hepatitis C virus-related cirrhosis and multiple hepatocellular carcinomas received a hepatic right lobe graft from his identical twin. No immunosuppression was administered, not even intraoperative bolus steroids. IRI was assessed by serum transaminases as well as by proinflammatory interleukin (IL) IL-1 beta, tumor necrosis factor (TNF)-alpha, IL-8 cytokines and for potent regenerative/anti-inflammatory (IL-6, IL-10) mediators.
Results. Despite no administration of steroids, low peak levels of serum transaminases were observed. Serum IL-6 and IL-10 dramatically and rapidly increased during liver transplantation, namely, 160 and 20 times higher than baseline, respectively. In contrast, IL-10 and TNF-alpha remained low during and after transplantation and an increase in IL-8 was less obvious.
Conclusion. Syngeneic LDLT without intraoperative bolus steroids is feasible, yielding no penalty in terms of IRI. A predominance of protective cytokines was observed in the absence of steroids. Thus, the concept that intraoperative administration of steroids is necessary to protect liver transplants from IRI must be revisited.

DOI： 10.1016/j.transproceed.2004.12.272

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Language：English   Publisher：BLACKWELL PUBLISHING ASIA  

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CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

Auxilliary partial orthotopic liver transplantation (APOLT) was introduced initially as a tentative or permanent support for patients with potentially reversible fulminant hepatic failure and has extended its indication to congenital metabolic disorder of the liver that has otherwise normal functional integrity. Postoperative management of APOLT is complicated because of functional portal flow competition between the native and graft liver. The native portal vein diversion to the graft is sometimes indicated to prevent functional competition; however, it is still an open question whether this technique can be theoretically indicated for APOLT patients. The authors report a on patient with ornithine transcarbamylase deficiency who received APOLT from a living donor without native portal vein diversion. Because of functional portal vein competition between the native and graft liver, the patient had to have portal vein diversion, portal vein embolization, and finally native hepatectomy to induce the graft regeneration after APOLT. After the experience of the current case, primary portal vein diversion for APOLT with noncirrhotic metabolic liver disease patients to prevent functional portal flow competition is recommended.

DOI： 10.1016/j.jpedsurg.2004.03.079

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In the development of adult-to-adult living donor liver transplantation (LDLT), the small-for-size graft has been associated with poor clinical outcome. Persistent portal hypertension or portal venous overperfusion are considered to be causative factors, and partial diversion of portal flow to systemic circulation may be effective for avoiding injuries that occur in the small-for-size (SFS) graft. Recently, we constructed an end-to-side portocaval shunting using 1 of the portal branches and anastomosed the other branch with the portal vein of the graft in 2 cases of LDLT recipients transplanted with a SFS graft. With the suppression of portal hypertension, as well as sufficient portal flow to the graft, the recipients recovered successfully with favorable graft function. This new and simple technique may be able to be used as a feasible and effective method to attenuate the SFS syndrome.

DOI： 10.1002/lt.20164

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To clarify the clinical applicability of intestinal absorptive barriers, we have quantified messenger ribonucleic acid (mRNA) expression levels of multidrug resistance 1 (MDR1) protein and cytochrome P450 (CYP) 3A4 in intestinal biopsy specimens from 2 small-bowel transplant recipients. Postoperative immunosuppressive therapy was started with intravenous and oral administrations of tacrolimus and a small amount of steroids. The daily dosage of tacrolimus was modified mainly on the basis of trough levels. After confirmation that the enterocyte MDR1 level was decreasing, tacrolimus was administered via the oral route only. The mRNA levels in the biopsy specimens varied widely throughout the period. With high-dose steroid-pulse treatment, the enterocyte mRNA expression of CYP3A4, but not of MDR1, was markedly enhanced. The mRNA levels of MDR1, but not CYP3A4, correlated well with the concentration/oral dose ratio and the oral dosage of tacrolimus. The good progress after transplantation in both cases suggested that monitoring the change in expression of MDR1 mRNA in the graft intestine might be helpful for understanding the pharmacokinetic profile and determining when to change the route of tacrolimus administration in small-bowel transplant recipients.

DOI： 10.1016/j.clpt.2003.11.374

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DOI： 10.1097/01.TP.0000110319.60723.31

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BACKGROUND: The only therapeutic option for patients with a failing allograft is retransplantation. Living donor liver transplantation (LDLT) is a well-accepted therapeutic option for end-stage liver disease, but retransplantation from a living donor (Re-LDLT) has not previously been discussed. METHODS: A total of 547 LDLTs were performed in 519 children (<18 years old) at Kyoto University Hospital from June 1990 to October 2002. During the same study period, a total of 28 Re-LDLTs were performed in 27 recipients (Re-LDLT performed twice in 1 patient). Patient survival was analyzed with respect to various preoperative factors, such as functional status, pretransplantation apheresis, cause of primary graft failure, interval from primary to subsequent transplants, and laboratory values of total bilirubin and creatinine. RESULTS: Kaplan-Meier survival rate from the date of Re-LDLT to 1 year was 47.6%. Functional status, pretransplantation apheresis, interval to Re-LDLT, and bilirubin and creatinine levels all exerted an adverse impact on survival after Re-LDLT. Pathologically proven major causes of primary graft failure were chronic rejection (n=10, 35.7%), chronic cholangitis (n=6, 21.4%), and vascular complications (n=7, 25.0%). Among these causes, vascular complications displayed the strongest adverse impact on survival, compared with chronic cholangitis and chronic rejection (1-year survival was 35.7% in vascular complications; 66.7% in chronic cholangitis; and 60.0% in chronic rejection). CONCLUSIONS: Re-LDLT can save patients with a failing allograft. To achieve better results after Re-LDLT, further investigations are necessary to understand the factors leading to poor outcome after Re-LDLT.

DOI： 10.1097/01.TP.0000080068.22576.3B

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With the extensive use of living donor liver grafts in adult patients, controversy over small-for-size syndrome has escalated in recent years. Although several symptoms have been suggested as manifestations of the syndrome, small-for-size syndrome remains difficult to diagnose because these symptoms are neither specific nor inevitable. The occurrence of small-for-size syndrome also seems to depend on a number of recipient and graft factors. Potential pathogenic mechanisms include persistent portal hypertension and portal overperfusion. At present, several techniques are being explored in an attempt to ameliorate the impact of small-for-size syndrome. Recent experience suggests that the occurrence of small-for-size syndrome is multifactorial and that complications relating to small-for-size grafts should be examined in relation to a variety of graft, recipient, and technical factors.

DOI： 10.1053/jlts.2003.50198

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BACKGROUND: Living-donor liver transplantation is now an established technique to treat children with end-stage liver disease. Implantation of left-lateral segment grafts can be a problem in small infants because of a large-for-size graft. We report 10 cases of transplantation using monosegment grafts from living donors. METHOD: Of 506 children transplanted between June 1990 and June 2002, 10 patients (median age 196 days, median weight 5.9 kg) received monosegment living-donor liver transplants. The indication for using this technique was infants with an estimated graft-to-recipient weight ratio of over 4.0%. RESULTS: Graft and patient survival was 80.0%. There were no differences in donor operation time and blood loss between monosegmentectomy and left-lateral segmentectomy (n=281). Monosegmental transplantation had a high incidence of vascular complications (20.0%). CONCLUSION: Monosegmental living- donor liver transplantation is a feasible option with satisfactory graft survival in small babies with liver failure.

DOI： 10.1097/01.TP.0000079446.94204.F9

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Living-donor liver transplantation (LDLT) using the left lateral segment or left-lobe graft has been widely accepted, but currently, right-lobe grafts are more commonly used in many LDLT programs with yet unknown risks for donors. METHODS: We investigated our initial 200 donors of righ-lobe grafts to focus on the incidence and variety of surgery-related morbidity. Changes in liver function tests were also analyzed to clarify the relation with donor age, steatosis of the liver, and residual liver volume (RLV). Complications were surveyed for a median period of 28.7 months. RESULTS: In all the donors, liver enzymes and bilirubin were normalized within 1 month. Enzymes on day 1 were significantly higher in donors with older age, macrovesicular steatosis, and larger RLV. Bilirubin on day 1 was significantly higher in donors with smaller RLV. Biliary enzyme was not normalized in the majority at 1 month after donation. Seventy-five complications occurred in 69 donors. Biliary complications were most common, which consisted of 26 bile leakages (13%) and 3 biliary strictures (1.5%) in 27 donors. No significant dependence of the incidence was observed either for donor age (>or=50 years), body mass index (BMI) (>or=25 kg/m2), estimated RLV (<40%), or medical history. None of the complications led either to mortality or to long-term sequelae. CONCLUSIONS: Complications occurred in a significant proportion of right-lobe donors irrespective of donor age, BMI, estimated RLV, and medical history. Living-liver donor surgery requires more care in right-lobe transplants.

DOI： 10.1097/01.TP.0000072372.42396.47

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Infantile hepatic hemangioendothelioma (IHHE) is a rare vascular tumor that presents before the age of 6 months. The patients with IHHE suffer from high-output congestive heart failure caused by major arteriovenous fisutulas in the liver, which leads to respiratory compromise and results in a high mortality rate despite medical treatments. A case of 4-month-old baby with liver failure caused by IHHE is reported. The baby received an urgent liver transplantation from a living donor. A monosegmental graft was used to mitigate graft-to- recipient size mismatching. The surgical procedure of monosegmental living donor liver transplantation also is discussed.

DOI： 10.1016/S0022-3468(03)00206-9

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Alagille syndrome (AGS) is an autosomal dominant genetic disorder characterized by chronic cholestasis, congenital heart disease, peculiar facies, butterfly-like vertebrae, and posterior embryotoxon. Liver dysfunction is the common presentation of AGS, and liver transplantation may be indicated. This study examines the outcome of living-related liver transplantation (LRLT) for AGS. Twenty patients with AGS (median age 5.0 years, range 0.6-12.9) underwent LRLT at Kyoto University Hospital between June 1990 and February 2002. Five potential donors were excluded because of paucity of intrahepatic bile ducts diagnosed by preoperative liver biopsy and one because of a hepatic vascular anomaly. The overall 5-year patient survival was 80.4%. Three patients died as the result of the following: complications related to surgery, heart failure caused by progressive pulmonary artery stenosis, and a graft with unsuspected bile duct paucity. Liver dysfunction was improved in all successful cases, and catch-up growth occurred in 90% of patients. LRLT is an efficacious treatment modality for AGS if donors are selected by cautious evaluation to rule out unsuspected bile duct paucity.

DOI： 10.1097/01.TP.0000066804.33006.17

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PubMed

Language：English  

CiNii Research

Language：English   Publisher：Transplantation Proceedings  

Background. Living donor liver transplant (LDLT) program has been started from 1990 in Japan, and is still major form of liver transplantation because of the scarcity of cadaveric donor organs. In small infants, implantation of left lateral segment grafts can be a problem because of a large-for-size graft. Until November 2002, we performed 867 transplants for 828 patients (561 children and 306 adults), and 14 cases received monosegment grafts from living donors. Method. Fifteen patients, median age 211 days, median weights 5.95 kg, received monosegmental LDLT. The indication for using this technique was infants with an estimated graft-to-recipient weight ratio of over 4.0%. Results. Graft and patient survival is 85.7%. There were no differences in donor operation time and blood loss between monosegmentectomy and left lateral segmentectomy. Segment III grafts were indicated in 13 cases. Two vascular complications were observed (one hepatic artery thrombosis and one portal vein thrombosis). Conclusion. Monosegental living donor liver transplantation is a feasible option with satisfactory graft survival in small babies with liver failure.

DOI： 10.1016/S0041-1345(03)00445-7

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PubMed

Language：English   Publisher：W B SAUNDERS CO  

Web of Science

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Although living-donor liver transplantation (LDLT) has been accepted for adult populations, the occurrence and pathogenesis of small-for-size syndrome remain highly controversial. METHODS: Portal venous pressure (PVP) was measured in 79 cases of LDLT from anhepatic phase to day 14. PVP was monitored through a catheter inserted via the inferior mesenteric vein. In a separate series of seven cases of adult LDLT, the splenic artery was ligated following arterial reperfusion. RESULTS: For days 2 to 4 and 9 to 11, recipients of small-for-size graft (<0.8% of body weight) displayed significantly higher PVP than recipients of larger grafts. The 13 patients with elevated mean PVP (>or=20 mm Hg) early in the first week (days 0-4) demonstrated significantly worse survival (84.5% vs. 38.5% at 6 months; P < 0.01), but this was not applicable to elevated mean PVP late in the first week (days 5-7). Elevated PVP early in the first week was also associated with higher incidence of bacteremia, cholestasis, prolonged prothrombin time, and ascites. Splenic artery ligation (SAL) immediately reduced PVP from 10 to 20 mm Hg (median, 16 mm Hg) to 9 to 13 mm Hg (median, 11 mm Hg; P = 0.02). Posttransplant PVP was significantly lower in SAL patients than in non-SAL patients from days 2 to 7 despite small graft size. Early PVP in SAL patients was consistently below 20 mm Hg, and survival was significantly better than in non-SAL patients with high early PVP (P < 0.01). CONCLUSION: Elevated PVP in the early phase is strongly associated with poor patient survival attributable, at least in part, to small-for-size graft. Further elucidation of the pathogenesis behind this phenomenon and efforts to modify PVP will be key to improving results.

DOI： 10.1097/01.TP.0000063707.90525.10

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

In cadaveric liver transplantation, the Milan criteria have been accepted as the selection criteria for hepatocellular carcinoma (HCC) patients in considering organ allocation. However, the situation is different in living-donor liver transplantation (LDLT), in which the donor has a strong preference for altruism. The authors describe herein their experience with LDLT for HCC patients using their patient selection criteria. From February 1999 to March 2002, right lobe LDLT was performed in 56 patients with HCC. The authors' exclusion criteria included only those with extrahepatic metastasis or vascular invasion detected during preoperative evaluation. Thirty patients (54%) were in tumor, node, metastases stage IVa and 25 patients (45%) did not meet the Milan criteria at the time of LDLT. The follow-up period was 1 to 39 months (median, 11 months). The overall survival rates at 1 and 3 years were 73% and 55%, respectively, and the latter was significantly lower than that of adult right lobe LDLT without HCC (71% at 3 years). Fourteen patients died because of postoperative complications without tumor recurrence. Thirty-six patients survived without recurrence and six patients had recurrence. Among the six patients with recurrence, four had survived for 11 to 36 months after LDLT. In the analysis of patients who survived longer than 3 months after transplantation, 19 of 20 within the Milan criteria survived without recurrence. However, 15 of 20 patients beyond the criteria also survived without recurrence for 3 to 33 months (median, 12 months) and three of five patients with recurrence were alive for 11 to 36 months (median, 20 months). Histopathologic grading and microscopic portal venous invasion had significant negative impact on tumor recurrence. LDLT was an effective treatment for uncontrollable hepatocellular carcinoma. Because many patients who did not meet the Milan criteria survived without tumor recurrence after transplantation, different patient selection criteria are necessary in LDLT to save those with advanced HCC.

DOI： 10.1097/01.TP.0000047029.02806.16

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PubMed

Publisher：南江堂  

DOI： 10.15106/j00393.2003163850

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

Liver transplantation is a fundamental treatment for patients with end-stage hepatic failure. In order to perform living-donor liver transplantations under safer conditions, apheresis plays a major role in Japan due to the prevalence of living-donor liver transplantation wherein later retransplantation is difficult. In our department, the roles of apheresis in liver transplantation are as follows: as bridge therapy to liver transplantation (n = 45); as a supplement to the graft liver until the recovery of hepatic function (n = 77); as treatment for multiple organ failure including posttransplantation renal failure (n = 15); and as a means with which to reduce antibody titers for antibodies such as anti-A or anti-B in persons with ABO blood type = incompatible liver transplantation (n = 23). In our department, we have performed 822 liver transplantations at present. Of those cases, 183 were selected wherein apheresis was performed around the time of the operation. In all cases, transplantation with sufficient apheresis was performed before the surgical operation, however, 22 patients (48.9%) died after undergoing surgery. Among the patients who underwent the postoperative apheresis, those in the nonsurvivor group had lower grafted liver weights compared to those of the survivor group. The kidney was the organ that most frequently failed due to postoperative complications. In cases of ABO blood type-incompatible liver transplantations, patients with high preoperative anti-A/B IgM antibody titers sustained bile duct complications, patients with high preoperative anti-IgG antibody titers sustained hepatic necrosis, and patients with high postoperative anti-A/B IgM and anti-IgG antibody titers sustained hepatic necrosis most frequently.

DOI： 10.1046/j.1526-0968.2002.00460.x

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Human leukocyte antigen (HLA) matching is, at present, not used for the allocation of cadaveric hepatic allografts because the liver is generally believed to be less susceptible to HLA-mediated rejection. However, the exact role of HLA compatibility in the long-term outcome of liver transplantation is not yet clearly defined. One of the advantages of living-related liver transplantation (LRLT) could be a better histocompatibility between donor and recipient. This study aimed at an assessment of the influence of HLA compatibility in a large series of LRLTs. METHODS: A total of 321 pediatric patients who underwent ABO-identical or ABO-compatible primary LRLT from the parental donors in the period between June 1990 and August 2000 were involved in the study. Graft survival, rejection episodes, and immunosuppression were evaluated from the viewpoint of HLA compatibility. RESULTS: The overall 1- and 5-year graft survivals were 85.7% and 84.1%, respectively. The cumulative 5-year graft survivals in HLA 0-, 1-, 2- and 3-mismatch groups (A, B, and DR) were 100% (n=10), 78.9% (n=19), 86.2% (n=87), and 82.9% (n=205), respectively (P=0.525). The overall incidence of rejection during the follow-up period (median 66 months, range 16-139 months) was 46.1%. No significant difference was found in the incidence of rejection and rejection-free survival among the four groups. However, steroid-resistant rejection that necessitated OKT3 treatment (n=6) and chronic rejection (n=2) were recognized only in the 3-mismatch group. The whole-blood trough level of tacrolimus and the duration of steroid administration were not significantly different among the groups. The rate of the patients who succeeded in withdrawal from immunosuppression was also similar among the groups. However, the trough level of tacrolimus needed for maintenance of an acceptable liver function test during the chronic phase tended to be lower in well-matched pairs, and a high percentage of immunosuppressant-free patients were found in the 0-mismatch group. Fatal graft-versus-host disease developed in one patient with a complete one-way HLA-matched transplant. CONCLUSION: We could not find any supportive evidence of beneficial effects of HLA-matching in pediatric LRLT. The potential benefit of HLA-matching for the reduction protocol for immunosuppressants may play a role in the withdrawal program. It appears unnecessary to pay attention to HLA compatibility in donor selection in LRLT, except for one-way HLA matching, or to adjust immunosuppression according to HLA compatibility.

DOI： 10.1097/00007890-200210270-00020

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PubMed

Language：Japanese  

CiNii Research

Language：English   Publisher：ELSEVIER SCIENCE INC  

DOI： 10.1016/S0041-1345(02)02980-9

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Scopus

PubMed

Language：Japanese   Publisher：日本アフェレシス学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

The mucosal layer is the initial site of small bowel (SB) graft injury sustained during cold storage. Vascular administration of preservation solutions alone is unable to prevent ischemic injury of this layer during clinically relevant storage periods. The SB is unique in that it possesses both a vascular and a luminal route by which preservation solutions can be administered. We hypothesized that addition of a luminal-delivered solution, formulated on amino acid requirements for energy- and non-energy-related reactions, would provide site-specific preservation of mucosal energetics, barrier function and morphology throughout an extended period of cold storage. Of the three luminal solutions containing amino acids which were tested (UWG, AA1, AA2), only the two groups (AA1, AA2), containing glutamine plus 18 other amino acids, +/- osmotic agent (lactobionate) and buffer (BES), exhibited significant improvements in energetics, barrier function, and histology compared to the clinical standard of isolated vascular University of Wisconsin (UW) solution. Although the AA1 and AA2 groups preserved barrier function and morphology up to 24h better than all other solutions tested, AA2 proved to be the only luminal solution with values of permeability, conductance, and short-circuit current not significantly different from freshly isolated tissues. Furthermore, the greatest reduction in histologic injury was effected by AA2 treatment (median grade 2 compared to control, UW(v), grade 8). This study documents that a luminal-delivered solution, formulated on physiologic SB requirements, provides targeted preservation of the SB mucosa.

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Glutamine (gln)-supplemented University of Wisconsin (UW) solution improves overall small bowel (SB) preservation. Sustained gln metabolism in a system devoid of hepatic detoxification will necessarily result in the accumulation of pH active end products leading to nonphysiologic pH shifts. We hypothesized that simultaneous addition of N,N-bis[2-hydroxyethyl]-2-aminoethane sulfonic acid (BES), a known buffering agent, would potentiate the beneficial effect of gln supplementation by addressing the fundamental metabolic principle of pH homeostasis. METHODS: Sprague-Dawley SB rats were administered a vascular flush with one of four solutions: UW; UW+90 mM BES (UWB); UW+2% gln (UWG); or UW+2% gln+90 mM BES (UWBG). Indices of energetics, barrier function, gln catabolism, and histology (light and electron microscopy) were assessed over a 10-hr cold storage time course. RESULTS: Superior gln utilization in the UWBG group was indicated by elevated levels of key catabolites (glutamate, aspartate, glycine, ammonia). The addition of BES and gln resulted in significantly higher levels of all energetic parameters (ATP, total adenylates) at 10 hr compared with UW, UWB, and/or UWG. Barrier function was markedly improved after 10 hr storage in the UWBG group; mannitol permeability was 169 nmol/cm2/hr versus 572 and 445 nmol/cm(2)/hr (for UW and UWG, respectively). Histologic injury at 10 hr was 5.5, 7.5, and 8 (Park's grade) for UWBG, UWG, and UW. Ultrastructural damage was markedly reduced with UWBG, as assessed by grade of mitochondria damage. CONCLUSION: This study strongly supports that the beneficial effects of gln-enriched UW solution can be amplified when combined with an effective buffering agent such as BES.

PubMed

Language：English   Publisher：ELSEVIER SCIENCE INC  

DOI： 10.1016/S0041-1345(00)01205-7

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

A living-related small bowel transplantation (SBT) was performed in two pediatric patients with short bowel syndrome. In both cases, the donor was the patient's mother. The distal ileum (100 cm, 120 cm) was harvested and the ileocolic vessels, ileocecal valve, and terminal ileum were left intact. The two donors were discharged from the hospital on postoperative days 15 and 6, respectively. Recipient 1 was a 2 year 6 month-old boy with short bowel syndrome who underwent SBT due to loss of venous access. The graft vein was anastomosed to the recipient's infrarenal inferior vena cava. Despite triple immunosuppression (tacrolimus, steroid, and azathioprine), there were four episodes of rejection. The patient had been on total parenteral nutrition for almost his entire posttransplant course. He died from Pneumocystis carinii pneumonia 16 months after the transplantation. Recipient 2 was a 4 year 5 month-old girl with short bowel syndrome who underwent an isolated small bowel transplantation because of recurrent line sepsis. Her pretransplant bilirubin was 8.0 mg/dl and a biopsy showed severe fibrosis. The graft vein was anastomosed to the recipient's inferior mesenteric vein. After transplantation, her bilirubin level became normal within 10 days. Triple immunosuppression (tacrolimus, steroid, and cyclophosphamide) together with a 3-day course of OKT-3 made her post-transplant course feasible. After overcoming a single episode of rejection she left the hospital 4 months after SBT The patient is currently (10 months after transplantation) hospitalized due to rejection, which is being successfully controlled, and she is off total parenteral nutrition. From our experience, harvesting of the distal ileum for use as a bowel graft can be safely performed. The advantages of living-related grafts, optimal graft length, and choice of vascular reconstruction in SBT are yet to be explored. © Springer-Verlag 2000.

DOI： 10.1111/j.1432-2277.2000.tb02015.x

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PubMed

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本消化器外科学会  

CiNii Research

Language：Japanese   Publisher：特定非営利活動法人 日本小児外科学会  

DOI： 10.11164/jjsps.35.3_574_1

CiNii Research

Language：English   Publisher：ELSEVIER SCIENCE INC  

DOI： 10.1016/S0041-1345(98)01093-8

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PubMed

Language：English   Publisher：ELSEVIER SCIENCE INC  

DOI： 10.1016/S0041-1345(97)01216-5

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Language：Japanese   Publisher：特定非営利活動法人 日本小児外科学会  

DOI： 10.11164/jjsps.34.5_949_1

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

Intestinal failure has been managed with total parenteral nutrition (TPN), but occasionally complications such as obliteration of venous access or liver dysfunction occur. To overcome such complications, small bowel transplantation (SET) was introduced. Since the introduction of tacrolimus in 1990, successful SET cases have been reported. We performed SET by using a living donor for a child with short bowel syndrome. The recipient (2.5 years old, male) was born with intestinal necrosis secondary to midgut volvulus. The length of the remaining small bowel was 30 cm. While being managed with TPN, his venous access gradually obliterated. Long-term survival could not be expected because of the difficulty in securing TPN access. The donor was his mother, whose distal ileum (100 cm) was used as a graft. The immunosuppression regimen consisted of tacrolimus, steroids and azathioprine. Three episodes of severe rejection and subsequent episodes of viral (EBV, CMV) infection were managed with steroid pulse therapy and antiviral drugs, respectively. The recipient suffered from anastomotic stenosis, and an operation was performed 13 months after transplantation to resect the stenotic segment. However, the patient died of Pneumocystis carinii pneumonia 16 months after transplantation. We conclude that organ retrieval from a living donor can be performed safely for SET, but further study of the management of rejection as well as of viral infection is necessary, as it is for non-living-related SET. © Munksgaard 1998.

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PubMed

Language：Japanese   Publisher：特定非営利活動法人 日本小児外科学会  

DOI： 10.11164/jjsps.33.3_575_2

CiNii Research

Language：Japanese   Publisher：特定非営利活動法人 日本小児外科学会  

DOI： 10.11164/jjsps.33.3_444_2

CiNii Research

Language：Japanese   Publisher：特定非営利活動法人 日本小児外科学会  

DOI： 10.11164/jjsps.31.3_527_1

CiNii Research

Total pages：Vi, 134 p.   Language：English

CiNii Books