眞田 幸弘

BACKGROUND: We present retrospective analysis of our 15-year experience with pediatric living donor liver transplantation, focusing on the risk factors, treatments, and long-term prognosis for posttransplant biliary complications (BCs). METHODS: Between May 2001 and December 2017, 290 living donor liver transplantations were performed. The median age was 1.4 years old. The median observation period was 8.4 years. Biliary strictures were classified as anastomotic stricture (AS) or non-AS (NAS). RESULTS: Overall incidence of biliary complications was 18.6%, including AS in 46 cases, NAS in 6, and other classifications in 2. The mean period to diagnosis of the AS was 641 ± 810 postoperative days. The multivariate analysis showed that hepaticojejunostomy without external stent was an independent risk factor for AS (P = 0.011). The first treatments for AS were percutaneous transhepatic biliary drainage (PTBD) in 25 cases, double-balloon enteroscopy (DBE) in 19, and surgical reanastomosis in 2. The success and recurrence rates of PTBD treatments were 90.9% and 22.7%, respectively. The success and recurrence rates of endoscopic interventions under DBE were 93.6% and 75.3%, respectively. The 15-year graft survival rates in patients with and without AS were 95.7% and 89.1%, respectively (P = 0.255), but 2 patients with cholangitis due to multiple NAS underwent retransplantation. CONCLUSIONS: Posttransplant AS can be prevented by hepaticojejunostomy using external stent, and the long-term prognosis is good with early treatments using DBE or PTBD. However, the prognosis of multiple NAS is poor.

BACKGROUND: We present a retrospective analysis of our experience with pediatric liver transplantation (LT), focusing on the long-term outcome of percutaneous transhepatic biliary drainage (PTBD) for post-transplant biliary strictures. METHODS: Fifty-three PTBDs were performed for 41 pediatric recipients with biliary strictures. The median ages at LT and PTBD were 1.4 and 4.4 years, respectively. The median observation period was 10.6 years. RESULTS: Post-transplant biliary strictures comprised anastomotic stricture (AS) in 28 cases, nonanastomotic stricture (NAS) in 12, anastomotic obstruction (AO) in 8, and nonanastomotic obstruction (NAO) in 5. The success rate of PTBD was 90.6%, and the 15-year primary patency rate of PTBD was 52.6%. The recurrence rate of biliary strictures after PTBD was 18.8% (9/48), and among the four NAS cases with recurrence, two underwent re-LT. The biliary obstruction rate was 27.1% (13/48). Among the eight cases with AO, five underwent the rendezvous method and three underwent surgical re-anastomosis. Among the five cases with NAO, one underwent re-LT. The recipient survival rate of PTBD treatment was 100%. CONCLUSIONS: The graft prognosis of AS by PTBD treatment is good and AO is curable by the rendezvous method and surgical re-anastomosis. However, the graft prognosis of NAS and NAO is poor.

BACKGROUND: Intracranial and pulmonary vascular anomalies are well-known complications and causes of mortality in AGS; however, visceral artery anomalies are less commonly recognized. Herein, we present a retrospective analysis of our experience with pediatric LDLT that focuses on the current problems with and treatments for visceral artery anomalies in AGS after LDLT. METHODS: Between May 2001 and December 2017, 294 LDLTs were performed for 285 pediatric recipients. Of these, 13 LDLTs (4.4%) for 12 AGS patients were performed. We classified the visceral artery anomalies into aneurysms and stenosis. RESULTS: The overall incidence of visceral aneurysm was 2 of 12 recipients (16.7%) and included a SMA aneurysm in one patient and an IPDA aneurysm with a subsequent SPA aneurysm in one patient; the ages of the diagnosis of visceral aneurysm were 16.3, 21.1, and 21.7 y, respectively. An endovascular treatment was performed for a progressive IPDA saccular aneurysm (12.0 × 14.5 × 15.0 mm). The overall incidence of visceral artery stenosis was 7 of 12 recipients (58.3%) and the median age at the diagnosis of visceral artery stenosis was 15.5 y (range 1.7-22.9 y). All 3 AGS patients with RA stenosis suffered from renal dysfunction (eGFR of 51, 78, and 51 mL/min/1.73m2 ). CONCLUSION: The morbidity of visceral artery anomalies is not negligible. The performance of periodic imaging examinations is necessary, even for infants, because it is difficult to detect visceral vascular anomalies in the infant stage.

There are few long-term outcome reports for interventional radiology (IVR) treatments for vascular and biliary complications following pediatric living donor liver transplantation (LDLT). Herein, we presented our institution's experience and investigated the efficacy and issues of long-term outcome with IVR treatments. Between May 2001 and September 2016, 279 pediatric LDLTs were performed. The median age at LDLT was 1.4 years old, and the median observation period was 8.2 years. All the biliary reconstructions at LDLT were hepaticojejunostomy. The IVR treatments were selected as endovascular, radiological, or endoscopic interventions. Post-transplant hepatic vein, portal vein, hepatic artery, and biliary complications were present in 7.9%, 14.0%, 5.4%, and 18.3%, respectively. IVR treatment was the first treatment option in 81.8%, 94.9%, 46.7%, and 94.1%, respectively. The recurrence and cure rates following IVR treatment were 42.1%, 21.1%, 44.4%, and 34.0% and 84.2%, 97.4%, 100%, and 88.0%, respectively. The graft survival rates in patients with and without post-transplant vascular and biliary complications were 94.4% and 90.6%, respectively (P = 0.522). The IVR treatments for vascular and biliary complications following pediatric LDLT are the first choice option. Although the recurrence following IVR treatment is a major problem and it is necessary to carefully perform long-term follow-up, IVR treatments have good treatment outcomes.

BACKGROUND: The genesis of the "complex type" classification of pancreaticobiliary maljunction (PBM) is unclear, and the pancreaticobiliary anatomy is also varied according to each case. We encountered a patient with PBM and incomplete pancreatic divisum (PD). We herein discussed about the embryological etiology of pancreaticobiliary system predicted from PBM with incomplete PD. CASE PRESENTATION: A 67-year-old man was found to have a dilatation of the common bile duct (CBD) during a medical examination at 62 years of age. The dilatation of the CBD subsequently progressed, and he was admitted to our hospital for surgical treatment. Magnetic resonance cholangiopancreatography revealed a dilatation from the common hepatic duct to the middle bile duct with PBM. Endoscopic retrograde cholangiopancreatography from the papilla of Vater revealed the pancreatic main duct via the pancreatic branch duct, and PBM with dilatation of the CBD and incomplete PD were revealed. We performed an extrahepatic bile duct resection and hepaticojejunostomy because of high risk of malignant transformation. Taping and transection of the bile duct without dilatation on the pancreatic side were performed, and thereafter, two orifices of the common channel and ventral pancreatic duct were ligated. The level of amylase in the bile was 7217 IU/L, and a histological examination of the CBD showed an inflammatory change of CBD, not a malignant transformation. CONCLUSION: It is somewhat easy to identify the pancreatobiliary anatomy when the cause of embryology of both PBM and PD is thought to be an abnormal embryology of the ventral pancreas.

Congenital portosystemic shunt (CPS) is classified into type I (congenital absence of the portal vein) and type II, depending on the presence or absence of the intrahepatic portal vein. Reports still exist on cases in which psychiatric diseases or mental retardation was diagnosed or cases in which diagnosis and treatment are not performed until severe pulmonary complications occur, indicating the need to recognize CPS. Herein, we reviewed epidemiology, etiology, classification, symptom, diagnosis, and treatment based on clinical view points of CPS. For clinical view points, classification according to (1) the presence or absence of the intrahepatic portal venous system (IPVS) and (2) the extrahepatic or intrahepatic of shunt sites, facilitates the understanding of pathophysiological conditions and is useful in selecting a treatment for symptomatic CPS. Radiological and pathological examinations are important in IPVS evaluations, and IPVS evaluations are currently essential to make diagnoses by portography with balloon occlusion and liver biopsy. Symptomatic CPS (hepatic nodular lesions, portosystemic encephalopathy, and pulmonary complications, etc.) is an indication of treatment by shunt closure, but an indication of treatment for asymptomatic CPS is the challenge going forward.

PURPOSE: When living donor liver transplantation (LDLT) is performed on small infant patients, the incidence of hepatic artery complications (HACs) is high. Here, we present a retrospective analysis that focuses on our surgical procedure for hepatic arterial reconstruction and the outcomes of monosegmental LDLT. METHODS: Of the 275 patients who underwent LDLT between May 2001 and December 2015, 13 patients (4.7 %) underwent monosegmental LDLT. Hepatic artery reconstruction was performed under a microscope. The size discrepancy between the graft and the recipient's abdominal cavity was defined as the graft to recipient distance ratio (GRDR) between the left hepatic vein and the portal vein (PV) bifurcation on a preoperative computed tomography scan. HACs were defined as hepatic arterial hypoperfusion. RESULTS: Recipient hepatic arteries were selected for the branch patch technique in five cases (38.5 %), and the diameter was 2.2 ± 0.6 mm. The anastomotic approaches selected were the dorsal position of the PV in seven cases (53.8 %) and the ventral position in six, and the GRDRs were 2.8 ± 0.4 and 1.9 ± 0.5, respectively (p = 0.012). The incidence rate of HACs caused by external factors, such as compression or inflammation around the anastomotic site, was significantly higher in monosegmental than in non-monosegmental graft recipients (15.4 vs. 1.1 %, p < 0.001). CONCLUSION: Although monosegmental graft recipients experienced HACs caused by external factors around the anastomotic field, hepatic arterial reconstruction could be safely performed. Important components of successful hepatic arterial reconstructions include the employment of the branch patch technique and the selection of the dorsal approach.

Utilizing the opened round ligament as venous grafts during liver transplantation is useful but controversial, and there are no pathological analyses of this procedure. Herein, we describe the first reported case of a pathological analysis of an opened round ligament used as a venous patch graft in a living donor liver transplantation (LDLT). A 13-year-old female patient with biliary atresia underwent LDLT using a posterior segment graft from her mother. The graft had two hepatic veins (HVs), which included the right HV (RHV; 15 mm) and the inferior RHV (IRHV; 20 mm). The graft RHV and IRHV were formed into a single orifice using the donor's opened round ligament (60 mm × 20 mm) as a patch graft during bench surgery; it was then anastomosed end-to-side with the recipient inferior vena cava. The recipient had no post-transplant complications involving the HVs, but she died of septic shock with persistent cholangitis and jaundice 86 d after LDLT. The HV anastomotic site had no stenosis or thrombus on autopsy. On pathology, there was adequate patency and continuity between the recipient's HV and the donor's opened round ligament. In addition, the stains for CD31 and CD34 on the inner membrane of the opened round ligament were positive. Hepatic venous reconstruction using the opened round ligament as a venous patch graft is effective in LDLT, as observed on pathology.

BACKGROUND: Hepatocellular nodules caused by congenital extrahepatic portosystemic shunts (CEPS) occur as a result of abnormal portal blood flow, and are mostly cases of benign focal nodular hyperplasia (FNH). However, hepatocellular adenomas (HCA) and hepatocellular carcinomas have been documented in the CEPS patients. HCA can now be immunohistochemically diagnosed; therefore, the concept of hepatocellular nodules resulting from CEPS should be revisited. In this study, we performed a retrospective immunohistochemical investigation of hepatocellular nodules from livers isolated from the CEPS patients undergoing living donor liver transplantation (LDLT). METHODS: Hepatocellular nodules from livers of five patients with CEPS who underwent LDLT between June 2004 and October 2012 at our institution were immunohistochemically investigated. HCA were classified into four subtypes (HNF1α-inactivated HCA (H-HCA); inflammatory HCA; β-catenin-activated HCA (b-HCA); unclassified HCA). RESULTS: Sixteen hepatocellular nodules were collected from livers of five patients with CEPS who underwent LDLT. Ten hepatocellular nodules were categorized as FNH (62.5%), five were categorized as b-HCA (31.3%), and one was categorized as H-HCA (6.2%). CONCLUSIONS: Some of the hepatocellular nodules resulting from CEPS were indicative of HCAs, especially the b-HCA subtype which has the potential for malignant transformation. Surgical or interventional treatments might have to be performed when hepatocellular nodules appear in the CEPS patients.

Studies suggest that prophylactic intra-abdominal drains are unnecessary for cadaveric liver transplantation using whole liver grafts because there is no benefit from drainage. However, no studies have investigated on the necessity of prophylactic drains after LDLT using split-liver grafts or reduced-liver grafts, which may present a high risk of post-transplant intra-abdominal infections. This retrospective study investigated whether the ascitic data on POD 5 after LDLT can predict intra-abdominal infections and on the post-transplant management of prophylactic drains. Between March 2008 and March 2013, 90 LDLTs were performed. We assessed the number of ascitic cells, biochemical examinations, and cultivation tests at POD1 and POD5. The incidence rates of post-transplant intra-abdominal infections were 24.4%. The multivariate analysis showed that left lobe and S2 monosegment grafts were a significant risk factor for intra-abdominal infections (p = 0.006). The patients with intra-abdominal infections had significantly higher acsitic LDH levels and the positive rate of ascitic culture at POD5 in comparison with patients without infections (p < 0.001 and p = 0.014, respectively). LDLT using left lobe and S2 monosegment grafts yields a high risk for post-transplant intra-abdominal infections, and ascitic LDH and cultivation tests at POD5 via prophylactic drains can predict intra-abdominal infections.

BACKGROUND: Although endotoxin (Et) has been used as a biological index of bacterial infections, Et can also be used to evaluate liver functions because Et present in the portal vein blood is processed by the hepatic reticuloendothelial system. In the field of posttransplant management, it is important for liver transplant recipients to monitor the presence of posttransplant bacterial infections and graft liver functions because these results are directly correlated with a graft prognosis. Therefore, the measurement of Et during liver transplantation (LT) may be the detection of posttransplant infections and graft liver functions. This retrospective study investigated whether Et measured by the Et activity assay (EAA) in the peripheral venous blood during living donor LT (LDLT) can predict the incidence of posttransplant bacterial infections and graft liver functions. MATERIALS AND METHODS: The study subjects consisted of 21 patients who underwent LDLT between April 2010 and February 2011. Et activity (EA) was measured using the EAA in peripheral venous blood samples collected 1 or 2 days before LDLT, and on postoperative days (PODs) 1, 5, 7, and 14. We included LDLT recipients with intra-abdominal infections, respiratory infections, and bacteremia in the group with posttransplant bacterial infections. RESULTS: The incidence rates of posttransplant bacterial infections or hyperbilirubinemia after LDLT were 57.1%. The LDLT recipients with posttransplant bacterial infections or hyperbilirubinemia had significantly higher levels of EA in comparison with patients without complications before LDLT (0.22 ± 0.10 vs. 0.07 ± 0.05, p < 0.001), but they had no statistically significant increase of EA between PODs 1 and 14. Based on a receiver operating characteristic curve analysis of pretransplant levels of EA in patients with posttransplant bacterial infections or hyperbilirubinemia, the recommended cutoff value to diagnose posttransplant bacterial infections or hyperbilirubinemia was set at 0.16 (sensitivity 83.3%, specificity 88.9%, and area under the curve 0.940). CONCLUSION: At a pretransplant level of EA greater than 0.16, patients had an augmented risk for developing posttransplant bacterial infections or hyperbilirubinemia.

The use of donors with coagulation FIX deficiency is controversial, and there are no current protocols for peri-transplant management. We herein describe the first reported case of a pediatric LDLT from an asymptomatic donor with mild coagulation FIX deficiency. A 32-yr-old female was evaluated as a donor for her 12-month-old daughter with biliary atresia. The donor's pretransplant coagulation tests revealed asymptomatic mild coagulation FIX deficiency (FIX activity 60.8%). Freeze-dried human blood coagulation FIX concentrate was administered before the dissection of the liver and 12 h afterwards by bolus infusion (40 U/kg) and was continued on POD 1. The bleeding volume at LDLT was 590 mL. On POD 1, 3, 5, and 13, the coagulation FIX activity of the donor was 121.3%, 130.6%, 114.6%, and 50.2%, respectively. The donor's post-transplant course was uneventful, and the recipient is currently doing well at 18 months after LDLT. The FIX activity of the donor and recipient at nine months after LDLT was 39.2% and 58.0%, respectively. LDLT from donors with mild coagulation FIX deficiency could be performed effectively and safely using peri-transplant short-term coagulation FIX replacement and long-term monitoring of the plasma FIX level in the donor.

BACKGROUND: Hepatic artery complications (HAC) are a serious complication in pediatric liver transplant recipients because its incidence is high and it can occasionally lead to graft liver failure. We herein present a retrospective analysis of our 10-year experience with pediatric living donor liver transplantation (LDLT) focusing on the risk factors and treatments for HAC. METHODS: Between May 2001 and November 2011, 209 LDLTs were performed for 203 pediatric recipients. We performed the multivariate analyses to identify the factors associated with HAC and showed the therapeutic strategy and outcome for HAC. RESULTS: The overall incidence of HAC was 7.2%, and the graft survival of recipients with HAC was 73.3%. The multivariate analysis showed that the pediatric end-stage liver disease score (≥20), post-transplant laparotomy except for HAC treatment and extra-anatomical hepatic artery reconstruction were independent risk factors for HAC (P = 0.020, P = 0.015 and P = 0.002, respectively). Eleven surgical interventions and 13 endovascular interventions were performed for 15 recipients with HAC. The serum aspartate aminotransferase levels pre- and post-treatment for HAC were significantly higher in the surgical group than in the endovascular group (P = 0.016 and P = 0.022, respectively). CONCLUSIONS: It is important for recipients with risk factors to maintain strict post-transplant management to help prevent HAC and detect it in earlier stages. Endovascular intervention can be a less invasive method for treating HAC than surgical intervention, and can be performed as an early treatment.

AIM: To assessed the clinical significance of protocol liver biopsy (PLB) in pediatric liver transplantation (LT). METHODS: Between July 2008 and August 2012, 89 and 55 PLBs were performed in pediatric patients at two and five years after LT, respectively. We assessed the histopathological findings using the Metavir scoring system, including activity (A) and fibrosis (F), and we identified factors associated with scores of ≥ A1 and ≥ F1. Our results clarified the timing and effectiveness of PLB. RESULTS: The incidences of scores of ≥ A1 and ≥ F1 were 24.7% and 24.7%, respectively, at two years after LT and 42.3% and 34.5%, respectively, at five years. Independent risk factors in a multivariate analysis of a score of ≥ A1 at two years included ≥ 2 h of cold ischemic time, no acute cellular rejection and an alanine amino transaminase (ALT) level of ≥ 20 IU/L (P = 0.028, P = 0.033 and P = 0.012, respectively); however, no risk factors were identified for a score of ≥ F1. Furthermore, no independent risk factors associated with scores of ≥ A1 and ≥ F1 at five years were identified using multivariate analysis. A ROC curve analysis of ALT at two years for a score of ≥ A1 demonstrated the recommended cutoff value for diagnosing ≥ A1 histology to be 20 IU/L. The incidence of scores of ≥ A2 or ≥ F2 at two years after LT was 3.4% (three cases), and all patients had an absolute score of ≥ A2. In contrast to that observed for PLBs at five years after LT, the incidence of scores of ≥ A2 or ≥ F2 was 20.0% (11 cases), and all patients had an absolute score of ≥ F2. In all cases, the dose of immunosuppressants was increased after the PLB, and all ten patients who underwent a follow-up liver biopsy improved to scores of ≤ A1 or F1. CONCLUSION: PLB at two years after LT is an unnecessary examination, because the serum ALT level reflects portal inflammation. In addition, immunosuppressive therapy should be modulated to maintain the ALT concentration at a level less than 20 IU/L. PLB at five years is an excellent examination for the detection of early reversible graft fibrosis because no serum markers reflect this finding.

Some studies have found that gender mismatch between donors and recipients are related to poor graft prognosis after liver transplantation. However, few studies have investigated the impact of gender mismatch on acute cellular rejection (ACR) in pediatric living donor liver transplantation (LDLT). This retrospective study investigated the clinical significance of these factors in ACR after pediatric LDLT. Between November 2001 and February 2012, 114 LDLTs were performed for recipients with biliary atresia (BA) using parental grafts. We performed univariate and multivariate analyses to identify the factors associated with ACR. The donor-recipient classifications included mother donor to daughter recipient (MD; n = 43), mother to son (n = 18), father to daughter (FD; n = 33), and father to son (n = 20) groups. The overall incidence rate of ACR in the recipients was 36.8%. Multivariate analysis showed that gender mismatch alone was an independent risk factor for ACR (P = 0.012). The FD group had a higher incidence of ACR than the MD group (P = 0.002). In LDLT, paternal grafts with gender mismatch were associated with a higher increased incidence of ACR than maternal grafts with gender match. Our findings support the possibility that maternal antigens may have an important clinical impact on graft tolerance in LDLT for patients with BA.

Chromosomal and genomic instability due to telomere dysfunction is known to play an important role in carcinogenesis. To study telomere shortening in the epidermis surrounding actinic keratosis, we measured telomere lengths of basal, parabasal, and suprabasal cells in epidermis with actinic keratosis (actinic keratosis group, n = 18) and without actinic keratosis (sun-protected, n = 15, and sun-exposed, n = 13 groups) and in actinic keratosis itself as well as in dermal fibroblasts in the 3 groups, using quantitative fluorescence in situ hybridization. Among the 3 cell types, telomeres of basal cells were not always the longest, suggesting that tissue stem cells are not necessarily located among basal cells. Telomeres of basal cells in the sun-exposed group were shorter than those in the sun-protected group. Telomeres in the background of actinic keratosis and in actinic keratosis itself and those of fibroblasts in actinic keratosis were significantly shorter than those in the controls. Our findings demonstrate that sun exposure induces telomere shortening and that actinic keratosis arises from epidermis with shorter telomeres despite the absence of any histologic atypia.

Fluid collection is common after living donor liver transplantation (LDLT), and can include hematomas, bilomas, abscesses, and seromas. Although accumulated fluid rarely becomes infected and usually remains localized, localized ascites can sometimes be sufficiently extensive to induce vascular complications. This report presents three such cases in pediatric patients that underwent LDLT. A 33-month-old patient showed an increase in the volume of localized ascites around the hepatic vein anastomoses together with low hepatic vein flow on postoperative day (POD) 47. An 82-month-old patient showed an increase in the volume of localized ascites around the portal vein anastomoses together with low portal vein flow on POD 71. A 63-month-old patient showed an increase in the size of a localized abscess around the hepaticojejunostomy with dilatation of all of the intrahepatic bile ducts on POD 20. These cases illustrate the need for awareness of possible vascular or biliary complications due to compressive localized ascites after LDLT.

Along with the increasing need for living-donor liver transplantation (LDLT), the issue of organ shortage has become a serious problem. Therefore, the use of organs from elderly donors has been increasing. While the short-term results of LDLT have greatly improved, problems affecting the long-term outcome of transplant patients remain unsolved. Furthermore, since contradictory data have been reported with regard to the relationship between donor age and LT/LDLT outcome, the question of whether the use of elderly donors influences the long-term outcome of a graft after LT/LDLT remains unsettled. To address whether hepatocyte telomere length reflects the outcome of LDLT, we analyzed the telomere lengths of hepatocytes in informative biopsy samples from 12 paired donors and recipients (grafts) of pediatric LDLT more than 5 years after adult-to-child LDLT because of primary biliary atresia, using quantitative fluorescence in situ hybridization (Q-FISH). The telomere lengths in the paired samples showed a robust relationship between the donor and grafted hepatocytes (r = 0.765, p = 0.0038), demonstrating the feasibility of our Q-FISH method for cell-specific evaluation. While 8 pairs showed no significant difference between the telomere lengths for the donor and the recipient, the other 4 pairs showed significantly shorter telomeres in the recipient than in the donor. Multiple regression analysis revealed that the donors in the latter group were older than those in the former (p = 0.001). Despite the small number of subjects, this pilot study indicates that donor age is a crucial factor affecting telomere length sustainability in hepatocytes after pediatric LDLT, and that the telomeres in grafted livers may be elongated somewhat longer when the grafts are immunologically well controlled.

BACKGROUND: Endotoxin (Et) in the portal vein blood is processed by the hepatic reticuloendothelial system. Thus, it is possible that the Et kinetics of the peripheral venous blood may be useful as a biological index that can be used to evaluate liver function. In this study, we measured Et using the endotoxin activity assay in peripheral venous blood during living donor liver transplantation (LDLT), to study its clinical significance. METHODS: Subjects were 17 patients who underwent LDLT. In the perioperative peripheral venous blood, was measured Et activity (EA) using the endotoxin activity assay at 1 or 2 d before LT, and then on 1, 5, 7, 14, and 21 postoperative days. RESULTS: Patients with infections had significantly higher EA levels compared with those without complications before LDLT and 14 postoperative days (P = 0.038 and 0.027, respectively). The average EA level of patients with infections and without complications before LT was 0.22 and 0.08, respectively (P = 0.038). Patients with an EA level higher than 0.20 before LDLT had a significantly longer period of hospitalization compared with those without complications (P = 0.038). CONCLUSIONS: A preoperative EA level more than 0.20 is a high risk factor for post-transplant infection and a prolonged period of hospitalization.

BACKGROUND: Endotoxin (Et) in the portal vein blood is processed by the hepatic reticuloendothelial system, and therefore, it is possible that the hepatic clearance of Et may become a biological index for liver function. In this study, Et levels of preoperative peripheral and portal vein blood at the time of liver transplantation (LT) were measured in order to study the meaning. METHODS: The study population comprised 19 patients in whom pediatric living donor LT was performed. In the preoperative peripheral and the portal vein blood at the time of LT, we measured Et activity (EA) by the Et activity assay (EAA) and the Limulus amebocyte lysate (LAL) method. RESULTS: The preoperative peripheral vein blood showed a low EA in all cases. In the EA of the peripheral and the portal vein blood, the latter showed a significantly high level (p = 0.049). With the LAL method, 5.3% (2/38) of patients were positive for Et. CONCLUSIONS: The EAA is considered to be superior to the LAL method for the detection of Et, even in low endotoxinemia, and is also capable of elucidating the Et kinetics by accurately reflecting hepatic clearance.

BACKGROUND: Posttransplant portosystemic shunts may result in severe fatty changes, portal vein complications, or graft liver failure because they reduce the effectiveness of portal perfusion through a portal steal phenomenon. However, the indications and timing of surgical and interventional treatments for posttransplant portosystemic shunts are still a matter of debate. We performed a retrospective investigation of the present state of long-term outpatients with posttransplant portosystemic shunts. METHODS: This study comprised 150 outpatients who underwent liver transplantation between October 1988 and August 2006 in our department and other facilities. The diagnosis was based on the presence of any portosystemic shunts with the diameter of more than 5 mm indicated by computed tomography. RESULTS: A total of 16 patients (16/150, 10.7 %) were diagnosed as having posttransplant portosystemic shunt. Among them, eight patients (8/16, 50.0 %) developed portal vein complications, and 1 (1/16, 6.3 %) developed graft liver failure. CONCLUSIONS: The persistence of posttransplant portosystemic shunts results in portal vein complications or graft liver failure. Therefore, surgical and interventional treatment for patients with posttransplant portosystemic shunts should be performed based on the clinical and radiologic findings.

BACKGROUND: The pediatric end-stage liver disease (PELD) score is not a direct index that reflects the degree of hepatocellular injury. Beta-D glucan (BDG) in the portal vein blood is processed by the hepatic reticuloendothelial system. It is possible that the hepatic clearance of BDG may be used as a biological index to assess the liver function. In this study, the relationship between PELD score and hepatic clearance of BDG was made clear in order to study the efficacy of measurement of the serum BDG. METHODS: This study including 21 patients with biliary atresia (BA) who underwent liver transplantation (LT) was performed. The BDG was measured in the preoperative peripheral vein blood and the portal vein blood at the time of LT. RESULTS: The portal vein blood showed a significantly high level of BDG than the peripheral vein blood (p < 0.01). There was a significant negative correlation between the PELD score and the hepatic clearance of BDG in the 10 patients who were indicated for LT due to liver failure (p < 0.01). CONCLUSION: The serum BDG can be used as a biological index in place of liver metabolism and should be measured in BA patients as a non-invasive indicator of the degree of progression of liver failure.

Hemophilia exposes patients to greater risks of bleeding complications during the perioperative period. However, there are no current protocols for factor replacement during LT. We herein describe a case of pediatric living donor LDLT performed for a patient with hemophilia B using perioperative short-term factor replacement. A 4-yr-old female patient with an extrahepatic portosystemic shunt and asymptomatic hemophilia B (factor IX activity 18.7%) underwent an ABO-compatible LDLT using a left lobe graft. The bleeding volume was 2980 mL. Freeze-dried human blood coagulation factor IX concentrate (Novact M, Kaketsuken, Japan) was administered at the induction of anesthesia and at the end of LDLT by bolus infusion (80 U/kg) and was continued by bolus infusion (40 U/kg) on POD 1, 2, 3, and 4. On POD 1, 5, 8, and 12, the factor IX plasma levels were 34.5%, 64.9%, 43.5%, and 53.1%, respectively. The postoperative course was uneventful, and the patient is currently doing well at 2.5 yr after LDLT. Factor concentrate should be administered at the induction of anesthesia and at the end of LT by bolus infusion, and thereafter be continued for a few days after LT by bolus infusion.

In the field of pediatric living donor liver transplantation, the indications for apheresis and dialysis, and its efficacy and safety are still a matter of debate. In this study, we performed a retrospective investigation of these aspects, and considered its roles. Between January 2008 and December 2010, 73 living donor liver transplantations were performed in our department. Twenty seven courses of apheresis and dialysis were performed for 19 of those patients (19/73; 26.0%). The indications were ABO incompatible-liver transplantation in 11 courses, fluid management in seven, acute liver failure in three, renal replacement therapy in two, endotoxin removal in two, cytokine removal in one, and liver allograft dysfunction in one. Sixteen courses of apheresis and dialysis were performed prior to liver transplantation for 14 patients. The median IgM antibody titers before and after apheresis for ABO blood type-incompatible liver transplantation was 128 and eight, respectively (P < 0.05). Eleven courses of apheresis and dialysis were performed post liver transplantation for 10 patients. The median PaO2/FiO2 ratio before and after dialysis for fluid overload was 159 and 339, respectively (P < 0.05). No bleeding or technical complications attributable to apheresis and dialysis occurred. The 1-year survival rate of the patients was 100%. Apheresis and dialysis in pediatric living donor liver transplantation are effective for antibody removal in ABO-incompatible liver transplantation, and fluid management for acute respiratory failure.

BACKGROUND: Liver transplantation for biliary atresia is indicated whenever a Kasai portoenterostomy is considered unfeasible. However, the timing of liver transplantation in biliary atresia has not been precisely defined. Excessive shortening of hepatocellular telomeres may occur in patients with biliary atresia, and therefore, telomere length could be a predictor of hepatocellular reserve capacity. METHODS: Hepatic tissues were obtained from 20 patients with biliary atresia who underwent LT and 10 age-matched autopsied individuals (mean age, 1.7 and 1.2 years, respectively). Telomere lengths were measured by Southern blotting and quantitative fluorescence in situ hybridization using the normalized telomere-centromere ratio. The correlation between the normalized telomere-centromere ratio for the hepatocytes in biliary atresia and the pediatric end-stage liver disease score was analyzed. RESULTS: The median terminal restriction fragment length of the hepatic tissues in biliary atresia was not significantly different from that of the control (p = 0.425), whereas the median normalized telomere-centromere ratio of hepatocytes in biliary atresia was significantly smaller than that of the control (p < 0.001). Regression analysis demonstrated a negative correlation of the normalized telomere-centromere ratio with the pediatric end-stage liver disease score in biliary atresia (p < 0.001). CONCLUSIONS: Telomere length analysis using quantitative fluorescence in situ hybridization could be an objective indicator of hepatocellular reserve capacity in patients with biliary atresia, and excessive telomere shortening supports the early implementation of liver transplantation.

BACKGROUND: Nonanastomotic biliary stricture is generally considered the most troublesome biliary complication after liver transplant. Nonanastomotic biliary stricture owing to immunologic cholangiopathy (such as acute cellular rejection) has not been reported. We describe 2 patients with the co-occurrence of nonanastomotic biliary stricture and acute cellular rejection after pediatric live-donor liver transplant. CASE 1: A 13-month-old male infant with liver cirrhosis underwent an ABO-identical live-donor liver transplant using a left lateral segment graft. Eighty days after the live-donor liver transplant, ever with liver dysfunction and dilatation of the intrahepatic bile duct occurred. Percutaneous transhepatic biliary drainage and a liver biopsy were performed. The histopathologic evaluation indicated the presence of acute cellular rejection. After percutaneous transhepatic biliary drainage and steroid pulse treatment, the patient showed good clinical outcome. CASE 2: A 21-month-old female infant with biliary atresia underwent an ABO-identical live-donor liver transplant using a left lateral segment graft. Twenty-six days after the live-donor liver transplant, percutaneous transhepatic biliary drainage for B3 and a liver biopsy were performed, owing to fever, with liver dysfunction, and dilatation of the intrahepatic bile duct. Histopathologic evaluation indicated the presence of acute cellular rejection. After percutaneous transhepatic biliary drainage and steroid pulse treatment, the patient showed good clinical outcome. CONCLUSIONS: It is important for patients with nonanastomotic biliary stricture to undergo early liver biopsy because the nonanastomotic biliary stricture may be coincident with, or caused by, acute cellular rejection.

BACKGROUND AND AIMS: Congenital extrahepatic portosystemic shunt (CEPS) is a rare venous malformation in which mesenteric venous blood drains directly into the systemic circulation. It is still a matter of debate whether conservative or operative strategies should be used to treat symptomatic CEPS. The aim of this study was to evaluate the role of operative intervention in the management of CEPS. METHODS: Between June 2004 and August 2010, 6 consecutive patients with symptomatic CEPS were treated in our department. There were 3 male and 3 female patients, with a median age of 3.5 years (range, 1-8). Their demographic, clinical, and laboratory data were analyzed. All patients were scheduled to undergo shunt ligation or liver transplantation (LT). RESULTS: Living donor LT was carried out in 4 patients, and shunt ligation in 2. After a median follow-up of 25 months, all the patients are alive currently with marked relief of symptoms. CONCLUSION: Shunt ligation or LT for symptomatic CEPS is potentially curative.

Bilioenteric anastomotic stricture after liver transplantation is still frequent and early detection and treatment is important. We established the management using double-balloon enteroscopy (DBE) and evaluated the intractability for bilioenteric anastomotic stricture after pediatric living donor liver transplantation (LDLT). We underwent DBE at Jichi Medical University from May 2003 to July 2009 for 25 patients who developed bilioenteric anastomotic stricture after pediatric LDLT. The patients were divided into two types according to the degree of dilatation of the anastomotic sites before and after interventional radiology (IVR) using DBE. Type I is an anastomotic site macroscopically dilated to five times or more, and Type II is an anastomotic site dilated to less than five times. The rate of DBE reaching the bilioenteric anastomotic sites was 68.0% (17/25), and the success rate of IVR was 88.2% (15/17). There were three cases of Type I and 12 cases of Type II. Type II had a significantly longer cold ischemic time and higher recurrence rate than Type I (P = 0.005 and P = 0.006). In conclusion, DBE is a less invasive and safe treatment method that is capable of reaching the bilioenteric anastomotic site after pediatric LDLT and enables IVR to be performed on strictures, and its treatment outcomes are improving. Type II and long cold ischemic time are risk factors for intractable bilioenteric anastomotic stricture.

PURPOSE: Bowel perforation after liver transplantation (LT) is a rare, but highly lethal complication with a poor prognosis. Here, we report the outcome of cases of bowel perforation after pediatric LT in our department. PATIENTS AND METHODS: The study subjects were 148 patients who underwent pediatric living donor liver transplantation. The 114 with biliary atresia (BA) were divided into two groups: those with associated bowel perforation (Group A) and those without (Group B). RESULTS: Four patients in all (2.5%) suffered bowel perforation. Their original disease was BA and emergency surgery was performed in all cases, with a mortality rate of 50.0%. Comparison of Groups A and B revealed significant differences in the patient age, body weight, duration of surgery, cold ischemic time, and blood loss volume. The survival rates in Groups A and B were 50.0 and 99.1%, respectively (p < 0.01). Duration of surgery was an independent risk factor (p = 0.05). CONCLUSION: Bowel perforation after LT is a potentially fatal complication. LT is a procedure that requires care and precision, and the possibility of bowel perforation should always be borne in mind during post-operative management, when the duration of surgery has been long.

Portal vein complications after liver transplantation (LT) are serious complications that can lead to graft liver failure. Although the treatment of interventional radiology (IVR) by means of balloon dilatation for portal vein stenosis (PVS) after LT is an effective method, the high rate of recurrent PVS is an agonizing problem. Anticoagulant therapy for PVS is an important factor for preventing short-term recurrence following IVR, but no established regimen has been reported for the prevention of recurrent PVS following IVR. In our population of 197 pediatric patients who underwent living donor liver transplantation (LDLT), 22 patients (22/197, 11.2%) suffered PVS. In the 9 earliest patients, unfractionated heparin was the only anticoagulant therapy given following IVR. In the 13 more recent patients, 3-agent anticoagulant therapy using low-molecular-weight heparin, warfarin, and aspirin was employed. In the initial group of 9 patients, 5 patients (55.6%) suffered recurrent PVS and required repeat balloon dilatation. Among the 13 more recent patients, none experienced recurrent PVS (P = 0.002). In conclusion, our 3-agent anticoagulant therapy following IVR for PVS in pediatric LDLT can be an effective therapeutic strategy for preventing recurrent PVS.

A 7-month-old boy with biliary atresia accompanied by situs inversus and absent inferior vena cava (IVC) underwent living-donor liver transplantation (LDLT). Because a constriction in the recipient hepatic vein (HV) was detected during the preparation of the HV in LDLT, a dissection in the cranial direction and a total clamp of the suprahepatic IVC was performed, and the suprahepatic IVC and the graft HV were anastomosed end-to-end. Postoperatively, atelectasis in the left upper lobe and ventilator failure accompanied by an elevation of the left hemidiaphragm were observed and mechanical ventilation was repetitively required. Paralysis in the left phrenic nerve was diagnosed by chest radiograph and ultrasonography. In our patient, conservative treatment was administrated, because weaning him from mechanical ventilation was possible a few days after intubation and the ventilator function was expected to be improved with growth. The disease course was good, and he was discharged from the hospital at 78 days after LDLT. Complications of paralysis in the phrenic nerve after cadaveric liver transplantation have been reported to be high. Although using a conventional technique during the reconstruction of the HV may injure the phrenic nerve directly, use of the piggyback technique with preservation of the IVC is rare. Even if LDLT was undertaken, a dissection of the HV or a total clamp of the suprahepatic IVC as a conventional technique can directly injure the phrenic nerve. Therefore, a dissection of the HV or a total clamp of the suprahepatic IVC at the reconstruction of the HV in LDLT should be carefully performed, and the possibility of paralysis in the phrenic nerve should be considered in patients with a relapse of respiratory symptoms and an elevation of the hemidiaphragm after LDLT.