Necrotizing enterocolitis in the setting of milk allergy after pediatric living donor liver transplantation.

NEC is an idiopathic intestinal mucosal injury that may progress to transmural bowel necrosis without mesenteric ischemia. NEC usually affects 7- to 10-day-old neonates following enteral feeding. A 10-month-old girl with no history of laparotomy underwent LDLT for acute liver failure. After starting enteral feeding on postoperative day 5, she developed abdominal distention. Diffuse PVG and PI were detected by radiologic modalities. Exploratory laparotomy revealed patchy necrosis of the intestine without perforation. The microscopic findings of a resected specimen revealed transmural coagulative necrosis with multiple small thromboses compatible with neonatal NEC features, and eosinophil infiltration was also observed. Subsequently, after the resumption of enteral feeding with cow's milk, she developed severe diarrhea, the symptoms of which were eliminated after the administration of cow's milk was stopped. These clinical and pathological findings support the speculation that NEC might have been induced by a CMA. Food allergies, which can be induced by immunosuppressive agents, should be considered as a potential cause of NEC in the setting of pediatric liver transplantation.

Optimizing hepatic venous outflow reconstruction for hepatic vein stenosis with indwelling stent in living donor liver retransplantation.

The patient was a boy of 7 years and 5 months of age, who underwent LDLT for acute liver failure at 10 months of age. HV stent placement was performed 8 months after LDLT because of intractable HV stenosis. At 7 years of age, his liver function deteriorated due to chronic rejection. The patient therefore underwent living donor liver retransplantation from his father. The HV was transected with the stent in situ. The IVC was resected due to stenosis. The pericardial cavity was opened and detached around the IVC to elongate the IVC. The divided ends of the IVC were joined by suturing to the posterior wall of the IVC. A new triangular orifice was made by adding an incision on the anterior wall of the IVC. The graft HV was then anastomosed to the new orifice with continuous sutures in the posterior wall and interrupted sutures in the anterior wall using 5-0 non-absorbable sutures. Doppler ultrasound showed a triphasic waveform. We successfully performed HV reconstruction without a vascular graft. This is a feasible procedure for overcoming HV stenosis in LDLT patients with an indwelling stent.

Living donor liver transplantation during the first 3 months of life.

Living donor liver transplantation (LDLT) is now an established technique for treating children with end-stage liver disease. Few data exist about liver transplantation (LT) for exclusively young infants, especially infants of <3 months of age. We report our single-center experience with 12 patients in which LDLT was performed during the first 3 months of life and compare the results with those of older infants who underwent LT. All of the patients were treated at the National Center of Child Health and Development, Tokyo, Japan. Between November 2005 to November 2016, 436 children underwent LT. Twelve of these patients underwent LT in the first 3 months of life (median age, 41 days; median weight, 4.0 kg). The indications for transplantation were fulminant hepatic failure (n = 11) and metabolic liver disease (n = 1). All the patients received the left lateral segment (LLS) in situ to mitigate the problem of graft-to-recipient size discrepancy. A reduced LLS graft was used in 11 patients and a segment 2 monosegment graft was used in 1 patient. We compared the results with those of infants who were 4-6 months of age (n = 67) and 7-12 months of age (n = 110) who were treated in the same study period. There were significant differences in the Pediatric End-Stage Liver Disease score and the conversion rate of tacrolimus to cyclosporine in younger infants. Furthermore, the incidence of biliary complications, bloodstream infection, and cytomegalovirus infection tended to be higher, whereas the incidence of acute cellular rejection tended to be lower in younger infants. The overall cumulative 10-year patient and graft survival rates in recipients of <3 months of age were both 90.9%. LDLT during the first 3 months of life appears to be a feasible option with excellent patient and graft survival. Liver Transplantation 23 1051-1057 2017 AASLD.

Successful resumption of peritoneal dialysis following living donor liver transplantation in children with end-stage renal disease.

Children with ESRD in need of RRT are commonly managed by PD due to difficulty with vascular access for HD and the relatively large extracorporeal blood volume required. Major abdominal surgery may result in injury to the peritoneum and consequent adhesion, thereby resulting in a reduction in the anatomical capacity and transport capability across the peritoneal membrane. Here, we report successful resumption of PD after LDLT in two pediatric patients. The causes of ESRD were PH1 and juvenile nephronophthisis, respectively. Both patients were managed by PD prior to LDLT. PD was converted to HD starting three days before LDLT and was continued postoperatively until resumption of PD on days 13 and 28, respectively. The PD weekly Kt/V urea was maintained before and after LDLT. The patients continued to do well on PD without complications. Meticulous intra-operative techniques during LDLT allow postoperative PD resumption by preservation of peritoneal integrity with effective transport capability and without added risk of peritonitis.

Sequential analysis of variable markers for predicting outcomes in pediatric patients with acute liver failure.

AIM: Our aim was to analyze serial changes in the predictive variables and a scoring system retrospectively adapted to evaluate outcomes in pediatric patients with acute liver failure (ALF). METHODS: We retrospectively collected data on 65 patients with ALF. The 65 patients were divided into two groups according to the need for liver transplantation (LT) as follows: LT group (n = 54) and non-LT group (n = 11). The early determination scoring system of the indications for LT proposed by the Intractable Hepato-Biliary Diseases Study Group of Japan (JIHBDSG) was used in our study. The area under the receiver operating characteristic curve (AUROC) was calculated for the JIHBDSG score between the LT group and non-LT group at the time of diagnosis (day 0) and day 3, and day 5 after the diagnosis. RESULTS: A JIHBDSG score of >3 at day 5 was found to identify the patients requiring LT with 83.7% sensitivity, 81.8% specificity, and 83.3% diagnostic accuracy. Based on a comparison of AUROC values, the JIHBDSG score on day 5 (AUROC 0.91) was higher than that on day 0 (AUROC 0.75) and day 3 (AUROC 0.84). CONCLUSION: We showed that a serial analysis of the JIHBDSG score might be useful for predicting outcomes of ALF in pediatric patients who fulfilled the criteria of LT indication in our center. However, further studies are needed to validate our results.

Hyperammonemia in ornithine transcarbamylase-deficient recipients following living donor liver transplantation from heterozygous carrier donors.

Ornithine transcarbamylase deficiency (OTCD) is a urea cycle disorder of X-linked inheritance, affecting the detoxification of excess nitrogen and leading to hyperammonemia (hyper-NH3 ). Living donor liver transplantation (LDLT) has been applied for the treatment of OTCD. This case series retrospectively reviewed two OTCD patients who experienced hyper-NH3 following LDLT. The first case was a 5-year-old girl who had onset of OTCD at 2 years of age. Ornithine transcarbamylase (OTC) enzyme activity was 62% for the donor and 15% for the recipient. The patient suffered from recurrence of hyper-NH3 within 2 months following LDLT. The second case was a 5-year-old girl who had onset of OTCD at 3 years of age. OTC enzyme activity was 42.6% for the donor and 9.7% for the recipient. The patient suffered hyper-NH3 for 12 days starting on the date of surgery. Both of the patients transiently required continuous veno-venous hemodialysis; however, they are currently doing well without intensive medical treatment. The use of asymptomatic OTCD heterozygous donors in LDLT has been accepted with careful examination. However, an OTCD heterozygous carrier donor should be avoided if there is another donor candidate, due to the potentially fatal condition of hyper-NH3 following LDLT.

Benefit of early inflow exclusion during living donor liver transplantation for unresectable hepatoblastoma.

BACKGROUND: Hepatoblastoma (HB) is a highly malignant primary liver tumor in children. Although liver transplantation (LT) is an effective treatment for unresectable HB with good long-term outcomes, post-transplant survival is mainly affected by recurrence, despite adjuvant chemotherapy. Novel strategies are needed to improve the outcomes in patients undergoing LT for unresectable HB. PATIENTS AND METHODS: Twelve children received LT for unresectable HB. In 9 patients, we applied early exclusion of hepatic inflow (hepatic artery and portal vein) and creation of a temporary portocaval shunt during LT. RESULT: There were differences in the duration of and the blood loss during operation as compared with previously reports. The estimated glomerular filtration rate was well preserved at 3, 6, and 12months and the latest follow-up after LT, and the recurrence-free survival was 88.9%. CONCLUSION: Early inflow control during LT for unresectable HB may benefit recurrence-free survival by minimizing blood loss and tumor dissemination, preserving renal function and allowing early adjuvant chemotherapy.

Reno- and splenoportal anastomosis for a retransplant patient with situs inversus.

PV thrombosis following pediatric LT is a serious complication that may lead to graft loss. LDLT poses limitations with regard to the availability of vein grafts for complex PV reconstructions. We herein report a unique reconstruction of the PV inflow in a one-yr-old boy with situs inversus undergoing re-LDLT. The inflow was derived from the SPV and the RRV. A common channel was created utilizing a donor IMV and the recipient explant LHV as vascular conduits. With the application of innovative surgical reconstructions, pre-existing portomesenteric thrombosis may be amenable to re-LDLT in the pediatric population.

Chemotherapy-induced B-cell depletion in hepatoblastoma patients undergoing ABO-incompatible living donor liver transplantation.

LT from ABO-I donors requires preconditioning regimens to prevent postoperative catastrophic AMR. NAC for HBL is known to cause myelosuppression leading to a reduction in the number and function of lymphocytes. We investigated this chemotherapy-induced myelosuppression in HBL patients listed for LT from ABO-I donors with reference to the kinetics of B, T cells, and anti-ABO blood type isoagglutinin titers. Between 2005 and 2015, of the 319 patients who underwent LDLT at our institute, 12 were indicated for unresectable HBL. Three patients with unresectable HBL who underwent LDLT from ABO-I donors are included in this study. Immunosuppression consisted of a standard regime of tacrolimus and low-dose steroids as in ABO compatible/identical LDLT. No additional preoperative therapies for B-cell depletion were used. Absolute lymphocyte counts, lymphocyte subsets (including CD20+ B cells, CD3+CD4+ T cells and CD3+CD8+ T cells), and anti-ABO blood type isoagglutinin titers were measured before LDLT and postoperatively. The median age at diagnosis was 19 months (range, 3-31 months). The median follow-up was seven months (range, 6-15 months). The median interval from the last NAC to LDLT was 33 days (range, 25-52 days). The median interval from LDLT to adjuvant chemotherapy was 28 days (range, 22-36 days). The counts of CD20+ B cells before LDLT were depleted to median 5 cells/mm(3) (range, 0-6 cells/mm(3)). There was a transient rebound in the CD20+ B cell counts on day seven (maximum of 82 cells/mm(3)) followed by a decline starting at 14 days after LDLT that was sustained for the duration of adjuvant chemotherapy. Anti-ABO blood type isoagglutinin titers were lowered to between 1:1 and 1:16 before LDLT and remained low for the duration of follow-up in this study. All of the three patients remained in good health without either acute cellular or AMR after LDLT. The B-cell depletion that occurs after cisplatin-based chemotherapy for HBL may help accomplish safe ABO-I LDLT in children without the use of additional conditioning regimens for prevention of AMR.

Living donor domino liver transplantation using a maple syrup urine disease donor: A case series of three children - The first report from Japan.

As the priority of LD-Domino LT is the safety of the first recipient, limitations and technical difficulties in the second recipient often occur. The most technically challenging part of LD-Domino LT is the reconstruction of the vessels. For the reconstruction of HVs, the native HVs were exteriorized as far as possible using a CUSA because longer extensive HVs are essential for facilitating the reconstruction. At the back table, the HVs of the domino graft were sutured together, and the single cuff of the HVs was anastomosed to the IVC by joining the orifices. The HAs, the presence of insufficient length, and multiple vessels in the whole liver rendered the reconstruction more difficult. We determined the dividing sites of the vessels according to the preoperative 3D-CT findings obtained in two institutions. This is the first case series using grafts in DLT obtained from LDLT for patients with MSUD between two institutions. In conclusion, LD-Domino LT is a safe and feasible therapeutic option to expand the donor pool by technical refinement in the reconstruction of the second recipient. Further studies with a greater accumulation of patients and a longer follow-up will be necessary to establish LD-Domino LT using an MSUD donor.

A central approach to splenorenal shunt in pediatric living donor liver transplantation.

The management of LSRS is a crucial problem to ensure a sufficient PV flow during pediatric LT. Although several techniques have been indicated to solve this problem, a more appropriate approach to LSRS is still needed in pediatric LT. We herein present a modified surgical approach to the ligation of LSRS via the left side of the IVC for a nine-month-old boy with severe portal hypertension and a history of Kasai portoenterostomy. LSRS was identified and exposed through the left side of the IVC and the dorsal surface of the pancreas from the superior side of the body of the pancreas. The post-operative course was uneventful with an excellent PV flow. The central approach for the ligation of LSRS is worth considering as an alternative procedure for a patient with collateral vessels and a history of multiple laparotomies.

The degree of spleen stiffness measured on acoustic radiation force impulse elastography predicts the severity of portal hypertension in patients with biliary atresia after portoenterostomy.

BACKGROUND/PURPOSE: Acoustic radiation focus impulse (ARFI) elastography is a new method for assessing the degree of tissue stiffness. We herein evaluated the degree of spleen stiffness (SS) using ARFI elastography in patients with biliary atresia (BA) after Kasai portoenterostomy (KPE). METHODS: We retrospectively collected the liver stiffness (LS) and SS values on ARFI elastography from 43 patients undergoing KPE between September 2010 and November 2013. We analyzed the correlations between these values and variables related to the severity of liver dysfunction and portal hypertension (PHT). The data were expressed as the standard deviation score (z-score) relative to the previously reported normal values for the patient's age. RESULTS: The SS value was significantly associated with the spleen diameter and development of collateral vessels, in comparison to the LS value. Interestingly, there was a significant correlation between SS value and the portal vein (PV) diameter. Thirty patients (69.8%) consequently underwent LT; these patients showed higher SS values and smaller PV diameters than the patients monitored without LT. CONCLUSIONS: The degree of SS measured on ARFI elastography can be used to predict the severity of PHT in BA patients after KPE.

The classification based on intrahepatic portal system for congenital portosystemic shunts.

BACKGROUND/PURPOSE: Liver transplantation was previously indicated as a curative operation for congenital absence of portal vein. Recent advances in radiological interventional techniques can precisely visualize the architecture of the intrahepatic portal system (IHPS). Therefore, the therapeutic approach for congenital portosystemic shunt (CPS) needs to be reevaluated from a viewpoint of radiological appearances. The aim of this study was to propose the IHPS classification which could explain the pathophysiological characteristics and play a complementary role of a therapeutic approach and management for CPS. METHODS: Nineteen patients with CPS were retrospectively reviewed. The median age at diagnosis was 6.8 years old. Eighteen of these patients underwent angiography with a shunt occlusion test and were classified based of the severity of the hypoplasia of IHPS. RESULTS: The eighteen cases who could undergo the shunt occlusion test were classified into mild (n=7), moderate (n=6) and severe types (n=5) according to the IHPS classification. The IHPS classification correlated with the portal venous pressure under shunt occlusion, the histopathological findings, postoperative portal venous flow and liver regeneration. Shunt closure resulted in dramatic improvement in the laboratory data and subclinical encephalopathy. Two patients with the severe type suffered from sepsis associated with portal hypertension after treatment, and from the portal flow steal phenomenon because of the development of unexpected collateral vessels. The patients with the severe type had a high risk of postoperative complications after shunt closure in one step, even if the PVP was relatively low during the shunt occlusion test. CONCLUSION: The IHPS could be visualized by the shunt occlusion test. The IHPS classification reflected the clinicopathological features of CPS, and was useful to determine the therapeutic approach and management for CPS.

Successful living domino liver transplantation in a child with protein C deficiency.

PC is produced in the liver and inhibits blood coagulation by catalyzing active factors V and VIII. PC deficiency causes abnormal blood clotting that is difficult to regulate by anticoagulative treatments. Four reports of PC deficiency treated with LTx have been published; however, no report of DLT as a therapy for PC deficiency is available. We describe a case of a 23-month-old girl who received DLT for compound heterozygous PC deficiency. Her PC activity was below 5%. She developed intracranial lesion and frequent refractory purpura fulminans. Both her parents had heterozygous mutations of PC genes and were excluded as living donors. Furthermore, she was a low priority on the waiting list of deceased-donor transplantation. We performed living DLT using the liver from a patient with MSUD. Activated PC concentrate safely supported the perioperative period. After DLT, she maintained normal PC activities and BCAA levels. This is the first case of PC deficiency successfully treated by living DLT with MSUD. We propose that DLT using liver from patients with MSUD is a treatment option for PC deficiency.

Evaluation of the immune function assay in pediatric living donor liver transplantation.

The immune function (ImmuKnow) assay is a measure of cell-mediated immunity based on the peripheral CD4+ T cell ATP activity. The efficacy of ImmuKnow in pediatric LDLT is not well documented. The aim of this study was to assess the correlations between the ImmuKnow and the clinical status in pediatric LDLT recipients. A total of 716 blood samples were obtained from 60 pediatric LDLT recipients (one month to 16 yr of age). The recipient's status was classified as follows: stable, infection, or rejection. The ImmuKnow values in the pediatric LDLT recipients with a clinically stable status had a lower immune response (IQR 85-297 ATP ng/mL) than that previously reported in adults. Meanwhile, the ImmuKnow values of the stable patients were not correlated with age. Furthermore, a significant difference was found in the ImmuKnow values between the bacterial or fungal infection and stable groups, but not between the CMV or EBV infection and stable groups. The ImmuKnow levels in the pediatric LDLT were lower than those observed in the adult LDLT. The proposed reference value is between 85 and 297 ATP ng/mL in pediatric LDLT recipients. We conclude that the ImmuKnow assay could be helpful for monitoring pediatric LDLT recipients with bacterial or fungal infections.

Two-step transplantation for primary hyperoxaluria: a winning strategy to prevent progression of systemic oxalosis in early onset renal insufficiency cases.

Several transplant strategies for PH1 have been proposed, and LT is performed to correct the metabolic defects. The patients with PH1 often suffer from ESRD and require simultaneous LKT, which leads to a long wait due to the shortage of suitable organ donors. Five patients with PH1 underwent LDLT at our institute. Three of the five patients were under dialysis before LDLT, while the other two patients were categorized as CKD stage 3. An isolated LDLT was successfully performed in all but our first case, who had complicated postoperative courses and consequently died due to sepsis after retransplantation. The renal function of the patients with CKD stage 3 was preserved after LDLT. On the other hand, our second case with ESRD underwent successful LDKT six months after LDLT, and our infant case is waiting for the subsequent KT without any post-LDLT complications after the early establishment of PD. In conclusion, a two-step transplant strategy may be needed as a life-saving option for patients with PH1 and may be possible even in small infants with systemic oxalosis. While waiting for a subsequent KT, an early resumption of PD should be considered from the perspective of the long-term requirement of RRT.

Luminal injection of hydrogen-rich solution attenuates intestinal ischemia-reperfusion injury in rats.

BACKGROUND: Luminal preservation of the intestine is an attractive method to locally mitigate preservation injury and ischemic-reperfusion injury in small bowel transplantation (SBT) because this method has a potential to maintain the intestinal graft integrity. Hydrogen is noted as an antioxidant material by reducing hydroxyl radicals. We hypothesized that hydrogen-containing solution can be an optimum material for luminal preservation method in SBT. METHODS: Ischemic reperfusion was induced in Lewis rats by occlusion of the supramesenteric artery and vein for 90 min. Experimental protocols were divided into four groups: sham operation group, no luminal injection (control) group, luminal injection of 5% glucose saline (GS) solution group, and luminal injection of hydrogen-rich GS (HRGS) group. Two milliliters of experimental solution was locally injected into the lumen of the intestine before declamping of vessels. Oxidative stress markers, proinflammatory cytokines, apoptosis in the crypt cells, and morphologic changes of the intestine were assessed. RESULTS: The production of malondialdehyde and 8-hydroxydeoxyguanosine, as oxidative stress markers, were markedly suppressed in HRGS group. The level of proinflammatory cytokines, such as inducible nitric oxide synthase and interleukin-6, was significantly inhibited in HRGS group. Crypt apoptosis was also significantly suppressed in HRGS group. Histopathologically, integrity of villus in intestine was maintained in HRGS group in comparison to the other groups. CONCLUSION: Luminal injection of hydrogen-rich solution can reduce oxidative stress and consequently ameliorate ischemic-reperfusion injury. Hydrogen-containing solution can be a novel and promising luminal preservation material in SBT.

Basiliximab treatment for steroid-resistant rejection in pediatric patients following liver transplantation for acute liver failure.

An IL-2 receptor antagonist, basiliximab, decreases the frequency of ACR in liver transplant (LT) recipients as induction therapy. The aim of this study was to evaluate the effectiveness of basiliximab against SRR as rescue therapy in pediatric LT patients with ALF. Forty pediatric ALF patients underwent LT between November 2005 and July 2013. Among them, seven patients suffering from SRR were enrolled in this study. The median age at LT was 10 months (6-12 months). SRR was defined as the occurrence of refractory rejection after more than two courses of steroid pulse therapy. Basiliximab was administered to all patients. The withdrawal of steroids without deterioration of the liver function was achieved in six patients treated with basiliximab therapy without patient mortality, although one patient developed graft loss and required retransplantation for veno-occlusive disease. The pathological examinations of liver biopsies in the patients suffering from SRR revealed severe centrilobular injuries, particularly fibrosis within one month after LT. We demonstrated the effectiveness and safety of rescue therapy consisting of basiliximab for SRR in pediatric LT recipients with ALF.

Technical refinement in living-donor liver transplantation for hepatoblastoma with main portal vein tumor thrombosis - a pullout technique.

We present a case of a two-yr-old boy diagnosed with HBT with complete main PVTT. HBT was located in the bilateral lobe with PVTT involving the confluence of the SMV and the SpV. Cisplatin-based neoadjuvant chemotherapy was delivered; main tumor shrank and AFP levels decreased to below one hundredth. However, PVTT remained in the bilateral portal branches to the main trunk of PV. We describe the technical details of the portal venous tumor thrombectomy that was succeeded by a LDLT. The patient remained healthy 2.5 yr after LDLT, showing good patency of the PV with no evidence of recurrence of tumor.

Hepatic artery reconstruction preserving the pancreaticoduodenal arcade in pediatric liver transplantation with celiac axis compression syndrome: report of a case.

CACS is rare, although it has been reported to be a potential risk factor for hepatic artery thrombosis following LT. We herein present the case of a 14-yr-old male with stenosis of the origin of the celiac trunk. Preoperative CT and color ultrasonography showed narrowing of the proximal celiac artery. The patient underwent DDLT with standard arterial reconstruction without dividing the gastroduodenal artery. His postoperative course was uneventful, with an excellent hepatic artery flow on Doppler ultrasonography. Applying a meticulous preoperative evaluation and the appropriate surgical technique is crucial in patients with CACS.