Kengo Sasaki

Technical considerations of living donor hepatectomy of segment 2 grafts for infants

BACKGROUND The selection of an adequate graft to mitigate the problems associated with a large-for-size graft is essential to ensure the success of liver transplantation for smaller children. Reduced left lateral segment (LLS) grafts have been introduced to overcome this issue. METHODS Five infants underwent living donor liver transplantation (LDLT) with segment 2 grafts. In the preoperative assessment, the graft-to-recipient weight ratio (GRWR) and the ratio of the thickness of the donor LLS were used as a reference index for graft size matching, and a 3-dimensional (3D) computer-generated model of the donor liver was used for the analysis of the intrahepatic vasculature. During the donor operation, the relevant portal vein branches feeding to the reduced part of segment 3 were first exposed and divided, and then the parenchymal transection was performed. RESULTS Segment 2 grafts were selected in 3 cases and reduced segment 2 grafts were selected in the other 2 cases. The graft reduction was achieved with 46.6 ± 8.2% of the actual LLS, and thus the GRWR was reduced from 5.33 ± 2.09% to 2.70 ± 0.82%. The actual graft thickness was reduced by approximately half after the graft reduction. Primary abdominal closure was performed in all of the recipients. No surgical complications occurred in any of the donors or recipients. CONCLUSION A segment 2 graft could be a valuable option for graft type selection in LDLT for smaller children. Precise planning using a 3D computer-generated model of the donor liver and meticulous operative procedures are necessary to obtain a viable graft.

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.

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.

A xenogeneic-free system generating functional human gut organoids from pluripotent stem cells

Functional intestines are composed of cell types from all 3 primary germ layers and are generated through a highly orchestrated and serial developmental process. Directed differentiation of human pluripotent stem cells (hPSCs) has been shown to yield gut-specific cell types; however, these structures do not reproduce critical functional interactions between cell types of different germ layers. Here, we developed a simple protocol for the generation of mature functional intestinal organoids from hPSCs under xenogeneic-free conditions. The stem cell-derived gut organoids produced here were found to contain distinct types of intestinal cells, including enterocytes, goblet cells, Paneth cells, and enteroendocrine cells, that were derived from all 3 germ layers; moreover, they demonstrated intestinal functions, including peptide absorption, and showed innervated bowel movements in response to stimulation with histamine and anticholinergic drugs. Importantly, the gut organoids obtained using this xenogeneic-free system could be stably maintained in culture for prolonged periods and were successfully engrafted in vivo. Our xenogeneic-free approach for generating gut organoids from hPSCs provides a platform for studying human intestinal diseases and for pharmacological testing.

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 patients 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.

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.

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.

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

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).

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.