Early Use of Everolimus as a Third Immunosuppressive Agent for Intestinal Transplantation: A Report of 2 Cases

Ueno T., Toyama C., Deguchi K., et al. Early Use of Everolimus as a Third Immunosuppressive Agent for Intestinal Transplantation: A Report of 2 Cases. Transplantation Proceedings 54, 472 (2022); https://doi.org/10.1016/j.transproceed.2022.01.010.Background: In patients with intestinal transplantation (ITx), renal function is easily impaired because of long-term parenteral nutrition and side effects of tacrolimus. Everolimus was used in patients with renal insufficiency in our study. Methods: We administered everolimus as a third immunosuppressive agent in addition to tacrolimus and steroids for renal sparing in patients who received ITx. We assessed everolimus levels, complications, and renal function. Results: Two patients received everolimus after ITx. Patient 1 was a 13-year-old boy who underwent ITx for an allied disorder of Hirschsprung's disease. After induction therapy with rabbit antithymocyte globulin, maintenance therapy consisted of tacrolimus and steroids. Everolimus was introduced 3 months after ITx for renal sparing. Seven months later, the patient required partial intestinal graft resection owing to bowel obstruction. Everolimus was suspended for only 2 weeks. Four years after ITx, the trough level of tacrolimus was maintained at 3 to 5 ng/mL. The trough level of everolimus was maintained at 3 to 5 ng/mL. Patient 2 was a 32-year-old man who underwent deceased ITx for short gut syndrome. Induction and maintenance immunosuppression was the same as for patient 1. Everolimus was introduced 1 month after surgery. Two years after ITx, trough levels of tacrolimus and everolimus were the same as in patient 1. No rejection was observed in either patient, and renal function was well maintained. We observed no side effects caused by everolimus. Conclusions: Everolimus could be used safely and effectively after ITx. Early use of everolimus after ITx did not affect wound healing

Impact of serum autotaxin level correlating with histological findings in biliary atresia

Ueno T., Toyama C., Yoneyama T., et al. Impact of serum autotaxin level correlating with histological findings in biliary atresia. Journal of Pediatric Surgery 56, 1174 (2021); https://doi.org/10.1016/j.jpedsurg.2021.03.034.Purpose: Portoenterostomy is the standard treatment for biliary atresia (BA) that reduces jaundice in two thirds of cases. However, progressive liver fibrosis is common, leading to cirrhosis in most patients. Autotaxin is a new marker for the progression of hepatic fibrosis. We examined the relationship between serum autotaxin levels and liver histological findings in patients with BA. Methods: BA patients with native livers were identified in our hospital. Patients underwent protocol liver biopsies every 1 to 5 years, and liver fibrosis was evaluated based on the METAVIR score. Serum autotaxin levels were compared with the last available pathological findings. Results: Thirty-five patients were included and the median age was 10.6 years. Serum autotaxin levels was median 1.6 mg/L. The mean autotaxin level was 1.08 mg/L in F0, 1.07 mg/L in F1, 0.95 mg/L in F2, 2.17 mg/L in F3, and 2.50 mg/L in F4; it was significantly higher in F4 than in F0–F2 (P<0.0024). For predicting cirrhosis (F4) and advanced liver fibrosis (≥F3), autotaxin had the almost same areas under the curve (AUCs 0.78 and 0.90, respectively) as well as M2BPGi. Conclusion: Autotaxin levels could be used to evaluate the status of native liver fibrosis

Impact of Monosegment Graft Use for Infants in Pediatric Living Donor Liver Transplantation

Ueno T., Toyama C., Deguchi K., et al. Impact of Monosegment Graft Use for Infants in Pediatric Living Donor Liver Transplantation. Transplantation Proceedings 54, 391 (2022); https://doi.org/10.1016/j.transproceed.2021.12.034.Background: Left lateral segment grafts are generally used for very young pediatric patients undergoing living donor liver transplantation (LDLT). Recently, graft reduction techniques were developed for LDLT. Monosegment grafting has been used in newborns. The aim of this study was to determine the usefulness of monosegment grafting for infants. Methods: Recipients <2 years of age who underwent LDLT with a monosegment graft between 2010 and 2020 were gathered. Parents comprised all LDLT donors. A segment 2 monosegment graft was resected as a graft from the donor. Standard liver volume (SLV) was estimated using Urata's equation. Graft type, graft weight (GW), and native liver weight were assessed. Results: Eight patients were included in the study. Original diseases consisted of biliary atresia (n = 6) and fulminant hepatitis (n = 2). Final graft type included monosegment (n = 5) and reduced monosegment (n = 3). Median final GW/body weight after reduction was 3% (range, 2%-3.4%). Median native liver weight/SLV was 134% except in patients with fulminant hepatitis. Median pre-reduction graft volume (GV)/estimated GV was 113% (range, 60%-208%). Median pre-reduction GV/SLV of monosegment grafts that required reduction (n = 3) was 109% (range, 106%-121%). Median final reduced graft GV/SLV was 80% (range, 74%-91%). Complications due to large-for-size grafts were not observed. One case of bile leakage due to graft reduction occurred as a complication. Grafts were functioning well with the exception of one graft loss due to antibody-mediated rejection. Conclusion: Estimated GV in infants varies widely. Monosegment grafting can be useful for infants as well as newborns

Long-Term Outcome of Portal Vein Stenting After Pediatric Living Donor Liver Transplantation

Ueno T., Toyama C., Deguchi K., et al. Long-Term Outcome of Portal Vein Stenting After Pediatric Living Donor Liver Transplantation. Transplantation Proceedings 54, 454 (2022); https://doi.org/10.1016/j.transproceed.2022.01.008.Background: Portal vein (PV) stenosis is sometimes seen in pediatric living donor liver transplantation (LDLT). PV stents have been attempted in adults with persistent stenosis. However, long-term usefulness of PV stenting is unknown because stents do not expand with growth. We investigated the effect and long-term outcome of PV stenting for stenosis after pediatric LDLT. Methods: We included patients aged <18 years who underwent LDLT from 1998 to 2020 and who underwent PV stenting for stenosis. We assessed age at procedure, stent complications, and long-term outcomes. Results: Five patients underwent PV stent placement. The median age at LDLT was 10 years (range, 0.8-18.1 years). The median interval between LDLT and stent placement was 25 months. The median age at stent placement was 16 years (range, 3-20 years). The median body weight was 38 kg (range, 13-63 kg). The median stent diameter was 8 mm. The median observation period after stent placement was 8 years. On average, body weight increased 1.6 times. One complication associated with stent placement was PV thrombosis, which resulted in stent failure, but we observed no portal hypertension. In the other 4 patients, the stent has remained functioning, and there was no clinical evidence of portal hypertension. Conclusions: PV stents are effective for intractable PV stenosis in children. PV stents were successfully placed in children as young as 3 years old and weighing 13 kg. Our data suggests that a stent placed in young children does not cause portal hypertension as patients grow

Long-Term Outcome After Tacrolimus-Related Neurotoxicity in Pediatric Living Donor Liver Transplantation

Ueno T., Toyama C., Deguchi K., et al. Long-Term Outcome After Tacrolimus-Related Neurotoxicity in Pediatric Living Donor Liver Transplantation. Transplantation Proceedings 54, 468 (2022); https://doi.org/10.1016/j.transproceed.2021.12.036.Background: Tacrolimus-related neurotoxicity is a serious complication. Posterior reversible encephalopathy syndrome, which is severe neurotoxicity after pediatric living donor liver transplantation (LDLT), is a medication-induced complication related to calcineurin inhibitors. The purpose of this study was to evaluate the long-term outcome of tacrolimus-related neurotoxicity after pediatric LDLT. Methods: Pediatric patients who underwent LDLT between 2007 and 2020 at our institution and developed neurologic symptoms with tacrolimus were included in the study. Tacrolimus-related encephalopathy was defined as encephalopathy that resolved after tacrolimus was discontinued. All patients received tacrolimus and a steroid for immunosuppression starting just after LDLT. Results: During the study period, 128 patients underwent LDLT. All patients received tacrolimus and a steroid. Six patients (5%) developed tacrolimus-related encephalopathy. The median age at transplant was 1.6 years. The original diseases were biliary atresia (n = 5) and progressive familial intrahepatic cholangiopathy type 2 (n = 1). Patients developed encephalopathy at a median of 9 days after LDLT. All patients recovered with conversion to cyclosporine. Posterior reversible encephalopathy syndrome was confirmed by magnetic resonance imaging in 3 patients. The mean tacrolimus level at encephalopathy was 11 ng/dL (range, 5.6-14.6 ng/dL). White blood cell count elevation was observed in all patients. One patient died of pancreatitis. Surviving patients (n = 5) were followed for a median of 9 years. All patients resumed tacrolimus a median of 8 months from onset. No neurologic complications were observed after resuming tacrolimus. Conclusion: We observed tacrolimus-induced encephalopathy in 5% of patients after pediatric LDLT. Patients can resume tacrolimus safely without further neurologic symptoms

ゼツメツキグシュ オグラセンノウ ノ ハツガトクセイ

絶滅に瀕しているオグラセンノウSilene kiusiana （Makino） H. Ohashi et H. Nakai は半自然草原に生育する大陸系遺存植物である。本研究ではオグラセンノウの種子発芽特性を明らかにした。低温湿層処理（無処理，15日，30日）を行った種子を用いた段階温度法による種子発芽試験の結果，温度下降系は温度上昇系と比較して低い発芽率を示した。このことから本種の種子は短期間の高温環境下で二次休眠が誘導されたと考えられる。異なる光条件（暗黒区，光量子束密度30，60，150 µmol m－2 s－1）の発芽試験において，本種は光発芽性を持たないことが明らかになった。また生育地の種子結実・散布期の温度環境29/14℃（オグラセンノウの生育地8・9月期の最高・最低平均気温）の変温条件と変温条件の平均温度21.5℃の恒温条件の発芽試験の結果，本種の種子は変温要求性をもつと考えられる。このことから本種の種子は地表面付近においては結実後の当年に発芽できると考えられる。本種の種子寿命は不明であるが埋土された種子は永続的埋土種子集団を形成すると考えられる。Silene kiusiana (Makino) H. Ohashi et H. Nakai (Caryophyllaceae), a threatened species, is a persistent continental plant in semi-natural grasslands. The purpose of this study was to determine seed germination traits of S. kiusiana. Germination tests based on gradually increasing (IT) and decreasing (DT) the temperatures of seeds treated by cold stratification for different periods (no treatment, 15-days, 30-days) indicated that an IT regime had a higher germination rate than a DT regime. The findings inferred that high temperatures for short periods of time induced secondary dormancy in the seeds of this species. Germination tests under different light conditions (darkness, PPFD : 30, 60, 150 µmol m－2 s－1) revealed that germination of the seeds of S. kiusiana showed no response. Seeds germinated at alternating temperatures of both 29 and 14℃ which is the average of the highest and lowest temperatures during August and September during the fruiting season at the growing site, but did not germinate when subjected to a constant temperatures of 21.5℃ (median of the highest and lowest temperatures). The findings suggest that the seeds germinate on the ground surface in the year after seed set. The seed longevity of this species is unknown, but its buried seeds contribute to a persistent seed bank

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