Comprehensive analyses of neurodevelopmental outcomes and quality of life of children with biliary atresia.

OBJECTIVES: To holistically evaluate neurodevelopmental outcomes and quality of life (QOL) of Japanese patients with biliary atresia (BA) and to investigate the factors associated with the outcomes. METHODS: This study enrolled patients with BA aged 5-18 years who visited Osaka University Hospital in 2021. Neurodevelopmental assessments were performed to evaluate intellectual ability, cognitive functions and adaptive skill levels. Furthermore, emotional and behavioral issues, characteristics of attention deficit hyperactivity disorder, and QOL were concomitantly assessed in the same cohort. Biochemical and social factors associated with the results were examined. RESULTS: Fifty-three patients, with a median age of 11.2 years were included in the analyses. Patients with BA had a significantly lower Full-Scale Intelligence Quotient or developmental quotient (FSIQ/DQ) score and Vineland Adaptive Behavior Scale (VABS) composite score than the general Japanese population. Household education level and short stature were associated with low and borderline FSIQ/DQ and VABS composite scores, respectively. Among patients with low and borderline FSIQ/DQ scores, those with average or high VABS composite scores received significantly less neuroeducational care than those with low and borderline VABS composite scores. Despite the low FSIQ/DQ and VABS composite scores, the total QOL scores were higher than those of the general population. CONCLUSION: Patients with BA had intellectual and behavioral impairments. Notably, patients with intellectual impairments are overlooked and not followed up, especially if adaptive skills are maintained.

Balloon dilatation for congenital esophageal stenosis associated with esophageal atresia.

PURPOSE: Congenital esophageal stenosis (CES) associated with esophageal atresia (EA) is rare, and no standard treatment has been established. We reviewed cases of EA-associated CES to assess the clinical characteristics and treatment outcomes, especially the feasibility of endoscopic dilatation. METHODS: We retrospectively examined patients with EA-associated CES. We also compared treatment outcomes of EA-associated CES with those of EA patients without CES who developed postoperative anastomotic stricture. RESULTS: Among 44 patients with EA, ten had CES (23%). Postoperative complications were not significantly different between EA patients with CES and those without CES but with anastomotic stricture. All CES patients underwent balloon dilatation as initial treatment. Eight of nine patients (89%) were successfully treated by dilatation only, and one patient underwent surgical resection. The median number of balloon dilatations for CES was five (2-17), which was higher than that for anastomotic stricture in patients without CES (p = 0.012). Esophageal perforation occurred in five patients with CES (5/9, 56%) after dilatation, but all perforations were successfully managed conservatively with an uneventful post-dilatation course. CONCLUSIONS: Twenty-three percent of patients with EA had CES. Although balloon dilatation for EA-associated CES required multiple treatments and carried a risk of perforation, balloon dilatation showed an 89% success rate and all perforations could be managed conservatively.

Impact of Total Parenteral Nutrition on Preoperative Management of Pediatric Living-Donor Liver Transplantation for Biliary Atresia Under 2 Years Old.

BACKGROUND: Liver failure and gastrointestinal bleeding occur in the end-stage of biliary atresia (BA). Living-donor liver transplantation (LDLT) is a standard treatment in Japan. Our program actively provides pre-transplant total parenteral nutrition (TPN) for such patients, and here we report its efficiency and safety. METHODS: Patients with BA for whom LDLT was indicated were identified. Those with a long-term external central venous catheter and TPN, longer than 4 weeks before LDLT, were analyzed. Ascites was controlled with diuretics. TPN indications, efficacy, and complications were assessed along with patient growth, biochemical markers, and gastrointestinal bleeding. RESULTS: Fourteen patients were included in the study, of whom 8 were girls and 6 were boys. The median age at LDLT was 0.9 years. Body weight (BW) at TPN initiation averaged 6799 g, and the median serum total bilirubin was 9.5 mg per dL. The median catheterization duration was 54 days, and 1 patient received home TPN. Indications for TPN were gastrointestinal bleeding and/or massive esophageal varices in 4 patients and poor nutritional status in 10 patients. No complications were observed except for 1 catheter infection and 1 catheter occlusion. The median final body weight before LDLT was 7906 g. The mean rate of BW gain was significantly higher after TPN than before (149 vs 32 g/wk, respectively, P = .0002). Mean prothrombin time and levels of albumin, cholinesterase, and total bilirubin were not significantly different at the start and end of TPN. CONCLUSIONS: Pre-transplant TPN was safe and effective for patients with end-stage BA.

Plasma Concentration of Antifungal Agent Micafungin for Pediatric Living Donor Liver Transplantation.

BACKGROUND: Pediatric living-donor liver transplantation (LDLT) candidates often receive long-term antibiotic treatment. Micafungin has been used as an antifungal agent after LDLT, but the adequate dose after pediatric LDLT was unknown. Here, we report micafungin blood concentrations after pediatric LDLT and discuss its safety and adequate dosing. METHODS: Pediatric patients with data on micafungin concentrations after LDLT were identified. Those with surgical complications were excluded. All patients received standard tacrolimus-based immunosuppression. A micafungin dose of 1 mg/kg was administered once daily for 10 days starting on postoperative day (POD) 1. The trough and peak micafungin blood concentrations were evaluated on PODs 1, 4, 7, and 10. Beta D glucan levels and liver function tests were assessed to determine micafungin effectiveness and safety. RESULTS: Ten patients were enrolled, with a median age of 1.2 years. The median graft vs body weight ratio was 2.7%. The primary diseases were biliary atresia (n = 7), Alagille syndrome (n = 2), and progressive familial intrahepatic cholestasis type 2 (n = 1). Mean peak micafungin levels were 4.47, 6.27, 5.47, and 5.47 µg/mL on PODs 1, 4, 7, and 10, respectively. Mean trough levels were 2.03, 1.88, and 2.66 µg/mL on PODs 4, 7, and 10, respectively. The micafungin half-lives were 13.7, 14.7, and 14.0 hours on PODs 4, 7, and 10, respectively. Beta D glucan levels were 4.4 pg/mL and 3.7 pg/mL before and after transplantation, respectively, indicating no significant difference (P = .3). No clinical fungal infections were observed. CONCLUSION: Micafungin administration is safe and effective after pediatric LDLT.

Clinical Implications of Serum Mac-2 Binding Protein in Patients After Living Donor Liver Transplantation for Biliary Atresia.

BACKGROUND: Patients who undergo pediatric living donor liver transplantation (LDLT) sometimes develop graft fibrosis. Recently, Mac-2 binding protein glycosylation-modified isomer (M2BPGi) was developed as a new marker of hepatic fibrosis progression. We performed this study to examine the relationship between serum M2BPGi levels and liver histologic findings in patients after LDLT for biliary atresia. METHODS: Patients aged <19 years who underwent LDLT for biliary atresia at our institution and followed up for at least 1 year after LDLT were eligible. There were 56 patients in this study. Pathologic findings of the last available biopsy were assessed. Portal vein (PV) stenosis was confirmed with angiography. M2BPGi levels were compared with pathologic fibrosis scores and PV stenosis findings. RESULTS: The mean age at transplant was 4.3 years. The mean observation period was 8.6 years. In terms of the degree of liver fibrosis, F0 was observed in 7 patients, F1 in 36, and F2 in 13. The median serum M2BPGi value was 0.8 cut-off index (COI) overall and 0.60 COI for F0, 0.74 COI for F1, and 1.07 COI for F2. The mean M2BPGi value in F2 was higher than that in F0 (P = .016) and F1 (P = .012). Mean serum M2BPGi values were 1.57 COI (0.29 COI) in patients with PV complications (n = 5) and 0.72 COI in patients without PV complications (n = 51) (P = .0001). CONCLUSION: M2BPGi is a novel marker for liver fibrosis in patients after pediatric LDLT. It is especially useful for follow-up of pediatric patients after LDLT to support liver biopsy interpretation.

Present state of intestinal transplantation in Japan.

INTRODUCTION: Intestinal transplantation (ITx) is the ultimate treatment for intestinal failure (IF). In Japan, most cases of IF are a result of pediatric disease, including secondary or congenital intestinal disease or allied disorders of Hirschsprung's disease. Here, we report the results of the Japanese ITx registry. METHODS: A web-based survey form was completed. We investigated the number, age, sex, indication, surgical procedure, immunosuppressants, postoperative course, and the effects of transplantation in patients who underwent cadaveric or living-donor ITx. RESULTS: By the end of 2022, 42 cases of ITx have been performed in 38 patients in Japan. The donor sources included cadavers (29 cases) and living donors (13 cases). The surgical method was isolated ITx (N = 40) and combined liver and ITx (n = 2). Survival rates were 92%, 73%, and 59% at 1 year, 5 years, and 10 years, respectively. Ninety percent of patients completely discontinued parenteral nutrition. Approximately 80% of the patients had a performance status of 1 or less, indicating that the QOL of patients after ITx was extremely good. CONCLUSION: The results of ITx are acceptable to treat IF patients and the QOL after transplantation is also good.

Liver-Spleen Volume Ratio as a Predictor of Native Liver Survival in Patients with Biliary Atresia.

BACKGROUND: The appropriate timing of liver transplantation (LT) in patients with biliary atresia (BA) who survived with their native livers until adolescence remains controversial. The liver-spleen volume ratio (LSR) has been reported to be efficacious in predicting the prognosis of chronic liver disease. We investigated whether LSR could predict long-term native liver prognosis and serve as an indication for LT in patients with BA. METHODS: Patients with BA who survived with their native liver until the age of 15 years were included. These patients were classified into 2 groups. The unfavorable prognosis group included patients who underwent or were awaiting LT or developed complications such as refractory cholangitis or gastrointestinal bleeding due to esophagogastric or intestinal varices. The favorable prognosis group included patients who survived with their native liver without complications. We compared the 2 groups regarding LSR, hematological, and histologic data. RESULTS: Of 19 patients, 8 were in the unfavorable prognosis group, and 11 were in the favorable prognosis group. LSR was significantly lower in the unfavorable prognosis group (P = .009). Analysis of the receiver operating characteristic curve showed that the area under the curve of the LSR was 0.891, which was higher than the area under the curve of liver fibrosis markers. The optimal LSR cut-off value for predicting poor native liver prognosis was 1.97, with a sensitivity of 75.0% and a specificity of 87.5%. CONCLUSIONS: The LSR reflects splenomegaly and liver atrophy. The LSR might be a reliable predictor of native liver prognosis and could guide decisions about LT in patients with BA.

Tension-free thoracoscopic repair of congenital diaphragmatic hernia combined with a percutaneous extracorporeal closure technique: how to do it.

PURPOSE: Thoracoscopic repair (TR) of congenital diaphragmatic hernia (CDH) is associated with a higher recurrence rate than the conventional open method. We evaluated the effectiveness of our strategy for quality improvement, named "tension-free TR of CDH". METHODS: The subjects of this retrospective analysis were 11 consecutive patients with CDH who underwent TR at our hospital between 2017 and 2021. Tension-free TR of CDH included the proactive use of an oversized patch for dome-shaped reconstruction and gapless suturing. We developed a percutaneous extracorporeal closure technique for secure suturing using a commercially available needle. RESULTS: Patch repair was performed in 8 (73%) patients and none required conversion to open surgery because of technical difficulties. Recurrence developed in one patient (9%), who underwent successful reoperation via TR. All patients had an uneventful postoperative course. CONCLUSION: Tension-free TR combined with extracorporeal closure could reduce the difficulty of suturing and the risk of recurrence of CDH.

Factors reducing psychological satisfaction after the Nuss procedure in pediatric patients.

PURPOSE: We examined patient satisfaction with postoperative chest appearance after Nuss procedure and analyzed the factors for postoperative low satisfaction. METHODS: We retrospectively reviewed data of 133 patients who underwent the Nuss procedure from 2000 to 2016. Their medical records, X-rays, and computed tomography scans were evaluated. Haller index and concave rate were used as objective indices of the deformity. The questionnaires were used to evaluate satisfaction with the chest appearance by a linear scale including five markers (1: dissatisfaction, 5: satisfaction). The patients were divided into two groups: the low satisfaction (score = 1, 2) and the high satisfaction (score = 3-5). RESULTS: The median age during the Nuss procedure was 7.6 (interquartile range, 5.8-12.8) years. Out of 133, 65 patients replied, and the mean postoperative satisfaction score was 3.8 ± 0.2. Out of the 65 respondents, 16 patients (24.6%) were classified as low satisfaction group. Haller index and concave rate were significantly higher and the previous instances of chest operation history were more frequent in the low satisfaction group than in the high satisfaction group, although there was no significant intergroup difference in terms of the postoperative concave rate. CONCLUSIONS: Severe deformity and previous chest operation history were considered to be factors for low satisfaction.

Treatment and follow-up of late onset intra hepatic bile duct stones in congenital biliary dilatation.

PURPOSE: The postoperative course after surgery for congenital biliary dilatation (CBD) has some complications. Intrahepatic bile duct (IHBD) stones were known as a late complication. We report on the treatment and long-term follow-up of postoperative IHBD stones in our department. METHODS: Patients who underwent CBD surgery at age 15 years or younger in our department were identified. Those followed up for 5 years or more were enrolled. Annual blood chemistry tests and abdominal ultrasonography were performed. Each patient's surgical procedure, IHBD stone diagnosis, treatments, and outcomes were retrospectively assessed. RESULTS: Fifty-one patients were analyzed. The median age at the last visit was 24 years (range 7-45 years), and the median age at CBD surgery was 3 years. Eight patients (16%) developed late-onset IHBD stones. The median age at onset was 25 years, and the median duration after surgery was 20 years. The initial treatment was double-balloon enteroscopy (DBE) in 4 cases, which resulted in stone removal in 3 of the 4 patients (75%). CONCLUSION: Since CBD may cause late-onset IHBD stones, continuous follow-up is required even in adulthood. In this study, DBE was effective and minimally invasive, and it is recommended as the initial treatment.

Early detection of liver fibrosis with serum Mac-2 binding protein glycosylation-modified isomer (M2BPGi) during follow-up intestinal failure patients without intestinal failure-associated liver disease (IFALD).

PURPOSE: Mac-2 binding protein glycosylation-modified isomer (M2BPGi) is a new marker for hepatic fibrosis progression. We examined the relationship between serum M2BPGi levels and liver histological findings in intestinal failure (IF) patients without IF-associated liver disease (IFALD). METHODS: This study included IF patients without IFALD followed at our hospital. All patients underwent routine liver biopsies per protocol every 1-2 years. We examined M2BPGi levels and histological findings in relation to aspartate aminotransferase (AST) to platelet ratio index, fibrosis-4 index, and AST/ALT ratio. Liver fibrosis was evaluated based on the METAVIR score. RESULTS: Total 18 liver biopsies out of eight patients were included. The median age was 11.5 years. Mean M2BPGi was 0.44 cutoff index (COI) in patients with F0 fibrosis, 0.78 COI in patients with F1 fibrosis and 1.63 COI in patients with F2 fibrosis. Mean M2BPGi was significantly higher in patients with F2 versus F1 or F0 fibrosis (P < 0.016 and P < 0.028, respectively). M2BPGi levels were more strongly correlated with fibrosis stage than with other conventional fibrosis markers. CONCLUSION: Serum M2BPGi is a novel marker of liver fibrosis in patients with IF. It is useful for follow-up prior to IFALD. Serum M2BPGi levels can support the interpretation of liver status.

Suppression of xenogeneic innate immune response by a membrane-type human surfactant protein-A.

Macrophage-mediated xenogeneic rejection is a major immunological obstacle. We recently reported that membrane-type surfactant protein-D (SP-D) on swine endothelial cells (SECs) suppressed macrophage-mediated rejection. Similar to SP-D, the carbohydrate recognition domain of surfactant protein-A (SP-A) can induce inhibitory signals in effector cells. The present study aimed to examine the suppressive effect of SP-A on macrophage-mediated xenogeneic rejection. Naive SECs and SPA-transfected SECs (SEC/SP-A) were co-cultured with THP-1 cells and cytotoxicity was evaluated. To investigate the effect of SP-A on phagocytosis, human macrophages were co-cultured with SEC or SEC/SP-A, and the extent of phagocytosis and production of reactive oxygen species were assessed via flow cytometry. The mRNA expression levels of inflammatory cytokines in macrophages were determined using reverse transcription-PCR. Additionally, the effects of THP-1-Lucia NF-κB cells on transcription factors were evaluated. The cytotoxicity and phagocytosis of SEC/SP-A were significantly decreased compared with those of naive SEC. Furthermore, the co-culture of human macrophages with SEC/SP-A decreased reactive oxygen species production, and the mRNA expression levels of TNFα were decreased in macrophages, whereas those of IL-10 were increased. In addition, NF-κB transcription was decreased in SEC/SP-A compared with that in SEC. In conclusion, the ectopic expression of human SP-A in porcine cells represents an attractive method for suppressing macrophage-mediated cytotoxicity.

Laparoscopic Percutaneous Extraperitoneal Closure for Hydrocele of the Canal of Nuck in Children.

Background: Hydrocele of the canal of Nuck (HCN) is a rare cause of inguinal swelling in women. The optimal surgical procedure for HCN in children remains unclear. To assess the safety and efficacy of laparoscopic percutaneous extraperitoneal closure (LPEC) for HCN in a pediatric population, a retrospective study was conducted. In addition, to clarify the pathogenesis of HCN, we assessed the morphological findings of the internal inguinal ring (IIR). Materials and Methods: We retrospectively analyzed 10 consecutive female patients with HCN who underwent LPEC at our hospital between January 2010 and May 2020. Age, operative time, and complications were recorded. Concerning the findings of the IIR, we classified the morphological features as follows: Type 1 (flat), Type 2 (narrow patent processus vaginalis [PPV] with a peritoneal veil), and Type 3 (widely opening PPV). Results: The median age of patients who underwent LPEC was 3 (1-12) years. Although 2 patients showed contralateral inguinal hernia (IH), there were no cases of ipsilateral IH. All patients showed ipsilateral PPV, and the morphological features of the IIR were mostly classified as Type 3 (70%). In total, 6 of 8 HCN cases without preoperatively diagnosed contralateral IH had contralateral PPV (75%), and all were closed by LPEC. All operations were accomplished laparoscopically, and the postoperative course was uncomplicated, with no recurrences observed during the study period. Conclusions: LPEC is a safe and simple surgical approach to repair the HCN in children with minimal complications.

Ileocecal valve-sparing surgery for duplication cysts in the terminal ileum: two case reports and literature review.

BACKGROUND: Duplication cysts close to the ileocecal valve are usually treated with ileocecal resection. However, loss of the ileocecal valve will lead to problems, especially in infants. Mucosectomy of the cyst would be a better alternative that preserves the ileocecal valve. We report two cases of duplication cyst in the terminal ileum successfully treated with mucosectomy. CASE PRESENTATION: Case 1. A 3-month-old boy with bilious emesis and abdominal distention was referred to our hospital with a diagnosis of small bowel obstruction caused by an abdominal cyst. Computed tomography revealed a cystic mass compressing the terminal ileum and causing mechanical small bowel obstruction. His general condition deteriorated quickly; emergency laparotomy was performed. Although the small intestines were dilated and partially twisted, there was no necrosis. Following intestinal decompression, a cystic mass adjacent to the terminal ileum was confirmed on the mesenteric side. Cyst mucosectomy was performed to preserve the ileocecal valve. CASE 2: A 5-month-old boy with sudden onset of hematochezia was referred to our hospital with a diagnosis of intussusception. Following unsuccessful contrast enemas, emergency surgery was performed. A cystic mass adjacent to the terminal ileum was confirmed; there was no intussusception. Cyst mucosectomy was performed. Both patients had an uneventful postoperative course. CONCLUSIONS: Cyst mucosectomy, which preserves the ileocecal valve, is safe and effective for treating duplication cysts in the terminal ileum.

Clinical implications of serum autotoxin in regular follow up after pediatric living donor liver transplantation for biliary atresia.

BACKGROUND: Pediatric patients sometimes develop graft fibrosis after living donor liver transplant (LDLT). Autotaxin is a recently developed serum marker for hepatic fibrosis. We studied the relationship between serum autotaxin levels and histological findings in patients after LDLT for biliary atresia (BA). METHODS: Information on patients aged <19 years who received LDLT for BA and were followed for at least 1 year after LDLT was gathered. Autotaxin levels were compared with pathological fibrosis scores. RESULTS: The study included 52 patients, of whom 4 patients had no fibrosis (F0), 36 patients had F1 fibrosis, and 12 patients had F2. The median serum autotaxin level was 0.89 mg/L. In patients with portal vein (PV) complications such as stenosis or thrombosis (n = 7), the mean autotoxin level was 1.25 mg/L compared with 0.95 mg/L in patients without PV complications (p = 0.004). Among patients without PV complications, the mean autotaxin level was 0.90, 0.88, and 1.18 mg/L in F0, F1, and F2 fibrosis, respectively. The mean autotaxin was higher in F2 fibrosis than in F0 or F1 fibrosis (p<0.05). Autotoxin had a high area under the curve (0.86) with the cut-off level of 0.897 mg/L. CONCLUSION: Serum autotaxin is a novel marker for liver fibrosis in patients after pediatric LDLT for BA. TYPE OF STUDY: Study of Diagnostic Test. LEVEL OF EVIDENCE: Level II.

Effect of a C5a receptor antagonist on macrophage function in an intestinal transplant rat model.

BACKGROUND: C5a promotes alloreactivity via the C5a receptor 1 (C5aR1) on immune cells, but this has not been confirmed in the case of small intestine transplantation immunity. In the present study, we examined the effect of C5aR1 antagonist (PMX53) on macrophage function in small intestinal transplantation. METHODS: The model was created by heterotopic intestinal transplantation using donor Dark Agouti and recipient Lewis rats. PMX53 was administered starting on the day of operation until postoperative day 7. The graft survivals were compared, and HE staining of grafts, lymphocyte mixed reaction test (MLR, mixed culture of T cells from lymph nodes and spleen cells from donors), and changes in macrophage and T cell accumulation in grafts on day 6 after transplantation were evaluated. In addition, the effect of PMX53 on macrophage differentiation and activation was assessed using macrophages derived from bone marrow (BMDM). RESULTS: Graft survival was significantly prolonged in the therapeutic group compared to the untreated group. Histological evaluation showed that PMX53 inhibited the shortening of the graft villus, and the stimulation index of MLR was significantly lower in the therapeutic group compared to the untreated group. In the therapeutic group, the accumulation of macrophages in intestinal graft and monocyte in blood were reduced, compared with the untreated group. PMX53 decreased the differentiation in BMDM and the mRNA expression of IL-1ß and TNF-α in activated BMDM. CONCLUSION: Inhibition of C5a/C5aR1 signaling appears to regulate macrophage differentiation and suppress rejection in small intestine transplantation immunity.

Inhibition of cIAP1 in the effective suppression of chemotherapy­resistant hepatoblastoma.

Cellular inhibitor of apoptosis protein­1 (cIAP1) is a key regulator of programmed cell death and is known to be associated with chemotherapeutic resistance. The present study aimed to investigate the antitumor efficacy of birinapant, a novel selective inhibitor of cIAP1, against cisplatin (CDDP)­resistant hepatoblastoma (HB) cells. Western blot analysis was used to investigate the antitumor effect of birinapant on cIAP1 expression in Huh6 cells at the protein level. A WST­8 assay was performed to evaluate the tumor growth inhibitory effect of birinapant on the human HB cell lines, Huh6 and HepG2. Huh6 cells were exposed to CDDP and/or birinapant in order to confirm tumor growth inhibition. The antitumor efficacy of birinapant plus CDDP combination therapy was significantly higher than that of CDDP monotherapy in a dose­dependent manner (P=0.035). The study also investigated the antitumor efficacy of birinapant plus CDDP combination therapy in an established xenograft model of SCID mice. Compared with CDDP monotherapy, birinapant combined with CDDP showed better inhibition of tumor growth (P=0.121). It was observed that the mRNA expression of cIAP1 in tumors was significantly enriched in the CDDP monotherapy group compared with that in the untreated group. Furthermore, immunohistochemical staining was performed to compare cIAP1 expression in pre­ and post­chemotherapy specimens in patients with HB, and a significant increase was observed in the post­chemotherapy specimens (P<0.001). CDDP­resistant Huh6 (Huh6­CDDPR) cells were also established following repeated exposure to CDDP. Birinapant was substantially more effective against the Huh6­CDDPR cells than against the Huh6 wild­type cells. Taken together, these findings suggest that repeated exposure to CDDP enhances cIAP1 expression in HB cells and that birinapant is a promising therapeutic drug for CDDP­resistant HB.

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

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.

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

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.

Clinical outcomes of surgical management for rare types of progressive familial intrahepatic cholestasis: a case series.

BACKGROUND: Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of genetic autosomal recessive diseases that cause severe cholestasis, which progresses to cirrhosis and liver failure, in infancy or early childhood. We herein report the clinical outcomes of surgical management in patients with four types of PFIC. CASE PRESENTATION: Six patients diagnosed with PFIC who underwent surgical treatment between 1998 and 2020 at our institution were retrospectively assessed. Living-donor liver transplantation (LDLT) was performed in 5 patients with PFIC. The median age at LDLT was 4.8 (range: 1.9-11.4) years. One patient each with familial intrahepatic cholestasis 1 (FIC1) deficiency and bile salt export pump (BSEP) deficiency died after LDLT, and the four remaining patients, one each with deficiency of FIC1, BSEP, multidrug resistance protein 3 (MDR3), and tight junction protein 2 (TJP2), survived. One FIC1 deficiency recipient underwent LDLT secondary to deterioration of liver function, following infectious enteritis. Although he underwent LDLT accompanied by total external biliary diversion, the patient died because of PFIC-related complications. The other patient with FIC1 deficiency had intractable pruritus and underwent partial internal biliary diversion (PIBD) at 9.8 years of age, pruritus largely resolved after PIBD. One BSEP deficiency recipient, who had severe graft damage, experienced recurrence of cholestasis due to the development of antibodies against BSEP after LDLT, and eventually died due to graft failure. The other patient with BSEP deficiency recovered well after LDLT and there was no evidence of posttransplant recurrence of cholestasis. In contrast, recipients with MDR3 or TJP2 deficiency showed good courses and outcomes after LDLT. CONCLUSIONS: Although LDLT was considered an effective treatment for PFIC, the clinical courses and outcomes after LDLT were still inadequate in patients with FIC1 and BSEP deficiency. LDLT accompanied by total biliary diversion may not be as effective for patients with FIC1 deficiency.