Donor Complications Following Living Donor Hepatectomy: 17-Year Experience of a Single Team in One Institution of Japan.

OBJECTIVES: Donor safety is paramount in living donor liver transplantation. However, there remains a risk of postoperative complications for some donors. Here, we provide a comprehensive assessment of donor morbidity by a single team with 17 years of experience at a single center. MATERIALS AND METHODS: We retrospectively reviewed 453 donor hepatectomies of living donor liver transplants at Kumamoto University from August 2000 to March 2017. Posterior segment graft cases were excluded in this study. RESULTS: The donors were classified by graft type as follows: right lobe (n = 173), left lobe (n = 149), and left lateral segment (n = 131). The overall complication rate was 29.8%, and the severe complication (Clavien-Dindo grade IIIa or higher) rate was 9.1%. The most frequent complication was bile leakage, with an overall incidence of 13.9% and severe incidence of 4.6%. Among the 3 types of graft, there were no significant differences in bile leakage with any Clavien-Dindo grade. However, upper gastrointestinal complications, such as a duodenal ulcer and gastric stasis, were related to left lobe donation. CONCLUSIONS: There were no significant differences in the incidence of postoperative donor complications, except upper gastrointestinal complications, among the 3 types of graft.

Discordant responses of bone formation and absorption markers in Japanese infants with vitamin D deficiency: a comprehensive matched case-control study.

Vitamin D deficiency during infancy has been associated with increased bone turnover rate and bone mineral loss. However, few studies have examined bone turnover markers (BTMs) for both bone formation and resorption in infants with vitamin D deficiency. Here, we analyzed serum concentrations of 25OHD, intact parathormone (iPTH), and BTMs including total alkaline phosphatase (ALP), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), and serum type I collagen N-telopeptide (NTx) as well as basic clinical characteristics of 456 infants (626 samples) aged less than 12 mo born at Saitama City Hospital, Japan (latitude 35.9° North) between January 2021 and December 2022. One hundred sixteen infants (147 samples) were classified as having vitamin D deficiency (25OHD < 12.0 ng/mL), and 340 infants (479 samples) had sufficient vitamin D levels (25OHD ≥ 12.0 ng/mL). In addition to 25OHD and ALP, both TRACP-5b and sNTx were measured in 331 infants (418 samples), while 90 infants (105 samples) had only TRACP-5b measured and 101 infants (103 samples) had only sNTx measured. Statistical comparison of 104 subjects each in the vitamin D deficiency and sufficiency groups after matching for the background characteristics revealed that the vitamin D deficiency group had significantly higher levels of ALP and iPTH compared with the sufficiency group (P = <.0001, .0012, respectively). However, no significant differences were found in TRACP-5b and NTx levels between the 2 groups (P = .19, .08, respectively). Our findings suggest discordant responses between bone formation and resorption markers in subclinical vitamin D deficiency during infancy.

Characterization of heterozygous ATTR Tyr114Cys amyloidosis-specific induced pluripotent stem cells.

Hereditary transthyretin (TTR) amyloidosis (ATTRv amyloidosis) is autosomal dominant and caused by mutation of TTR gene. Heterozygous ATTR Tyr114Cys (p.Tyr134Cys) amyloidosis is a lethal disease with a life expectancy of about 10 years after onset of the disease. However, the molecular pathogenesis of ATTR Tyr114Cys amyloidosis is still largely unknown. In this study, we took advantage of disease-specific induced pluripotent stem (iPS) cells and generated & characterized the heterozygous ATTR Tyr114Cys amyloidosis-specific iPS cells (Y114C iPS cells), to determine whether Y114C iPS cells could be useful for elucidating the pathogenesis of ATTR Tyr114Cys amyloidosis. We successfully differentiated heterozygous Y114C iPS cells into hepatocyte like cells (HLCs) mainly producing TTR protein. On day 27 after differentiation, the expression of hepatocyte maker albumin was detected, and TTR expression was significantly increased in HLCs differentiated from Y114C iPS cells. LC-MS/MS analysis showed that both WT TTR & ATTR Y114C protein were indeed expressed in the HLCs differentiated from Y114C iPS cells. Notably, the number of detected peptides derived from ATTR Y114C protein was lower than that of WT TTR protein, indeed indicating the clinical phenotype of ATTR Tyr114Cys amyloidosis. Taken together, we first reported the heterozygous Y114C iPS cells generated from patient with ATTR Tyr114Cys amyloidosis, and suggested that Y114C iPS cells could be a potential pathological tool, which may contribute to elucidating the molecular pathogenesis of heterozygous ATTR Tyr114Cys amyloidosis.

The First Successful Living Donor Liver Transplantation for Acute-on-Chronic Liver Failure Caused by Severe Acute Necrotizing Pancreatitis: A Case Report.

Liver transplantation (LT) is the only life-saving option when acute-on-chronic liver failure (ACLF) does not improve with conservative therapy. Acute pancreatitis (AP) can cause chronic liver disease progression to ACLF. However, deceased donor LT for patients with AP has had mixed results, and no consensus has been established regarding the indication for LT. We report the first successful living donor LT (LDLT) for ACLF caused by severe AP. The 38-year-old patient with alcoholic liver disease was transferred to our institute with worsening refractory ascites. During the pretransplant workup, she developed severe acute necrotizing pancreatitis, resulting in grade 3 ACLF. The patient's clinical course was further complicated by high levels of donor-specific antibodies and immune thrombocytopenia. The AP gradually improved after intensive care combined with artificial liver support. The patient successfully underwent urgent LDLT with upfront splenectomy and desensitization therapy, including plasm exchange, high-dose intravenous immunoglobulin, and anti-thymocyte globulin. No infection or recurrence of AP was observed postoperatively. We conclude that LDLT is a feasible option for ACLF patients caused by severe AP if a deceased donor is not readily available.

Reappraisal of anatomical liver resection for hepatoblastoma in children.

Background: The principle of hepatoblastoma (HB) treatment is complete resection. The removal of tumor-bearing section(s) or hemiliver is widely accepted. However, neither the standardized anterior approach for right hepatectomy nor parenchymal sparing anatomical liver resection has been described for HB. Methods: We retrospectively reviewed the clinical course of two pediatric HB patients who underwent extended right hepatectomy using the anterior approach with the liver hanging maneuver and one who underwent parenchymal sparing anatomical liver resection of S4 apical+S8 ventral/dorsal+S7. The critical aspects of surgical techniques are described in detail. Results: In all three patients, R0 resection was achieved without complications and are currently alive without recurrence after an average follow-up of 23 months. Intraoperative cardiac hemodynamics were stable, even in a trisomy 18 patient with cardiac disease. Conclusions: Our findings suggest that these innovative techniques established in adults are safe and feasible for HB in children. These techniques also allow optimal anatomical liver resection to accomplish curative surgery while maintaining the functional reserve of the remnant liver.

Incidence and clinical risk factors of Bednar's aphthae in Japanese newborns.

BACKGROUND: The etiology of Bednar's aphthae remains unclear. Our aim was to investigate the incidence of, and factors associated with, Bednar's aphthae in a Japanese newborn cohort. METHODS: A retrospective cross-sectional study was conducted on neonates discharged from the well-baby nursery at Saitama City Hospital, Japan. The principal investigator carefully examined each neonate's oral cavity, up to and including the pharynx, with a light-emitting diode (LED) headlight to determine the presence of Bednar's aphthae. Maternal and neonatal clinical characteristics were first compared between neonates with and those without Bednar's aphthae by univariate analysis. Variables with significant inter-group differences upon univariate analysis were entered into a multivariable logistic-regression model. RESULTS: This study enrolled 1996 infants. We observed Bednar's aphthae in 9.3% of the Japanese newborn infants who were included. When restricted to infants who were born via vaginal delivery, 13.2% of them had aphthae. Multivariable logistic regression analysis identified vaginal delivery (odds ratio = 6.19, p < 0.0001) in Model 1, and vaginal delivery (odds ratio = 6.73, p < 0.0001) and birth weight (odds ratio = 0.9995, p = 0.034) in Model 2 as independent risk factors for the disease. CONCLUSION: This is the first report of the prevalence of Bednar's aphthae among Japanese neonates. Vaginal delivery was identified as the strongest risk factor. Although confounding between mode of delivery and mechanical stimuli associated with sucking was not found in this study, the findings pave the way for a better understanding of the etiology of Bednar's aphthae.

Precision anatomy for minimally invasive spleen-preserving distal pancreatectomy in children: A case report of solid-pseudopapillary neoplasm in a 12-year-old girl.

INTRODUCTION: Solid pseudopapillary neoplasm (SPN) is a rare and low malignant tumor found mainly in young females. There is no standardized procedure for SPN of the pancreatic body and tail in children. In adults, an international consensus on precision anatomy for minimally invasive distal pancreatectomy (MIDP) was established recently (PAM-HBP Surgery Project). The aim of this study is to demonstrate that precision anatomy can also be safely and effectively implemented in the pediatric population. PRESENTATION OF CASE: A 12-year-old girl with an incidentally found SPN located in the pancreatic tail was referred to our hospital. She successfully underwent an R0 resection by laparoscopic spleen-preserving distal pancreatectomy (LSPDP) under the concept of precision anatomy. The patient recovered uneventfully and was discharged on day 7. DISCUSSION: This is the first successful report of LSPDP under the concept of precision anatomy in children. In accordance with the recommendations from the international consensus, the "anterior approach" was selected to dissect and encircle the splenic artery based on the vascular anatomy identified by preoperative imaging. The dorsal dissection border of the pancreas along the anterior layer above the Gerota's fascia was carefully maintained and the splenic vessels were preserved taking into consideration the low malignant potential of SPN and to decrease the risk of complications associated with splenectomy, which were also the essential issues of the consensus. CONCLUSION: The implementation of precision anatomy for pediatric pancreas surgery should facilitate the safe diffusion of MIDP for SPN and other benign or low-malignant tumors in children.

Hepatic venous outflow obstruction after adult living donor liver transplantation.

Hepatic venous outflow obstruction (HVOO) is a rare but critical vascular complication after adult living donor liver transplantation. We categorized HVOOs according to their morphology (anastomotic stenosis, kinking, and intrahepatic stenosis) and onset (early-onset < 3 mo vs. late-onset ≥ 3 mo). Overall, 16/324 (4.9%) patients developed HVOO between 2000 and 2020. Fifteen patients underwent interventional radiology. Of the 16 hepatic venous anastomoses within these 15 patients, 12 were anastomotic stenosis, 2 were kinking, and 2 were intrahepatic stenoses. All of the kinking and intrahepatic stenoses required stent placement, but most of the anastomotic stenoses (11/12, 92%) were successfully managed with balloon angioplasty, which avoided stent placement. Graft survival tended to be worse for patients with late-onset HVOO than early-onset HVOO (40% vs. 69.3% at 5 y, p = 0.162) despite successful interventional radiology. In conclusion, repeat balloon angioplasty can be considered for simple anastomotic stenosis, but stent placement is recommended for kinking or intrahepatic stenosis. Close follow-up is recommended in patients with late-onset HVOO even after successful treatment.

Risk assessment of assisted reproductive technology and parental age at childbirth for the development of uniparental disomy-mediated imprinting disorders caused by aneuploid gametes.

BACKGROUND: Our previous study suggested that assisted reproductive technology (ART) may be a possible risk factor for the development of epimutation-mediated imprinting disorders (epi-IDs) for mothers aged ≥ 30 years. However, whether ART or advanced parental age facilitates the development of uniparental disomy-mediated IDs (UPD-IDs) has not yet been investigated. RESULTS: We enrolled 130 patients with aneuploid UPD-IDs including various IDs confirmed by molecular studies and obtained ART data of the general population and patients with epi-IDs from a robust nationwide database and our previous report, respectively. We compared the proportion of ART-conceived livebirths and maternal childbearing age between patients with UPD-IDs and the general population or patients with epi-IDs. The proportion of ART-conceived livebirths in patients with aneuploid UPD-IDs was consistent with that in the general population of maternal age ≥ 30 years and was lower than that in the patients with epi-IDs, although there was no significant difference. The maternal childbearing age of patients with aneuploid UPD-IDs was skewed to the increased ages with several cases exceeding the 97.5th percentile of maternal childbearing age of the general population and significantly higher than that of patients with epi-IDs (P < 0.001). In addition, we compared the proportion of ART-conceived livebirths and parental age at childbirth between patients with UPD-IDs caused by aneuploid oocytes (oUPD-IDs) and that by aneuploid sperm (sUPD-IDs). Almost all ART-conceived livebirths were identified in patients with oUPD-IDs, and both maternal age and paternal age at childbirth were significantly higher in patients with oUPD-IDs than in patients with sUPD-IDs. Because maternal age and paternal age were strongly correlated (rs = 0.637, P < 0.001), higher paternal age in oUPD-IDs was explained by the higher maternal age in this group. CONCLUSIONS: Different from the case of epi-IDs, ART itself is not likely to facilitate the development of aneuploid UPD-IDs. We demonstrated that advanced maternal age can be a risk factor for the development of aneuploid UPD-IDs, particularly oUPD-IDs.

Elevated Alfa-Fetoprotein and Des-Gamma-Carboxy Prothrombin Levels Predict Poor Outcomes After Liver Transplantation for Hepatocellular Carcinoma Beyond the Japan Criteria.

AIM: The Japan criteria (Milan criteria + 5-5-500 rule) was established recently to select cirrhotic patients with hepatocellular carcinoma for liver transplantation. We evaluated factors associated with poor prognosis after liver transplantation and investigated whether a further extension of the criteria would be worthwhile. METHODS: We retrospectively analyzed 86 patients who underwent liver transplantation for hepatocellular carcinoma at Kumamoto University Hospital since 2004; 69 patients (80.2%) met the Japan criteria (the JCIN group), and 17 patients (19.8%) did not (the JCOUT group). RESULTS: The 5-year cancer-specific survival rates of the JCIN group (92.2%) were significantly better than that of the JCOUT group (39.2%; P < .001). In univariable analysis, alfa-fetoprotein and des-gamma-carboxy prothrombin were significant independent factors associated with cancer-specific survival rates. According to the receiver operating characteristic curves, the cutoff values of alfa-fetoprotein and des-gamma-carboxy prothrombin that predicted hepatocellular carcinoma recurrence after liver transplantation were 756 ng/mL and 1976 mAU/mL, respectively. The JCOUT group was divided into 2 subgroups according to alfa-fetoprotein and des-gamma-carboxy prothrombin: low risk (alfa-fetoprotein level <756 ng/mL and des-gamma-carboxy prothrombin level <1976 mAU/mL) and high risk (alfa-fetoprotein level ≥756 ng/mL and/or des-gamma-carboxy prothrombin level ≥1976 mAU/mL). The 5-year cancer-specific survival rate in the low-risk group (67.5%) was significantly better than that in the high-risk group (0%; P < .001). CONCLUSIONS: Alfa-fetoprotein levels of <756 ng/mL and des-gamma-carboxy prothrombin levels of <1976 mAU/mL may help identify cirrhotic patients with hepatocellular carcinoma who do not meet the Japan criteria but still benefit from liver transplantation.

Recent advances in surgical strategies and liver transplantation for hepatoblastoma.

Hepatoblastoma (HB) is the most common malignant liver tumor in children. Although the development of treatment strategies with advances in chemotherapy has greatly improved the prognosis of HB, surgical resection and liver transplantation still play a vital role in the treatment of HB. In recent years, technological innovations have led to the development of new surgical approaches for HB. In this review, we describe the latest research on the surgical management of HB, including new imaging technologies, minimally invasive approaches, and the application of associating liver partition portal vein ligation for staged hepatectomy. We also discuss the current role of liver transplantation, use of ante-situm or ex-situ liver resection with auto-transplantation, and management of metastatic HB.

Seasonal variation in vitamin D status of Japanese infants starts to emerge at 2 months of age: a retrospective cohort study.

Vitamin D seasonality has been reported in adults and children, suggesting that sunlight exposure has effects on 25(OH)D production. While vitamin D deficiency among infants has received significant attention, little is known about the extent to which vitamin D status during early infancy is affected by sunlight exposure. Here, we retrospectively analysed serum 25(OH)D levels of 692 samples obtained from healthy infants aged 1-2 months born at Saitama City Hospital, Japan (latitude 35·9° North) between August 2017 and September 2021. Data regarding the frequency of outdoor activities, formula intake and BMI were also collected and analysed. Month-to-month comparisons of vitamin D levels revealed significant variation in 25(OH)D levels in breastfed infants starting at 2 months, with maximal and minimal levels in September and January, respectively. An outdoor activity score of 0 was most common at 1 month (83·9 %) and a score of 3 was most common at 2 months (81·2 %), suggesting an increased amount of sunlight exposure at 2 months. Multiple linear regression analysis revealed the amount of formula intake to be significantly associated with vitamin D status at both 1 (t = 17·96) and 2 months (t = 16·30). Our results comprise the first evidence that seasonal variation of vitamin D begins at 2 months among breastfed infants from East Asia, though dietary intake appears to be the major determinant of vitamin D status. These findings provide new insights into the influence of dietary and non-dietary factors on vitamin D status during early infancy.

CDKN1C hyperexpression in two patients with severe growth failure and microdeletions affecting the paternally inherited KCNQ1OT1:TSS-DMR.

BACKGROUND: Two imprinting control centres, H19/IGF2:IG-differentialy methylated region (DMR) and KCNQ1OT1:TSS-DMR, reside on chromosome 11p15.5. Paternal deletions involving the KCNQ1OT1:TSS-DMR result in variable phenotypes, namely, normal phenotype, Silver-Russel syndrome (SRS) and fetal demise. However, expression analyses for CDKN1C in these patients are very limited. CASES: Patient 1 (adult woman) and patient 2 (boy in early childhood) showed prenatal and postnatal growth failure and clinical suspicion of SRS. MOLECULAR ANALYSES: Both patients showed hypermethylation of the KCNQ1OT1:TSS-DMR caused by the paternal heterozygous de novo deletions involving the KCNQ1OT1:TSS-DMR, but not including CDKN1C enhancers. The deletion sizes were 5 kb and 12 kb for patients 1 and 2, respectively. CDKN1C gene expressions in immortalised leucocytes of both patients were increased compared with those of controls. CONCLUSION: Paternal deletions involving the KCNQ1OT1:TSS-DMR, but not including CDKN1C enhancers, disrupt KCNQ1OT1 expression, strongly activate CDKN1C expression and consequently cause severe growth failure.

Pathogenic Copy Number and Sequence Variants in Children Born SGA With Short Stature Without Imprinting Disorders.

CONTEXT: Children born small-for-gestational-age with short stature (SGA-SS) is associated with (epi)genetic defects, including imprinting disorders (IDs), pathogenic copy number variants (PCNVs), and pathogenic variants of genes involved in growth. However, comprehensive studies evaluating these 3 factors are very limited. OBJECTIVE: To clarify the contribution of PCNVs and candidate pathogenic variants to SGA-SS. DESIGN: Comprehensive molecular analyses consisting of methylation analysis, copy number analysis, and multigene sequencing. METHODS: We enrolled 140 patients referred to us for genetic testing for SGA-SS. Among them, we excluded 42 patients meeting Netchine-Harbison clinical scoring system criteria for Silver-Russell syndrome and 4 patients with abnormal methylation levels of the IDs-related differentially methylated regions. Consequently, we conducted copy number analysis and multigene sequencing for 86 SGA-SS patients with sufficient sample volume. We also evaluated clinical phenotypes of patients with PCNVs or candidate pathogenic variants. RESULTS: We identified 8 (9.3%) and 11 (12.8%) patients with PCNVs and candidate pathogenic variants, respectively. According to the American College of Medical Genetics standards and guidelines, 5 variants were classified as pathogenic and the remaining 6 variants were classified as variants of unknown significance. Genetic diagnosis was made in 12 patients. All patients with PCNVs or candidate pathogenic variants did not correspond perfectly to characteristic clinical features of each specific genetic cause. CONCLUSION: We clarified the contribution of PCNVs and pathogenic variants to SGA-SS without IDs. Comprehensive molecular analyses, including copy number analysis and multigene sequencing, should be considered for patients with unknown SGA-SS etiology.

Frequency and clinical characteristics of distinct etiologies in patients with Silver-Russell syndrome diagnosed based on the Netchine-Harbison clinical scoring system.

Silver-Russel syndrome (SRS) is a representative imprinting disorder (ID) characterized by growth failure and diagnosed by clinical features. Recently, international consensus has recommended using the Netchine-Harbison clinical scoring system (NH-CSS) as clinical diagnostic criteria. Loss of methylation of H19/IGF2:intergenic differentially methylated region (H19LOM) and maternal uniparental disomy chromosome 7 (UPD(7)mat) are common etiologies of SRS; however, other IDs, pathogenic variants (PVs) of genes, and pathogenic copy number variants (PCNVs) have been reported in patients meeting NH-CSS. To clarify the frequency and clinical characteristics of each etiology, we conducted (epi)genetic analysis in 173 patients satisfying NH-CSS. H19LOM and UPD(7)mat were identified in 34.1%. PCNVs, other IDs, and PVs were in 15.0%. Patients with all six NH-CSS items were most frequently observed with H19LOM and UPD(7)mat. This study confirmed the suitability of NH-CSS as clinical diagnostic criteria, the (epi)genetic heterogeneity of SRS, and showed the necessity of further discussion regarding the "SRS spectrum".

A boy with overgrowth caused by multi-locus imprinting disturbance including hypomethylation of MEST:alt-TSS-DMR.

Most imprinting disorders (IDs) entail growth abnormalities. Some patients with IDs caused by epimutation have multi-locus imprinting disturbance (MLID) showing aberrant methylation patterns in multiple differentially methylated regions (DMRs). Patients with MLID often have typical ID-specific symptoms. However, certain MLID cases have only non-specific symptoms, and it is necessary to clarify the association between their clinical features and the affected DMRs. We report a case of MLID presenting with overgrowth and temporarily impaired glucose tolerance. Genome-wide methylation analysis for the DMRs revealed hypomethylation of PLAGL1:alt-TSS-DMR, MEST:alt-TSS-DMR, and other DMRs. Because no MEST expression and increased PLAGL1 expression cause growth failure and transient neonatal diabetes mellitus, hypomethylation of MEST:alt-TSS-DMR and PLAGL1:alt-TSS-DMR may have caused overgrowth and temporary impaired glucose tolerance in our case. In cases with multiple non-specific ID-related symptoms, such as growth abnormalities, psychomotor developmental delay, and mild glucose metabolic disorders, multi-locus methylation analysis needs to be considered.

The cut-off values of vitamin D deficiency in early infancy.

BACKGROUND: Several cut-off points for 25-hydroxyvitamin D (25(OH)D) levels have been proposed to determine vitamin D deficiency or insufficiency. However, the level for 25(OH)D deficiency in early infancy remains unclear. The serum 25(OH)D value at which parathyroid hormone level plateaus, called the "inflection point," is considered the most appropriate criterion for defining an adequate vitamin D status. METHODS: This was a single-center retrospective study involving 305 1-month-old and 252 2-month-old Japanese infants. Nonlinear segmented regression analysis was performed based on the correlation between 25(OH)D and parathyroid hormone levels to determine vitamin D deficiency cut-off points. RESULTS: Inflection points were 7.90 ng/mL for 1-month-old (95% confidence interval, 6.31-9.49) and 6.74 ng/mL for 2-month-old (95% confidence interval, 5.80-7.68) Japanese infants, which were lower than previously reported. Cut-off values were also lower in the high-body mass index (BMI) group than in the low-BMI group for both 1-month and 2-month-old infants. CONCLUSION: These results imply the need for nutritional rickets prevention via policy recommendations in most full-term newborns in Japan. Although validation studies are required, these results can still be used to guide vitamin D insufficiency treatment options in early infancy.

Surgical Outcomes of Domino Liver Transplantation Using Grafts From Living Donors With Familial Amyloid Polyneuropathy.

Domino liver transplantation (DLT) using grafts from donors with familial amyloid polyneuropathy is an acceptable procedure for expanding the donor pool. The vascular and biliary reconstructions in living donor DLT (LDDLT) are technically demanding, and data on the short-term and long-term surgical outcomes of domino donors and recipients in LDDLT are limited. In this study, we identified 25 domino recipients from our liver transplantation program (1999-2018), analyzed the vascular and biliary reconstructions performed, and evaluated the surgical outcomes, including graft survival. Piggyback technique was adopted in all 25 domino donors. The only surgical complication in domino donors was hepatic vein (HV) stenosis with an incidence rate of 4%. In 22 domino recipients, right HV and middle/left HV were reconstructed separately. A total of 10 recipients had 2 arteries anastomosed, and 18 underwent duct-to-duct biliary anastomosis. HV stenosis and biliary stricture had incidence rates of 8% and 24%, respectively, in the recipients, but none of them developed hepatic artery thrombosis. The 1-year and 5-year graft survival rates were 100% each in the domino donors, and 84.0% and 67.3% in the domino recipients, respectively. In conclusion, LDDLT has acceptable outcomes without increasing the operative risk in donors despite the demanding surgical technique involved.

Intellectual development of patients with biliary atresia who underwent living donor liver transplantation in infancy.

BACKGROUND: The impact of pediatric liver transplantation on intellectual development has yet to be determined. We investigated the intellectual outcomes of school-aged patients after living donor liver transplantation for biliary atresia in infancy. METHODS: The Wechsler Intelligence Scale for Children-fourth edition test was administered to 20 patients who survived [Formula: see text] 5 years after living donor liver transplantation. Borderline full scale intelligence quotient was defined as ≤ 85. Pre-, peri-, and postoperative data were compared between patients with > 85 and ≤ 85 to identify predictive factors of borderline performance. RESULTS: The one-sample t test demonstrated that the mean full scale intelligence quotient of patients after transplantation for biliary atresia was significantly lower than that of the general population (91.8 vs. 100.0, p = 0.026) and 7 (35%) were classified as intellectual borderline functioning. Multivariable logistic regression models were unable to identify any factors predictive of full scale intelligence quotients of ≤ 85. CONCLUSION: This is the first study to indicate that the mean full scale intelligence quotient among school-aged patients who underwent living donor liver transplantation for biliary atresia in infancy is significantly lower than that of the general population.

A patient with Silver-Russell syndrome with multilocus imprinting disturbance, and Schimke immuno-osseous dysplasia unmasked by uniparental isodisomy of chromosome 2.

Silver-Russell syndrome (SRS) is a congenital disorder characterized by prenatal and postnatal growth failure and craniofacial features. Hypomethylation of the H19/IGF2:IG-differential methylated region (H19LOM) is observed in 50% of SRS patients, and 15% of SRS patients with H19LOM had multilocus imprinting disturbance (MLID). Schimke immuno-osseous dysplasia (SIOD), characterized by spondyloepiphyseal dysplasia and nephropathy, is an autosomal recessive disorder caused by mutations in SMARCAL1 on chromosome 2. We report a patient with typical SRS-related features, spondyloepiphyseal dysplasia, and severe nephropathy. Molecular analyses showed H19LOM, paternal uniparental isodisomy of chromosome 2 (iUPD(2)pat), and a paternally inherited homozygous frameshift variant in SMARCAL1. Genome-wide methylation analysis showed MLID in this patient, although it showed no MLID in another patient with SIOD without SRS phenotype. These results suggest that iUPD(2)pat unmasked the recessive mutation in SMARCAL1 and that the SMARCAL1 gene mutation may have no direct effect on the patient's methylation defects.