Hideaki Okajima

Introduction: Perivascular epithelioid cell neoplasms originating in the urinary bladder are rare, and their standard treatment methods have not been established. Case Presentation: A 14‐year‐old girl with intermittent macroscopic hematuria was referred to our hospital. Ultrasonography and magnetic resonance imaging revealed a 5 cm spherical mass in the bladder neck and transurethral biopsy revealed a perivascular epithelioid cell neoplasm. Chromosome G‐banding analysis indicated a transcription factor E3 gene rearrangement. The mTOR inhibitor, sirolimus, was administered for six months, followed by partial cystectomy. No tumor recurrence was observed after 15 months. Conclusion: This case suggests the potential efficacy of partial cystectomy combined with neoadjuvant mTOR inhibitor therapy for transcription factor E3 gene rearrangement‐positive perivascular epithelioid cell neoplasms.

Purpose: The aim of this study was to assess the real-world perioperative safety and reoperation risk of laparoscopic transvesical ureteral reimplantation (TVUR), using intravesical open ureterocystoneostomy as a reference procedure, in patients with primary vesicoureteral reflux (VUR). Materials and Methods: We retrospectively reviewed patients with primary VUR who underwent laparoscopic TVUR or intravesical open ureterocystoneostomy in Japan (2012-2022). Laparoscopic TVUR was defined as a laparoscopic intravesical (vesicoscopic) transvesical approach; robot-assisted intravesical procedures were excluded. Propensity score matching was performed using age, sex, height, weight, bilaterality, duplex ureter, ureterocele, and maximum VUR grade. The primary outcome was reoperation. Secondary outcomes included operative time, catheter removal, hospital stay, and complications. Results: Among 1330 patients (laparoscopic TVUR: n = 514; intravesical open ureterocystoneostomy: n = 816), 868 were matched (434 per group). Laparoscopic TVUR required longer operative time (median [interquartile range]: 262 [220-321] vs 182 [151-229] min; P < .001) but was associated with earlier catheter removal (3 [2-5] vs 6 [3-7] days; P < .001) and shorter hospitalization (5 [3-7] vs 7 [5-9] days; P < .001). Intraoperative and postoperative complications were more frequent with laparoscopic TVUR (4.4% vs 0.5% and 12.4% vs 4.1%, respectively; P < .001). Urinary peritonitis occurred only after laparoscopic TVUR. Reoperation was more common in this group (2.8% vs 0.7%; hazard ratio: 3.74, 95% confidence interval: 1.05-13.24; P = .041). Conclusions: In this multicenter propensity score–matched cohort of patients with primary VUR, laparoscopic TVUR was associated with earlier catheter removal and shorter hospitalization but higher complication and reoperation rates than intravesical open ureterocystoneostomy, underscoring the importance of careful patient selection and meticulous technique.

Background: To evaluate the efficacy, safety, and pharmacokinetics of rifaximin in children with hepatic encephalopathy (HE). Methods: We conducted a multicenter, open-label, phase II/III study, comprising a 12-week treatment period, in children aged <18 years with hyperammonemia (≥66 μg/dL) and grade I or II HE or suspected HE, and compared the results with those previously obtained in adults. Patients were treated with 400 mg rifaximin 3 times daily, as for adults. The primary endpoint was the blood ammonia concentration, and other endpoints were changes in mental state and number connection test (NCT)-A and -B results from baseline. The safety endpoints were adverse events and fecal microbial composition. The pharmacokinetics of rifaximin were also assessed. Results: Of 21 patients (median age 11.0 years old, Q1–Q3 [8.0–14.0]), 18 completed the study, with a median [Q1–Q3] treatment duration of 84.0 [83.0–85.0] days. The most common underlying disease was a congenital portosystemic shunt. Thirteen patients were suspected of having HE, and 8 were diagnosed with coma grade I. The serum ammonia concentration remained lower than that at baseline during treatment with rifaximin, although the difference did not reach statistical significance. There were significant reductions from baseline in the mental state associated with HE and NCT-B results at all time points. No new clinically relevant safety issues or marked changes in the composition of the gut microbiota were identified. Conclusion: This is the first pediatric clinical study to demonstrate the efficacy, safety, and pharmacokinetics of rifaximin in pediatric patients with HE. The efficacy signals were driven primarily by clinical and neurocognitive measures rather than biochemical (ammonia) changes. The safety and pharmacokinetics of rifaximin were similar to those for adult patients.

The C-terminus of the Y14 protein, which is also known as RBM8A and is encoded by the gene responsible for human thrombocytopenia absent radius syndrome, contains two serines that undergo phosphorylation inside an intrinsically disordered region (IDR). Although both serines are frequently phosphorylated in cells, their biological role remains unclear; therefore, we estimated the peptide structure using PEPstrMOD, which predicts peptide conformations through molecular dynamics. For this analysis, amino acid residues 151–174 of Y14, identified as an IDR in UniProt, were targeted. Structural prediction via PEPstrMOD revealed that the target peptide adopts an elongated structure in its unphosphorylated state, while simulating its phosphorylated state revealed an increase in hydrogen bonds and a more compact conformation. The compact structure of Y14 induced by phosphorylation may aid in the formation of the exon–exon junction complex at the exon–exon junction, which facilitates mRNA transport and translation. The prevalence of phosphorylated Y14 in cells may indicate that this higher-order structure is also essential for mRNA metabolism.

Tracheal agenesis (TA) is a rare congenital anomaly with an incidence of 1 per 50,000 newborns. It appears at birth with severe respiratory distress, cyanosis, and inaudible crying. Prompt esophageal intubation and long-term management of the esophageal airway are essential to overcome this catastrophic condition. In the long-term management, external stenting of the esophageal airway has been reported as promising to support the fragile esophageal wall; this technique was taken from the surgery for tracheomalacia. We experienced a case of an infant with tracheal agenesis whose respiratory status was stabilized after external esophageal stenting. The stenting was performed based on a lesson learned in the extensive experience in the surgical treatment for tracheomalacia, and the surgical techniques for successful stenting are herein described.

Tracheal agenesis (TA) is a rare congenital anomaly with the incidence of 1 per 50,000 newborns. It appears at birth with severe respiratory distress, cyanosis, and inaudible crying. Prompt esophageal intubation and long-term management of the esophageal airway is essential to overcome the catastrophic condition. In the long-term management, external stenting of the esophageal airway has been reported promising to support the fragile esophageal wall and “trachealize,” which technique was implanted from the surgery for tracheomalacia. We experienced a case of an infant with tracheal agenesis whose respiratory status was stabilized after trachealization of the esophagus using external stenting technique. The stenting was performed based on a lesson learned in the extensive experience in the surgical treatment for tracheomalacia and the surgical techniques for successful stenting in are herein described.

Background.: In some pediatric patients undergoing living-donor liver transplantation, segment IV without the middle hepatic vein can be added to a left lateral segment graft to obtain larger graft volume. Because no clear consensus on this technique exists, this study investigated the effects of congested areas on postoperative outcomes in pediatric patients with biliary atresia undergoing living-donor liver transplantation.Methods.: We retrospectively reviewed data of recipients with biliary atresia aged ≤15 y who had undergone living-donor liver transplantation at Kyoto University Hospital between 2006 and 2021 and with graft-to-recipient weight ratios (GRWR) of ≤2%. Based on the percentage of congested area in the graft, patients were classified into the noncongestion (n = 40; ≤10%) and congestion (n = 13; >10%) groups. To compare the differences between groups with similar nooncongestive GRWRs and investigate the effect of adding congested areas, patients in the noncongestion group with GRWRs of ≤1.5% were categorized into the small noncongestion group (n = 24).Results.: GRWRs and backgrounds were similar between the noncongestion and congestion groups; however, patients in the congestion group demonstrated significantly longer prothrombin times, higher ascites volumes, and longer hospitalization. Further, compared with the small noncongestion group, the congestion group had significantly greater GRWR and similar noncongestive GRWR; however, the congestion group had significantly longer prothrombin time recovery (P = 0.020, postoperative d 14), higher volume of ascites (P < 0.05, consistently), and longer hospitalization (P = 0.045), requiring significantly higher albumin and gamma-globulin transfusion volumes than the small noncongestion group (P = 0.027 andP = 0.0083, respectively). Reoperation for wound dehiscence was significantly more frequent in the congestion group (P = 0.048).Conclusions.: In pediatric liver-transplant recipients, adding a congested segment IV to the left lateral segment to obtain larger graft volume may negatively impact short-term postoperative outcomes.

Antibody-mediated rejection (AMR) of liver allograft transplantation was considered as anecdotal for many decades. However recently, AMR has gained clinical awareness as a potential cause of chronic liver injury, leading to liver allograft fibrosis and eventual graft failure. (1) Methods: Literature on chronic AMR (cAMR) in pediatric post-liver transplant patients was reviewed for epidemiologic data, physiopathology, diagnosis, and treatment approaches. (2) Results: Accurate incidence of cAMR in pediatric liver transplantation remains unknown. Diagnostic criteria of cAMR were suggested by the Banff Working Group in 2016 and are based on standardized histopathological findings, C4d staining pattern, associated with the presence of donor-specific antibodies (DSA). Physio-pathological mechanisms are not clear for the technically difficult-to-obtain animal models reproducing cAMR. Treatment protocols are not established, being limited to case reports and case series, based on experience in ABO incompatible transplantation and kidney transplantation. Immunosuppression compliance with adequate dose adjustment may prevent cAMR. Conversion of Cyclosporine to Tacrolimus may improve pathological findings if treated in early phase. The association of steroids, Mycophenolate Mofetil (MMF) and mTOR inhibitors have shown some synergistic effects. Second-line treatments such as intravenous immunoglobulin (IVIG) and plasma exchange may decrease antibody titers based on ABO incompatible transplant protocols. The use of anti-CD20 (Rituximab) and proteasome inhibitors (Bortezomib) is controversial due to the lack of qualified studies. Therefore, multicenter randomized trials are needed to establish the best therapeutic strategy. In refractory cases, re-transplantation is the only treatment for allograft failure. (3) Conclusions: This literature review collects recent clinical, histopathological, and therapeutical advances of cAMR in liver allograft transplantation of pediatric patients. There are many physio-pathological aspects of cAMR to be clarified. Further efforts with multicenter prospective protocols to manage patients with cAMR are needed to improve its outcome.