Rapid and long-lasting efficacy of high-dose ambroxol therapy for neuronopathic Gaucher disease: A case report and literature review.

Gaucher disease (GD) is a lysosomal storage disorder caused by a deficiency in the GBA1-encoded enzyme, ß-glucocerebrosidase. Enzyme replacement therapy is ineffective for neuronopathic Gaucher disease (nGD). High-dose ambroxol has been administered as an alternative treatment for a group of patients with nGD. However, little is known about the clinical indication and the long-term outcome of patients after ambroxol therapy. We herein report a case of a female patient who presented with a progressive disease of GD type 2 from 11 months of age and had the pathogenic variants of p.L483P (formerly defined as p.L444P) and p.R502H (p.R463H) in GBA1. A combined treatment of imiglucerase with ambroxol started improving the patient's motor activity in 1 week, while it kept the long-lasting effect of preventing the deteriorating phenotype for 30 months. A literature review identified 40 patients with nGD, who had received high-dose ambroxol therapy. More than 65% of these patients favorably responded to the molecular chaperone therapy, irrespective of p.L483P homozygous, heterozygous or the other genotypes. These results highlight the long-lasting effect of ambroxol-based chaperone therapy for patients with an expanding spectrum of mutations in GBA1.

The Effectiveness of Deflux® Treatment for Vesicoureteral Reflux Following Pediatric Renal Transplantation: A Single-Institution Challenging Experience.

PURPOSE: To validate the effectiveness of Deflux® treatment for vesicoureteral reflux (VUR) following pediatric renal transplantation (RT), based on our single-institution experience. METHOD: A retrospective study was conducted using the medical records of pediatric patients who underwent Deflux® treatment for VUR after RT from April 2008 to March 2022. RESULTS: Sixty-eight pediatric patients underwent RT. VUR was subsequently detected in 22 (32 %) of these patients. Seven of the 22 patients (32 %) underwent Deflux® treatment to avoid renal dysfunction due to urinary infection (UTI). The median age at the time of RT was 4 years (range:2-12). All 7 patients had urinary UTIs before Deflux® treatment. The median estimated glomerular filtration rate (eGFR) before Deflux® treatment was 67 ml/min/1.73 m2 (range:42-138 ml/min/1.73 m2). After Deflux® treatment, VUR was downgraded in three cases (43 %). Four patients (57 %) experienced postoperative UTI, two of who underwent a second Deflux® treatment, one underwent submuscular tunnel reconstruction, and the other one experienced UTI without VUR after 1st Deflux® treatment but did not reoccur. All seven patients continued prophylactic medication after Deflux® treatment, without any history of recurrent UTIs during the observation period after treatment (median 37 months [range 7-86 months]). Furthermore, the eGFRs did not significantly decrease after Deflux® treatment (median eGFR 58 ml/min/1.73 m2 [range:33-99 ml/min/1.73 m2], p > 0.1). CONCLUSION: Deflux® treatment for VUR after RT is technically challenging because the new ureteral orifice is ventrally anastomosed at the bladder. We believe our results indicate the possibility of reducing the frequency of UTIs and contributing to preservation of the renal function after RT. TYPE OF STUDY: Retrospective Study. LEVEL OF EVIDENCE: Level III.

The Volume of Intestinal Decompression can Predict the Necessity of Surgical Intervention for Adhesive Small Bowel Obstruction.

BACKGROUND: There is no standard timing for switching to surgical management for children with adhesive small bowel obstruction (ASBO) who initially receive conservative treatment. We hypothesized that an increased gastrointestinal drainage volume may indicate the need for surgical intervention. METHODS: The study population included 150 episodes in the patients less than 20 years of age who received treatment for ASBO in our department from January 2008 to August 2019. Patients were divided into two groups: the successful conservative treatment group (CT) and the eventual surgical treatment group (ST). Following the analysis of all episodes (Study 1), we limited our analysis to only first ASBO episodes (Study 2). We retrospectively reviewed their medical records. RESULTS: There were statistically significant differences in the volume on the 2nd day in both Study 1 (9.1 ml/kg vs. 18.7 ml/kg; p < 0.01) and study 2 (8.1 ml/kg vs. 19.7 ml/kg; p < 0.01). The cut-off value was the same for both Study 1 and Study 2 (11.7 ml/kg). CONCLUSIONS: The gastrointestinal drainage volume on the 2nd day in ST was significantly larger than that in CT. Accordingly, we considered that the drainage volume may predict eventual surgical intervention for children with ASBO who initially receive conservative treatment. LEVEL OF EVIDENCE: Level IV.

Necrotizing enterocolitis associated with food protein-induced enterocolitis syndrome: A case report.

INTRODUCTION: Food protein-induced enterocolitis syndrome (FPIES) is a T-cell-mediated allergy that can occur in newborns and infants who are introduced to milk protein. Some of the serious complications of FPIES include necrotizing enterocolitis (NEC), massive bloody stools, and disseminated intravascular coagulation. Here we report a case of NEC caused by FPIES. PRESENTATION OF CASE: A 28-day-old girl born at full term suddenly developed marked abdominal distention and shock a few hours after being fed highly regulated milk protein. Emergency laparotomy was performed, and extensive small-intestinal necrosis was found. The histological examination showed chronic inflammation with typical ghost crypts, hemorrhage, and extensive pneumatosis intestinalis, a presentation consistent with NEC. DISCUSSION: In this case, the fragile intestinal mucosa associated with FPIES was stimulated by milk protein, leading to NEC. The greatest diagnostic difficulty is the lack of a definitive method for distinguishing between NEC and FPIES. The allergen-specific lymphocyte stimulation test with lactotransferrin was positive, indicating that the primary condition was FPIES. However, no eosinophilic infiltrate was found in the histological examination, but there was chronic inflammation with typical ghost crypts, hemorrhage, and extensive pneumatosis intestinalis. Consequently, the final histological diagnosis in our case was NEC rather than FPIES. CONCLUSION: FPIES has a variable clinical course, and severe FPIES may become exacerbated even after ingestion of highly regulated milk protein. Taking appropriate actions after correct diagnosis can prevent progression to surgical emergency and secondary NEC.

Stercoral ulcer after Hirschsprung's disease surgery.

Constipation and stercoral ulcer are risk factors associated with Hirschsprung's disease (HD); long-term follow-up is, thus, essential. In postoperative HD associated with Down syndrome (DS) with intellectual disability, vigilant follow-up is required to avoid severe constipation because DS predisposes the patients to constipation and caregivers cannot easily understand the symptoms.

Endoscopic Surgical Approach for Pediatric Solid Tumors That Permits Complete Curability and Exhibits Cosmetic Advantages.

Background: We actively use novel endoscopic surgical approaches with complete curability and good cosmetic outcomes to facilitate the removal of resected tumors from the body via a small incision. Patients and Methods: This retrospective study reviewed the medical records of patients who underwent endoscopic surgery for treating solid tumors in the abdominal, thoracic, and urogenital regions between April 2013 and March 2020. Results: At our institution, minimally invasive surgery (MIS) is performed for malignant tumors with a maximum diameter of ≤5 cm and nonmalignant tumors without diameter restrictions, although both need to have no vascular encasement. In total, 135 pediatric solid tumor resections were performed at our institution during the aforementioned period, among whom 37 patients satisfied the MIS criteria. Among them, 28 patients underwent endoscopic surgeries, whereas 9 underwent open surgeries. The median surgical durations were 192 and 138 minutes in the MIS and open groups, respectively (P = .096). The median volume of blood loss was 1 and 8 mL in the MIS and open groups, respectively (P = .086). The median lengths of hospital stay were 8 and 7 days in the MIS and open groups, respectively (P = .178). One patient in each group had Clavien-Dindo grade ≥Ⅲ complications. However, there was no surgery-related death. All patients receiving MIS had satisfactory operative scarring, early recovery, and good cosmetic outcomes. Conclusion: MIS can be used for pediatric solid tumors, considering the patient's quality of life while allowing complete curability and providing endoscopic surgical advantages.

Abdominal esophageal banding for esophageal atresia with tracheoesophageal fistula in neonates with severe associated anomalies.

PURPOSE: The aim of this study was to evaluate the materials used for abdominal esophageal banding, and to evaluate the complications associated with abdominal esophageal banding. METHODS: The medical records of seven patients with esophageal atresia (EA) and tracheoesophageal fistula (TEF) who underwent abdominal esophageal banding between December 2009 and January 2020 were retrospectively reviewed. RESULTS: The patients were banded with vinyl tape (n = 1), silicone tape (n = 2), polyacetal resin clips (n = 1), or an expanded polytetrafluoroethylene (ePTFE) sheet (n = 3). Banding with vinyl tape resulted in banding failure at postoperative day (POD) 89. One patient with silicone tape developed banding failure at POD 177. In the other patient, it was discovered during radical surgery that the silicone tape had slipped through the abdominal esophagus. Polyacetal resin clip banding resulted in esophageal wall perforation at POD 27. One patient banded with an ePTFE sheet underwent upper gastric transection at POD 650, while another underwent TEF resection at POD 156; in the third patient, the banding condition was maintained for more than 100 days. CONCLUSION: Abdominal esophageal banding is useful as a palliative treatment for EA/TEF with severe associated anomalies. Surgeons should plan the next surgery depending on the patient's condition.

Congenital intestinal atresia associated with a mesenteric cystic lymphangioma in a low birth weight neonate: A case report.

INTRODUCTION: Congenital intestinal atresia requires emergency surgery soon after birth. Lymphangioma, a benign tumor, is caused by an anomalous lymphatic system. We report a case of congenital intestinal atresia associated with a mesenteric cystic lymphangioma in a low birth weight neonate. PRESENTATION OF CASE: At 21 weeks of pregnancy, ultrasonography revealed a cystic lesion in the fetal abdominal cavity. At 31 weeks, magnetic resonance imaging showed dilatation of the small intestine. This low birth weight (1752 g) male infant was born by vaginal delivery at 32 weeks 3 days' gestation. Laparotomy on day 2 of life revealed jejunal atresia and a mesenteric cyst. The cyst was removed and intestinal anastomosis was performed. Histologically, the cyst proved to be a mesenteric lymphangioma. DISCUSSION: The most popular theories regarding the mechanism of congenital intestinal atresia include reperfusion injury and intestinal tract blood flow disturbance. In this fetus, intestinal torsion had occurred around the mesenteric cystic lymphangioma, which apparently disturbed the mesenteric blood flow and caused intestinal atresia. CONCLUSION: There have been few reports of the combination of a mesenteric cystic lymphangioma and congenital intestinal atresia. This case supports the theory that small bowel atresia and stenosis are caused by accidental blood flow disturbance.

Which Is the Better Approach for Late-Presenting Congenital Diaphragmatic Hernia: Laparoscopic or Thoracoscopic? A Single Institution's Experience of more than 10 Years.

Aim: We evaluated a series of late-presenting congenital diaphragmatic hernia (Late-CDH) cases and assessed the reliability and risks of laparoscopic and thoracoscopic approaches for Late-CDH at a single institution. Materials and Methods: From 2005 to 2017, we experienced totally 11 patients with Late-CDH who received endoscopic repairs. We retrospectively surveyed the approach, defect size, operating time, and postoperative outcomes, including recurrence. Results: Eleven patients (Bochdalek, n = 10; Morgagni, n = 1) underwent a total of 14 endoscopic repairs (laparoscopy, n = 10; thoracoscopy, n = 4). The average defect size was ∼3.1 × 1.5 cm. In all 14 endoscopic repairs, patients received intracorporeal interrupted nonabsorbable stitches and extracorporeal knot tying were applied, without the use of an artificial patch. In the laparoscopic repairs, 7 patients received left-handed suturing when closing the diaphragmatic defect, because the reduced viscera lay directly below the posterior rim of the diaphragmatic defect, making it difficult to confirm the rim. In contrast, in the thoracoscopic repairs, the viscera were reduced over the diaphragmatic defect, so the surgeons could easily perform suturing. The average operating time was 172 minutes for laparoscopy and 194 minutes for thoracoscopy. No major intraoperative or postoperative complications occurred in association with either of the approaches. Among the 11 patients, 2 experienced a total of 3 recurrences (all after laparoscopic repairs). Conclusion: Although there were few differences between the laparoscopic and thoracoscopic approaches, because of the technical difficulty of the procedure and the possibility of recurrence with the laparoscopic approach, a thoracoscopic approach may be better for the repair of Late-CDH.

Reference growth curves for normal appendiceal diameter in childhood.

The aim of this study was to investigate the relationship between the appendiceal diameter (AD) and age, sex, height, and body weight in children and to verify how does the normal AD grows in childhood. We evaluated the AD of patients younger than 16 years of age who underwent laparoscopic surgery at our hospital. We statistically examined the relationship between the AD and the age, sex, height, and weight. A final cohort of 188 patients participated in the study. The median AD for the sample population was 5 mm (range, 3.2-8.1). There was no significant difference in the AD between males and females in the multivariate analysis (P = 0.500). There was a positive correlation between the age and the AD (R = 0.396, P < 0.001). The AD had a significant positive correlation with the height and weight (P < 0.001, P < 0.001, respectively). The reference curve with regard to the AD can be useful in clinical situations, although it should be kept in mind that the range of individual differences in AD is large, and the growth degree by age is not uniform during childhood.

Continuous Skill Training Using the Disease-Specific Endoscopic Surgical Simulator to Promote Young Pediatric Surgeons: Learning Curve for Trainees.

Purpose: This study aimed to evaluate the learning effects of continuous training with a disease-specific endoscopic surgical simulator for young pediatric surgeons. Materials and Methods: Participants trained with a laparoscopic fundoplication simulator for 1 hour every 10 days. At the start of each training session, we assessed the participant's surgical technique using the surgical skill evaluation system, which evaluates the following items: (1) task time, (2) right-left balance of suturing, (3) suture spacing between the three ligatures, (4) total path length traveled by forceps, (5) velocity of the forceps tips, (6) length of the wrap, (7) number of ligature failures, and (8) comparison of improvements according to assessment point. We examined the learning effects of this continuous training program. Results: Task time, right-left balance of suturing, and sum of the distance traveled by each forceps showed significant progressive improvements (P < .05). Suture spacing and average velocity of forceps tips did not change significantly with training (P = .5781, P = .0781, respectively). However, the ratio of traveled distance between left and right forceps significantly improved (P < .05). There was a significant trend for the wrap length to approach the target value (P < .05). According to the linear mixed-effects model, the number of training sessions required for learning was not uniform and varied depending on the skill. Conclusion: This simulator training program can help pediatric surgeons to acquire surgical skills easily, economically, and safely. In the future, we need to evaluate how surgical skills acquired during this continuous training are reflected in clinical operations.

Balloon tracheoplasty as initial treatment for neonates with symptomatic congenital tracheal stenosis.

Neonates with congenital tracheal stenosis (CTS) sometimes develop respiratory distress and may be difficult to intubate. We used balloon tracheoplasty with a rigid bronchoscope for emergency airway management in neonates with symptomatic CTS. Herein, we describe the balloon tracheoplasty procedure and the early outcomes following its use as the initial treatment of neonatal symptomatic CTS. We performed a retrospective analysis of five neonates with CTS who were initially treated with balloon tracheoplasty at our institution from January 2010 to December 2013. Five patients with a mean birthweight of 2,117 g were treated during the study period. Of these, four developed respiratory distress after birth, and all patients had difficult intubations. In all five patients, definitive diagnosis of CTS was made by rigid bronchoscopy and 3-dimensional reconstruction scan. A total of nine balloon dilatations were performed in five patients. Following balloon tracheoplasty, two patients were extubated, one was extubated after resection and end-to-end anastomosis following initial balloon dilatation, and one remained hospitalized with tracheostomy for tracheomalacia. The remaining patient died from tracheal bleeding associated with congenital heart disease. Although our sample size was small, balloon tracheoplasty is a potentially effective initial treatment for selected cases with neonatal symptomatic CTS.

Surgical reconstruction and endoscopic pancreatic stent for traumatic pancreatic duct disruption.

Nonoperative management is acceptable treatment for minor pancreatic injuries. However, management of major pancreatic duct injury in children remains controversial. We present our experience in treating isolated pancreatic duct injury. We describe the cases of three male patients treated for complete pancreatic duct disruption in the past 5 years at our institution. We performed pancreatic duct repair to avoid distal pancreatectomy and to maintain normal pancreatic function. All patients underwent enhanced computed tomography and endoscopic retrograde cholangiopancreatography in the early period. The injuries were classified as grade III according to the American Association for the Surgery of Trauma classification. In two cases, we performed end-to-end anastomosis of the pancreatic duct during the delayed period. In the third case, we placed a stent across the disruption to the distal pancreatic duct. The patients' postoperative courses were uneventful, and the average hospitalization was 25.6 days after the procedure. At a median follow-up of 36 months (range 14-54 months), all patients remain asymptomatic, with normal pancreatic function, but with persistent distal pancreatic duct dilatation. We suggest that distal pancreatectomy should not be routinely performed in patients with isolated pancreatic duct injury.