Recent progress and current status of pancreatobiliary interventional endoscopic ultrasound in children.

In recent years, the usefulness of endoscopic ultrasound (EUS) has been recognized in children. A dedicated pediatric EUS scope has not been developed; in our experience, however, an adult EUS scope can be used. The American Society for Gastrointestinal Endoscopy Technical Committee status assessment report on pediatric endoscopy equipment provides some guidance on the feasibility of EUS according to body size. Careful monitoring is required, keeping in mind potential adverse events such as cervical esophageal perforation and unstable breathing due to tracheal compression. Most devices designed for interventional pancreatobiliary endoscopy are also available for children. Sedation or intubated general anesthesia (GA) is mandatory when performing interventional EUS (I-EUS). I-EUS for children is generally performed using GA in the operating room, but sedation in the endoscopy room is also possible under appropriate monitoring by pediatricians. I-EUS in the operating room is sometimes difficult for endoscopists to perform because of the unsuitable fluoroscopic imaging and the lack of familiar equipment and staff. Compared to GA, sedation in the endoscopy room facilitates easier and quicker repetition of procedures when necessary. Adult pancreatobiliary endoscopists perform most I-EUS procedures in the pediatric population because most pediatric endoscopists have few opportunities to perform EUS-related procedures and thus have difficulty maintaining their skills. To popularize I-EUS techniques for children, it will be necessary to establish a training program for developing pediatric endoscopists.

The RNA-binding protein quaking is upregulated in nitrofen-induced congenital diaphragmatic hernia lungs at the end of gestation.

BACKGROUND: The RNA-binding protein Quaking (QKI) increases during epithelial-to-mesenchymal transition and its expression is controlled by microRNA-200 family members. Here, we aimed to describe the expression of QKI in the developing lungs of control and nitrofen-induced congenital diaphragmatic hernia lungs (CDH). METHODS: To investigate the expression of QKI, we dissected lungs from control and nitrofen-induced CDH rats on embryonic day 15, 18, 21 (E15, E18, E21). We performed immunofluorescence (IF) and quantitative reverse transcription PCR (RT-qPCR) for QKI expression. Additionally, we assessed Interleukin-6 (IL-6) abundance using IF. RESULTS: On E21, IF showed that the abundance of all three QKI isoforms and IL-6 protein was higher in CDH lungs compared to control lungs (QKI5: p = 0.023, QKI6: p = 0.006, QKI7: p = 0.014, IL-6: p = 0.045, respectively). Furthermore, RT-qPCR data showed increased expression of QKI5, QKI6, and QKI7 mRNA in E21 nitrofen lungs by 1.63 fold (p = 0.001), 1.63 fold (p = 0.010), and 1.48 fold (p = 0.018), respectively. CONCLUSIONS: Our data show an increase in the abundance and expression of QKI at the end of gestation in nitrofen-induced CDH lungs. Therefore, a disruption in the regulation of QKI during the late stage of pregnancy could be associated with the pathogenesis of abnormal lung development in CDH.

Mitochondrial viability in neurogenic bladder urothelium after sigmoidocolocystoplasty. Implications for persistent vesicoureteral reflux.

PURPOSE: We investigated whether inflammatory cell infiltration (ICI), fibrosis, and mitochondrial viability of the neurogenic bladder urothelium are involved in the mechanism of persistent vesicoureteral reflux (VUR) after sigmoidocolocystoplasty (SCP). METHODS: Bladder biopsies obtained 1994-2023 from 62 neurogenic bladder patients were examined by hematoxylin and eosin for ICI, Masson's trichrome for fibrosis, and immunofluorescence for urothelial growth differentiation factor 15 (GDF15; a mitochondrial stress-responsive cytokine) (positive/negative) and heat shock protein 60 (HSP60; a mitochondrial matrix marker) (strong ≥ 50%/weak≤ 50%) expression. GDF15 + /weak HSP60 indicated compromised mitochondrial viability. Cystometry measured neobladder compliance/capacity. RESULTS: Mean ages (years) at SCP and bladder biopsies were 9.4 ± 4.6 and 14.2 ± 7.1, respectively. VUR was present in 38/62 patients (51 ureters) at SCP and resolved with SCP alone in 4/38 patients, with SCP and ureteroneocystostomy in 17/38, and persisted in 17/38. Fibrosis was significantly denser in GDF15 + (n = 24)/weak HSP60 (n = 31) compared with GDF15- (n = 38)/strong HSP60 (n = 31) (p < 0.001 and p < 0.01, respectively). Differences in ICI were significant for GDF15 + vs. GDF15- (p < 0.05) but not for HSP60. Patients with VUR after SCP had higher incidence of GDF15 + /weak HSP60 compared with cases without VUR (p < 0.05 and p < 0.001, respectively). CONCLUSION: Viability of mitochondria appears to be compromised with possible etiologic implications for VUR persisting after SCP.

Comprehensive meta-analysis of surgical procedure for congenital diaphragmatic hernia: thoracoscopic versus open repair.

PURPOSE: Previous studies have shown a higher recurrence rate and longer operative times for thoracoscopic repair (TR) of congenital diaphragmatic hernia (CDH) compared to open repair (OR). An updated meta-analysis was conducted to re-evaluate the surgical outcomes of TR. METHODS: A comprehensive literature search comparing TR and OR in neonates was performed in accordance with the PRISMA statement (PROSPERO: CRD42020166588). RESULTS: Fourteen studies were selected for quantitative analysis, including a total of 709 patients (TR: 308 cases, OR: 401 cases). The recurrence rate was higher [Odds ratio: 4.03, 95% CI (2.21, 7.36), p < 0.001] and operative times (minutes) were longer [Mean Difference (MD): 43.96, 95% CI (24.70, 63.22), p < 0.001] for TR compared to OR. A significant reduction in the occurrence of postoperative bowel obstruction was observed in TR (5.0%) compared to OR (14.8%) [Odds ratio: 0.42, 95% CI (0.20, 0.89), p = 0.02]. CONCLUSIONS: TR remains associated with higher recurrence rates and longer operative times. However, the reduced risk of postoperative bowel obstruction suggests potential long-term benefits. This study emphasizes the importance of meticulous patient selection for TR to mitigate detrimental effects on patients with severe disease.

Evaluating perioperative stresses in children by noninvasive modalities using salivary cortisol and autonomic reactivity.

PURPOSE: Salivary cortisol (SalC) and low to high pulse ratio (LHR) were used for evaluating perioperative stresses in children. METHODS: Children aged 6 months-16 years having elective general (thoracic/abdominal) or minor (open/minimally invasive: MI) procedures underwent pulse monitoring during AM (08:00-12:00) and PM (17:00-21:00) saliva collections from the day before surgery (S-1) to 3 days after surgery (S + 3). SalC/LHR were correlated with age, sex, caregiver attendance, operative time, and surgical site/approach using mixed model analysis and face/numeric pain rating scales (FRS/NRS). RESULTS: Mean ages (years): minor-open (n = 31) 4.7 ± 2.0, thoracic-open (n = 2) 8.7 ± 4.9, thoracic-MI (n = 6) 9.6 ± 6.1, abdominal-open (n = 14) 4.3 ± 4.1, and abdominal-MI (n = 32) 8.0 ± 5.0. Postoperative SalC increased rapidly and decreased to preoperative levels by S + 3 (p < 0.001). LHR increased slightly without decreasing (p = 0.038). SalC correlated positively with operative time (p = 0.036) and open surgery (p = 0.0057), and negatively with age (p < 0.0001) and caregiver attendance (p < 0.001). SalC correlated positively with FRS (n = 51) at S + 2(PM) (p = 0.023), S + 3(AM) (p < 0.001), S + 3(PM) (p = 0.012) and NRS (n = 34) at S + 1(AM) (p = 0.031), S + 3(AM) (p < 0.044). LHR positively correlated with age (p = 0.0072), female sex (p = 0.0047), and caregiver attendance (p = 0.0026). Postoperative SalC after robotic-assisted MI was significantly lower than after open surgery at S + 2(AM) (p = 0.020). CONCLUSIONS: SalC correlated with pain. Caregiver attendance effectively alleviated stress.

Cholestasis after Kasai operation predicts portal hypertension in native liver survivors of biliary atresia: a multicenter study.

PURPOSE: This study evaluated portal hypertension (PHT) and its predictors among native liver survivors (NLS) of biliary atresia (BA) after Kasai portoenterostomy (KPE). METHODS: This was a multicenter study using prospectively collected data. The subjects were patients who remained transplant-free for 5 years after KPE. Their status of PHT was evaluated and variables that predicted PHT were determined by regression analysis and receiver operating characteristic (ROC) curve. RESULTS: Six centers from East Asia participated in this study and 320 subjects with KPE between 1980 to 2018 were analyzed. The mean follow-up period was 10.6 ± 6.2 years. At the 5th year after KPE, PHT was found in 37.8% of the subjects (n = 121). Patients with KPE done before day 41 of life had the lowest percentage of PHT compared to operation at older age. At 12 months after KPE, PHT + ve subjects had a higher bilirubin level (27.1 ± 11.7 vs 12.3 ± 7.9 µmol/L, p = 0.000) and persistent jaundice conferred a higher risk for PHT (OR = 12.9 [9.2-15.4], p = 0.000). ROC analysis demonstrated that a bilirubin level above 38 µmol/L at 12 months after KPE predicted PHT development (sensitivity: 78%, specificity: 60%, AUROC: 0.75). CONCLUSIONS: In BA, early KPE protects against the development of PHT among NLSs. Patients with persistent cholestasis at one year after KPE are at a higher risk of this complication. They should receive a more vigilant follow-up. LEVEL OF EVIDENCE: Level III.

Microinjection With Nanoparticles to Deliver Drugs in Prenatal Lung Explants - A Pilot Study for Prenatal Therapy in Congenital Diaphragmatic Hernia.

BACKGROUND: Fetoscopic endoluminal tracheal occlusion (FETO) improves the survival rate in fetuses with severe congenital diaphragmatic hernia (CDH). We hypothesize that prenatal therapies into the trachea during FETO can further improve outcomes. Here, we present an ex vivo microinjection technique with rat lung explants to study prenatal therapy with nanoparticles. METHODS: We used microsurgery to isolate lungs from rats on embryonic day 18. We injected chitosan nanoparticles loaded with fluorescein (FITC) into the trachea of the lung explants. We compared the difference in biodistribution of two types of nanoparticles, functionalized IgG-conjugated nanoparticles (IgG-nanoparticles) and bare nanoparticles after 24 h culture with immunofluorescence (IF). We used IF to mark lung epithelial cells with E-cadherin and to investigate an apoptosis (Active-caspase 3) and inflammatory marker (Interleukin, IL-6) and compared its abundance between the two experimental groups and control lung explants. RESULTS: We detected the presence of nanoparticles in the lung explants, and the relative number of nanoparticles to cells was 2.49 fold higher in IgG-nanoparticles than bare nanoparticles (p < 0.001). Active caspase-3 protein abundance was similar in the control, bare nanoparticles (1.20 fold higher), and IgG-nanoparticles (1.34 fold higher) groups (p = 0.34). Similarly, IL-6 protein abundance was not different in the control, bare nanoparticles (1.13 fold higher), and IgG-nanoparticles (1.12 fold higher) groups (p = 0.33). CONCLUSIONS: Functionalized nanoparticles had a higher presence in lung cells and this did not result in more apoptosis or inflammation. Our proof-of-principle study will guide future research with therapies to improve lung development prenatally. LEVELS OF EVIDENCE: N/A TYPE OF STUDY: Animal and laboratory study.

Retroperitoneoscopic Simple Nondismembered Pyeloplasty with Da Vinci Si Assistance to Prevent Alignment Shift.

Aims: Retroperitoneoscopic simple nondismembered pyeloplasty (SNDP) with da Vinci Si assistance was developed because of a possible risk for alignment shift after retroperitoneoscopic diamond-shaped bypass pyeloplasty (Diamond-Bypass; DP). Outcomes of SNDP and DP were compared. Materials and Methods: For SNDP, a small longitudinal incision is made on the border of the dilated pelvis and narrowed ureter at the ureteropelvic junction (UPJ). Extending this incision toward the pelvis allows identification of mucosa while maintaining the integrity of surrounding tissues that are so thin and fragile that they will not influence lumen alignment. Data for DP were obtained from a previously published article. Results: For SNDP (n = 3), mean age at surgery was 2.67 years (range: 1-4), mean operative time was 176 minutes. Mean postoperative Society of Fetal Urology (SFU) grades for hydronephrosis were 1.2, 0.7, and 0.6, 1, 2, and 3 months after stent removal, respectively. Postoperative diethylenetriaminepentaacetic acid (DTPA) was normal (n = 3). For DP (n = 5) mean age at surgery was 4.3 years (range: 1-14), mean operative time was 189 minutes. Mean postoperative SFU grades were 2.8, 2.2, and 1.6, respectively. Postoperative DTPA was normal (n = 4) and delayed (n = 1). All SNDP and DP were asymptomatic by 3 months after stent removal. Conclusion: Both SNDP and DP have favorable outcomes. If the UPJ is located at the lowest end of the renal pelvis, SNDP may improve hydronephrosis more quickly.

Bile acid profiles in adult patients with biliary atresia who achieve native liver survival after portoenterostomy.

Bile acids have received increasing attention as a marker of the long-term prognosis and a potential therapeutic target in patients with biliary atresia, which is a progressive disease of the hepatobiliary system. A detailed analysis of serum and urinary bile acid compositions was conducted to assess the characteristics of bile acid profiles and the correlation between bile acid profiles and liver fibrosis markers in adult patients with biliary atresia who achieved bilirubin normalization. Serum total bile acids and glucuronide-conjugated (glyco- and tauro-) cholic acids (GCA and TCA) and chenodeoxycholic acids (GCDCA and TCDCA) were significantly higher in patients with biliary atresia than in healthy controls, whereas unconjugated CA and CDCA showed no significant difference. There were no significant differences in CA to CDCA ratios and glycine-to-taurine-conjugated ratios. Urinary glycocholic acid 3-sulfate (GCA-3S) was significantly higher in patients with biliary atresia. Serum GCDCA showed a strong positive correlation with Mac-2 binding protein glycosylation isomer (M2BPGi). These results demonstrate that bile acid congestion persists into adulthood in patients with biliary atresia, even after cholestasis has completely improved after Kasai portoenterostomy. These fundamental data on bile acid profiles also suggest the potential value of investigating bile acid profiles in patients with biliary atresia.

Pulmonary artery diameter ratio as a prognostic indicator of congenital diaphragmatic hernia.

Background: Following on from an earlier study published in 2008 about left pulmonary artery (LPA) flow measured on serial echocardiography being strongly prognostic in left-sided congenital diaphragmatic hernia (CDH) and the ratio of LPA to right pulmonary artery (RPA) diameters being a simple and reliable indicator for commencing nitric oxide (NO) therapy, the ratio of LPA:RPA diameters (PA ratio or PAR) was hypothesized to possibly reflect cardiopulmonary stresses accompanying CDH better. Methods: Subjects with isolated left-sided CDH treated between 2007 and 2020 at a single pediatric surgical center were recruited and classified according to survival. Data obtained retrospectively for subject demographics, clinical course, LPA/RPA diameters, and PAR were compared between survivors and non-survivors. The value of PAR for optimizing the prognostic value of PA diameter data in CDH were analyzed with receiver operating characteristic (ROC) curve analysis. Results: Of 65 subjects, there were 54 survivors (82.3%) and 11 non-survivors (17.7%); 7 of 11 non-survivors died before surgical repair could be performed. Mean PAR for survivors (0.851±0.152) was significantly higher than for non-survivors (0.672±0.108) (p=0.0003). Mean PAR for non-survivors was not affected by surgical repair. Characteristics of survivors were: LPA ≥2 mm (n=52 of 54; mean PAR=0.866±0.146) and RPA ≥3 mm (n=46 of 54; mean PAR=0.857±0.152). Non-survivors with similar LPA and RPA diameters to survivors had significantly lower mean PAR. ROC curve cut-off for PAR was 0.762. Subjects with high PAR (≥0.762) required high-frequency oscillatory ventilation/NO less than subjects with low PAR (<0.762) (p=0.0244 and p=0.0485, respectively) and subjects with high PAR stabilized significantly earlier than subjects with low PAR (1.71±0.68 days vs 3.20±0.87 days) (p<0.0001). Conclusions: PAR would appear to be strongly correlated with clinical outcome in CDH and be useful for planning management of cardiopulmonary instability in CDH.

Optical Trocar Access for Retroperitoneal Robotic-Assisted Pyeloplasty in Children with Ureteropelvic Junction Obstruction.

Purpose: Retroperitoneal robotic-assisted pyeloplasty (ret-RAP) for ureteropelvic junction obstruction (UPJO) requires a larger retroperitoneal space (RS) to maintain specified distances between robotic (da Vinci) trocars and between trocars and the region of interest. A modified closed technique (MOT) and conventional closed technique (COT) were compared for creating an adequate RS with optical trocars. Methods: RS access in children with UPJO who underwent ret-RAP (n = 30) was MOT (n = 15) and COT (n = 15). All patients were positioned laterally. For MOT, a 5 mm optical trocar was inserted at the angle formed between the 12th rib and the erector spinae muscles. As the trocar was advanced under direct vision, it pierced the superficial subcutaneous layer, Scarpa's fascia, lumbar fascia, internal/external oblique and transversus abdominalis muscles, and the posterior renal fascia. Once in the RS, the tip of the scope was used for blunt dissection of perirenal fat, the tip was withdrawn until it was outside the perirenal fascia, and used to dissect toward the anterior abdomen in the pararenal fat layer. Results: Ages and weights at ret-RAP were similar (MOT: 5.6 ± 1.8 years versus COT: 7.8 ± 4.6 years; MOT: 20.6 ± 10.1 kg versus COT: 27.6 ± 13.9 kg). Times for RS access were similar (MOT: 1.6 ± 0.5 minutes versus COT: 1.9 ± 0.7 minutes), but RS expansion was significantly quicker in MOT (32.3 ± 8.7 minutes versus 52.0 ± 15.1 minutes; P < .001). Peritoneal injury caused carbon dioxide leakage in 4 of 15 COT cases and 0 of 15 MOT cases. Conclusion: RS expansion with MOT was safer because there were no peritoneal injuries and MOT was quicker than COT.

Advantages of Urethroplasty Terminating at the Corona for Severe Hypospadias: Complications, Uroflowmetry, and Esthetics.

PURPOSE: Mid-shaft/proximal (msp) and penoscrotal/scrotal/perineal (pssp) hypospadias treated by urethroplasty (UP) terminating at the corona (UPC) or UP terminating at the tip of the glans (UPG) were compared. METHODS: UP performed at a single institute (n = 234) between 2003 and 2020 were grouped as: msp-UPC (n = 23), msp-UPG (n = 75), pssp-UPC (n = 81), and pssp-UPG (n = 55) to compare data obtained from medical records for post-UP complications (PUC; urethral stenosis, urethrocutaneous fistula, diverticulum formation, and bleeding; n = 234), post-UP uroflowmetry (PUF; average flow rate (Qave), maximum flow rate (Qmax), voiding time (VT), voided volume (VV) and urine flow curves) in 57 UP patients [msp-UPC (n = 5), msp-UPG (n = 12), pssp-UPC (n = 32), pssp-UPG (n = 8)] and 9 controls, and post-UPC esthetics (EST; n = 104). P < 0.05 was considered significant. RESULTS: Mean ages at UP (years) were: msp-UPC (3.1 ± 3.0), msp-UPG (3.3 ± 1.4), pssp-UPC (4.6 ± 2.4), and pssp-UPG (3.4 ± 1.4); p < 0.0001 by ANOVA test. Overall, there were significantly more PUC in pssp-UPG compared with pssp-UPC except for bleeding. Ages at PUF assessment were similar. Mean Qave (mL/s) for pssp-UPG (4.0 ± 1.0) was significantly less than pssp-UPC (5.9 ± 2.5; p < 0.05) and both were significantly less than controls (6.9 ± 1.8; p < 0.05, p < 0.01, respectively). Mean Qmax (mL/s) for pssp-UPC (11.4 ± 4.8) was significantly better than pssp-UPG (7.8 ± 2.3; p < 0.05) and for controls (14.9 ± 4.4) was significantly better than pssp-UPG (7.8 ± 2.3; p < 0.01). All VT (seconds) were similar to controls; all urine flow curves were normal. For EST in UPC (n = 104), 3 cases requested meatal advancement. CONCLUSIONS: UPC may be a valid option for treating pssp hypospadias because of significant differences in PUC/PUF and minimal EST issues compared with UPG. LEVEL OF EVIDENCE: Prognosis Study Level-Ⅱ.