Cutting-edge regenerative therapy for Hirschsprung disease and its allied disorders.

Hirschsprung disease (HSCR) and its associated disorders (AD-HSCR) often result in severe hypoperistalsis caused by enteric neuropathy, mesenchymopathy, and myopathy. Notably, HSCR involving the small intestine, isolated hypoganglionosis, chronic idiopathic intestinal pseudo-obstruction, and megacystis-microcolon-intestinal hypoperistalsis syndrome carry a poor prognosis. Ultimately, small-bowel transplantation (SBTx) is necessary for refractory cases, but it is highly invasive and outcomes are less than optimal, despite advances in surgical techniques and management. Thus, regenerative therapy has come to light as a potential form of treatment involving regeneration of the enteric nervous system, mesenchyme, and smooth muscle in affected areas. We review the cutting-edge regenerative therapeutic approaches for managing HSCR and AD-HSCR, including the use of enteric nervous system progenitor cells, embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells as cell sources, the recipient intestine's microenvironment, and transplantation methods. Perspectives on the future of these treatments are also discussed.

The advantages of duct-to-duct biliary reconstruction in pediatric living donor liver transplantation.

BACKGROUND/PURPOSE: Whether Roux-en-Y hepatic jejunectomy (HJ) or duct-to-duct biliary reconstruction (DD) is more useful in pediatric living donor liver transplantation has not yet been fully investigated. Therefore, to assess the feasibility and safety of DD, we compared the surgical outcomes of DD to HJ. METHODS: We divided 45 patients, excluding those with biliary atresia, into the DD group (n = 20) and the HJ group (n = 25), according to the type of biliary reconstruction they received. RESULTS: The 5-year survival rates (DD vs. HJ = 79.7% vs. 83.6%, p = 0.70) and the incidence of biliary complications, including bile leakage and stricture (DD vs. HJ = 1 [5.0%] vs. 1 [4.0%], p = 0.87) were not significantly different between the groups. However, intestinal complications, including bowel perforation or ileus, were significantly common in the HJ group (9/25 [36.0%]) than in the DD group (1/20 [5.0%]; p = 0.01). The three patients in the HJ group with intestinal perforation all suffered perforation at the anastomosed site in the Roux-en-Y procedure. The subgroup analysis showed the non-inferiority of DD to HJ for biliary or intestinal complications in patients weighting < 10 kg. CONCLUSION: With a proper selection of cases, DD should be a safe method for biliary reconstruction in pediatric recipients with little risk of biliary complications equivalent to HJ and a reduced risk of intestinal complications.

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.

The Factors Associated with the Selection of Early Excision Surgery for Congenital Biliary Dilatation with a Prenatal Diagnosis.

PURPOSE: The aim of this study was to clarify the appropriate management after birth for congenital biliary dilatation (CBD, choledochal cyst) patients with a prenatal diagnosis. METHOD: Thirteen patients with a prenatal diagnosis of CBD who underwent liver biopsy during excision surgery were divided into two groups and retrospectively analyzed: group A, with liver fibrosis above F1 and group B, without liver fibrosis. RESULTS: Excision surgery was performed earlier in group A (F1-F2), at a median of 106 days old (p = 0.04). There were significant differences between the two groups in the presence symptoms and sludge, the cyst size, and the level of serum bilirubin and gamma glutamyl transpeptidase (GGT) before excision surgery (p < 0.05). Especially, in group A, prolonged serum GGT elevation and larger cysts were consistently observed from birth. The cut-off values of predictions for the presence of liver fibrosis in serum GGT and cyst size were 319 U/l and 45 mm. No significant differences were observed in the postoperative liver function or complications during the follow-up period. CONCLUSION: In patients with prenatally diagnosed CBD, the postnatal serial changes of serum GGT values and cyst size, in addition to symptoms, could help to prevent progressive liver fibrosis. LEVEL OF EVIDENCE: Ⅲ. TYPE OF STUDY: Treatment Study.

Palisading-like arrangement of immature ganglion cell in myenteric ganglia is a unique pathological feature of immaturity of ganglia.

BACKGROUND: Immaturity of ganglia (IG), an allied disorder of Hirschsprung disease (AD-HSCR), develops as neonatal ileus, but the dysmotility spontaneously resolves after several months. The diagnosis of IG using HE staining is often difficult. We herein report a new pathological finding of IG called the 'palisading-like pattern', which may be helpful for improving the diagnostic accuracy. METHODS: Cases of IG that were managed over the past 28 years were retrospectively reviewed. We investigated the clinical course and pathological findings for Hematoxylin-Eosin (HE) staining. The conventional diagnostic criteria for IG were (1) a normal or slightly increased number of ganglion cells and (2) ganglion cells with small nuclei. RESULTS: Among the 155 cases, 28 were diagnosed with IG, and 10 were retrospectively confirmed by HE staining. A palisading-like pattern was confirmed at the time of the initial ileostomy (median age, 2.5 days), and the palisading-like pattern had completely disappeared by the time of stoma closure (median age, 215 days) in all 10 cases. A palisading-like pattern is not present in other diseases. CONCLUSIONS: Even if immunostaining data are not available for a further analysis, the detection of a palisading-like pattern on HE staining makes an accurate diagnosis possible. LEVEL OF EVIDENCE: LEVEL IV.

Ultrasound-guided double central venous access for azygos vein via the ninth and tenth intercostal veins.

Some patients with intestinal failure, who are dependent on total parenteral nutrition for long periods, suffer from a lack of suitable conventional venous access points, including axillary, external jugular, internal jugular, subclavian, saphenous, and the brachio-cephalic and femoral veins, due to their occlusion. Furthermore, extensive central venous stenosis and/or thrombosis of the superior and inferior vena cava may preclude further catheterization, so uncommon routes must be used, which can be challenging. In such patients, the azygos vein via the intercostal vein is a viable candidate. Thoracotomy-assisted, thoracoscopy-assisted, and cut-down procedures are currently suggested such access. We found that ultrasound-guided percutaneous puncture method was a safe and minimally invasive approach and successfully placed two central venous lines in preparation for small bowel transplantation via two different intercostal veins (ninth and tenth). Although the lung was actually located just below the target veins, an ultrasound provided augmented and clear vision, which contributed to the safe performance of the procedure without the need for invasive surgical intervention, such as thoracotomy, thoracoscopy, or rib resection using the cut-down technique. Furthermore, constant positive-pressure ventilation during vein puncture under general anesthesia also helps avoid venous collapse. Despite carrying a slight risk of light injury to the lung, artery, and nerve along with the vein compared to other procedures, we believe that ultrasound-guided puncture under general anesthesia is feasible as a minimally invasive method.

Biliary atresia in a preterm and extremely low birth weight infant: a case report and literature review.

BACKGROUND: Biliary atresia in very low birth weight (VLBW) and extremely low birth weight (ELBW) infants is rarely reported, and the optimal timing of Kasai portoenterostomy (KPE) in these cases remains unclear. CASE PRESENTATION: We report a case of biliary atresia in a preterm female infant of 24 weeks of gestation who weighed 824 g. She underwent exploratory laparotomy and intraoperative cholangiography at 58 days of age (weight, 1336 g). Despite the diagnosis of biliary atresia with a type I cyst, we could only perform gallbladder drainage at that time due to the unstable intraoperative condition. While we waited for her body weight to increase, KPE was performed at 122 days of age (corrected age: 16 days), when the patient weighed 2296 g. Although she initially became jaundice-free, her liver function deteriorated due to cholangitis, and she developed decompensated cholestatic liver cirrhosis. Living donor liver transplantation was successfully performed at 117 days after KPE, and the postoperative course was uneventful. The timing of KPE is difficult to determine and a review of the relevant literature revealed that a poor prognosis in VLBW and ELBW infants with BA. CONCLUSIONS: Early KPE and careful postoperative follow-up, including liver transplantation is important for the improvement of outcomes.