Pediatric Surgery International最新文献

Purpose: Recently, children with trisomy 18 have been receiving more active treatment for malignancies. We report herein seven cases complete resection was achieved, and discuss multidisciplinary treatment for hepatoblastoma in patients with trisomy 18.

Method: The medical records of children with trisomy 18 who were treated at the study center between 2010 and 2023 were reviewed.

Result: Six of 69 patients had hepatoblastoma development, and three of these underwent multidisciplinary treatment. In addition, 6 patients had been referred by another hospital for treatment, and four of these underwent multidisciplinary treatment. Among the seven patients who underwent multidisciplinary treatment, three, two, and two were categorized in Pre-treatment Extent of Disease (PRETEXT) classification group I, II, and III, respectively. Neoadjuvant chemotherapy resulting in tumor reduction was performed in three cases. In all the cases, complete resection was achieved with pathologically safe margins. Perioperative complications included circulatory failure in one case and bile leakage in two cases. Adjuvant chemotherapy was administered in four cases. The postoperative observation period ranged from 3 months to 11 years, and all the patients are recurrence-free.

Conclusion: Children with trisomy 18 complicated with hepatoblastoma whose cardiopulmonary conditions are stable may be good candidates for chemotherapy and surgery.

Purpose: Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is defined as a congenital visceral myopathy with genetic mutations. However, the etiology and pathophysiology are not fully understood. We aimed to generate a gene leiomodin-1a (lmod1a) modification technique to establish a zebrafish model of MMIHS.

Methods: We targeted lmod1a in zebrafish using CRISPR/Cas9. After confirming the genotype, we measured the expression levels of the target gene and protein associated with MMIHS. A gut transit assay and spatiotemporal mapping were conducted to analyze the intestinal function.

Results: Genetic confirmation showed a 5-base-pair deletion in exon 1 of lmod1a, which caused a premature stop codon. We observed significant mRNA downregulation of lmod1a, myh11, myod1, and acta2 and the protein expression of Lmod1 and Acta2 in the mutant group. A functional analysis of the lmod1a mutant zebrafish showed that its intestinal peristalsis was fewer, slower, and shorter in comparison to the wild type.

Conclusion: This study showed that targeted deletion of lmod1a in zebrafish resulted in depletion of MMIHS-related genes and proteins, resulting in intestinal hypoperistalsis. This model may have the potential to be utilized in future therapeutic approaches, such as drug discovery screening and gene repair therapy for MMIHS.

Purpose: Severe pilonidal diseases have refractory symptoms despite multiple surgeries and optimal therapy remains unclear. We hypothesized that standardized minimally invasive protocol could be an effective rescue treatment.

Methods: We prospectively collected data from symptomatic patients who underwent ≥ 1 pilonidal excision prior to presentation at our clinic 2019-2023. We treated these patients with standardized protocol incorporating local wound care, regular manual/laser epilation, and selective debridement/pit trephination.

Results: We treated 34 refractory patients (23 males) with median follow-up 405 days. Median age of first symptoms was 17.1 years; presentation to our clinic 20.0 years. Prior to our clinic, 27 received one surgery (cleft lift-2, excision no closure-1, excision primary closure-18, wound vac after excision-3, excision flap closure-3); 7 had two surgeries (excision without closure + cleft lift-1, primary closure after excision twice-3, flap closure after excision twice-2, excision primary closure + excision without closure-1). We treated all patients with regular epilation ± local wound care. 14 (41%) underwent trephination ± debridement. All patients achieved complete resolution after median 52 days. Five (14.7%) recurred and were treated with trephination + debridement-2 or wound care alone-3. Symptom length had no correlation with resolution time, skin type, hair amount.

Conclusions: Standardized minimally invasive protocol requiring only selective surgical intervention can treat refractory pilonidal disease with low recurrence rate.

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.

Purpose: The aim of this study was to detect candidate oncogenes of rhabdoid tumor of the kidney (RTK) and evaluate their roles in RTK in vitro.

Methods: An integrated analysis of messenger RNA (mRNA) and microRNA (miRNA) sequencing was performed to determine the expression profile of exosome-derived miRNAs and mRNAs in human RTK-derived cell lines and a human embryonic renal cell line. A Gene Ontology enrichment analysis was performed to analyze the functional characteristics of differentially expressed mRNAs in RTK cells. Matrigel invasion and wound-healing assays were performed to evaluate the cell invasion and migration abilities.

Results: Forty mRNAs were highly expressed in RTK cells targeted by exosomal miRNAs, the expression of which was lower in RTK cells than in the controls. These mRNAs were primarily related to cell adhesion. Of these mRNAs, we selected neuropilin 1 (NRP1) as a candidate oncogene because its upregulated expression is associated with a poor prognosis of several types of tumors. RTK cells in which NRP1 had been knocked down exhibited decreased invasive and migratory abilities.

Conclusion: Our study indicates that NRP1 acts as an oncogene by promoting the invasion and migration of RTK cells and that it could serve as a therapeutic target.

Purpose: Surgical procedures for anorectoplasty for anorectal malformations (ARMs), particularly rectourethral fistula (RUF), depend on the institution. We investigated the diagnosis and treatment of RUF in male patients with ARMs in Japan using a questionnaire survey.

Methods: An online survey inquiring about the diagnosis and treatment (diagnostic modalities, surgical approaches, fistula dissection devices, and fistula closure techniques) of each type of ARM in male patients was conducted among institutional members of the Japanese Study Group of Anorectal Anomalies. Fisher's exact test was used to compare surgical methods between posterior sagittal anorectoplasty (PSARP) and laparoscopy-assisted anorectoplasty (LAARP).

Results: Sixty-one institutions (100%) completed the survey. LAARP was the preferred approach for high-type ARM (75.4%). PSARP was preferred for intermediate-type ARM (59.0%). Monopolar devices were most commonly used (72.1%) for RUF dissection. Blunt dissection was more frequent in the PSARP group (PSARP vs. LAARP: 55.6 vs. 20.0%, p < 0.005). Cystoscopy/urethroscopy to confirm the extent of dissection was used more frequently in the LAARP group (70.0% vs. 25.0%, p < 0.005). Clips and staplers were used more frequently in the LAARP group (p < 0.05).

Conclusion: Distinct fistula management strategies for PSARP and LAARP were revealed. Further studies are needed to investigate the postoperative outcomes associated with these practices.

Purpose: We aimed to identify factors predicting the need for future liver transplantation (LT) at 18 years of age in patients with biliary atresia (BA).

Methods: BA patients with native liver survival at > 18 years of age were retrospectively reviewed. The clinical characteristics, outcomes, hepatobiliary function, and liver fibrosis markers of native liver survivors (NLS group) were compared with patients who subsequently underwent LT (LT group).

Results: The study population included 48 patients (NLS, n = 34; LT, n = 14). The male-to-female ratio, age at Kasai procedure, and type of BA in the two groups did not differ to a statistically significant extent. There was no significant difference in the MELD scores between the groups at 18 years of age. The aspartate aminotransferase-to-platelet ratio index (APRI), albumin-bilirubin (ALBI), and BA liver fibrosis (BALF) scores at 18 years of age were significantly higher in the LT group. The AUCs for APRI, ALBI, and BALF were 0.91, 0.79, and 0.85, respectively.

Conclusion: Adult BA patients have limited options for LT owing to the lack of donor candidates and the low prevalence of deceased donors. The elucidation of prognostic factors for LT in adulthood is important. APRI was the most useful marker in this study.

Purpose: We aimed to investigate whether prediction of liver fibrosis using two-dimensional shear wave elastography (2D-SWE) and vascular tree grading using superb microvascular imaging (SMI) are useful for postoperative follow-up in patients with biliary atresia (BA).

Methods: We retrospectively collected data from medical records of 134 patients who underwent ultrasound examination with 2D-SWE or SMI, including 13 postoperative patients with BA and 121 non-BA patients. We investigated the distribution of liver stiffness values with SWE and vascular tree grading with SMI and evaluated correlations between these findings and biochemical indices of liver fibrosis in postoperative BA patients.

Results: The SWE values of the BA group were not significantly different from that of any other disease groups in non-BA patients. In postoperative BA patients, SWE values correlated significantly with aspartate aminotransferase to platelet ratio index (Spearman rank correlation coefficient [r_s] = 0.6380, p = 0.0256) and with the Fib-4 index (r_s = 0.6526, p = 0.0214). SMI vascular tree grading of the BA group was significantly higher than that of the choledochal cyst group (p = 0.0008) and other hepatobiliary disorder group (p = 0.0030). In postoperative BA patients, SMI vascular tree grading was not positively correlated with any biochemical marker of fibrosis.

Conclusion: 2D-SWE appears to be useful for follow-up in postoperative BA patients.

Purpose: We performed animal and organoid study to evaluate the anti-fibrotic effect of steroid on biliary atresia (BA) and the underlying patho-mechanism.

Methods: BA animal models were created by inoculation of mice on post-natal day 1 with rhesus rotavirus (RRV). They received either 20 µl phosphate-buffered saline (PBS) or steroid from day 21 to day 34. On day 34, their serum samples were collected for hormonal markers. Necrosis, fibrosis and CK 19 expression in the liver were evaluated. Liver organoids were developed and their morphology as well as bulk RNA sequencing data were analyzed.

Results: Twenty-four mice developed BA features after RRV injection and were equally divided into steroid and PBS groups. On day 34, the weight gain of steroid group increased significantly than PBS group (p < 0.0001). All mice in the PBS group developed liver fibrosis but only one mouse in the steroid group did. Serum bilirubin and liver parenchymal enzymes were significantly lower in steroid group. The morphology of liver organoids were different between the two groups. A total of 6359 differentially expressed genes were found between steroid group and PBS group.

Conclusion: Based on our findings obtained from RRV-induced BA animal and organoid models, steroid has the potential to mitigate liver fibrosis in BA.