Postnatal treatment and evolution patterns of giant fetal hepatic hemangioma: a case series of 29 patients.

OBJECTIVES: To explore the clinical characteristics, postnatal treatment and prognosis of giant fetal hepatic hemangioma (GFHH). METHOD: Retrospective analysis was performed on children with giant fetal hepatic hemangioma (maximum tumor diameter > 40 mm) diagnosed by prenatal ultrasound and MRI from December 2016 to December 2020. These patients were observed and treated at the Children's Hospital of Fudan University after birth. The clinical data were collected to analyze the clinical characteristics, treatment, and prognosis of GFHH using independent sample t tests or Fisher's exact tests. RESULTS: Twenty-nine patients who were detected by routine ultrasound in the second and third trimester of pregnancy with giant fetal hepatic hemangiomas were included. The first prenatal ultrasound diagnosis of gestational age was 34.0 ± 4.3 weeks, ranging from 22 to 39 weeks. Of the patients, 28 had focal GFHHs and 1 had multifocal GFHHs. Surgery was performed, and the diagnosis was confirmed histopathologically in two patients. There were 8 cases with echocardiography-based evidence of pulmonary hypertension, 11 cases had a cardiothoracic ratio > 0.6, and 4 cases had hepatic arteriovenous fistula (AVF). The median follow-up time was 37 months (range: 14-70 months). During the follow-up, 12 patients received medical treatment with propranolol as the first-line therapy. The treatment group had a higher ratio of cardiothoracic ratio > 0.6 (P = 0.022) and lower albumin levels (P = 0.018). Four (14.8%) lesions showed postnatal growth before involuting. Complete response was observed in 13 (13/29) patients, and partial response was observed in 16 (16/29) patients. CONCLUSIONS: Fetal giant hepatic hemangioma is mainly localized, and its clinical outcome conforms to RICH (rapidly involuting) and PICH (partially involuting), but some fetal giant hepatic hemangiomas will continue to grow after birth and then gradually decrease. For uncomplicated giant fetal hepatic hemangioma, postnatal follow-up is the main concern, while those with complications require aggressive medical treatment. Propranolol may have no effect on the volume change of GFHH.

Single-cell RNA sequencing of solid pseudopapillary neoplasms of the pancreas in children.

Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare pancreatic tumor in children. Its origin remains elusive, along with its pathogenesis. Heterogeneity within SPN has not been previously described. In addition, low malignant but recurrent cases have occasionally been reported. To comprehensively unravel these profiles, single-cell RNA sequencing was performed using surgical specimens. We identified the cell types and suggested the origin of pancreatic endocrine progenitors. The Wnt/ß-catenin pathway may be involved in tumorigenesis, while the epithelial-to-mesenchymal transition may be responsible for SPN recurrence. Furthermore, NOV, DCN were nominated as primary and S100A10, MGP as recurrent SPN marker genes, respectively. Our results provide insight into the pathogenesis of SPN.

Gastric Peroral Endoscopic Pyloromyotomy for Infants With Congenital Hypertrophic Pyloric Stenosis.

INTRODUCTION: Congenital hypertrophic pyloric stenosis (CHPS), the most common infantile disease requiring surgical intervention, is routinely treated with open or laparoscopic pyloromyotomy. Recently, gastric peroral endoscopic pyloromyotomy (G-POEM) has been used for adult gastroparesis. We aimed to evaluate the efficacy and safety of G-POEM in treating infantile CHPS. METHODS: We reviewed data from 21 G-POEM-treated patients at 3 tertiary children's endoscopic centers in China between January 2019 and December 2020. Clinical characteristics, procedure-related parameters, perioperative management, and follow-up outcomes were summarized. RESULTS: G-POEM was performed successfully in all patients. The median operative duration was 49 (14-150) minutes. The submucosal tunnels were successfully established along the greater curvature of the stomach in 19 cases, and 2 cases were switched to the lesser curvature because of difficulty. No perioperative major adverse events occurred. Minor adverse events included inconsequential mucosal injury in 5 cases and unsatisfactory closure of the mucosal incision in 1 case. Upper gastrointestinal contrast radiography in all patients showed smooth passage of the contrast agent through the pylorus on postoperative day 3. The growth curves of the patients reached normal levels 3 months after the procedure. No recurrent clinical symptoms occurred in any patient during the median follow-up period of 25.5 (14-36) months. DISCUSSION: G-POEM is feasible, safe, and effective for infants with CHPS, with satisfactory clinical responses over a short-term follow-up. Further multicenter studies should be performed to compare the long-term outcomes of this minimally invasive technique with open or laparoscopic pyloromyotomy.

Clinical features and treatment outcomes of Castleman disease in children: a retrospective cohort in China.

Castleman disease (CD) is a rare lymphoproliferative disorder of undetermined etiology. Unicentric CD (UCD) and multicentric CD (MCD) are two phenotypes of CD diagnosed by the histopathology of lymph nodes. We attempted to describe a pediatric CD cohort to optimize the management of this disease. We reviewed the medical records of pediatric patients diagnosed with CD between April, 2004, and October, 2022, at the Children's Hospital of Fudan University. Prognosis information was collected in January, 2023, by telephone inquiry. Twenty-two patients with UCD and 2 patients with MCD were identified, all with hyaline vascular (HV) type. The median ages at diagnosis were 10.75 years (IQR 8, 12.81) for UCD and 14.42 years (IQR 13.42, 15.42) for MCD. The most common lesion location of UCD was the neck (9/22, 40.91%) and abdomen (9/22, 40.91%). Systematic symptoms occurred on 10/22 (45.45%) patients with UCD and 1/2 (50%) patients with MCD, and abnormal laboratory indexes were detected in both. Resection and biopsy were performed on all patients. One out of two patients with MCD also received rituximab for upfront therapy. After a median of 4 years (IQR 1.5, 6) of follow-up time, the overall survival was 100% and the complete remission rate in UCD was 63%. There was no relapse or progression. CONCLUSIONS: Our series demonstrated that HV-UCD was the most common type in children. Resection and biopsy were used for both deterministic diagnoses and treatments. Despite the high possibility to develop systematic inflammation, children with CD showed promising outcomes. WHAT IS KNOWN: • Castleman disease is a rare lymphoproliferative disorder with limited cohort studies, especially in pediatrics. • The ubiquity of delayed confirmations and misdiagnoses points to a lack of knowledge about etiology and characteristics, which is a prerequisite for novel therapeutics. WHAT IS NEW: • We retrospectively reviewed and analyzed the clinical and pathological symptoms, laboratory and imaging features, and treatment outcomes of a Chinese pediatric cohort with Castleman disease. • Our work may improve the recognition and optimize the management of this rare disease in children.

[Analysis of a child with Very early onset inflammatory bowel disease due to compound heterozygous variants of IL10RA and DUOX2 genes].

OBJECTIVE: To explore the genetic basis of a child with Very early onset inflammatory bowel disease (VEOIBD). METHODS: A female child who had presented at the Children's Hospital of Fudan University on May 23, 2018 due to occurrence of diarrhea and fever 6 days after birth was selected as the study subject. Clinical data of the child was collected. Family-based whole-exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing and PCR of the patient and her parents. RESULTS: The child had developed the symptoms 6 days after birth, with main manifestations including diarrhea, fever, failure to thrive, rectovestibular fistula and hypothyroidism. An enterostomy was performed at the age of 3.5 months due to severe intestinal adhesion and obstruction. Based on her clinical manifestations, colonoscopic finding, and results of biopsies, she was diagnosed with VEOIBD in conjunct with congenital hypothyroidism. Replacement treatment of levothyroxine was given since one month of age. Family-based WES revealed that the child has harbored compound heterozygous variants of the DUOX2 gene, namely c.2654G>T (p.R885L) and c.505C>T (p.R169W), in addition with a heterozygous c.301C>T (p.R101W) variant of the IL10RA gene. Re-analysis of the WES data revealed that the patient also had a 333 bp deletion spanning exon 1 of the IL10RA gene (Chr11: 117857034_117857366). CONCLUSION: For patients with VEOIBD, genetic testing is recommended. Presence of additional DUOX2 gene variants might have exacerbated the clinical symptoms in this patient. Above finding has facilitated genetic counseling and prenatal diagnosis for this family, and raised clinicians' awareness of this rare disease.

Downregulation of MEG3 and upregulation of EZH2 cooperatively promote neuroblastoma progression.

Neuroblastoma (NB), an embryonic tumour originating from sympathetic crest cells, is the most common extracranial solid tumour type in children with poor overall prognosis. Accumulating evidence has demonstrated the involvement of long non-coding RNA (lncRNA) in numerous biological processes and their associations with embryonic development and multiple diseases. Ectopic lncRNA expression is linked to malignant tumours. Previous studies by our team indicate that MEG3 attenuates NB autophagy through inhibition of FOXO1 and epithelial-mesenchymal transition via the mTOR pathway in vitro. Moreover, MEG3 and EZH2 negatively regulate each other. In present study, we first collected 60 NB tissues and 20 adjacent tissues for Quantitative real-time polymerase chain reaction (Q-PCR) experiments and performed clinical correlation analysis of the results. At the same time, nude mice were used for subcutaneous tumour formation to detect the effect of MEG3 in vivo. Two NB cell lines, SK-N-AS and SK-N-BE(2)C, were overexpressed MEG3 and rescued with EZH2 and then were subjected to proliferation, migration, invasion, apoptosis and autophagy experiments. RNA-binding protein immunoprecipitation (RIP) and Co-Immunoprecipitation (Co-IP) experiments were performed to explore the molecular mechanism of MEG3 and EZH2 interaction. Q-PCR revealed that MEG3 expression was negatively correlated with INSS stage and risk grade of NB. Moreover, MEG3 overexpression was associated with inhibition of NB growth in vivo. MEG3 exerted an anti-cancer effect via stimulatory effects on EZH2 ubiquitination leading to its degradation. Conversely, EZH2 interacted with DNMT1 and HDAC1 to induce silencing of MEG3. The EZH2 inhibitor, DZNep, and HDAC inhibitor, SAHA, displayed synergistic activity against NB. Combined treatment with DZNep and SAHA inhibited proliferation, migration and invasion of NB through suppression of the PI3K/AKT/mTOR/FOXO1 pathway. In conclusion, downregulation of MEG3 and upregulation of EZH2 forms a feedback loop that concertedly promotes the development of NB. Combined blockage of EZH2 and HDAC1 with the appropriate inhibitors may therefore present an effective treatment strategy for NB cases with low MEG3 and high EZH2 expression.

Propranolol inhibits the angiogenic capacity of hemangioma endothelia via blocking ß-adrenoceptor in mast cell.

BACKGROUND: Propranolol, a non-selective blocker of the ß-adrenoceptor (AR), is a first-line treatment for infantile hemangioma (IH). Mast cells have been implicated in the pathophysiology of propranolol-treated hemangioma. However, the function of mast cells remains unclear. METHODS: HMC-1s (Human mast cell line) having been treated with propranolol for 24 h were centrifuged, washed with PBS twice, and maintained in cell culture medium for another 24 h. The supernatants with propranolol which were named as propranolol-treated HMC-1s supernatants were obtained. The expression of cytokines and mediators was examined among HMC-1s dealt with propranolol. HemECs (hemangioma endothelial cells) were co-cultured with propranolol-treated HMC-1s supernatants, and their proliferation and apoptosis were investigated. The autophagic-related protein was examined in HemECs using immunoblot. RESULTS: In propranolol-treated HMC-1s, the expressions of ADRB1 (ß1-AR) and ADRB2 (ß2-AR) were reduced by 70% and 60%, respectively, and that of cytokines and mediators were reduced. The proliferation was decreased, but apoptosis and autophagy were induced in HemECs treated with propranolol-treated HMC-1s supernatants. However, propranolol can work well in shRNA-ADRB1 or shRNA-ADRB2 transfected HMC-1s. CONCLUSIONS: Propranolol inhibit the proliferation of HemECs and promote their apoptosis and autophagy through acting on both ß1 and ß2 adrenoceptor in mast cell. IMPACT: Treated with propranolol, ß1, and ß2 adrenoceptor on human mast cell expression was reduced significantly. After hemangioma endothelial cell treated with the supernatants from propranolol-treated human mast cell, its proliferation was decreased, but apoptosis and autophagy were significantly induced. Propranolol can work well in shRNA-ADRB1 or shRNA-ADRB2 transfected HMC-1s. Mast cells may have a role in the action of propranolol in infantile hemangioma through both ß1 and ß2 adrenoceptors to inhibit the angiogenic capacity of hemangioma endothelial cells.

ARID1B/SUB1-activated lncRNA HOXA-AS2 drives the malignant behaviour of hepatoblastoma through regulation of HOXA3.

It has been becoming increasingly evident that long non-coding RNAs (lncRNAs) play important roles in various human cancers. However, the biological processes and clinical significance of most lncRNAs in hepatoblastoma (HB) remain unclear. In our previous study, genome-wide analysis with a lncRNA microarray found that lncRNA HOXA-AS2 was up-regulated in HB. Stable transfected cell lines with HOXA-AS2 knockdown or overexpression were constructed in HepG2 and Huh6 cells, respectively. Our data revealed knockdown of HOXA-AS2 increased cell apoptosis and inhibited cell proliferation, migration and invasion in HB. Up-regulation of HOXA-AS2 promoted HB malignant biological behaviours. Mechanistic investigations indicated that HOXA-AS2 was modulated by chromatin remodelling factor ARID1B and transcription co-activator SUB1, thereby protecting HOXA3 from degradation. Therefore, HOXA-AS2 positively regulates HOXA3, which might partly demonstrate the involvement of HOXA3 in HOXA-AS2-mediated HB carcinogenesis. In conclusion, HOXA-AS2 is significantly overexpressed in HB and the ARID1B/HOXA-AS2/HOXA3 axis plays a critical role in HB tumorigenesis and development. These results might provide a potential new target for HB diagnosis and therapy.

Emerging role of long noncoding RNA-encoded micropeptides in cancer.

Increasing evidence has indicated that long noncoding RNAs (lncRNAs) play various important roles in the development of cancers. The widespread applications of ribosome profiling and ribosome nascent chain complex sequencing revealed that some short open reading frames of lncRNAs have micropeptide-coding potential. The resulting micropeptides have been shown to participate in N6-methyladenosine modification, tumor angiogenesis, cancer metabolism, and signal transduction. This review summarizes current information regarding the reported roles of lncRNA-encoded micropeptides in cancer, and explores the potential clinical value of these micropeptides in the development of anti-cancer drugs and prognostic tumor biomarkers.

Circulating tumor DNA in neuroblastoma.

As a sympathetic nervous system-derived tumor, aggressive neuroblastoma (NB) is currently attracting interest from researchers seeking diagnostic and prognostic markers via less invasive procedures. The analysis of circulating tumor DNA (ctDNA) in peripheral blood can provide genetic information from multiple tumor lesions and is not dependent on a surgical procedure. The identification of genetic alterations, chromosomal variations, and hypermethylation contained within plasma DNA yields clinical value in the diagnosis, risk stratification, monitoring of treatment effects, and survival prediction for patients. With the widespread application of genome sequencing, droplet digital polymerase chain reaction, and other advanced technologies, the detection of ctDNA may guide therapeutic schedules, enhance the quality of life, and improve the prognosis for patients with NB.

Complications of enterostomy and related risk factor analysis of very early onset inflammatory bowel disease with interleukin-10 signalling deficiency: a single-centre retrospective analysis.

BACKGROUND: Interleukin-10 (IL10) signalling pathway deficiency results in severe very early onset inflammatory bowel disease (VEOIBD), and enterostomy is often inevitable. However, studies in these surgical populations are lacking. This study aims to determine the enterostomy characteristics, postoperative complications and related risk factors in enterostomy patients. METHODS: From March 1, 2015, to December 31, 2018, patients with IL10R-mutation who underwent enterostomy were recruited for analysis. We collected data on the patients' clinical characteristics, enterostomy characteristics, postoperative complications and related risk factors. RESULTS: Twelve patients required emergency enterostomy, and 10 patients underwent elective enterostomy. Twelve patients experienced postoperative complications, including wound infection (27.3%), wound dehiscence (18.2%), reoperation (18.2%), etc. Compared with the pre-enterostomy values, there was a decrease in C-reactive protein (CRP) (P = 0.001), an increase in albumin (P = 0.001) and an improvement in the weight-for-age (P = 0.029) and body mass index (BMI) Z-scores (P = 0.004) after enterostomy. There was a significant difference between the pre-operation and postoperation medicine expenses (P = 0.002). Univariate binary logistic regression analysis revealed a statistically significant influence of CRP (OR: 1.43, 95% CI: 1.07-1.91, P = 0.016) and a tendency towards a significant influence of intestinal perforation, albumin level, BMI Z-score and weighted paediatric Crohn's disease activity index (wPCDAI). Multivariate logistic regression analysis showed that CRP (OR: 1.40), wPCDAI (OR: 2.88) and perforation (OR: 1.72) showed a tendency to behave as independent risk factors for postoperative complications, but the results were not significant (all P > 0.05). CONCLUSIONS: Surgery and enterostomy showed benefits for VEOIBD with IL-10 signalling deficiency. The timing of intervention, potential postoperative complications, economic burden and other related problems should be considered.

Retroperitoneal kaposiform hemangioendothelioma complicated by Kasabach-Merritt phenomenon and obstructive jaundice: A retrospective series of 3 patients treated with sirolimus.

We present a retrospective case series of 3 patients with retroperitoneal kaposiform hemangioendothelioma (KHE) complicated by Kasabach-Merritt phenomenon (KMP) and biliary obstruction. We found sirolimus to be a safe and effective treatment for these patients who were refractory to other treatment modalities. However, our patients were slow to respond in comparison to published reports of sirolimus use for KHE without biliary obstruction. We postulate that therapeutic serum levels of sirolimus may be affected by biliary obstruction and improved with surgical alleviation of the obstruction.

Clinical characteristics and prognosis of adrenocortical tumors in children.

PURPOSE: The purpose of this study was to review the clinical characteristics and prognosis of children with adrenocortical tumors (ACT). METHODS: We retrospectively reviewed the medical records of 28 patients with ACT at our hospital between March 2010 and March 2017. RESULTS: The main clinical presentations were sexual prematurity (n = 17) and Cushing's syndrome (n = 15). All patients without metastasis underwent complete resection by laparotomy (n = 19) or laparoscopic surgery (n = 9). Pathological diagnosis confirmed adrenocortical carcinomas (ACC, n = 12) and adrenocortical adenomas (ACA, n = 16). Dehydroepiandrosterone (939.4 ± 148.2 µg/dl vs 630.9 ± 376.3 µg/dl; p = 0.031) and testosterone (235.7 ± 89.1 ng/dl vs 164.6 ± 47.5 ng/dl; p = 0.012) were significantly increased in ACC compared with ACA. The ACC tumor volumes were larger than those in ACA (107.5 ± 69 vs 25.5 ± 23.1 cm3; average diameter 6 cm vs 4 cm p = 0.001) and the immunochemical expression of Ki-67 was higher in ACC than in ACA (30.2 ± 22.7 vs 9.9 ± 4.9 p = 0.013). The mean follow-up of patients with ACA was 40 ± 23 months without recurrence. Seven patients with ACC had postoperative distant metastases and five patients died within 2 years. Five patients with ACC survived with a median follow-up of 27 months. The 2-year overall survival was 44.6%. CONCLUSIONS: Patients with ACC had significantly larger tumor volumes than those with ACA. The discordantly elevated serum levels of sexual corticosteroid hormones and lactate dehydrogenase may predict the malignant nature of these tumors. The prognosis of patients with ACA was good, while those with ACC had high postoperative metastasis and mortality rates.

Reoperation after Ladd's procedure in the neonatal period.

AIM OF THE STUDY: To investigate (1) the indications for reoperation after neonatal Ladd's procedure, (2) the type of reoperation and (3) its outcome. METHODS: We reviewed all neonatal Ladd's procedures in our hospital from 2003 to 2017 and the outcomes of reoperation in these patients. MAIN RESULTS: 252 neonates had Ladd's procedure: 59 were laparoscopic (23.4%) and 193 open (76.6%). 15 (6.0%) required reoperation with no difference between laparoscopic and open (p = 0.12). Overall, the indications for reoperation were: adhesive intestinal obstruction (n = 10, 4.0%), recurrent midgut volvulus (n = 4, 1.6%), and missed diagnosis of associated anomaly (n = 1, 0.4%). The incidence of recurrent midgut volvulus was higher after laparoscopic Ladd's procedure (3/59; 5.1%) compared to open Ladd's procedure (1/193; 0.5%) (p = 0.04). Adhesive intestinal obstruction developed after both open (8/193, 4.1%) or laparoscopic Ladd's procedure (2/59, 3.3%). The duration of reoperation and the length of post-operative hospital stay were 63.4 ± 27.1 min and 10.1 ± 5.2 days, respectively. After reoperation, there were no post-operative complications. All children were well at follow-up (6 months-14 years). CONCLUSIONS: In neonates, laparoscopic Ladd's procedure compared to the open Ladd's procedure is associated with a significantly higher risk of recurrent volvulus. The risk of developing this potentially dangerous complication after laparoscopic Ladd's procedure raises doubts about the effectiveness and safety of the laparoscopic approach in neonates.

Expression Profiling Identifies Circular RNA Signature in Hepatoblastoma.

BACKGROUND/AIMS: Hepatoblastoma is the most common malignant pediatric liver cancer. circular RNAs (circRNAs) play important roles in fine-tuning gene expression and are often deregulated in cancers. However, the expression profile and clinical significance of circRNAs in hepatoblastoma is still unknown. METHODS: Circular RNA microarray was conducted to identify hepatoblastoma-related circRNAs. GO analysis, pathway analysis, and miRNA response elements analysis was conducted to predict the potential roles of differentially expressed circRNAs in hepatoblastoma. MTT assays, Ki67 staining, and Transwell assays were conducted to clarify the role of circRNA in hepatoblastoma in vitro. Bioinformatics analysis and in vitro experiments were conducted to clarify the mechanism of circRNA-mediated gene regulation in hepatoblastoma cell. RESULTS: 869 differentially expressed circRNAs were identified between hepatoblastoma and adjacent normal liver samples, including 421 up-regulated circRNAs and 448 down-regulated circRNAs. The significant enriched GO term of hepatoblastoma-related circRNAs in biological process, cellular component, and molecular function were "chromosome organization", "cytoplasm", and "organic cyclic compound binding". Tight junction signaling pathway was ranked the Top 1 potentially affected by circRNA-mediated regulatory network. circ_0015756 was significantly up-regulated in human hepatoblastoma specimens and metastatic hepatoblastoma cell lines. circ_0015756 silencing decreased hepatoblastoma cell viability, proliferation, and invasion in vitro. circ_0015756 acted as miR-1250-3p sponge to regulate hepatoblastoma cell function. CONCLUSIONS: circRNAs are involved in the pathogenesis of hepatoblastoma. circ_0015756 is a promising target for the prognosis, diagnosis, and treatment of hepatoblastoma.

Comparison of long-term prognosis of laparoscopic and open adrenalectomy for local adrenal neuroblastoma in children.

OBJECTIVE: To investigate and compare long-term outcomes in children undergoing laparoscopic or open adrenalectomy for local adrenal neuroblastoma. METHODS: A retrospective review was conducted of 37 children with local adrenal neuroblastoma treated between January 2005 and December 2013 in our hospital. These patients met inclusion criteria for having adrenal neuroblastoma and undergoing operative resection. All patients were successfully followed up until December 2017. RESULTS: The local adrenal neuroblastoma cases included 25 males and 12 females with an average age of 37.24 ± 37.55 months (range from 5 days to 158 months). Left adrenal lesions were present in 13 cases, the right in 24 cases. According to the INSS staging system, 27 patients were classified as stage I and 10 as stage II. Open adrenalectomy was performed in 24 patients. Laparoscopic adrenalectomy was performed in the other 13 patients, 2 of whom were converted to open surgery because of adhesions to renal vessels and diaphragmatic rupture. Significant differences were observed between the laparoscopic surgery and open surgery groups regarding tumor size (P = 0.005). There were two recurrence cases in open surgery, but there was no recurrence in laparoscopic surgery. The average follow-up time was 86.78 ± 24.52 months. The overall 5-year survival rate of open and laparoscopic surgery were 86.2 and 100% (P = 0.316). CONCLUSIONS: Laparoscopic adrenalectomy for neuroblastoma is feasible and can be performed with equivalent recurrence and mortality rates with open resection. For small tumor size and absence of vascular encasement, the adrenal neuroblastoma may be preferred laparoscopic surgery.

Clinical and pathological features of patients with biliary atresia who survived for more than 5 years with native liver.

PURPOSE: The objective of this study was to determine the predictive index for prognosis in patients with biliary atresia (BA). METHODS: A total of 71 patients were divided into two groups. Group A included 39 postoperative BA patients who survived for more than 5 years with normal liver function and did not present cirrhosis, and group B included 32 patients who died from liver failure within 1 year after surgery. The clinical data of the two study groups were compared, and liver pathology was evaluated using a scoring system. RESULTS: The average age and weight were similar in the two groups (64.1 ± 16.8 days vs. 60.7 ± 19.3 days, p > 0.05; 4.9 ± 0.9 kg vs. 4.7 ± 0.8 kg, p > 0.05). There were no significant intergroup differences in preoperative total bilirubin (TB), direct bilirubin (DB), alanine transaminase, aspartate transaminase, and international normalized ratio. The preoperative levels of gamma-glutamyl transpeptidase (γ-GT) and albumin in group A were significantly higher than those in group B (γ-GT: 956.8 ± 503.8 IU/L vs. 620.2 ± 437.1 IU/L, p = 0.00; ALB: 40.8 ± 2.5 g/L vs. 36.8 ± 3.6 g/L, p = 0.04), whereas alkaline phosphatase was significantly lower in group A compared to group B (512.2 ± 224.6 IU/L vs. 631.7 ± 254.7 IU/L, p = 0.02). The postoperative TB and DB after 2 weeks of the Kasai procedure decreased significantly more in group A than in group B (TB: 53.9 vs. 21.4%, p = 0.00; DB: 51.0 vs. 22.7%, p = 0.00), whereas γ-GT increased significantly less in group A than in group B (48.3 vs. 142.1%, p = 0.00). Cystic structures were observed at the porta hepatis on ultrasound in more patients from group A (28.2 vs. 3.2%, p < 0.00). There was no significant difference in the total pathological score between the two groups (p = 0.38) whereas the score of bile plugs was significantly higher in group A (0.95 vs. 0.38, p = 0.03). CONCLUSION: The cystic structures observed at the porta hepatis on ultrasound preoperatively and the rapid decrease in TB and DB within 2 weeks postoperatively predict good long-term prognosis, whereas a significant increase in γ-GT with a lower preoperative level predicts poor long-term prognosis. The development of bile plugs may be an indicator of favorable prognosis.

Downregulation of bone morphogenetic protein receptor 2 promotes the development of neuroblastoma.

Neuroblastoma (NB) is the most common extracranial solid tumor of childhood. In this study, we examined the expression of bone morphogenetic protein receptor 2 (BMPR2) in primary NB and adjacent non-tumor samples (adrenal gland). BMPR2 expression was significantly downregulated in NB tissues, particularly in high-grade NB, and was inversely related to the expression of the NB differentiation markers ferritin and enolase. The significance of the downregulation was further explored in cultured NB cells. While enforced expression of BMPR2 decreased cell proliferation and colony-forming activity, shRNA-mediated knockdown of BMPR2 led to increased cell growth and clonogenicity. In mice, NB cells harboring BMPR2 shRNA showed significantly increased tumorigenicity compared with control cells. We also performed a retrospective analysis of NB patients and identified a significant positive correlation between tumor BMPR2 expression and overall survival. These findings suggest that BMPR2 may play an important role in the development of NB.

Analysis of clinical features and outcomes for inflammatory myofibroblastic tumors in China: 11 years of experience at a single center.

PURPOSE: Inflammatory myofibroblastic tumor (IMT) is a rare benign neoplasm. The purpose of this study was to review the clinical characteristics, imaging and pathological features, and outcomes of children with IMTs from a single center in China. METHODS: A retrospective file review was conducted involving 23 cases of pathologically confirmed IMTs treated at the Children's Hospital between April 2003 and April 2014. RESULTS: The tumor locations included multiple anatomic sites, as follows: abdomen or pelvis (n = 17); lungs (n = 2); head and neck (n = 1); trunk (n = 1); and extremities (n = 2). The tumors were associated with various clinical presentations. The predominant symptoms included an anemic appearance, fevers, and an asymptomatic mass. Computed tomography scanning showed solid, heterogeneous, well-demarcated masses; the appearance of enhancement was variable. MRI appeared hypointense on T1-weighted images and hypointense or hyperintense on T2-weighted images. Immunohistochemical staining revealed anaplastic lymphoma kinase was negative in 11 of 13 cases tested. One patient quit treatment for the unresectable mass after biopsy and died 2 years later, and another patient with incompletely resection is alive at 30 months following chemotherapy. The remaining 21 cases had complete resections; one patient died due to a recurrence, and the other 20 patients survived and were tumor free. The follow-up ranged from 7 to 141 months, with a mean of 56 months. The 3-year OS was 88 % (95 % CI, 57-97 %). CONCLUSIONS: IMT is a benign neoplasm that rarely presents with malignant features. Complete resection is curative in most patients. ALK+ is variable for diagnosis. Close follow-up is necessary for patients who undergo surgical resection.

Exome sequencing of hepatoblastoma reveals novel mutations and cancer genes in the Wnt pathway and ubiquitin ligase complex.

UNLABELLED: Hepatoblastoma (HB) is the most common primary liver tumor in children. Mutations in the ß-catenin gene that lead to constitutive activation of the Wnt pathway have been detected in a large proportion of HB tumors. To identify novel mutations in HB, we performed whole-exome sequencing of six paired HB tumors and their corresponding lymphocytes. This identified 24 somatic nonsynonymous mutations in 21 genes, many of which were novel, including three novel mutations targeting the CTNNB1 (G512V) and CAPRIN2 (R968H/S969C) genes in the Wnt pathway, and genes previously shown to be involved in the ubiquitin ligase complex (SPOP, KLHL22, TRPC4AP, and RNF169). Functionally, both the CTNNB1 (G512V) and CAPRIN2 (R968H/S969C) were observed to be gain-of-functional mutations, and the CAPRIN2 (R968H/S969C) was also shown to activate the Wnt pathway in HB cells. These findings suggested the activation of the Wnt pathway in HB, which was confirmed by immunohistochemical staining of the ß-catenin in 42 HB tumors. We further used short hairpin RNA (shRNA)-mediated interference to assess the effect of 21 mutated genes on HB cell survival. The results suggested that one novel oncogene (CAPRIN2) and three tumor suppressors (SPOP, OR5I1, and CDC20B) influence HB cell growth. Moreover, we found that SPOP S119N is a loss-of-function mutation in HB cells. We finally demonstrated that one of the mechanisms by which SPOP inhibits HB cell proliferation is through regulating CDKN2B expression. CONCLUSION: These results extend the landscape of genetic alterations in HB and highlight the dysregulation of Wnt and ubiquitin pathways in HB tumorigenesis.