Colonoscopy diagnosis of recurrent abdominal pain in a 4-year-old boy with intestinal duplication cyst involving colon, appendix, and ileum: a case report.

BACKGROUND: Intestinal duplication cyst is an infrequent congenital malformation that can involve all the segments of the gastrointestinal tract. The cases of intestinal duplication cyst involving the colon, appendix, and ileum in children are particularly uncommon. The symptoms of abdominal pain are similar to other acute abdominal diseases in children, such as appendicitis, intussusception, and intestinal obstruction, so sometimes its diagnosis is challenging and leads to misdiagnosis. CASE PRESENTATION: We report a 4-year-old Asian boy who presented to the pediatric emergency department with abdominal pain and vomiting but no fever, peritonitis, or mass. No abdominal abnormality was found via radiology and ultrasonography. After 2 days' anti-inflammatory therapy, the patient was discharged with pain relief. A total of 9 months later, he was readmitted to the pediatric emergency department for the same complaint as the first admission. Abdominal physical examination and ultrasound examination were still negative. Barium examination found a large mass in the colon. Colonoscopy was performed before operation to confirm the rare co-cavity intestinal duplication cyst involving the colon, appendix, and ileum. After resection of intestinal duplication and ileocolonic anastomosis, the patient's abdominal pain and vomiting has not recurred for 5 years postoperatively. CONCLUSIONS: The diagnosis of intestinal duplication cyst in children is difficult, especially the rare co-cavity and long segmental intestinal duplication, which is easily misdiagnosed. Colonoscopy may be an effective auxiliary diagnostic method, especially for diseases that are difficult to diagnosed clinically, such as recurrent abdominal pain.

Laparoscopic-assisted sclerotherapy in pediatric retroperitoneal lymphatic malformations.

Background: Retroperitoneal lymphatic malformations (LMs) are rare. Currently, the treatment of retroperitoneal LMs remains challenging. This study aimed to examine the safety and efficacy of laparoscopic-assisted sclerotherapy for retroperitoneal LMs in pediatric patients. Methods: We retrospectively reviewed patients treated with laparoscopic-assisted sclerotherapy for retroperitoneal LMs in a single tertiary medical center between July 2020 and February 2023. Doxycycline was prepared into a solution with a concentration of 10 mg/ml for use in sclerotherapy. Demographic data, clinical features, details of management, and outcomes were collected and analyzed. Results: A total of six patients, comprising three males and three females, were identified. The LMs were categorized into four macrocystic and two mixed-cystic types. The mean age and weight were 52.2 months (range, 11-108 months) and 20 kg (range, 12.5-27.5 kg), respectively. Three patients presented with abdominal pain or distension, while the other three patients were asymptomatic. All six patients underwent a total of eight sclerotherapy sessions. Two patients experienced intra-cystic hemorrhage and required a second sclerotherapy session. Only one patient presented with vomiting after sclerotherapy, which resolved spontaneously. Five patients met the complete response criteria, and one patient met the effective criteria. The mean reduction in lesion size was 92.3% (range, 69.9%-99.6%). No further complications or recurrence were recorded during follow-up. Conclusion: Laparoscopic-assisted sclerotherapy is a safe and effective approach for treating retroperitoneal LMs. This technique is applicable for both macrocystic and mixed-cystic retroperitoneal LMs.

Tracking changes in image-defined risk factors during neoadjuvant chemotherapy and their predictive value for surgical outcomes based on the International Neuroblastoma Surgical Report Form.

BACKGROUND: The capacity of presurgical image-defined risk factors (IDRFs) to predict secondary surgical outcomes in patients with neuroblastoma is controversial. METHODS: The International Neuroblastoma Surgical Report Form (INSRF) was employed to retrospectively collect the clinical data of 53 patients diagnosed with neuroblastoma at our hospital from April 2014 to April 2020. IDRFs were identified at the time of diagnosis and reassessed during the course of neoadjuvant chemotherapy. Various statistical tests were used to evaluate the correlation between IDRFs and secondary surgical outcomes. RESULTS: A total of 195 IDRFs were identified. Notably, by two courses of neoadjuvant chemotherapy, the number of "two body compartments," "intraspinal tumor extension," and "trachea-compressing" IDRFs decreased significantly (p = .001). The primary tumor volumes and the number of IDRFs decreased significantly by four courses of neoadjuvant chemotherapy, especially in "intraspinal tumor extension" IDRFs (p = .034). The median number of IDRF per patient was four (interquartile range [IQR]: 1-5) at diagnosis, which diminished to one (IQR: 1-3) subsequent to neoadjuvant chemotherapy. The presence of preoperative IDRFs was not associated with surgical complications (p = .286) or the extent of surgery (p = .188). However, the number of preoperative IDRFs linked to the extent of surgery (p = .002), not to operative complications (p = .669). Specifically, presurgery "renal vessel contact" IDRFs were predictive of surgical complications, while presurgery "infiltration of vital structures" IDRFs were associated with the extent of surgery. CONCLUSION: The number of IDRFs decreased significantly by four courses of neoadjuvant chemotherapy. The number and type of presurgery IDRFs may predict secondary surgical outcomes, surpassing the mere consideration of their presence or absence.

Misdiagnosis of scrotal and retroperitoneal lymphangioma in children.

BACKGROUND: Scrotal and retroperitoneal lymphangioma (SRL) in children is relatively rare and its clinical symptoms are usually difficult to distinguish from other conditions such as hydrocele and incarcerated inguinal oblique hernia. This study aimed to explore the clinical diagnosis and treatment of abdominal scrotal lymphangioma in children, and thus, to increase our understandings of this disease in clinical practice. METHOD: This study enrolled nine boys, aged 1-10, who were admitted to Shanghai Children's Hospital from January 2019 to December 2020 and who were finally confirmed with lymphangioma in the inguinal area. The clinical manifestations, diagnosis, and treatment of these children were analyzed retrospectively. The length of diagnostic process ranged from 3 weeks to 20 months. We also reviewed other cases of initially misdiagnosed cases of SRL in English publications from 2000 to 2022. RESULTS: The nine cases were misdiagnosed as hydrocele, hematoma, or inguinal hernia. Three patients received intracystic injection of bleomycin, three underwent laparoscopic mass resection, and three underwent resection of the inguinal lymphangioma under direct vision. Postoperative pathological analysis of the surgical specimens confirmed the diagnosis of benign cystic lesions and lymphangioma. Meanwhile, among the 14 cases of SRL in literature review, eight were misdiagnosed. Six were initially diagnosed as hydrocele, one as inguinal oblique hernia, and one as testicular tumor, all of which underwent ultrasonography scans. All cases were confirmed as lymphangioma after pathological examination. CONCLUSION: The non-specific clinical manifestations may contribute to the misdiagnosis of scrotal masses in children. A detailed and accurate medical history, careful physical examination, and imaging findings are important factors contributing to the preoperative differential diagnosis of scrotal lumps in children, but the final diagnosis is based on pathological examination.

Extracranial Germ Cell Tumors in Children: Ten Years of Experience in Three Children's Medical Centers in Shanghai.

OBJECTIVE: The aim was to describe the clinical features of extracranial germ cell tumors (GCTs) in pediatrics and study the clinical risk factors related to survival for malignant germ cell tumors (MGCTs) in order to optimize therapeutic options. METHODS: The clinical data of children with extracranial GCTs in three children's medical centers in Shanghai were retrospectively analyzed. RESULTS: In total, 1007 cases of extracranial GCTs diagnosed between 2010 and 2019 were included in this study, including teratomas (TERs) 706 (70.11%) and MGCTs 301 (29.89%). There were twice as many TER cases as MGCT cases. Approximately 50% of children with GCTs were <3 years old (43.39% for TERs, 67.13% for MGCTs). GCTs in children of different ages show differences in tumor anatomical locations and pathological subtypes. The 5-year event-free survival (EFS) and overall survival (OS) of all patients with MGCTs were 82.33% (95% CI, 77.32%, 86.62%) and 94.13% (95% CI, 90.02%, 96.69%), respectively. The multivariate Cox regression analysis identified a primary site in the mediastinum and alpha fetoprotein (AFP) levels ≥10,000 ng/mL as independent adverse prognostic factors (p < 0.0.0001, χ2 = 23.6638, p = 0.0225, χ2 = 5.2072.). There were no significant differences in OS among children receiving various chemotherapy regimens, such as the BEP, PEB, JEB and other regimens (VBP/VIP and AVCP/IEV) (p < 0.05). CONCLUSIONS: The clinical features of GCTs in Chinese pediatrics are similar to those reported in children in Europe and America. The age distribution of pathological types and primary sites in GCTs reflect the developmental origin of type I and type II GCTs transformed from mismigration primordial germ cells (PGCs). Optimizing the current platinum-based chemotherapy regimens and exploring the treatment strategies for MGCTs of the mediastinum are future research directions.

Pathogenicity of p.Phe147del in RET in familial Hirschsprung's disease.

OBJECTIVE: The study aimed to explore the pathogenicity of RET p.Phe147del in a Hirschsprung'irschspru (HSCR) family and facilitate the deeper understanding of HSCR families. METHODS: Whole-exome sequencing (WES) was performed to decipher a HSCR family. We used a "GlycoEP" tool to analyze RET protein glycosylation. A series of molecular biological approaches including mutated plasmid construction, cell transfection, polymerase chain reaction, immunofluorescence and immunoblotting were introduced to determine the mutation status and altered expression of RET as well as its related genes or proteins. MG132 was applied to analyze the mechanism of mutated RET. RESULTS: WES and Sanger results revealed that p.Phe147del in-frame mutation (IM) was a potential pathogenetic factor for familial HSCR. Moreover, the IM led to disrupted N-glycosylation of RET accompanied with protein structural change, resulting in the decreased transcriptional and protein level of RET, CCND1, VEGF and BCL2, and the decreased protein level of phosphorylated ERK and STAT3. Further studies revealed that the IM-evoked RET decline was reversed by inhibiting proteosome in a dose dependent manner, thus suggesting that the decrease in intracellular RET protein levels interrupted the transportation of RET protein from the cytoplasm to the cell surface. CONCLUSION: The newly found p.Phe147del IM of RET is pathogenic to familial HSCR and it disrupts RET structure and abundance via the proteasome pathway, representing evidence for the early prevention, clinical diagnosis and treatment of HSCR.

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.

Single-cell transcriptomics uncovers cellular architecture and developmental trajectories in hepatoblastoma.

BACKGROUND AND AIMS: Hepatoblastoma (HB) is the predominant type of childhood liver cancer. Treatment options for the clinically advanced HB remain limited. We aimed to dissect the cellular and molecular basis underlying HB oncogenesis and heterogeneity at the single-cell level, which could facilitate a better understanding of HB at both the biological and clinical levels. APPROACH AND RESULTS: Single-cell transcriptome profiling of tumor and paired distal liver tissue samples from five patients with HB was performed. Deconvolution analysis was used for integrating the single-cell transcriptomic profiles with the bulk transcriptomes of our HB cohort of post-neoadjuvant chemotherapy tumor samples. A single-cell transcriptomic landscape of early human liver parenchymal development was established for exploring the cellular root and hierarchy of HB oncogenesis. As a result, seven distinct tumor cell subpopulations were annotated, and an effective HB subtyping method was established based on their compositions. A HB tumor cell hierarchy was further revealed to not only fit with the classical cancer stem cell (CSC) model but also mirror the early human liver parenchymal development. Moreover, FACT inhibition, which could disrupt the oncogenic positive feedback loop between MYC and SSRP1 in HB, was identified as a promising epigenetic-targeted therapeutic strategy against the CSC-like HB1-Pro-like1 subpopulation and its related high-risk "Pro-like1" subtype of HB. CONCLUSIONS: Our findings illustrate the cellular architecture and developmental trajectories of HB via integrative bulk and single-cell transcriptome analyses, thus establishing a resourceful framework for the development of targeted diagnostics and therapeutics in the future.

SMAD9-MYCN positive feedback loop represents a unique dependency for MYCN-amplified neuroblastoma.

BACKGROUND: Neuroblastoma (NB) is the most common extracranial solid tumor occurring during childhood and high-risk NB patients have a poor prognosis. The amplified MYCN gene serves as an important determinant of a high risk of NB. METHODS: We performed an integrative screen using public NB tissue and cell line data, and identified that SMAD9 played an important role in high-risk NB. An investigation of the super-enhancers database (SEdb) and chromatin immunoprecipitation sequencing (ChIP-seq) dataset along with biological experiments of incorporating gene knockdown and CRISPR interference (CRISPRi) were performed to identify upstream regulatory mechanism of SMAD9. Gene knockdown and rescue, quantitative real-time PCR (Q-RT-PCR), cell titer Glo assays, colony formation assays, a subcutaneous xenograft model and immunohistochemistry were used to determine the functional role of SMAD9 in NB. An integrative analysis of ChIP-seq data with the validation of CRISPRi and dual-luciferase reporter assays and RNA sequencing (RNA-seq) data with Q-RT-PCR validation was conducted to analyze the downstream regulatory mechanism of SMAD9. RESULTS: High expression of SMAD9 was specifically induced by the transcription factors including MYCN, PHOX2B, GATA3 and HAND2 at the enhancer region. Genetic suppression of SMAD9 inhibited MYCN-amplified NB cell proliferation and tumorigenicity both in vitro and in vivo. Further studies revealed that SMAD9 bound to the MYCN promoter and transcriptionally regulate MYCN expression, with MYCN reciprocally binding to the SMAD9 enhancer and transactivating SMAD9, thus forming a positive feedback loop along with the MYCN-associated cancer cell cycle. CONCLUSION: This study delineates that SMAD9 forms a positive transcriptional feedback loop with MYCN and represents a unique tumor-dependency for MYCN-amplified neuroblastoma.

The composition of the gut microbiota is altered in biliary atresia with cholangitis.

Aim: To detect the composition of the gut microbiota in biliary atresia after Kasai surgery. Methods: Infants within six months after the Kasai operation who were diagnosed by cholangiography at Shanghai Children's Hospital were enrolled in the study. Fecal samples were collected from diapers, placed into sterile tubes in the inpatient department or outpatient department and frozen at -80°C within half an hour. The gut microbiota was detected by 16S rRNA sequences. Then, the patients that were followed up to one year after the Kasai operation who suffered from cholangitis at least one time were grouped into the BAcho group, and the others were grouped into the BAnoncho group. Results: Nine of 18 BA patients were grouped into the BAcho group, and the others were grouped into the BAnoncho group. In the BAcho group, AST, ALT and GGT were significantly increased compared to the BAnoncho group. The number of total OTUs (operational taxonomic units) in feces was more elevated in the BAnoncho group than in the BAcho group. In the BAnoncho group, the Chao index at the OTU level was significantly increased compared to that in the BAcho group (66.37 ± 21.5 vs. 45.64 ± 11.25, p = 0.02 < 0.05). Bifidobacterium was the most abundant genus in the BAnoncho group, accounting for 22.14%, and Klebsiella accounted for 22.74% in the BAcho group. Compared with the BAnoncho group, Bacteroides was significantly decreased in the BAcho group (p = 0.037). Conclusion: The composition of the gut microbiota was different between BA with cholangitis and BA without cholangitis.

Multi-omics integration reveals a six-malignant cell maker gene signature for predicting prognosis in high-risk neuroblastoma.

Background: Neuroblastoma is the most common extracranial solid tumor of childhood, arising from the sympathetic nervous system. High-risk neuroblastoma (HRNB) remains a major therapeutic challenge with low survival rates despite the intensification of therapy. This study aimed to develop a malignant-cell marker gene signature (MMGS) that might serve as a prognostic indicator in HRNB patients. Methods: Multi-omics datasets, including mRNA expression (single-cell and bulk), DNA methylation, and clinical information of HRNB patients, were used to identify prognostic malignant cell marker genes. MMGS was established by univariate Cox analysis, LASSO, and stepwise multivariable Cox regression analysis. Kaplan-Meier (KM) curve and time-dependent receiver operating characteristic curve (tROC) were used to evaluate the prognostic value and performance of MMGS, respectively. MMGS further verified its reliability and accuracy in the independent validation set. Finally, the characteristics of functional enrichment, tumor immune features, and inflammatory activity between different MMGS risk groups were also investigated. Results: We constructed a prognostic model consisting of six malignant cell maker genes (MAPT, C1QTNF4, MEG3, NPW, RAMP1, and CDT1), which stratified patients into ultra-high-risk (UHR) and common-high-risk (CHR) group. Patients in the UHR group had significantly worse overall survival (OS) than those in the CHR group. MMGS was verified as an independent predictor for the OS of HRNB patients. The area under the curve (AUC) values of MMGS at 1-, 3-, and 5-year were 0.78, 0.693, and 0.618, respectively. Notably, functional enrichment, tumor immune features, and inflammatory activity analyses preliminarily indicated that the poor prognosis in the UHR group might result from the dysregulation of the metabolic process and immunosuppressive microenvironment. Conclusion: This study established a novel six-malignant cell maker gene prognostic model that can be used to predict the prognosis of HRNB patients, which may provide new insight for the treatment and personalized monitoring of HRNB patients.

Graft-versus-host disease complicated with small bowel obstruction in children: A case report.

Graft-versus-host disease (GvHD) is a severe complication following hematopoietic cell transplantation (HCT). The clinical manifestations of GvHD can affect multiple systems. Although gastrointestinal (GI) GvHD is common, GI obstruction complications are rare. Here, we present a case of GI-GvHD after HCT for acute myeloid leukemia (AML) in a young girl from China. The patient suffered from watery diarrhea, which progressed to bloody diarrhea 40 days after HCT. She experienced prolonged and repeated mucous or bloody stool after the withdrawal of cyclosporine and the gradual reduction in methylprednisolone. The plain abdominal radiography and computed tomographic (CT) scan showed apparent bowel wall thickening and intestinal stenosis 10 months after HCT. Finally, the patient underwent surgery to remove the small intestinal stenosis at the age of 26 months. The patient recovered with the help of appropriate medical therapies and nutritional support during hospitalization. She remained stable, and there was no recurrence of GI symptoms 16 months after the surgery. In summary, surgery may be an optimal treatment for GvHD patients with persistent bowel obstruction and failure of appropriate immunosuppressive therapies.

A retrospective study about incidental appendectomy during the laparoscopic treatment of intussusception.

Purpose: We aim to see incidental appendectomy (IA) was worth or not during the laparoscopic treatment of intussusception. Methods: This study included forty-eight patients who underwent a laparoscopic procedure for idiopathic intussusception without intestinal resection between April 2014 and April 2021. The Chi-square or Fisher's exact tests for categorical variables and the Student t-test for continuous variables were used to analyze and compare patient characteristics. Results: IA was performed on 63% (30/48) of patients after surgical reduction, while 18 (37%), did not. Patients who underwent IA had a higher total cost (16,618 ± 2,174 vs.14,301 ± 5,206, P = 0.036), and a longer mean operation duration (59 ± 19 vs.45 ± 21, P = 0.025). The distribution of the PO time, length of hospital stay, PCs, and RI did not differ significantly. The histopathological evaluation of the 30 resected appendices revealed five (17%) with signs of acute inflammation, 20 (66%) with chronic signs of inflammation, and five (17%) with inconspicuous appendices. Conclusion: IA is linked to a longer average operation time and a higher total cost. There is insufficient evidence to recommend IA during laparoscopic intussusception treatment. The risks and benefits of IA need further study.

The relationship between contralateral patent processus vaginalis and metachronous contralateral inguinal hernia in children with unilateral inguinal hernia: a prospective observational study.

PURPOSE: Laparoscopic contralateral patent processus vaginalis (CPPV) repair in children is debatable due to the high CPPV rate, but low metachronous contralateral inguinal hernia (MCIH) rate. We conducted this study to find risk factors for MCIH. METHOD: We conducted a prospective, observational trial with patients recruited from Shanghai Children's Hospital. Eligible participants were patients under 16 years old with unilateral inguinal hernia whose parents did not opt for simultaneous CPPV repair. The subjects were followed for 24 to 34.1 months. Patients who developed MCIH were analyzed to identify the relationship between CPPV and MCIH. RESULTS: Between October 17, 2018, and July 31, 2019, we included 184 patients and 182 completed follow-up. MCIH occurred in ten patients, of which 7 (7.53%) had CPPV and three (3.37%) had no CPPV. Univariate analysis showed that age (p = 0.025, OR = 0.938) and CPPV diameter (p = 0.003, OR = 1.783) were related to the development of MCIH. In multivariate analysis, only diameter of CPPV (p = 0.008, OR = 1.411) was associated with MCIH. The receiver operating characteristic (ROC) curve was used to test, and it was found that when the diameter of CPPV was greater than 4 mm, the Youden index was the highest, with a specificity of 62.8% and a sensitivity of 100%. CONCLUSION: The incidence of MCIH was not statistically higher in patients with CPPV compared with those without CPPV, so there is no indication for routine CPPV repair. The risk of MCIH development increases with CPPV diameter. 4 mm is the optimal cutoff point. Large CPPVs (> 4 mm) could be treated to prevent future hernias. TRIAL REGISTRATION: The Chinese Clinical Trial Registry ( www.chictr.org.cn ), number ChiCTR2000041307.

Prognostic impact of tumor size on patients with neuroblastoma in a SEER-based study.

OBJECTIVE: The prognostic value of tumor size in neuroblastoma (NB) patients has not been fully evaluated. Our purpose is to elucidate the prognostic significance of tumor size in surgery performed on neuroblastoma patients. METHODS: Neuroblastoma patients diagnosed from 2004 to 2015 were selected from the Surveillance, Epidemiology, and End Results Program (SEER) for the study. Univariate and multivariate Cox proportional hazard regression models were used to identify risk factors and the independent prognostic influences of tumor size on NB patients. Overall survival (OS) was analyzed through univariate Cox regression analysis. To determine the optimal cutoff value of tumor size, we first divided the cohort into three groups (≤5 cm, 5-10 cm, >10 cm). Subsequently, the patients were divided into two groups repeatedly, with tumor size at 1 cm intervals. The cutoff value that maximized prognostic outcome difference was selected. Furthermore, we performed the Kaplan-Meier methods to visually present differences in prognosis between the optimal tumor size cutoff value in different subgroups. RESULTS: A total of 591 NB patients who met the inclusion criteria were selected from the SEER database in this study. Cox analysis showed that age >1 year (HR = 2.42, p < 0.0001), originate from adrenal site (HR = 1.7, p = 0.014), distant stage (HR = 6.4, p < 0.0001), undifferentiated grade (HR = 1.94, p = 0.002), and large tumor size (HR = 1.5, p < 0.0001) independently predicted poor prognosis. For tumor size, there were significant differences in tumor size distribution in different ages, tumor grade, disease stage, and primary site subgroup but not in sex, race, and histology subgroup. Furthermore, both univariate (HR = 4.96, 95% CI 2.31-10.63, p < 0.0001) and multivariable analysis (HR = 2.8, 95% CI 1.29-6.08, p < 0.0001) indicated the optimal cutoff value of tumor size was 4 cm for overall survival of NB patients. Using a 4 cm of tumor size cutoff in subgroups, we found that it can identify poor prognosis patients whatever their age or primary site. Interestingly, tumor size of 4 cm cutoff can only identify unfavorable NB patients with diagnosis at distant-stage disease, or differentiated grade tumor, but not with regional and local or undifferentiated tumor. CONCLUSIONS: Tumor size is first to be recognized as a key prognostic factor of neuroblastoma patients and a cutoff value >4 cm might predict poor prognosis, which should be included in the evaluation of prognostic factors for NB.

Primary omental torsion in children: single-center experience of 17 cases.

OBJECTIVE: Primary omental torsion (POT) is a rare condition in children often misdiagnosed because of a lack of clinical manifestations. Here we present insights gained from the treatment of pediatric POT cases at a single center over 8 years and summarize some influencing factors found in diagnosis and treatment, in order to reduce the misdiagnosis of POT in children in the future. METHODS: Demographic and clinical data of 17 children with POT treated in Shanghai Children's Hospital, Shanghai Jiaotong University from June 2012 to December 2020 were reviewed. RESULTS: The mean age of the 17 pediatric patients was 7.65 ± 2.12 years (range: 4-12 years), sixteen were male. The average time from the pain onset to operation was 73.82 ± 47.21 h (range: 21-144 h). In 5 cases, the ultrasound scan revealed a low-intensity inflammatory mass in the abdominal cavity. Only 1 of the 17 patients had normal body mass index, while others were overweight or obese. The mean computed tomography (CT) value of the mass in the lower right abdomen was - 58.74 ± 10.32 HU (range: - 70 to - 46 HU), which is close to that of its own abdominal wall fat [- 46.29 ± 9.45 HU (range: - 62 to - 32 HU)]. The location of the mass was located in front of the right colon in ten cases, except for two cases near the ligamentum teres. Five patients had whirl sign on CT images and 8 patients had pelvic fluid. Five cases were diagnosed as acute appendicitis and 12 were diagnosed as POT, the preoperative diagnosis was correct in 70.59% of cases. All 17 patients were treated with laparoscopic omentectomy. The average duration of hospitalization was 5.53 ± 1.12 days (range: 4-8 days). All cases were followed up. 1 case relapsed 8 months post operation, while the remaining cases had no complications. CONCLUSION: POT is rare in children with acute abdominal pain, which is more common in obese boys. The fatty mass in front of colon and between rectus abdominis sheath in CT image is specific, which is helpful for diagnosis of POT. Laparoscopy is an effective method for the treatment of POT in children.

Clinical and Molecular Characterizations of Papillary Thyroid Cancer in Children and Young Adults: A Multicenter Retrospective Study.

Background: Papillary thyroid carcinoma (PTC) is a rare malignancy in children and young adults (CAYA). It often presents with aggressive disease patterns and advanced stages, which are clinically distinct from those in adult patients. In this study, we sought to characterize and better understand the clinical variants of PTC in CAYA and explore the underlying mechanisms. Methods: CAYA patients (age ≤18 years) diagnosed with PTC between June 2006 and June 2018 were retrospectively recruited from five hospitals. Demographic information, pathological data, and follow-up status were recorded. Tumor samples obtained from 20 children (mean age 15.15 years) and 10 adults (mean age 38.80 years) underwent comprehensive whole transcriptome sequencing. Differentially expressed genes (DEGs), mutational landscape, and immune infiltration were analyzed. Results: A total of 217 CAYA-PTC patients (162 females and 55 males) with an average age of 14.38 ± 3.53 years (range 2-18) were included. Lymph node metastasis (LNM) was observed in 85.71%, of which 57.60% were in the lateral cervical compartment. Disease recurred in 28 of 217 (12.90%) patients with a median follow-up of 4.76 years. Multivariate logistic regression analysis revealed that age, bilateral disease, extrathyroidal extension, and coexisting Hashimoto's thyroiditis (co-HT) were independent risk factors for LNM, while co-HT was the only risk factor for recurrence. Using whole transcriptome sequencing of PTC tissues, we identified 301 DEGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that differences in immune mediators played important roles, based on the distributions of mutation frequencies, types, and expression levels between CAYA and adult patients. Based on the integrated data sets, we identified significantly mutated immune genes, cluster of differentiation 24 (CD24), coagulation factor 12 (F12), coagulation factor 5 (F5), integrin subunit alpha 3 (ITGA3), and retinoic acid early transcript 1L (RAET1L), which were then verified by immunohistochemistry. Furthermore, resting mast cells, resting natural killer cells, plasma cells, and regulatory T cells were different in the CAYA-PTC group and correlated with the expression of immune checkpoints. Conclusions: There are considerable variabilities that may contribute to the different clinical presentations between CAYA and adult PTC patients, among which the decrease in protective immune cells may be a factor. Collectively, our results add to the possible biological mechanisms involved in CAYA-PTC.

A Comprehensive Genomic Analysis Constructs miRNA-mRNA Interaction Network in Hepatoblastoma.

Hepatoblastoma (HB) is a rare disease but nevertheless the most common hepatic tumor in the pediatric population. For patients with advanced HB, the prognosis is dismal and there are limited therapeutic options. Multiple microRNAs (miRNAs) were reported to be involved in HB development, but the miRNA-mRNA interaction network in HB remains elusive. Through a comparison between HB and normal liver samples in the GSE131329 dataset, we detected 580 upregulated differentially expressed mRNAs (DE-mRNAs) and 790 downregulated DE-mRNAs. As for the GSE153089 dataset, the first cluster of differentially expressed miRNAs (DE-miRNAs) were detected between fetal-type tumor and normal liver groups, while the second cluster of DE-miRNAs were detected between embryonal-type tumor and normal liver groups. Through the intersection of these two clusters of DE-miRNAs, 33 upregulated hub miRNAs, and 12 downregulated hub miRNAs were obtained. Based on the respective hub miRNAs, the upstream transcription factors (TFs) were detected via TransmiR v2.0, while the downstream target genes were predicted via miRNet database. The intersection of target genes of respective hub miRNAs and corresponding DE-mRNAs contributed to 250 downregulated candidate genes and 202 upregulated candidate genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses demonstrated the upregulated candidate genes mainly enriched in the terms and pathways relating to the cell cycle. We constructed protein-protein interaction (PPI) network, and obtained 211 node pairs for the downregulated candidate genes and 157 node pairs for the upregulated candidate genes. Cytoscape software was applied for visualizing the PPI network and respective top 10 hub genes were identified using CytoHubba. The expression values of hub genes in the PPI network were subsequently validated through Oncopression database followed by quantitative real-time polymerase chain reaction (qRT-PCR) in HB and matched normal liver tissues, resulting in six significant downregulated genes and seven significant upregulated genes. The miRNA-mRNA interaction network was finally constructed. In conclusion, we uncover various miRNAs, TFs, and hub genes as potential regulators in HB pathogenesis. Additionally, the miRNA-mRNA interaction network, PPI modules, and pathways may provide potential biomarkers for future HB theranostics.

DRG1 Maintains Intestinal Epithelial Cell Junctions and Barrier Function by Regulating RAC1 Activity in Necrotizing Enterocolitis.

BACKGROUND: An immature intestine is a high-risk factor for necrotizing enterocolitis (NEC), which is a serious intestinal disease in newborns. The regulation of developmentally regulated GTP-binding protein 1 (DRG1) during organ development suggests a potential role of DRG1 in the maturation process of the intestine. AIM: To illustrate the function of DRG1 during the pathogenesis of NEC. METHODS: DRG1 expression in the intestine was measured using immunohistochemistry and q-PCR. Immunoprecipitation coupled with mass spectrometry was used to identify the interacting proteins of DRG1. The biological functions of the potential interactors were annotated with the Database for Annotation, Visualization and Integrated Discovery. Caco2 and FHs74Int cells with stable DRG1 silencing or overexpression were used to investigate the influence of DRG1 on cell junctions and intestinal barrier permeability and to elucidate the downstream mechanism. RESULTS: DRG1 was constitutively expressed during the intestinal maturation process but significantly decreased in the ileum in the context of NEC. Protein interaction analysis revealed that DRG1 was closely correlated with cell junctions. DRG1 deficiency destabilized the E-cadherin and occludin proteins near the cell membrane and increased the permeability of the epithelial cell monolayer, while DRG1 overexpression prevented lipopolysaccharide-induced disruption of E-cadherin and occludin expression and cell monolayer integrity. Further investigation suggested that DRG1 maintained cell junctions, especially adherens junctions, by regulating RAC1 activity, and RAC1 inhibition with NSC23766 attenuated intestinal injury and led to improved barrier integrity in experimental NEC. CONCLUSIONS: Our findings illustrate the mechanism underlying the effect of DRG1 deficiency on epithelial cell permeability regulation and provide evidence supporting the application of RAC1 inhibitors for protection against NEC.

Teratoid Wilms Tumor and Classical Wilms Tumor: A Retrospective 10-Year Single-Center Study and Literature Review.

BACKGROUND: One of the most prevalent forms of renal tumors detected among pediatric patients is the Wilms tumor (WT). Teratoid WT is a rare WT subclassification that is characterized by teratoma-like characteristics that include the features of many diverse tissue categories. Less than 70 teratoid Wilms tumor (TWT) cases have been explained up to now. METHODS: Between 2010 and 2020, patients with classical WT and TWT admitted to our hospital were included in this study. Clinicopathological characteristics, intraoperative findings, histopathological parameters, and prognostic outcomes were then compared between classical WT and TWT. To compare these variables, TWT and WT cases were matched at a 1:3 ratio. RESULTS: A total of 67 total WT cases, i.e., five diagnosed with TWT, were enrolled. While no significant differences in analyzed variables were detected between these groups, tumor volumes were notably larger in the TWT group relative to the classical WT group (203.30 ± 109.89 vs. 104.30 ± 66.97 cm3) despite similar tumor weight values in both groups (471.00 ± 80.65 vs. 432.67 ± 109.25 g). As for five patients diagnosed with TWT, all were alive during the follow-up, while one of them was diagnosed with pelvic metastasis. CONCLUSIONS: This study is the first to our knowledge to have reported on the incidence of TWT among Chinese children, and our results preliminarily suggest that a combination of surgery and chemotherapy may be appropriate for the treatment of patients with WT, although prognostic outcomes varied substantially among patients with different stages of the disease. TWT tumor density may be lower than classical WT tumor density. Further research regarding the basic biological characteristics of TWT and relevant theranostic markers associated with this tumor type is warranted to better guide the development of individualized treatments for this rare cancer type.