Development and multi-institutional validation of a deep learning model for grading of vesicoureteral reflux on voiding cystourethrogram: a retrospective multicenter study.

Background: Voiding cystourethrography (VCUG) is the gold standard for the diagnosis and grading of vesicoureteral reflux (VUR). However, VUR grading from voiding cystourethrograms is highly subjective with low reliability. This study aimed to develop a deep learning model to improve reliability for VUR grading on VCUG and compare its performance to that of clinicians. Methods: In this retrospective study in China, VCUG images were collected between January 2019 and September 2022 from our institution as an internal dataset for training and 4 external data sets as external testing set for validation. Samples were divided into training (N = 1000) and validation sets (N = 500), internal testing set (N = 168), and external testing set (N = 280). An ensemble learning-based model, Deep-VCUG, using Res-Net 101 and the voting methods was developed to predict VUR grade. The grading performance was assessed using heatmaps, area under the receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, and F1 score in the internal and external testing set. The performances of four clinicians (2 pediatric urologists and 2 radiologists) with and without the Deep-VCUG assisted to predict VUR grade were explored in external testing sets. Findings: A total of 1948 VCUG images were collected (Internal dataset = 1668; multi-center external dataset = 280). For assessing unilateral VUR grading, the Deep-VCUG achieved AUCs of 0.962 (95% confidence interval [CI]: 0.943-0.978) and 0.944 (95% [CI]: 0.921-0.964) in the internal and external testing sets, respectively, for bilateral VUR grading, the Deep-VCUG also achieved high AUCs of 0.960 (95% [CI]: 0.922-0.983) and 0.924 (95% [CI]: 0.887-0.957). The Deep-VCUG model using voting method outperformed single model and clinician in terms of classification based on VCUG image. Moreover, Under the Dee-VCUG assisted, the classification ability of junior and senior clinicians was significantly improved. Interpretation: The Deep-VCUG model is a generalizable, objective, and accurate tool for vesicoureteral reflux grading based on VCUG imaging and had good assistance with clinicians to VUR grading applicability. Funding: This study was supported by Natural Science Foundation of China, "Fuqing Scholar" Student Scientific Research Program of Shanghai Medical College, Fudan University, and the Program of Greater Bay Area Institute of Precision Medicine (Guangzhou).

Application of computer-assisted surgery in pediatric mediastinal tumor surgery.

BACKGROUND: Computer-assisted Surgery system (CAS) is an effective medical imaging simulation tool, which is widely used in preoperative planning of surgery. The objective of this study is to investigate the clinical application of CAS in pediatric mediastinal tumor resection. METHODS: This retrospective study investigated 74 children who underwent mediastinal tumor resection between June 2008 and June 2022 at the pediatric surgical center of the Affiliated Hospital of Qingdao University and Qingdao Women and Children's Hospital. Preoperative chest computed tomography imaging was performed on all children. A total of 44 children (the CAS-assisted group) underwent clinical image 3D reconstruction and preoperative simulation using Hisense CAS. The control group consisted of 30 children who underwent a conventional procedure without CAS. The demographic, preoperative, and complication data were analyzed and compared between the two groups. t-test, Mann-Whitney U test, X2 test, or Fisher's exact test were used accordingly in this study during analysis. RESULTS: The median operative duration was 119.00 min in the CAS-assisted group and 140.50 min in the control group. The median intraoperative blood loss of the CAS-assisted group and the control group was 14.00 and 31.00 ml respectively. Relative to the control groups, the CAS-assisted group experienced shorter operative duration time (p = 0.041), and less intraoperative blood loss (p < 0.001). The difference in postoperative drain indwelling between the CAS-assisted group (median:4.00 days) and the control group (median:7.00 days) reached a statistical significance (p = 0.001). And the duration of hospitalization after the operation for the CAS-assisted group (median:7.00 days) was shorter than that for the control group (median:9.00 days) (p = 0.001). No significant difference could be found in the rate of blood transfusion (p = 0.258) and the incidence of postoperative complications (p = 0.719) between the two groups. CONCLUSION: Hisense CAS could effectively assist surgeons to clearly determine the anatomical site of tumors and provide accurate preoperative simulation for surgeons, so as to assist surgeons to specify effective surgical plans for patients.

Surgical resection of pediatric PRETEXT III and IV hepatoblastoma: A retrospective study investigating the need for preoperative chemotherapy.

Objective: This study analyzed the feasibility of upfront surgical resection for pediatric PRETEXT III and IV hepatoblastoma (HB). Summary Background Data: Neoadjuvant chemotherapy is recommended for patients with PRETEXT III and IV HB to obtain a chance of curative surgery. However, chemotherapy can cause toxic side effects and adverse outcomes, and the PRETEXT staging system may overstage the patients. Therefore, whether preoperative chemotherapy is necessary for HB patients remains unclear. Methods: The clinical data of 37 children who underwent surgical resection for PRETEXT III and IV HB at our hospital were obtained retrospectively. Patients were divided into the neoadjuvant chemotherapy group (NCG; n = 19) and the routine surgery group (RSG; n = 18). Clinicopathologic characteristics, treatment regimens, and outcomes were compared between the groups. Results: The RSG had a lower incidence of portal vein involvement than the NCG (p < 0.002). The estimated 3-year event-free survival rates were similar (RSG: 89 ± 0.7% and NCG: 79 ± 0.9%, p = 0.3923). The RSG underwent fewer courses of chemotherapy than the NCG (five vs. six; p < 0.001). Furthermore, the RSG had lower incidences of febrile neutropenia, myelosuppression, and gastrointestinal reactions (all p < 0.05). The severity of surgery-related complications did not differ significantly. Conclusion: Upfront surgical resection in children with PRETEXT III and IV HB is safe and feasible, and reduces the total number of courses and side effects of chemotherapy. The degree of vascular involvement is the most important consideration when evaluating resectability during diagnosis.

Knockdown of long non-coding MIR210HG inhibits cell proliferation, migration, and invasion in hepatoblastoma via the microRNA-608-FOXO6 axis.

OBJECTIVE: Hepatoblastoma is the most common liver tumor. Recent research has found that long non-coding (lnc)RNAs are involved in multiple types of cancers, but the potential mechanism of lncRNA MIR210HG in hepatoblastoma remains unknown. The present study explored the molecular mechanism of MIR210HG in hepatoblastoma progression. METHODS: The cell counting kit-8 was used to detect cell viability, and Transwell assays assessed cell migration and invasion. Luciferase reporter assays showed the relationship between MIR210HG and microRNA (miR)-608 and between miR-608 and forkhead box O6 (FOXO6). Functional tests were verified in vivo by a tumor xenograft model. The expression of MIR210HG, miR-608, FOXO6, E-cadherin, N-cadherin, and vimentin was determined by quantitative reverse transcription polymerase chain reaction and western blotting. RESULTS: MIR210HG was shown to be highly expressed in hepatoblastoma tissues and cell lines. Knockdown of MIR210HG reduced proliferation, migration, and invasion in liver cancer cells, and suppressed tumor growth in vivo. MIR210HG competitively combined with miR-608, and miR-608 decreased FOXO6 expression. CONCLUSION: Our study demonstrated that knockdown of MIR210HG inhibits hepatoblastoma development through binding to miR-608 and downregulating FOXO6. Our results provide novel insights for hepatoblastoma treatment involving the MIR210HG-miR608-FOXO6 axis.

Application value of computer-assisted surgery system in pediatric hepatic hemangioma.

PURPOSE: To explore the treatment of pediatric hepatic hemangioma and the role of the Hisense computer-assisted surgery (Hisense CAS) system in diagnosis and treatment. METHODS: We collected the clinical and follow-up data of all pediatric hepatic hemangioma cases in our pediatric surgery department from March 2008 to March 2021 for retrospective analysis. The Hisense CAS system was used to create three-dimensional (3D) reconstructions based on computed tomography data. RESULTS: There were 71 patients, mainly infants (prenatal to 39 months). There were more males than females (42 vs. 29), and the alpha-fetoprotein level was significantly increased in 8 cases. 3D reconstruction by the Hisense CAS system showed that hepatic artery tracking was helpful for the differential diagnosis of pediatric hepatic hemangioma. Twenty-three children treated with propranolol showed significant differences in the tumour diameter, volume, and tumour-to-liver volume ratio after treatment (all P < 0.05). Compared with early surgical treatment, the curative effect of this approach was obvious. CONCLUSION: As a non-surgical treatment for symptomatic pediatric hepatic hemangioma, propranolol can replace surgical resection to a certain extent and reduce the proportion of children who need surgical intervention. Hisense CAS has advantages in evaluating the tumour volume before and after propranolol treatment. The liver volume and the liver tumour volume percentage provide new perspectives for evaluating the tumour outcome.

Identification of Novel Prognostic Risk Signatures of Soft Tissue Sarcoma Based on Ferroptosis-Related Genes.

BACKGROUND: The role of ferroptosis in tumorigenesis has been confirmed in previous studies. However, the comprehensive analysis of ferroptosis-related gene (FRG) to study the role of FRG in soft tissue sarcoma (STS) is lacking. METHODS: RNA sequencing profile of TCGA-SARC cohort and GTEx were used to select differentially expressed FRGs (DEFRGs). Univariate, LASSO, and multivariate Cox analyses were selected to determine overall survival (OS)- and disease-free survival (PFS)-related FRGs. Two prognostic signatures were established and validated in two independent sets from Gene Expression Omnibus (GEO). Finally, the expression of key FRGs were validated with RT-qPCR. RESULTS: In total, 198 FRGs (90.4%) were abnormally expressed in STS. Twelve DEFRGs were incorporated in the final signatures and showed favorable discrimination in both training and validation cohorts. Patients in the different risk groups not only showed different prognosis, but also showed different infiltration of immune cells. Two nomograms combining signature and clinical variables were established and the C-indexes were 0.852 and 0.752 for the OS and DFS nomograms, respectively. Finally, the expression of NOX5, HELLS, and RPL8 were validated with RT-qPCR. CONCLUSION: This comprehensive analysis of the FRG landscape in STS revealed novel FRGs related to carcinogenesis and prognosis. These findings have implications for prognosis and therapeutic responses, which revealed potential prognostic biomarkers and promote precision medicine.

Analysis of survival rates and prognosis of hepatoblastoma in children: a retrospective study from a single center in China.

Hepatoblastoma (HB) is the most common liver cancer in children, this study aims at analyzing the prognostic factors affecting the survival rates and summarizing the treatment experience. In this study, we reviewed patients with primary HB under the age of 14 years who underwent complete tumor resection from June 1997 to March 2019. The data of 72 patients were collected. Survival analysis was performed by Kaplan-Meier, multivariate Cox proportional hazards regression and linear mixed model for repeated measures (LMMRM). The 5-year and the 10-year event-free survival (EFS) of all patients were 78.2% and 73%, respectively. Both the 5-year and 10-year overall survival (OS) were 85.7%. Kaplan-Meier survival analysis showed that patients with tumor capsule infiltration (TCI) and patients with surgical margin less than 1 cm may also have a good prognosis. The Cox proportional hazards regression model analysis results were similar to the Kaplan-Meier analysis results. LMMRM analysis showed that there were significant differences in platelet, alpha-fetoprotein, C-reactive protein and hemoglobin values after surgery in the metastasis group (P < 0.05). This study suggests that patients with TCI or narrow surgical margin (<1 cm) may also have a good prognosis, and the risk stratification of HB can be used as the latest grading standard to evaluate the prognosis of patients.

Factors Associated With Perioperative Complications in the Treatment of Pediatric Retroperitoneal Teratoma.

BACKGROUND: Perioperative complications are common during the surgical treatment of pediatric retroperitoneal teratoma (RPT). Some clinical and radiographic features could be associated with perioperative complications. This study was designed to identify the factors associated with such complications. MATERIALS AND METHODS: We retrospectively analyzed the clinical data of RPT patients who underwent surgical treatment at the Department of Pediatric Surgery of The Affiliated Hospital of Qingdao University between January 2008 and January 2020, including demographics, imaging data, intraoperative findings, perioperative complications, pathological data, and outcomes. RESULTS: A total of 91 patients were included in this study, including 30 boys and 61 girls. Of these, 71 patients (78%) were 1 y old or younger. Thirty-eight patients (41%) had perioperative complications (44 intraoperative and 7 postoperative). Preoperative imaging studies showed that the tumor distorted adjacent arteries, veins, and organs in all patients. More veins and organs were displaced and distorted by the tumor in patients who had perioperative complications. Multivariate analysis showed that the number of organs compressed and distorted by the tumor was significantly related to perioperative complications (odds ratio 1.69, 95% confidence interval 1.19-2.41). CONCLUSIONS: Surgical treatment of RPT is complex and challenging. As majority are benign, a complete excision is usually curative. The number of organs compressed and distorted by the tumor is positively related to perioperative complications.

Toxoplasma gondii infection in patients with lung diseases in Shandong province, eastern China.

Toxoplasma gondii, an intracellular protozoan parasite, can induce various clinical symptoms. T. gondii has been considered to play an important role in the pathogenesis of lung diseases. This survey was conducted to explore the correlation between T. gondii infection and lung diseases through a case-control study carried out in Shandong province, eastern China. In the present survey, T. gondii IgG antibodies were found in 76/398 (19.10%) of patients with lung diseases, which was significantly higher (P < 0.001) than the level found in the control subjects (35/398; 8.79%) through serological diagnosis. Patients with lung cancer have the highest T. gondii seroprevalence (26.19%), followed by Pulmonary cyst (25.00%), Tuberculosis (17.07%), Pneumonia (16.33%) and chronic obstructive pulmonary disease (COPD) (16.05%). Moreover, a semi-nest PCR targeted T. gondii B1 gene was employed to detect the T. gondii DNA in the blood samples. T. gondii DNA was detected in 5.53% blood samples of patients with lung diseases and 2.51% control subjects, respectively. The present study firstly shows that T. gondii has a high probability to infect the patients with lung diseases. Thus, the potential presence of T. gondii in patients with lung diseases should be appreciated during in the course of treatment and safeguard procedures should be implemented to protect vulnerable patients with lung diseases.

Variations of the right branch of hepatic portal vein in children based on three-dimensional simulation technology.

PURPOSE: To study the variations of the right branch of the hepatic portal vein in children. METHODS: A total of 810 children's abdominal CT images were reconstructed with three-dimensional (3D) simulation software, Variations of the right branch of the hepatic portal vein were analyzed and classified. RESULTS: The most common anatomy (type A) was seen in 355 patients (43.83%). Trifurcation in the right anterior portal vein (type B) variation was seen in 250 cases (30.86%). The right posterior portal vein arched without obvious branching (type C) was seen in 71 cases (8.77%). There were 134 special variants (16.54%) named type D, including 14 cases (1.73%) with the right anterior branch in four sub-branches, 13 cases (1.60%) in one trunk and multiple sub-branches, 92 cases (11.36%) originating from the left trunk of the portal vein, and 15 cases (1.85%) with the VI segment of the portal vein originating from the right anterior branch of the portal vein. CONCLUSION: Variations in the right branch of the hepatic portal vein seems to be very frequent. Recognition of such variations is important in the preoperative evaluation of children with surgery planned, because these variations may have implications for anatomy-guided liver resection and for planning the operative approach.

Spontaneous regression of stage III neuroblastoma: A case report.

BACKGROUND: Neuroblastoma (NB) is the most common type of extracranial solid tumour in children. The overall prognosis of NB is poor, but at the same time, NB shows significant clinical diversity. NB can demonstrate spontaneous regression or can differentiate into benign ganglioneuroma. CASE SUMMARY: This study retrospectively analyzed the clinical data of a patient with spontaneous regression of stage III NB who was admitted in May 2015. Studies of the spontaneous regression of NB published from October 1946 to September 2019 were retrieved through PubMed. The clinical manifestations, diagnosis, treatment, and follow-up results were analysed. CONCLUSION: Spontaneous regression of stage III NB is rare in the clinic. The report of this case is an important supplement to the study of the spontaneous regression of NB.

HER2 and BRAF mutation in colorectal cancer patients: a retrospective study in Eastern China.

OBJECTIVE: To investigate the frequency and prognostic role of the human epidermal growth factor receptor 2 gene (HER2) and BRAF V600E gene mutation in Chinese patients with colorectal cancer (CRC). METHODS: Clinicopathological and survival information from 480 patients with stage I-III CRC were reviewed and recorded. HER2 amplification was analyzed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), BRAF V600E mutation was tested by IHC and Sanger sequencing. The relationship between HER2 and BRAF V600E mutation status and clinicopathological characteristics and outcomes were determined. RESULTS: The amplification of HER2 and BRAF V600E mutation were identified in 27 of 480 (5.63%) and 19 of 480 (3.96%) CRC patients, respectively. HER2 amplification significantly correlated with greater bowel wall invasion (P = 0.041) and more advanced TNM stage (I vs. II vs. III; 0 vs 5.78% vs. 7.41%, P = 0.013). Patients suffering from tumors with poor differentiation had a higher incidence rate of BRAF V600E mutation than those with moderate/well differentiation (7.77% vs 2.92%, P = 0.04). HER2 amplification was an independent prognostic factor for worse disease-free survival (DFS) (HR = 2.53, 95% CI: 1.21-5.30, P = 0.014). CONCLUSION: The prevalence of HER2 amplification and BRAF V600E mutation in stage I-III CRC patients in Chinese was 6% and 4%, respectively, and HER2 amplification appeared to be associated with a worse DFS. More comprehensive molecular classification and survival analysis are needed to validate our findings.

Toxoplasma gondii infection in children with lymphoma in Eastern China: seroprevalence, risk factors and case-control studies.

Epidemiological data for Toxoplasma gondii regarding malignancy have gained increasing attention; however, the information about T. gondii infection among children with malignant lymphoma (ML) in China is unclear. Therefore, 314 children with lymphoma and 314 healthy children, age- and gender-matched, were recruited to estimate the seroprevalence of T. gondii in the participants and identify the risk factors of infection. Blood samples from all participants were collected and examined for T. gondii IgG and IgM antibodies using ELISA. The results showed that the overall seroprevalence of T. gondii antibodies (including IgG and/or IgM) in ML patients and healthy controls was 19.8% and 9.9%, respectively. Contact with the cats, consumption of oysters and history of chemotherapy were estimated to be the risk factors for T. gondii infection in children with lymphoma by multivariable logistic regression analysis, whereas in healthy children, contact with cats and consumption of oysters were the risk factors. Moreover, among various histological types of lymphoma, individuals with NK/T-cell lymphoma, B-small lymphocytic lymphoma, marginal zone B-lymphoma and Hodgkin's lymphoma had a higher seroprevalence than healthy controls (P < 0.05). These findings indicated the high prevalence of T. gondii infection in children with lymphoma, and hence, efforts should be performed to evaluate the effect of the infection further in lymphoma patients.

Solitary juvenile xanthogranuloma with tibial involvement: a case report.

Juvenile xanthogranuloma (JXG) is a rare disease that is part of a spectrum of histiocytic dendritic cell disorders. Most patients present with a solitary cutaneous lesion; however, others present with extracutaneous manifestations or even with systemic involvement. We present the first report of an 11-month-old girl in whom was diagnosed a unifocal extracutaneous JXG involving the tibia. Histological and immunohistochemical staining results are presented. A review of the literature on these unusual lesions is conducted, along with discussion of their differential diagnosis and key aspects of the patient's evaluation, management, and pathological diagnosis.

Involvement of the nuclear factor-κB signaling pathway in the regulation of CXC chemokine receptor-4 expression in neuroblastoma cells induced by tumor necrosis factor-α.

Metastasis is a hallmark of malignant neuroblastoma and is the main reason for therapeutic failure and recurrence of the tumor. The CXC chemokine receptor-4 (CXCR4), a Gi protein-coupled receptor for the ligand CXCL12/stromal cell-derived factor-1α (SDF-1α), is expressed in various types of tumor. This receptor mediates the homing of tumor cells to specific organs that express the ligand, CXCL12, for this receptor and plays an important role in tumor growth, invasion, metastasis and angiogenesis. In the present study, the inflammatory cytokine, tumor necrosis factor­α (TNF­α) upregulated CXCR4 expression in neuroblastoma cells and increased migration to the CXCR4 ligand SDF­1α. In addition, this effect was dependent upon NF-κB transcriptional activity, as blocking the NF-κB pathway with pyrrolidinedithiocarbamic acid ammonium salt suppressed TNF-α­induced upregulation of CXCR4 expression and reduced the migration towards the CXCR4 ligand, SDF-1α. Treating neuroblastoma cells with TNF-α resulted in the activation of nuclear factor-kappa B (NF-κB) and subsequently, the translocation of NF-κB from the cytoplasm to the nucleus. Using immunohistochemistry, NF­κB and CXCR4 were significantly correlated with each other (P=0.0052, Fisher's exact test) in a cohort of neuroblastoma samples (n=80). The present study indicates that the inflammatory cytokine, TNF-α, partially functions through the NF­κB signaling pathway to upregulate CXCR4 expression to foster neuroblastoma cell metastasis. These findings indicate that effective inhibition of neuroblastoma metastasis should be directed against the inflammatory cytokine-induced NF­κB/CXCR4/SDF­1α signaling pathway.

NF-κB signaling pathway confers neuroblastoma cells migration and invasion ability via the regulation of CXCR4.

BACKGROUND: Accumulating evidence implicates the transcription factor NF-κB as a positive mediator of tumor metastasis, but the molecular mechanism(s) involved in this process remains largely unknown. In this study, we investigated the role of NF-κB signaling pathway in the regulation of CXC chemokine receptor-4 (CXCR4) in neuroblastoma metastasis. MATERIAL AND METHODS: NF-κB, CXCR4 mRNA and protein expression were measured by RT-PCR, and Western blot. Tumor necrosis factor-α (TNF-α) was used to induce the upregulation of NF-κB and CXCR4. The knockdown of NF-κB and CXCR4 was achieved by PDTC. Transwell assay was used to investigate the role of NF-κB (P65) in neuroblastoma cell migration and invasion. An in vitro co-culture system was established to investigate the role of tumor microenvironment in regulation of the NF-κB signaling pathway. RESULTS: Over-expression of NF-κB (p65) promoted tumor migration and invasion through the upregulation of CXCR4; however, knockdown of NF-κB(P65) inhibited tumor migration and invasion through blocking the expression of CXCR4. Consistently, in the co-culture system, the expression of CXCR4 was partly dependent on the expression of NF-κB (p65). CONCLUSIONS: Our studies reveal critical roles for the NF-κB signaling pathway in neuroblastoma migration and invasion. The mechanism may be through up-regulation of CXCR4, mediated by the NF-κB signaling pathways. Targeting NF-κB signalling pathways and ultimately CXCR4 could be a strategy in neuroblastoma therapy.