Prediction of MYCN Gene Amplification in Pediatric Neuroblastomas: Development of a Deep Learning-Based Tool for Automatic Tumor Segmentation and Comparative Analysis of Computed Tomography-Based Radiomics Features Harmonization.

OBJECTIVE: MYCN oncogene amplification is closely linked to high-grade neuroblastoma with poor prognosis. Accurate quantification is essential for risk assessment, which guides clinical decision making and disease management. This study proposes an end-to-end deep-learning framework for automatic tumor segmentation of pediatric neuroblastomas and radiomics features-based classification of MYCN gene amplification. METHODS: Data from pretreatment contrast-enhanced computed tomography scans and MYCN status from 47 cases of pediatric neuroblastomas treated at a tertiary children's hospital from 2009 to 2020 were reviewed. Automated tumor segmentation and grading pipeline includes (1) a modified U-Net for tumor segmentation; (2) extraction of radiomic textural features; (3) feature-based ComBat harmonization for removal of variabilities across scanners; (4) feature selection using 2 approaches, namely, ( a ) an ensemble approach and ( b ) stepwise forward-and-backward selection method using logistic regression classifier; and (5) radiomics features-based classification of MYCN gene amplification using machine learning classifiers. RESULTS: Median train/test Dice score for modified U-Net was 0.728/0.680. The top 3 features from the ensemble approach were neighborhood gray-tone difference matrix (NGTDM) busyness, NGTDM strength, and gray-level run-length matrix (GLRLM) low gray-level run emphasis, whereas those from the stepwise approach were GLRLM low gray-level run emphasis, GLRLM high gray-level run emphasis, and NGTDM coarseness. The top-performing tumor classification algorithm achieved a weighted F1 score of 97%, an area under the receiver operating characteristic curve of 96.9%, an accuracy of 96.97%, and a negative predictive value of 100%. Harmonization-based tumor classification improved the accuracy by 2% to 3% for all classifiers. CONCLUSION: The proposed end-to-end framework achieved high accuracy for MYCN gene amplification status classification.

The Characteristics of Real-time Transvaginal Sono-elastography in Endometrial Cancer.

Background: Endometrial cancer is the most common gynecological cancer among women in developed countries. Sono-elastography is an extended ultrasonographic technique that has been shown to be useful in a wide range of conditions ranging from breast, prostate, and thyroid nodules to chronic liver disease and musculoskeletal conditions. The aim of this study is to compare the sonoelastographic features of endometrial malignancy and normal endometrium. Methods: This case-control observational study was conducted at a single institution. Participants with histologically proven endometrial cancer according to the results from microcurettage or hysteroscopic biopsy and scheduled for total hysterectomy were included as cases, while asymptomatic women scheduled for routine screening ultrasound examination were recruited as controls. Both cases and controls underwent conventional B-mode transvaginal ultrasonography and strain elastography. Demographic, ultrasonographic, and histopathologic findings were analyzed. Results: A total of 29 endometrial cancer patients (cases) and 28 normal females (controls) were included in the analysis. There was no significant difference in the mean age between the two groups, but the mean body weight was significantly higher in the case group (P < 0.001). The strain ratio and elastographic thickness ratio of the endometrium were statistically significantly different between the case and the control group (P ≤ 0.05) due to increased endometrial stiffness in cancer patients as compared to the normal group. Conclusion: Our results suggest that endometrial cancer can result in increased stiffness that is detectable by transvaginal sonoelastography. Sonoelastography may serve as an adjunct to conventional ultrasound in evaluating the endometrium of women with abnormal uterine bleeding.

CT-based morphologic and radiomics features for the classification of MYCN gene amplification status in pediatric neuroblastoma.

PURPOSE: MYCN onco-gene amplification in neuroblastoma confers patients to the high-risk disease category for which prognosis is poor and more aggressive multimodal treatment is indicated. This retrospective study leverages machine learning techniques to develop a computed tomography (CT)-based model incorporating semantic and non-semantic features for non-invasive prediction of MYCN amplification status in pediatric neuroblastoma. METHODS: From 2009 to 2020, 54 pediatric patients treated for neuroblastoma at a specialized children's hospital with pre-treatment contrast-enhanced CT and MYCN status were identified (training cohort, n = 44; testing cohort, n = 10). Six morphologic features and 107 quantitative gray-level texture radiomics features extracted from manually drawn volume-of-interest were analyzed. Following feature selection and class balancing, the final predictive model was developed with eXtreme Gradient Boosting (XGBoost) algorithm. Accumulated local effects (ALE) plots were used to explore main effects of the predictive features. Tumor texture maps were also generated for visualization of radiomics features. RESULTS: One morphologic and 2 radiomics features were selected for model building. The XGBoost model from the training cohort yielded an area under the receiver operating characteristics curve (AUC-ROC) of 0.930 (95% CI, 0.85-1.00), optimized F1-score of 0.878, and Matthews correlation coefficient (MCC) of 0.773. Evaluation on the testing cohort returned AUC-ROC of 0.880 (95% CI, 0.64-1.00), optimized F1-score of 0.933, and MCC of 0.764. ALE plots and texture maps showed higher "GreyLevelNonUniformity" values, lower "Strength" values, and higher number of image-defined risk factors contribute to higher predicted probability of MYCN amplification. CONCLUSION: The machine learning model reliably classified MYCN amplification in pediatric neuroblastoma and shows potential as a surrogate imaging biomarker.

Occult Antenatal Fetal Abdominal Emergencies Resulting in Unplanned Preterm Delivery.

Acute abdomen in the fetus can present as nonspecific fetal distress, and occasionally necessitate emergency cesarean section for the mother and subsequent emergency neonatal surgery. Often, preoperative diagnosis in utero is challenging. The authors herein report two cases, a case of primary segmental antenatal intestinal volvulus resulting in the mother presenting at 35 wk with symptoms and decreased fetal movements, and another case of a rapidly distending fetal abdominal mass at 31 wk manifesting as fetal hydrops. The postdelivery newborn management issues are presented. Early identification by the maternal and neonatal team allows for early neonatal surgery and can reduce morbidity and mortality. This can be facilitated by advanced maternal and child health services and efficient patient transport systems.

Association of anesthetic and surgical risk factors with outcomes of initial diagnostic biopsies in a current cohort of children with anterior mediastinal masses.

Background: Diagnostic biopsies of pediatric anterior mediastinal masses (AMMs) are high-risk procedures in which general anesthesia (GA) is traditionally avoided. However, awareness of historically recognized risk factors and corresponding perioperative management have improved over time and may now no longer strictly preclude the use of GA. Therefore, in this study, we examined the association of anesthetic and surgical risk factors and modalities with resulting procedural and survival outcomes in a current patient cohort. Methods: We retrospectively reviewed charts of 35 children with AMMs who underwent initial diagnostic biopsies between January 2001 and August 2019, and determined tracheal compression and deviation from archival CT scans and procedural and disease outcomes. Results: Twenty-three (65%) patients underwent GA while 12 (35%) received sedation. Among patients with available CT measurements, 13 of 25 (52%) had >50% anteroposterior tracheal diameter reduction. Patients with >50% anteroposterior tracheal compression received sedation more frequently (p=0.047) and were positioned upright (p=0.015) compared with patients with ≤50% compression, although 4 of 13 and 9 of 12, respectively, still received GA. Intraoperative adverse events (AEs) occurred in four (11.4%) patients: three received GA, and all were positioned supine or lateral. AEs were not associated with radiographic airway risk factors but were significantly associated with morphine and sevoflurane use (p<0.001) and with thoracoscopic biopsies (p=0.035). There were no on-table mortalities, but four delayed deaths occurred (three related to disease and one from late procedural complications). Conclusions: In a current cohort of pediatric AMM biopsies, patients with >50% anteroposterior tracheal compression were more frequently managed with a conservative perioperative management strategy, though not completely excluding GA. The corresponding reduction in frequency of procedural AEs in this traditionally high-risk group suggests that increased awareness of procedural risk factors and appropriate risk-guided perioperative management choices may obviate the procedural mortality historically associated with pediatric AMM biopsies.

Cerebrospinal fluid cytokines in metastatic group 3 and 4 medulloblastoma.

BACKGROUND: Metastatic medulloblastoma (MB) portends a poor prognosis. Amongst the 4 molecular subtypes, Group 3 and Group 4 patients have a higher incidence of metastatic disease, especially involving the neuroaxis. At present, mechanisms underlying MB metastasis remain elusive. Separately, inflammation has been implicated as a key player in tumour development and metastasis. Cytokines and their inflammation-related partners have been demonstrated to act on autocrine and, or paracrine pathways within the tumour microenvironment for various cancers. In this study, the authors explore the involvement of cerebrospinal fluid (CSF) cytokines in Group 3 and 4 MB patients with disseminated disease. METHODS: This is an ethics approved, retrospective study of prospectively collected data based at a single institution. Patient clinicpathological data and corresponding bio-materials are collected after informed consent. All CSF samples are interrogated using a proteomic array. Resultant expression data of selected cytokines are correlated with each individual's clinical information. Statistical analysis is employed to determine the significance of the expression of CSF cytokines in Group 3 and 4 patients with metastatic MB versus non-metastatic MB. RESULTS: A total of 10 patients are recruited for this study. Median age of the cohort is 6.6 years old. Based on Nanostring gene expression analysis, 5 patients have Group 3 as their molecular subtype and the remaining 5 are Group 4. There are 2 non-metastatic versus 3 metastatic patients within each molecular subtype. Proteomic CSF analysis of all patients for both subtypes show higher expression of CCL2 in the metastatic group versus the non-metastatic group. Within the Group 3 subtype, the MYC-amplified Group 3 MB patients with existing and delayed metastases express higher levels of CXCL1, IL6 and IL8 in their CSF specimens at initial presentation. Furthermore, a longitudinal study of metastatic Group 3 MB observes that selected cytokines are differentially expressed in MYC-amplified metastatic Group 3 MB, in comparison to the non-MYC amplified metastatic Group 3 MB patient. CONCLUSION: This study demonstrates higher expression of selected CSF cytokines, in particular CCL2, in metastatic Group 3 and 4 MB patients. Although our results are preliminary, they establish a proof-of-concept basis for continued work in a larger cohort of patients affected by this devastating disease.

Posterior retroperitoneoscopic adrenalectomy for pediatric adrenal tumors.

BACKGROUND/AIMS: Posterior retroperitoneoscoic adrenalectomy has been reported as an option for adrenal tumor resection but is not commonly performed in children owing to the extreme semikneeling position advocated to flatten the lumbar lordosis in order to achieve adequate retroperitoneal space. As children have smaller lordosis angles, flattening of the lordosis and creation of optimal retroperitoneal space may be achieved with less hip flexion. We used pediatric lumbar lordosis measurements to develop a modified prone jackknife position and report our experiences with this setup for posterior retroperitoneoscopic adrenalectomy for adrenal tumors. METHODS: Lordosis angles were measured on sagittal computed tomography (CT) and magnetic resonance imaging (MRI) studies of patients with adrenal tumors and compared to normal references. The data were used to develop our modified prone jackknife position. Selected patients with adrenal tumors underwent posterior retroperitoneoscopic adrenalectomy in this position. Patient demographics, diagnoses, operative times, complications, postop analgesia requirements, and length of hospitalization were analyzed. RESULTS: CT and MRI studies were analyzed for 20 patients with adrenal tumors diagnosed in our institution from 2012 to 2017; median lordosis angle was 27.84° (range: 15.50°-36.48°) - less than reference lordosis angles of respective age groups, and flexion angles of common operating tables. Five patients underwent retroperitoneoscopic adrenalectomy between June 2016 and June 2018. Histological diagnoses were neuroblastoma, adrenal hyperplasia, pheochromocytoma, and adrenal angiomatoid fibrous histiocytoma. Median age was 4 years [range: 1-11]. Median operating time was 137 min [range 111-181 min]. No conversions to open surgery were required. One patient had intraoperative bleeding from the adrenal vein. Only 1 patient required postoperative opioids for analgesia. Median length of hospitalization after surgery was 2 days (range: 2-3 days). CONCLUSIONS: Pediatric patients can achieve flattening of lumbar lordosis with less extreme positioning. Posterior retroperitoneoscopic adrenalectomy in a modified prone jackknife position is a feasible operation for pediatric patients with small adrenal masses. TYPE OF STUDY: Clinical research paper. LEVEL OF EVIDENCE: Level III.

Retroperitoneal tumors and congenital variations in vascular anatomy of retroperitoneal great vessels.

BACKGROUND/OBJECTIVES: Variations in vascular anatomy (VIVAs) of the retroperitoneal great vessels are uncommon but can potentially complicate surgical procedures and negatively affect treatment outcomes, yet their incidence and clinical impact are poorly studied. We sought to assess the incidence and clinical impact of VIVAs of retroperitoneal great vessels in patients with retroperitoneal tumors. METHODS: We retrospectively analyzed imaging, surgical, treatment and survival data of all pediatric patients with retroperitoneal tumors who underwent resection between January 2007 and October 2016, comparing preoperative scans with corresponding intraoperative observations, and subsequent surgical outcomes. RESULTS: Among 66 children with renal, adrenal and paravertebral tumors, 6 (9%) had retroperitoneal VIVAs. Retroperitoneal VIVAs were present only with right-sided tumors and significantly associated with more frequent intraoperative complications (P = 0.013). While the presence of retroperitoneal VIVAs was not directly associated with survival outcomes, relapse was more frequent in patients with VIVAs (33%) than those without (18.3%, P = 0.378), and relapse was also associated with lower overall and event-free survival (P < 0.001). CONCLUSIONS: VIVAs of retroperitoneal great vessels occurred in 9% of our patients with retroperitoneal tumors. Retroperitoneal VIVAs were associated with higher rates of intraoperative complications and disease relapse but was not directly related to survival outcomes. TYPE OF STUDY: Retrospective review study. LEVEL OF EVIDENCE: Level III Retrospective comparative study.

Magnetic resonance imaging of the fetal central nervous system in Singapore.

INTRODUCTION: Fetal imaging has improved with the development of faster magnetic resonance imaging (MRI) sequences, obviating the requirement for sedation. It is useful in characterising abnormality of the central nervous system in fetuses with abnormal or equivocal antenatal ultrasound findings. We reviewed all cases of fetal brain and spine MRI performed in our institution. MATERIALS AND METHODS: All cases of fetal central nervous system MRI imaging from May 2006 to December 2008 were retrospectively reviewed, including fetal MRI, postnatal MRI and autopsy findings. RESULTS: Thirty-one fetuses were imaged with MRI for evaluation of the central nervous system of which 3 were specifically for spinal evaluation. On fetal MRI, there were 11 normal fetuses (2 with minor ventricular asymmetry), 4 fetuses with minor ventriculomegaly and 16 fetuses with significant abnormalities. Twenty-three fetuses were delivered and 8 were terminated. Fifteen of 23 babies underwent postnatal imaging, 21 had clinical follow-up and 2 were lost to clinical follow-up. Of the 11 fetuses reported as normal on fetal MRI, 3 had additional postnatal findings. A fetus with a megacisterna magna on fetal MRI was diagnosed with a posterior fossa arachnoid cyst on postnatal MRI. One, who had fetal MRI to assess suspected absent inferior cerebellar vermis, had intracranial calcifications from rubella infection. One was diagnosed with cerebro-occular-facio-skeletal (COFS) syndrome postnatally, 1 was lost to follow-up and the rest were discharged well. Seven out of 16 fetuses with significantly abnormal fetal MRI findings had confirmation of the findings on postnatal imaging. Postnatal MRI detected 2 cases of polymicrogyria which were not seen on fetal MRI. Autopsy was available in 1 abortus confirming intrauterine diagnosis of Dandy Walker malformation. A myelomeningocele was clinically obvious in 1 abortus. CONCLUSION: Fetal MRI is a good method of assessing brain and spine abnormalities in utero. However, disorders of neuronal migration remain a challenging diagnostic problem in fetal imaging.

Imaging findings of chronic subluxation of the os odontoideum and cervical myelopathy in a child with Beare-Stevenson cutis gyrata syndrome after surgery to the head and neck.

INTRODUCTION: Although uncommon, fractures of the os odontoideum are known to occur in children under 7 years old, following acute trauma. CLINICAL PICTURE: We report a case of chronic subluxation of the os odontoideum resulting in cervical myelopathy in a child with Beare-Stevenson cutis gyrata syndrome after surgery to the head and neck. TREATMENT AND OUTCOME: The patient was initially put in a Halo vest, following which occipital cervical fusion was performed. CONCLUSION: Subluxations and fractures at the odontoid synchondrosis are rare but should be anticipated in young children with risk factors for instability of the cervical spine.