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Glioblastoma multiforme (GBM) remains refractory to conventional therapy. CD133+ GBM cells have been recently isolated and characterized as chemo-/radio-resistant tumor-initiating cells and are hypothesized to be responsible for post-treatment recurrence. In order to explore the molecular properties of tumorigenic CD133+ GBM cells that resist treatment, we isolated CD133+ GBM cells from tumors that are recurrent and have previously received chemo-/radio-therapy. We found that the purified CD133+ GBM cells sorted from the CD133+ GBM spheres express SOX2 and CD44 and are capable of clonal self-renewal and dividing to produce fast-growing CD133− progeny, which form the major cell population within GBM spheres. Intracranial injection of purified CD133+, not CD133− GBM daughter cells, can lead to the development of YKL-40+ infiltrating tumors that display hypervascularity and pseudopalisading necrosis-like features in mouse brain. The molecular profile of purified CD133+ GBM cells revealed characteristics of neuroectoderm-like cells, expressing both radial glial and neural crest cell developmental genes, and portraying a slow-growing, non-differentiated, polarized/migratory, astrogliogenic, and chondrogenic phenotype. These data suggest that at least a subset of treated and recurrent GBM tumors may be seeded by CD133+ GBM cells with neural and mesenchymal properties. The data also imply that CD133+ GBM cells may be clinically indolent/quiescent prior to undergoing proliferative cell division (PCD) to produce CD133− GBM effector progeny. Identifying intrinsic and extrinsic cues, which promote CD133+ GBM cell self-renewal and PCD to support ongoing tumor regeneration may highlight novel therapeutic strategies to greatly diminish the recurrence rate of GBM.

Aim Localized intravascular coagulopathy (LIC) has been described in adults with venous malformation (VM) but rarely reported in children. This study aims to determine the prevalence of LIC in children with VM and associated risk factors. Methods Patients younger than 18 years with VM from 2010 to 2014 were reviewed. Diagnosis was confirmed by Doppler ultrasound and/or magnetic resonance imaging. Demographics data and VM characteristics including volume, site, extension, painful symptoms, and palpable phleboliths were studied. Plasma D-dimer level of greater than 500 ng/mL was considered as abnormal. Results Total 24 children were included, of whom 8 were boys. Median age of presentation was 9 months (range: 0-12 years). Head-and-neck VM occurred in 17 (70.8%) patients and 3 (12.5%) had multifocal lesions. Seven (29.2%) patients had VM volume greater than 10 mL. Five (20.8%) patients had painful symptoms. Palpable phleboliths were found in two patients. Plasma D-dimer was raised in eight cases (33.3%). One patient with Klippel-Trenaunay syndrome (KTS) had D-dimer level of 5,000 ng/mL. Raised D-dimer was found in 23.5% of small VM (volume < 10 mL) and 57.1% of large VM (p = 0.167). D-dimer was significantly raised in multifocal VM (p = 0.028) and showed increasing trend in lesions with palpable phleboliths (p = 0.101). All patients had sclerotherapy performed with indications (cosmesis 41.7%, enlarging lesion 29.2%, pain 20.8%, bleeding 8.3%). Perioperatively, bolus intravenous fluid and mannitol were given to selected patients. All patients had VM volume reduction after sclerotherapy. There were no major thromboembolic complications. Conclusion LIC with raised D-dimer level occurred in one-third of pediatric VM. It was more common in large, multifocal VM and in those with palpable phleboliths or KTS. [ABSTRACT FROM AUTHOR]

Somatosensory evoked potential (SSEP) and urodynamic studies (UD) are valuable tools for assessing patients with closed spinal dysraphism (CSD) before neurosurgical intervention. No studies have correlated their findings in this cohort and our aim is to study their correlation and prognostic value in pediatric patients with closed spinal dysraphism. Retrospective review of all patients referred to a multidisciplinary clinic in a tertiary pediatric surgical center over a 17 years period between April 2004 to September 2021 was performed. Inclusion criteria were <18 years old, diagnosed with CSD, with SSEP and UD done within 1 year of each other. Demographics data collected include age at presentation/at referral/at neurosurgical operation, gender, symptoms at presentation and intra-operative diagnoses. Pre-operative SSEP and UD findings were documented. Primary outcome was UD results in the group with normal and abnormal SSEP. Secondary outcome was urological and bowel function outcome in 4 groups of patients (Group A-both normal SSEP and UD, Group B- abnormal SSEP only, Group C - abnormal UD only and Group D-both abnormal SSEP and UD). A total of 45 patients were included for analysis. Mean follow up time was 118.9 months (24–216 months, SD 55.8 months). SSEP was normal in 20 patients and abnormal in 25 patients. Baseline demographics, preoperative symptoms and imaging were similar between 2 groups. Primary outcome Patients with abnormal SSEP were more likely to have abnormal UD results with a statistically significant difference (84% vs 40%, p < 0.05). They have a significantly higher end-fill detrusor pressure (12% vs 0%, p < 0.05), abnormal bladder compliance (20% vs 0%, p < 0.05), abnormal cystometric capacity (48% vs 10%, p < 0.05), poor emptying efficiency (24% vs 5%, p < 0.05) and sphincter incompetence (8% vs 0%, p < 0.05). Secondary outcome When compared to Groups A to C, patients in group D were more likely to be on anti-cholinergic (33.3% vs 4.3%, p < 0.05), required clean intermittent catheterization (42.9% vs 4.3%, p < 0.05) and had intravesical botulinum injection (19% vs 0%, p < 0.05). All the patients who had augmentation cystoplasty were in this group as well. Bowel function in terms of regular enema use was also statistically significantly higher in this group (33.4% p < 0.05). Pre-operative SSEP and UD results correlate well in patients with closed spinal dysraphism. Patients with abnormal SSEP and UD preoperatively have higher risk of urological deterioration over time. Close monitoring in this group is warranted. Summary Table Urological and bowel function outcome in group with both normal SSEP and UD versus group with both abnormal SSEP and UD results. Table 1 Group A Both normal SSEP and UD N = 12 Group B Abnormal SSEP only N = 4 Group C Abnormal UD only N = 8 Group D Both abnormal SSEP AND UD N = 21 P-value Median age at NS OT (months) 27 14.5 23 16.5 0.051 Median FU time (months) 102 66 120 120 0.087 Anti-cholinergic use 0 0 1 (12.5%) 7 (33.3%) 0.008∗ Clean intermittent catheterisation use 1 (8.3%) 0 0 9 (42.9%) 0.006∗ Intravesical botulinum injection 0 0 0 4 (19%) 0.039∗ Augmentation cystoplasty 0 0 0 3 (14.8%) 0.079 Urinary continence at last FU 0.433 • Continent without CIC 11 (91.7%) 2 (100%) 5 (71%) 12 (60%) • Continent on CIC 1 (8.3%) 0 1 (14.2%) 6 (30%) • Incontinent 0 0 1 (14.2%) 2 (10%) Abnormal renal function on last follow up 1 (8.3%) 0 0 1 (5.6%) 0.813 [ABSTRACT FROM AUTHOR]

Injection of methylene blue to testis has been shown to have adverse effect in animal studies but it is still being used frequently as lymphatic mapping agent during lymphatic sparing varicocelectomy in adolescent varicoceles. We aim to report postoperative ultrasound changes after subaortic injection of methylene blue in human testes. A retrospective observational study of consecutive patients under 18 years old undergoing laparoscopic varicocelectomy from August 2017 to August 2021 was performed. Demographics such as age, symptoms, pre-operative testicular volume was collected. Primary outcome was change on testicular ultrasound at 3, 6, 12 months after the operation. Secondary outcome was testicular volume difference between affected and unaffected testes, and growth rate of affected testis at 1 year after the operation. Fifty-eight patients were included, with median age of 15 years old (IQR 11–18 years). Thirty-one patients had non-lymphatic sparing varicocelectomy (Group A) and 27 patients had lymphatic sparing varicocelectomy (Group B). There was no statistical difference between the mean testicular volume difference between the two groups, but hydrocele rate was significantly higher in Group A (16% vs 0%, p = 0.03). In group B, 6 patients (22.2%, p = 0.005) developed testicular change detectable by ultrasound. No statistical difference could be demonstrated for median testicular size difference (between affected and unaffected testes) at 1 year between group with and without ultrasound change (−23% vs 0%, p = 0.36). Median follow up time was 20.4 months (IQR 5–32 months). Varicocele treatments improve testicular volume and increase total sperm concentration and lymphatic sparing surgery significantly decreased post-operative hydrocele rates [2]. Different agents have been used to delineate lymphatic vessels and one commonly used agent is methylene blue [10,15-16]. However it has been shown in other animal studies that intraparenchymal injection of methylene blue to rat testis result in degenerative changes [18]. Our study is the first to describe post-operative changes of human testes on imaging after lymphatic sparing varicocelectomy with subdartoic injection of methylene blue. Six patients (22.2%) demonstrated new onset testicular changes on post-operative ultrasound. Although no statistically significant testicular volume reduction was seen in the group with change on imaging, these observations may serve as a surrogate marker for testicular injury or reduced testicular function. It will be desirable for future studies if we can investigate it further with hormonal markers or semen analysis after puberty has been reached. Lymphatic sparing procedure reduced post-operative hydrocele in adolescent varicocele, however long-lasting effect on testis is evident with subdartoic injection of methylene blue. This agent must be used with caution and long term follow up of these patients are needed. [Display omitted] Comparison of groups with and without post-operative ultrasound changes. Group with USG changes N = 6 Group without USG changes N = 21 P value Median age at operation (Years, IQR) 12.5 (11–14.5) 15 (14–16) 0.13 Median testicular size difference between affected and unaffected testes (%, IQR): Pre-operatively −3.9% (−34%–12.5%) −17.7% (−23.3% to −11.1%) 0.41 At 3 months post-op −14.4% (−63.1%–1.1%) −6.5% (−19.5%–3.1%) 0.51 At 6 months post-op −18.5% (−47.7% to −5.9%) −1.4% (−16.9%–0%) 0.11 At 1-year post-op −23% (−43.2%–1.1%) 0% (−10%–4%) 0.36 Median growth rate of affected testis (pre-op to 1 year) 44.2% (17.5–107%) 24.4% (16–147.7%) 0.38 [ABSTRACT FROM AUTHOR]