The use of postoperative calibrations in Hirschsprung disease: a practice to reconsider?

PURPOSE: Daily postoperative anal dilations after endorectal pull-through for Hirschsprung disease (HD) are still considered a common practice. We analyzed the potential risks of this procedure and its effectiveness compared to a new internal protocol. METHODS: All infants (< 6 months of age) who underwent transanal endorectal pull-through between January 2021 and January 2023 were prospectively enrolled in a new postoperative protocol group without daily anal dilations (Group A) and compared (1:2 fashion) to those previously treated by postoperative anal dilations (Group B). Patients were matched for age and affected colonic tract. Patients with associated syndromes, extended total intestinal aganglionosis, and presence of enterostomy were excluded. Outcomes considered were: anastomotic complications (stenosis, disruption/leakage), incidence of enterocolitis, and constipation. RESULTS: Eleven patients were included in group A and compared to 22 matched patients (group B). There were no significant differences in the occurrence of anastomotic complications between the two groups. We found a lower incidence of enterocolitis and constipation among group A (p = 0.03 and p = 0.02, respectively). CONCLUSION: A non-dilation strategy after endorectal pull-through could be a feasible alternative and does not significantly increase the risk of postoperative anastomotic complications. Moreover, some preliminary advantages such as lower enterocolitis rate and constipation should be further investigated.

Lower Urinary Tract Dysfunction in Pediatric Patients with Multiple Sclerosis: Diagnostic and Management Concerns.

BACKGROUND: Multiple sclerosis (MS) is increasing in the pediatric population and, as in adults, symptoms vary among patients. In children the first manifestations can sometimes overlap with acute neurological symptoms. Urological symptoms have not been much studied in childhood. We shared our experience with MS urological manifestation in children. METHODS: This article is a retrospective evaluation of all children with MS, according to the Krupp criteria, who also present with urological symptoms. We collected demographic and clinical history, the MR localization of demyelinating lesions, urological symptoms, and exams. RESULTS: We report on six MS pediatric cases with urological manifestation. Urinary symptoms, characterized by urinary incontinence in five patients and urinary retention in one patient, appeared in a different time frame from MS diagnosis. Urodynamic exams showed both overactive and underactive bladder patterns. Treatment was defined according to lower urinary tract dysfunction, using clean intermittent catheterization, oxybutynin, and intradetrusor Onabotulinum Toxin-A injection. A low acceptance rate of invasive evaluation and urological management was observed. CONCLUSIONS: The MS diagnosis was traumatic for all our patients. We believe it is important to address urological care in young people from the time of diagnosis for prompt management; it could be useful to include a pediatric urologist in multidisciplinary teams.

Megacystis-microcolon-intestinal hypoperistalsis syndrome: don't forget the bladder.

PURPOSE: Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a well described clinical condition, but reports are focused on microcolon and intestinal hypoperistalsis, while data on bladder management are scant. Aim of the study is to present urological concerns in MMIHS. METHODS: Retrospective evaluation of clinical data on urological management of MMIHS patients treated in the last 10 years. RESULTS: Six patients were enrolled (3 male, 3 female). Three girls had prenatal diagnosis of megacystis (1 vesicoamniotic shunt was placed). All patients had genetic diagnosis: 5 had ACTG2 gene mutations and 1 MYH11 mutation. All patients were addressed to our attention for urinary symptoms, such as urinary retention, urinary tract infections, acute renal injury. Two patients presented frequent stoma prolapses. All children underwent a complete urological evaluation, and then started a bladder management protocol (clean intermittent catheterization, via urethra or cystostomy-tube placement), with improvement of urinary infections, upper urinary tract dilation and stoma prolapses, if present. All patients had good renal function at last follow-up. CONCLUSION: We believe that MMIHS patients must be addressed soon and before onset of symptoms for a multidisciplinary evaluation, including an early assessment by a pediatric urologist expert in functional disorder, to preserve renal function at its best.

Needle Fetal Thoracoscopy: A Technique to Assist with Ultrasound-Guided Placement of Challenging Thoracoamniotic Shunts.

INTRODUCTION: Fetal thoracoamniotic shunts are common lifesaving interventions but frequently require replacement. Needle fetal thoracoscopy is a technique that uses standard thoracoamniotic shunt introducer sheaths to permit direct visualization and even instrument manipulation during shunt deployment to facilitate optimal positioning and primary shunt function in the most challenging cases. CASE PRESENTATION: In this study, 5 patients who underwent needle fetal thoracoscopy-assisted thoracoamniotic shunt placement were reviewed. Three patients with large, macrocystic congenital pulmonary airway malformations (CPAMs) with evidence of worsening mediastinal shift and/or hydrops and 2 patients with large chylothorax with fetal hydrops were treated. Four cases had previous shunts that failed due to poor sonographic visualization during initial placement, cyst septations, shunt obstruction, or dislodgment. Needle fetal thoracoscopy was used to disrupt cyst walls and septations, clear hematoma, and confirm the optimal initial position of the shunt. In this series, 1 severe CPAM patient with a short cervix developed preterm labor postoperatively resulting in neonatal demise. The remaining 4 patients experienced resolution of hydrops and progressed to successful delivery with excellent neonatal outcomes. CONCLUSION: Needle fetal thoracoscopy is a procedure that may be selectively deployed in challenging thoracoamniotic shunt cases impacted by recurrent failure, poor sonographic windows, and challenging fetal positioning.

Ex-Utero Intrapartum Treatment-to-Airway for Obstructing Fetal Neck Masses: A Singular Methodology for Monochorionic and Dichorionic Twin Pregnancies.

Fetal airway obstruction in one twin of a diamniotic pregnancy presents unique challenges. Very few cases of ex-utero-intrapartum-treatment (EXIT) procedures for twin pregnancy have been reported and only in dichorionic pregnancies. We report a singular methodology for EXIT-to-airway procedures in two pregnancies involving monochorionic and dichorionic twins. Two cases of EXIT-to-airway in twin pregnancies were performed in 2018 and 2019 at a regional fetal treatment center. Case 1 involved a giant cervical teratoma in a monochorionic-diamniotic twin pregnancy with preterm labor at 29 weeks. Case 2 involved a dichorionic-diamniotic pregnancy with a large cervical lymphatic malformation with preterm labor at 36 weeks. In each case, the polyhydramnios caused the affected twin's amniotic sac to be the presenting sac for the surgical approach. Bronchoscopy and successful intubation was completed after 22 and 10 minutes of uteroplacental bypass, respectively. The bystander twins were delivered second without intubation and resuscitated without perinatal distress. EXIT-to-airway appears to be a reasonable option for twins including monochorionic pregnancies, via delivery of the affected twin first followed by delivery of the bystander twin. Thoughtful preparation and counseling by an experienced multidisciplinary team permits an EXIT-to-airway approach for twin pregnancies even in an emergent setting.

Nonparasitic Splenic Cysts in Children: Outcomes after Sclerotherapy or Surgical Resection as Initial Management.

Management of splenic cysts in children remains undefined. Sclerotherapy is an innovative, less invasive treatment. This study examined the safety and preliminary effectiveness of sclerotherapy for splenic cysts in children compared with those of surgical treatment. A retrospective review of pediatric patients treated for nonparasitic splenic cysts from 2007 to 2021 was performed at a single institution. Posttreatment outcomes for patients who underwent either expectant management, sclerotherapy, or surgery were reviewed. Thirty patients aged between 0 and 18 years met the inclusion criteria. Cysts in 3 of 8 patients who underwent sclerotherapy were either unresolved or recurred. Patients who underwent sclerotherapy and required surgery for residual symptomatic cyst had an initial cyst diameter of >8 cm. Symptoms resolved in 5 of 8 patients who underwent sclerotherapy, with a significantly reduced cyst size compared with that in patients with continued symptoms who underwent sclerotherapy (61.4% vs 7.0%, P = .01). Sclerotherapy is an effective treatment for splenic cysts, particularly those measuring <8 cm. However, surgical excision may be preferable for large cysts.

Intrafetal Laser Therapy Is a Feasible Treatment for Different Fetal Conditions: A Systematic Review.

INTRODUCTION: Over the past years, intrafetal laser (IFL) therapy has been increasingly used in the management of various prenatal conditions. The aim of our research was to clarify the effectiveness and safety of this technique. METHODS: A systematic review of the literature was carried out using MEDLINE/PubMed over a period of 20 years (2001-2021). RESULTS: A total of forty-one articles were selected in the literature search, including 194 cases of twin reversed arterial perfusion (TRAP) sequence, 56 cases of bronchopulmonary sequestrations (BPSs), 5 cases of placental chorioangiomas (PCA), 11 cases of sacrococcygeal teratoma (SCT), and 103 cases of embryo reduction (ER) managed using IFL. In TRAP sequence, perfusion of the acardiac twin was successfully disrupted in all cases. However, preterm premature rupture of membranes (P-PROMs) occurred in 6 out of 79 pregnancies (7.5%), and preterm birth (PTB) occurred in 36 out of 122 pregnancies (29.5%). In BPS, IFL was successfully performed in all cases with no significant fetal-maternal complications. The rates of P-PROM and PTB were, respectively, 3.2% and 12.5%. All PCA IFL-treated cases resulted in successful pregnancy outcomes; no cases of P-PROM were reported, but the rate of PTB reached a peak of 60% due to complications such as severe fetal growth restriction and fetal Doppler abnormalities. In SCT cases, complete cessation of blood flow was achieved in 4 patients (36.4%); P-PROM occurred in 2 cases (18.2%), whereas the rate of PTB was 87.5%. In ER, no intraoperative or major maternal complications were described in the literature. Rates of miscarriage and PTB differed between initial trichorionic triamniotic and dichorionic triamniotic triplet pregnancies. CONCLUSION: Our analysis suggests that IFL is a safe and feasible technique for the management of different fetal conditions. However, the overall risk of PTB, and its related morbidity and mortality, ranges from 12.5% in BPS to 87.5% in SCT IFL-treated cases. This information could aid in decision-making during prenatal counseling. However, final perinatal outcome depends on the severity of the disease itself.

The interplay between prenatal liver growth and lung development in congenital diaphragmatic hernia.

Objective: Liver herniation is a known risk factor for increased severity in CDH and is associated with clinically significant pulmonary hypoplasia and pulmonary hypertension. Better studies are needed to understand the growth of the herniated liver compared to the liver that remains in the abdomen and how this liver growth then affects lung development. Serial hi-resolution fetal MRI enables characterization of liver growth throughout gestation and examination of macroscopic features that may regulate liver growth. Here, we hypothesized that the nature of liver herniation affects liver growth and, in turn, affects lung growth. Methods: Clinical data were retrospectively collected from consecutive cases of prenatally diagnosed isolated left-sided or right-sided CDH from June 2006 to August 2021. Only those cases with MRI lung volumetry for both mid-gestation and late-gestation time points were recruited for analysis. Cases with fetal chromosomal abnormalities and other major structural abnormalities were excluded. Fractional liver volume and liver growth was indexed to estimated fetal weight and compared to lung growth. Results: Data was collected from 28 fetuses with a left liver-down CDH (LLD), 37 left liver-up CDH (LLU) and 9 right liver-up CDH (RLU). Overall, RLU fetuses had greater overall and fractional (intra-thoracic vs. intra-abdominal) liver growth when compared to LLD and LLU fetuses. Additionally, intra-thoracic liver growth was consistently slower than intra-abdominal liver growth for either right- or left-sided CDH. When the liver was not herniated, a positive correlation was seen between liver growth and lung growth. However, when the liver was herniated above the diaphragm, this positive correlation was lost. Conclusion: Right-sided CDH fetuses exhibit greater liver growth compared to left-sided CDH. Liver herniation disrupts the normal positive correlation between liver and lung growth that is seen when the liver is entirely within the abdomen.

A novel surgical toxicological-free model of diaphragmatic hernia in fetal rats.

BACKGROUND: Teratogen-induced congenital diaphragmatic hernia (CDH) rat models are commonly used to study the pathophysiology. We have created a new and reliable surgically induced diaphragmatic hernia (DH) model to obtain a purely mechanical DH rat model, and avoid the confounding teratogen-induced effects on the lung development. METHODS: Fetal DH was surgically created on fetuses at E18.5 and harvested at E21.5 in rats. Four groups were evaluated (n = 16): control (CONT), control exposed to Nitrofen (CONT NIT), DH surgically created (DH SURG), and CDH Nitrofen (CDH NIT). Body weight, total lung weights, and their ratio (BW, TLW, and TLBR) were compared. Air space (AS), parenchyma (PA), total protein, and DNA contents were measured to verify lung hypoplasia. Medial wall thickness (MWT) of pulmonary arterioles was also analyzed. RESULTS: DH SURG showed significant hypoplasia (decreased in total protein and DNA) vs CONT (p < 0.05); DH SURG vs CDH NIT were similar in TLW and TLBR. DH SURG has less AS than CONT (p < 0.05) and similar PA compared to CONT NIT and CDH NIT, MWT were similarly increased in CONT NIT, DH SURG, and CDH NIT. CONCLUSIONS: This novel surgical model generates fetal lung hypoplasia contributing to the study of the mechanical compression effect on fetal lung development in DH. IMPACT: There is a critical need to develop a surgical model in rat to complement the findings of the well-known Nitrofen-induced CDH model. This experimental study is pioneer and can help to understand better the CDH pathophysiological changes caused by herniated abdominal viscera compression against the lung during the final stage of gestation in CDH fetuses, and also to develop more efficient treatments in near future.

Long-term follow-up of surgical outcomes for patients with Wilms tumor and neuroblastoma.

BACKGROUND: There are minimal data on long-term surgical outcomes of patients who have undergone resection for Wilms tumor (WT) and neuroblastoma (NB). METHODS: A retrospective review of patients in a long-term survivor clinic between the years 1967 and 2016 in a pediatric tertiary care hospital (>5 years posttreatment) was performed. RESULTS: Eighty-six survivors of WT and 86 survivors of NB who had ongoing follow-up in the survivors' clinic were identified. The median age at diagnosis was 2.5 years (range, 0.4-15.7 years) with a mean follow-up of 22.3 years (±10.4 years) for WT. The median age at diagnosis for patients with NB was 0.9 years (range, 0.1-8.6 months); mean follow-up of 21.7 years (±7.9 years). Twelve patients with WT (14.0%) had at least 1 repeat laparotomy, 11.1% for bowel obstruction, at a median of 3 months from initial surgery. Twelve patients (14.0%) with NB required laparotomy and 8.1% for bowel obstruction, at a median of 12 years after initial surgery. The incidence of hypertension in patients with WT who had undergone nephrectomy was not outside of population norms. Patients who underwent thoracotomy for a NB have a higher incidence of scoliosis and Horner syndrome. CONCLUSIONS: Small bowel obstruction requiring laparotomy is significantly higher than the literature norms for both tumor patient populations and typically occurs in the early postoperative period for patients with WT and remotely in patients with NB. The long-term surgical complications of patients who underwent resection for NB and WT clearly merit follow-up and patient education within multidisciplinary long-term survivorship clinics.

Can a children's hospital still cut it? Comparing outcomes of pediatric, adolescent and young adult patients undergoing thoracic surgery for lung metastases.

BACKGROUND: Adolescents and young adults (AYAs) with cancer have unique medical challenges compared with younger children and older adults. Dedicated centers have been established to deliver cancer therapy to the AYA population; many of these programs are located in pediatric hospitals. Outcomes of AYA patients on pediatric protocols are generally superior to those on adult protocols. Little is understood about the impact of care within a pediatric environment for surgical care of young adults. METHODS: A retrospective institutional review was performed of patients undergoing thoracic metastectomy between 2012 and 2017. Demographics, procedural factors, cost, and outcomes were analyzed. Patients were divided into two groups: > 18 and <18 years. RESULTS: Ninety-one procedures were performed: 61.5% (n = 56) were in patients <18 years old and 38.5% (n = 35) were > 18 years old. The median age was 6.5 years for <18 years old and 28 years for > 18 years old. Older patients had a significantly longer operative time on thoracoscopic cases; 91 versus 63 minutes. Fifty percent of the > 18 group had > 1 lesion resected compared with one lesion resected in 80.8% in <18 years old. No significant differences were found between the two groups in the duration of chest tube or length of stay. The AYA group demonstrated more "adult type" comorbidities. CONCLUSION: AYA patients have unique developmental and emotional challenges. Surgical intervention in this special population of patients cared for within a pediatric environment shows no significant difference in outcome compared with pediatric patients undergoing the same procedure. AYA patients with "adult type" comorbidities can safely undergo multidisciplinary care including surgery within a pediatric environment without the need to fragment care.

Single-stage embolization with n-butyl cyanoacrylate and surgical resection of venous malformations.

PURPOSE: Sclerotherapy or surgical resection is options for symptomatic venous malformations (VM). Sclerotherapy may require repetitive intervention and resection is often avoided due to operative morbidity. The purpose of this study was to report use of single-stage n-butyl cyanoacrylate glue embolization and surgical resection of focal VM. METHODS: A review of patients with focal VM who underwent glue embolization followed by resection at a single tertiary care vascular malformations center was performed. All embolizations were performed with ultrasound and fluoroscopy under the same anesthetic as resection. Patient characteristics and outcomes were evaluated. RESULTS: Fifteen procedures were performed in 12 patients with a total of 20 VM addressed, as several patients had multiple VM. Mean age was 16 ± 9 years. Malformation locations included scalp, hip, gluteal, labial, toe, finger, face, lip, chest, and foot and size ranged from 1.0 to 10.5 cm. Median (range) of prior sclerotherapy treatments was 3 (0-5) and three patients previously underwent surgical resection. Median blood loss was zero (0-10) mL. Surgical complications occurred after five procedures (33%) including superficial wound dehiscence and cellulitis. No complications required readmission or reoperation. At a median follow up of 195 (103-266) days, no patients have required additional treatment. CONCLUSION: Glue embolization and resection of focal VM of variable size and location appears to have durable results and low surgical morbidity. This single-stage procedure, often performed as an outpatient, may be utilized as upfront treatment for symptomatic malformations or for VM refractory to other treatments.

Cell necrosis, intrinsic apoptosis and senescence contribute to the progression of exencephaly to anencephaly in a mice model of congenital chranioschisis.

Exencephaly/anencephaly is one of the leading causes of neonatal mortality and the most extreme open neural tube defect with no current treatments and limited mechanistic understanding. We hypothesized that exencephaly leads to a local neurodegenerative process in the brain exposed to the amniotic fluid as well as diffuse degeneration in other encephalic areas and the spinal cord. To evaluate the consequences of in utero neural tissue exposure, brain and spinal cord samples from E17 exencephalic murine fetuses (maternal intraperitoneal administration of valproic acid at E8) were analyzed and compared to controls and saline-injected shams (n = 11/group). Expression of apoptosis and senescence genes (p53, p21, p16, Rbl2, Casp3, Casp9) was determined by qRT-PCR and protein expression analyzed by western blot. Apoptosis was measured by TUNEL assay and PI/AV flow cytometry. Valproic acid at E8 induced exencephaly in 22% of fetuses. At E17 the fetuses exhibited the characteristic absence of cranial bones. The brain structures from exencephalic fetuses demonstrated a loss of layers in cortical regions and a complete loss of structural organization in the olfactory bulb, hippocampus, dental gyrus and septal cortex. E17 fetuses had reduced expression of NeuN, GFAP and Oligodendrocytes in the brain with primed microglia. Intrinsic apoptotic activation (p53, Caspase9 and 3) was upregulated and active Caspase3 localized to the layer of brain exposed to the amniotic fluid. Senescence via p21-Rbl2 was increased in the brain and in the spinal cord at the lamina I-II of the somatosensory dorsal horn. The current study characterizes CNS alterations in murine exencephaly and demonstrates that degeneration due to intrinsic apoptosis and senescence occurs in the directly exposed brain but also remotely in the spinal cord.

Intracisternal BioGlue injection in the fetal lamb: a novel model for creation of obstructive congenital hydrocephalus without additional chemically induced neuroinflammation.

OBJECTIVE: The authors hypothesized that new agents such as BioGlue would be as efficacious as kaolin in the induction of hydrocephalus in fetal sheep. METHODS: This study was performed in 34 fetal lambs randomly divided into 2 studies. In the first study, fetuses received kaolin, BioGlue (2.0 mL), or Onyx injected into the cisterna magna, or no injection (control group) between E85 and E90. In the second study, fetuses received 2.0-mL or 2.5-mL injections of BioGlue into the cisterna magna between E85 and E90. Fetuses were monitored using ultrasound to assess lateral ventricle size and progression of hydrocephalus. The fetuses were delivered (E120-E125) and euthanized for histological analysis. Selected brain sections were stained for ionized calcium binding adaptor 1 (Iba1) and glial fibrillary acidic protein (GFAP) to assess the presence and activation of microglia and astroglia, respectively. Statistical comparisons were performed with Student's t-test for 2 determinations and ANOVA 1-way and 2-way repeated measures for multiple determinations. RESULTS: At 30 days after injection, the lateral ventricles were larger in all 3 groups that had undergone injection than in controls (mean diameter in controls 3.76 ± 0.05 mm, n = 5). However, dilatation was greater in the fetuses injected with 2 mL of BioGlue (11.34 ± 4.76 mm, n = 11) than in those injected with kaolin (6.4 ± 0.98 mm, n = 7) or Onyx (5.7 ± 0.31 mm, n = 6) (ANOVA, *p ≤ 0.0001). Fetuses injected with 2.0 mL or 2.5 mL of BioGlue showed the same ventricle dilatation but it appeared earlier (at 10 days postinjection) in those injected with 2.5 mL. The critical threshold of ventricle dilatation was 0.1 for all the groups, and only the BioGlue 2.0 mL and BioGlue 2.5 mL groups exceeded this critical value (at 30 days and 18 days after injection, respectively) (ANOVA, *p ≤ 0.0001). Moderate to severe hydrocephalus with corpus callosum disruption was observed in all experimental groups. All experimental groups showed ventriculomegaly with significant microgliosis and astrogliosis in the subventricular zone around the lateral ventricles. Only kaolin resulted in significant microgliosis in the fourth ventricle area (ANOVA, *p ≤ 0.005). CONCLUSIONS: The results of these studies demonstrate that BioGlue is more effective than Onyx or kaolin for inducing hydrocephalus in the fetal lamb and results in a volume-related response by obstructive space-occupancy without local neuroinflammatory reaction. This novel use of BioGlue generates a model with potential for new insights into hydrocephalus pathology and the development of therapeutics in obstructive hydrocephalus. In addition, this model allows for the study of acute and chronic obstructive hydrocephalus by using different BioGlue volumes for intracisternal injection.

Small bowel-small bowel intussusception with high grade obstruction due to intramural submucosal ileal hamartoma in a 5-year-old child: A case report.

INTRODUCTION: Intussusception is a common cause of emergency in children. We report a unusual case of intestinal obstruction due to small bowel-small bowel intussusception with an intestinal hamartoma as the lead point. PRESENTATION OF THE CASE: A 5 year old boy presented to the ED with worsening abdominal pain, emesis and bloody diarrhea. An abdominal radiograph showed evidence of small bowel obstruction and US confirmed a small bowel-small bowel intussusception with a likely cystic mass as the lead point. Given these findings, surgery was performed and revealed an intestinal hamartoma as a lead point. DISCUSSION: Intussusception in children is mostly idiopathic and usually amenable to reduction by air enema. The presence of a lead point is unusual and usually requires surgical intervention. CONCLUSION: We report an unusual case of intussusception with small bowel obstruction due to intestinal hamartoma, a rare pathologic finding as a lead point for intussusception. Ultrasound was useful for diagnosing the intussusception and confirming the presence of a lead point.

CD200-CD200R imbalance correlates with microglia and pro-inflammatory activation in rat spinal cords exposed to amniotic fluid in retinoic acid-induced spina bifida.

Spina bifida aperta is a congenital malformation characterized by the failure of neural tube closure resulting in an unprotected fetal spinal cord. The spinal cord then undergoes progressive damage, likely due to chemical and mechanical factors related to exposure to the intrauterine environment. Astrogliosis in exposed spinal cords has been described in animal models of spina bifida during embryonic life but its relationship with neuroinflammatory processes are completely unknown. Using a retinoic acid-induced rat model of spina bifida we demonstrated that, when exposed to amniotic fluid, fetal spinal cords showed progressive astrogliosis with neuronal loss at mid-gestation (E15) compared to unexposed spinal cords. The number of microglial cells with a reactive phenotype and activation marker expression increased during gestation and exhibited progressive disruption in the inhibitory immune ligand-receptor system. Specifically we demonstrate down-regulation of CD200 expression and up-regulation of CD200R. Exposed spinal cords demonstrated neuroinflammation with increased tissue water content and cytokine production by the end of gestation (E20), which correlated with active Caspase3 expression in the exposed layers. Our findings provide new evidence that microglia activation, including the disruption of the endogenous inhibitory system (CD200-CD200R), may participate in the pathogenesis of spina bifida through late gestation.

Malignant tumors misdiagnosed as benign vascular anomalies.

BACKGROUND: Malignant soft tissue tumors are rare and difficult to diagnose in children. These can initially be misdiagnosed as benign vascular anomalies. Management of these two conditions differs drastically and delay in diagnosis may impact overall survival. PURPOSE: To predict qualities that may increase the index of suspicion for malignancy in patients presenting with lesions initially considered vascular anomalies. METHODS: A retrospective review at a quaternary hemangioma and vascular malformation center of all patients who presented between 2008 and 2016 with an initial diagnosis of a benign vascular malformation, which on further work-up was noted to be a malignancy. Demographics, clinical presentation, and laboratory and radiologic studies were analyzed. RESULTS: Eleven patients were identified; the median age at presentation was 2 months (0-24years). Ten out of 11 lesions had rapid growth, which prompted biopsy. Pain was an inconsistent finding (36%). Tumor markers were positive in only one case. Median follow-up was 3 years (range 6 months to 8 years); seven patients have no evidence of disease, two patients are under treatment for progression or relapse of disease, and two patients have died. CONCLUSION: Although malignant vascular tumors are rare, a clear index of suspicion needs to be maintained particularly with rapid growth or increasing symptoms. Differentiation of malignant tumor from benign lesions relies on the comprehensive evaluation of clinical manifestations, evolution of the lesion, and abnormal clinical behavior, by an experienced multidisciplinary vascular malformation team. There should be a low threshold for biopsy of unclear vascular lesions.

Sclerotherapy for intramuscular vascular malformations: A single-center experience.

BACKGROUND: Vascular malformations isolated to skeletal muscles are rare and often debilitating due to pain and very challenging to treat. Multi-modal management options include compression garments, medical therapy, sclerotherapy, and surgical resection. METHODS: A retrospective review of patients who underwent sclerotherapy for intramuscular venous malformations (IVM) between 2008 and 2016 was performed. Demographics, indications, and clinical follow-up were analyzed. RESULTS: Twenty patients underwent sclerotherapy for IVM. Six males and 14 females underwent 58 procedures. All patients presented with pain and were treated initially with compression garments. Median age at first treatment was 13years (+/- 5.06years). Initial protocol consisted of 2 sclerotherapy procedures with sodium tetradecyl sulfate (STS) within a 2-3month interval. Median volume of the lesion was 40cm3 (+/- 28.7), mostly located in the lower extremities (15/20). Median number of treatments was 2 (+/- 1.95). Treatment prior to puberty resulted in a median symptom-free time of 4years (+/- 2.18), while after puberty resulted in a symptom-free time of 2years (+/- 2.28). Two patients had an underlying coagulopathy and were admitted for observation and peri-procedural Lovenox. No procedure related complications were noted with a median follow-up of 4years (+/- 2.27). CONCLUSION: IVMs are rare but can be incapacitating secondary to pain. Sclerotherapy is a useful minimally invasive procedure generally requiring at least two consecutive treatments. Treatment of patients prior to puberty appears to provide a more durable result, and surgical resection may be avoided. TYPE OF STUDY: retrospective. LEVEL OF EVIDENCE: IV.

Excessive Reversal of Epidermal Growth Factor Receptor and Ephrin Signaling Following Tracheal Occlusion in Rabbit Model of Congenital Diaphragmatic Hernia.

Congenital diaphragmatic hernia (CDH) causes severe pulmonary hypoplasia from herniation of abdominal contents into the thorax. Tracheal occlusion (TO) for human CDH improves survival, but morbidity and mortality remain high, and we do not fully understand the cellular pathways and processes most severely impacted by CDH and TO. We created a left diaphragmatic hernia (DH) in rabbit fetuses with subsequent TO and collected left lung sections for NextGen mRNA sequencing. DH, TO, and DHTO fetuses had comparable body and organ growth to control except for lower lung weights in DH (p<0.05). Of 13,687 expressed genes, DHTO had 687 differentially expressed genes compared to DH, but no other group-group comparison had more than 10. Considering genes in combination, many of the genes reduced in DH were more highly expressed in DHTO than in control. Benchmarking fetal rabbit lung gene expression to published lung development data, both DH and DHTO lungs were more highly correlated with the gene expression of immature lung. DNA synthesis was upregulated in DHTO compared to DH and ribosome and protein synthesis pathways were downregulated. DH reduced total and epithelial cell proliferation by half and two-thirds respectively, and DHTO increased proliferation by 2.5 and 3.4-fold respectively. Signaling pathways downregulated by DH and upregulated in DHTO were epidermal growth factor receptor signaling, ephrin signaling, and cell migration; however, levels of ephrin and EGFR signaling in DHTO exceeded that of control. Identification and inhibition of the ligands responsible for this dysregulated signaling could improve lung development in CDH.

Management of fetal teratomas.

Fetal teratomas are the most common tumors diagnosed prenatally. The majority of these tumors are benign and cured by complete resection of the mass during the neonatal period. Prenatal diagnosis has improved the perinatal management of these lesions and especially for the teratomas that might benefit from fetal intervention. A comprehensive prenatal evaluation including conventional ultrasounds, Doppler, echocardiography and fetal MRI, is essential for an effective counseling and perinatal management. Antenatal counseling helps the parents to better understand the natural history, fetal intervention, and perinatal management of these tumors, which differ dramatically depending on their size and location. Fetal surgical debulking improves survival in cases of sacrococcygeal teratoma with cardiac decompensation. Additionally, the use of an EXIT procedure reduces the morbidity and mortality if a complicated delivery in cases of cervical and mediastinal teratomas. Here, we offer an overview of all fetal teratomas and their recommended management, with emphasis on in utero treatment options.