Pediatric Undifferentiated Pleomorphic Sarcoma of the Cecum.

Background: Undifferentiated pleomorphic sarcoma (UPS) is a high-grade neoplasm typically diagnosed in older adults and localized to the extremities or retroperitoneum. Because of poor response to therapy and high rates of recurrence, this neoplasm is associated with a poor prognosis. Case Report: A 12-year-old female presented with weight loss, abdominal pain, fatigue, and diarrhea. She was profoundly anemic with occult blood-positive stools. On endoscopy, a fungating cecal mass was biopsied and diagnosed as malignant sarcomatoid neoplasm. The neoplasm was resected with clear margins during subsequent surgery, and on final pathology was diagnosed as UPS. A suspicious lung nodule was also removed via video-assisted thoracoscopic surgery and found to be a granuloma positive for Histoplasma capsulatum for which the patient received antifungal therapy. The patient did not receive additional chemotherapy or radiotherapy and was doing well without signs of recurrence at 12 months postresection. Conclusion: This report of cecal UPS in a 12-year-old is rare because of the patient's age and tumor location. We have identified only 2 other case reports of pediatric gastrointestinal UPS. This case illustrates the need for a broad differential and prompt workup in pediatric patients presenting with weight loss and abdominal complaints. More information regarding the management and outcomes in cases of gastrointestinal UPS is needed to assist providers in determining the best treatment course and to allow for better prognostication.

Drain options after vertebral body tethering.

PURPOSE: Since the introduction of vertebral body tethering (VBT) for adolescent idiopathic scoliosis (AIS), a variety of post-operative chest drainage systems have been utilized. Most surgeons use formal chest tubes with a Pleur-evac, while others use smaller bulb suction drains (e.g., Blake drain). In addition, some centers utilize pleural closure. This multicenter study evaluates whether drain type or pleural closure impact perioperative and 90 day complication rates. METHODS: A retrospective review was conducted from three institutions with established VBT programs. All preoperative, perioperative and 90 day postoperative data were analyzed to determine differences in outcomes between three cohorts: standard chest tube (SCT), standard chest tube with pleural closure (SCTPC) and 10 French Bulb drain (BD). RESULTS: 104 patients were identified for the study. 57 SCT, 25 SCTPC and 22 BD. All data are listed in order: SCT, SCTPC, BD. Length of stay (3.7, 4.3, 3.0 days) was less in the BD group (p = 0.009); post-operative drainage (460, 761, 485 cc) was less in the SCT and BD groups (p < 0.001); intra-operative estimated blood loss (EBL) 146, 382, 64 cc was less in the BD group (p < 0.001). No significant difference in number of days (3.2, 3.2, and 2.8 days) drainage was in place, groups (p = 0.311). Complication profile was similar with 2 chest tube reinsertions in the SCT and one hemothorax that resolved spontaneously in BD group. CONCLUSIONS: In this series of 104 patients, SCT, SCTPC and BD all had a similar safety profile. All three methods were safe and effective in managing post-operative chest drainage after thoracic VBT. In the series, BD group had significantly shorter LOS than both groups that used chest tubes. LEVEL OF EVIDENCE: Level III, Retrospective cohort study.

A pediatric surgeon's dilemma: does cholecystectomy improve symptoms of biliary dyskinesia?

BACKGROUND: Biliary dyskinesia (BD) is a well-established gallbladder pathology in adult patients and rates of cholecystectomy for BD continue to rise in the United States. Many pediatric patients with vague abdominal pain of variable duration are evaluated for biliary dyskinesia. It remains unknown which cohort of pediatric patients diagnosed with BD are most likely to have sustained improvement in symptoms following laparoscopic cholecystectomy. We aimed to determine whether cholecystectomy resulted in symptom relief and led to a reduction in the number of medical visits related to gastrointestinal (GI) symptoms after surgery. METHODS: We performed a multi-institution retrospective review of all children < 18 years of age who underwent laparoscopic cholecystectomy for BD between January 2013 and April 2018 in our hospital system. GI symptoms and clinical visits related to a GI complaint were assessed preoperatively. Patients were followed for 2 years after surgery. At 6 months and 2 years postoperatively, symptoms and the rate of medical visits related to a GI complaint were quantified and compared to the preoperative values. RESULTS: In total, 45 patients met our inclusion criteria. Of these, 82% of patients were female. The average age was 14 years old (± 2.6) and 56% of patients met the criteria for being overweight or obese. The mean gallbladder ejection fraction was 13% (± 10.8). All patients had abdominal pain, 82% (37/45) presented with nausea, and 51% (23/45) presented with post-prandial pain. Six months postoperatively, 58% of patients experienced resolution of their abdominal pain which decreased to 38% of patients after 2 years. Similarly, 59% had resolution of their nausea at 6 months compared to 43% at 2 years, and 100% had resolution of their post-prandial pain at 6 months compared to 91% at 2 years. The total number of clinical visits related to a GI complaint decreased from 2.6 (± 2.4) preoperatively to 1.0 (± 1.3) within 6 months postoperatively. When followed to 2 years postoperatively, the 6-month rate of clinical visits related to a GI complaint decreased from a mean of 2.6 preoperatively to 0.71 following surgery. CONCLUSIONS: Following cholecystectomy, we observed a high percentage of durable symptom resolution in those patients with BD who presented with post-prandial pain. Patients with non-food-related abdominal pain, with or without nausea and vomiting, had a lower rate of symptom resolution after surgery and the rate declined with time. For patients without post-prandial pain, evaluation and treatment of alternative sources of pain should be considered prior to surgery. Regardless of their presenting symptoms, patients who underwent surgery for BD had fewer clinical GI-related visits after surgery. However, no specific gallbladder ejection fraction or symptom alone was predictive of a lower rate of clinical visits postoperatively.

Surgical Safety Checklists in Children's Surgery: Surgeons' Attitudes and Review of the Literature.

INTRODUCTION: Surgical safety checklists (SSCs) aim to create a safe operating room environment for surgical patients. Provider attitudes toward checklists affect their ability to prevent harm. Pediatric surgeons' perceptions surrounding SSCs, and their role in improving patient safety, are unknown. METHODS: American Pediatric Surgical Association members conducted an online survey to evaluate the use of and attitudes toward SSCs. The survey measured surgeons' perceptions of checklists, including the components that make them effective and barriers to participation. To better evaluate the available data on SSCs, the authors performed a systematic literature review on the use of SSCs with a focus on pediatric studies. RESULTS: Of the 353 survey respondents, 93.6% use SSCs and 62.6% would want one used in their own child's operation, but only 54.7% felt that checklists improve patient safety. Reasons for checklist skepticism included the length of the checklist process, a distraction from thoughtful patient care, and lack of data supporting use. Literature review shows that checklists improve communication, promote teamwork, and identify errors, but do not necessarily decrease morbidity. Staff perception is a major barrier to implementation. CONCLUSIONS: Almost all pediatric surgeons participate in SSCs at their institutions, but many question their benefit. Better pediatric surgeon engagement in checklist use is needed to change the safety culture, improve operating room communication, and prevent harm.

Torsion of a giant mesocolic lipoma in a child with Bannayan-Riley-Ruvalcaba syndrome.

A 6-year-old boy with Bannayan-Riley-Ruvalcaba syndrome (BRRS) presented to the emergency department with periumbilical abdominal pain for 12 h. A contrast-enhanced abdominal and pelvis CT examination revealed significant interval change in the size and appearance of a previously seen hypoattenuating right mesocolic fatty mass suggestive for lipoma, first observed 5 months prior. This lesion demonstrated new enhancing internal septations, a thickened capsule, interval development of adjacent mesenteric fat stranding and engorgement of the mesenteric vessels. Given the short follow-up interval and acute clinical presentation, imaging findings were suggestive for torsion. We present this case for the unusual imaging findings as well as to highlight the differential diagnosis for abdominal fat containing lesions by imaging in patients with BRRS and other hamartomatous syndromes.

Use of manipulated stem cells for prenatal therapy.

Prenatal stem cell therapy has broad potential for therapeutic application. "Stem cells" of interest include multipotent adult-derived stem cells, cord blood, amniotic fluid, or fetal stem cells, and embryonic or induced pluripotent stem cells. Potential manipulations of stem cells prior to their administration may include harvest, processing, enrichment, expansion, and genetic transduction. A complete description of the methodology related to all of the above is well beyond the scope of this chapter. In the interest of practical application and proven efficacy, we limit our description to adult-derived hematopoietic stem cells (HSCs) and their application to in utero transplantation with or without HSC-targeted gene transfer.

Animal models for prenatal gene therapy: rodent models for prenatal gene therapy.

Fetal gene transfer has been studied in various animal models, including rabbits, guinea pigs, cats, dogs, and nonhuman primate; however, the most common model is the rodent, particularly the mouse. There are numerous advantages to mouse models, including a short gestation time of around 20 days, large litter size usually of more than six pups, ease of colony maintenance due to the small physical size, and the relatively low expense of doing so. Moreover, the mouse genome is well defined, there are many transgenic models particularly of human monogenetic disorders, and mouse-specific biological reagents are readily available. One criticism has been that it is difficult to perform procedures on the fetal mouse with suitable accuracy. Over the past decade, accumulation of technical expertise and development of technology such as high-frequency ultrasound have permitted accurate vector delivery to organs and tissues. Here, we describe our experiences of gene transfer to the fetal mouse with and without ultrasound guidance from mid to late gestation. Depending upon the vector type, the route of delivery and the age of the fetus, specific or widespread gene transfer can be achieved, making fetal mice excellent models for exploratory biodistribution studies.

Early delivery as an alternative management strategy for selected high-risk fetal sacrococcygeal teratomas.

BACKGROUND: Large, prenatally diagnosed sacrococcygeal teratomas (SCTs) present a formidable challenge because of their unpredictable growth and propensity for complications. In our experience, even with aggressive serial imaging, many fetuses have died under a policy of "watchful waiting." We propose "early delivery" as the best option for selected cases of high-risk fetal SCT. METHODS: The medical charts of all fetuses with SCT followed up at our institution and delivered before 32 weeks of gestation were reviewed for radiologic findings, fetal interventions, delivery information, perinatal inpatient course, and autopsy or discharge report. RESULTS: Between 1996 and 2009, excluding those that underwent fetal surgery, 9 patients with fetal SCT were delivered before 32 weeks of gestation. Four had type I tumors, and 5 had type II tumors. Of the 9 fetuses, 4 survived the neonatal period. The only surviving patient delivered before 28 weeks underwent an ex utero intrapartum therapy procedure. CONCLUSIONS: A significant number of pregnancies complicated by high-risk SCT will manifest signs of fetal or maternal decompensation, or both, between 27 and 32 weeks of gestation. In the absence of fulminant hydrops, preemptive early delivery can be associated with surprisingly good outcomes in appropriately selected fetuses with high-risk SCT.

A tissue engineering approach for prenatal closure of myelomeningocele: comparison of gelatin sponge and microsphere scaffolds and bioactive protein coatings.

Myelomeningocele (MMC) is a common and devastating malformation. As an alternative to fetal surgical repair, tissue engineering has the potential to provide a less invasive approach for tissue coverage applicable at an earlier stage of gestation. We have previously evaluated the use of gelatin hydrogel composites composed of gelatin sponges and sheets as a platform for tissue coverage of the MMC defect in the retinoic acid induced fetal rat model of MMC. In the current study, we compare our previous composite with gelatin microspheres as a scaffold for tissue ingrowth and cellular adhesion within the amniotic fluid environment. We also examine the relative efficacy of various bioactive protein coatings on the adhesion of amniotic fluid cells to the construct within the amniotic cavity. We conclude from this study that gelatin microspheres are as effective as gelatin sponges as a scaffold for cellular ingrowth and amniotic fluid cell adhesion and that collagen type I and fibronectin coatings enhance amniotic fluid cell adhesion to the gelatin-based scaffolds. These findings support the potential for the development of a tissue-engineered injectable scaffold that could be applied by ultrasound-guided injection, much earlier and less invasively than sponge or sheet-based composites.

Predicting the severity of congenital high airway obstruction syndrome.

BACKGROUND: Congenital high airway obstruction syndrome (CHAOS) is caused by complete or near-complete obstruction of the fetal airway. Obstruction sets in motion a sequence of events that can ultimately lead to fetal demise. However, on rare occasions in utero airway decompression occurs, reversing syndromic findings and improving the prognosis. In our relatively large series of CHAOS patients, we have observed a spectrum of clinical severity. The aim of this study was to identify the prenatal characteristics of CHAOS predictive of a milder postnatal course. METHODS: The medical charts of all fetuses observed at our institution with the diagnosis of CHAOS were reviewed for radiologic findings, delivery information, perinatal course, autopsy or discharge report, and long-term follow-up. RESULTS: Between 1996 and 2008, 12 fetuses with CHAOS were identified. Four fetuses had no evidence of hydrops on initial imaging. Of the 8 fetuses displaying hydrops, 3 were terminated, 2 died in utero, and 1 with multiple anomalies died at birth. Six fetuses were delivered via the ex utero intrapartum therapy procedure for attempted salvage, and 5 of the 6 survived the neonatal period including all 4 fetuses without hydrops. Serial prenatal imaging demonstrated less severe signs of CHAOS in 3 fetuses, and in 2 of them, direct laryngoscopy revealed a tiny opening in the airway. All 3 fetuses that showed improvement on serial imaging survived the neonatal period and were discharged home by 2-10 weeks of age. CONCLUSIONS: Although the natural history of CHAOS is variable, trends in prenatal ultrasound findings are highly predictive of postnatal outcome and are a valuable guide to prenatal counseling.

Stem cell and genetic therapies for the fetus.

Advances in prenatal diagnosis have led to the prenatal management of a variety of congenital diseases. Although prenatal stem cell and gene therapy await clinical application, they offer tremendous potential for the treatment of many genetic disorders. Normal developmental events in the fetus offer unique biologic advantages for the engraftment of hematopoietic stem cells and efficient gene transfer that are not present after birth. Although barriers to hematopoietic stem cell engraftment exist, progress has been made and preclinical studies are now underway for strategies based on prenatal tolerance induction to facilitate postnatal cellular transplantation. Similarly, in-utero gene therapy shows experimental promise for a host of diseases and proof-in-principle has been demonstrated in murine models, but ethical and safety issues still need to be addressed. Here we review the current status and future potential of prenatal cellular and genetic therapy.

Prenatal stem cell transplantation and gene therapy.

At the present time, the most likely and eminent application of stem cell therapy to the fetus is in utero hematopoietic stem cell transplantation (IUHCT), and this stem cell type will be discussed as a paradigm for all prenatal stem cell therapy. The authors feel that the most likely initial application of IUHCT will use adult HSC derived from bone marrow (BM) or peripheral blood (PB), and will focus this article on this specific approach. The article also reviews the experimental data that support the capacity of IUHCT to induce donor-specific tolerance.