Critical elements of pediatric neuroblastoma surgery.

Neuroblastoma (NB) is the most common solid extracranial malignancy of childhood with an incidence of 1 per 100,000 in the United States compromising approximately 10 % of childhood cancer. Unfortunately, patients with high-risk NG continue to have long-term survival less than 50 %. Both Children's Oncology Group and the International Society of Paediatric Oncology have demonstrated the important role of surgery in the treatment of high-risk NB. Herein, we compose the results of an extensive literature review as well as expert opinion from leaders in pediatric surgical oncology, to present the critical elements of effective surgery for high-risk neuroblastoma.

Biological Insight and Recent Advancement in the Treatment of Neuroblastoma.

One of the most frequent solid tumors in children is neuroblastoma, which has a variety of clinical behaviors that are mostly influenced by the biology of the tumor. Unique characteristics of neuroblastoma includes its early age of onset, its propensity for spontaneous tumor regression in newborns, and its high prevalence of metastatic disease at diagnosis in individuals older than 1 year of age. Immunotherapeutic techniques have been added to the previously enlisted chemotherapeutic treatments as therapeutic choices. A groundbreaking new treatment for hematological malignancies is adoptive cell therapy, specifically chimeric antigen receptor (CAR) T cell therapy. However, due to the immunosuppressive nature of the tumor microenvironment (TME) of neuroblastoma tumor, this treatment approach faces difficulties. Numerous tumor-associated genes and antigens, including the MYCN proto-oncogene (MYCN) and disialoganglioside (GD2) surface antigen, have been found by the molecular analysis of neuroblastoma cells. The MYCN gene and GD2 are two of the most useful immunotherapy findings for neuroblastoma. The tumor cells devise numerous methods to evade immune identification or modify the activity of immune cells. In addition to addressing the difficulties and potential advancements of immunotherapies for neuroblastoma, this review attempts to identify important immunological actors and biological pathways involved in the dynamic interaction between the TME and immune system.

Laser Ablation of Pilonidal Sinus Disease: A Pilot Study.

BACKGROUND: Pilonidal disease is classically treated with wide local excision, although a number of minimally invasive approaches are currently under investigation. We aimed to determine the safety and feasibility of laser ablation of pilonidal sinus disease. IMPACT OF INNOVATION: Laser ablation provides a minimally invasive means of obliterating pilonidal sinus tracts without a need for excessive tract dilation. Laser ablation can be performed more than once on the same patient if necessary. TECHNOLOGY MATERIALS AND METHODS: This technique uses the NeoV V1470 Diode Laser (neoLaser Ltd, Caesarea, Israel) with a 2-mm probe. We performed laser ablation in adults and pediatric patients. PRELIMINARY RESULTS: We performed 27 laser ablation procedures in 25 patients, with a median operative time of 30 minutes. Eighty percent of patients reported either no pain or mild pain at the 2-week postoperative visit. The median time to return to work or school was 3 days. Eighty-eight percent of patients reported being satisfied or very satisfied with the procedure at their most recent follow-up (median, 6 mo). Eighty-two percent of patients were healed at 6 months. CONCLUSIONS AND FUTURE DIRECTIONS: Laser ablation of pilonidal disease is safe and feasible. Patients experienced short recovery time and reported low levels of pain and high levels of satisfaction.

Prophylactic antireflux procedures are not necessary in neurologically impaired children undergoing gastrostomy placement.

PURPOSE: Fundoplication is frequently used in children with neurologic impairment even in the absence of reflux due to concerns for future gastric feeding intolerance, but supporting data are lacking. We aimed to determine the incidence of secondary antireflux procedures (fundoplication or gastrojejunostomy (GJ)) post gastrostomy tube (GT) placement in children with and without neurologic impairment. METHODS: Children under 18 undergoing a GT placement without fundoplication between 2010 and 2020 were identified utilizing the PearlDiver Mariner national patient claims database. Children with a diagnosis of cerebral palsy or a degenerative neurologic disease were identified and compared to children without these diagnoses. The incidence of delayed fundoplication or conversion to GJ were compared utilizing Kaplan-Meier and Cox proportional hazards regression analyses. RESULTS: A total of 14,965 children underwent GT placement, of which 3712 (24.8%) had a diagnosis of neurologic impairment. The rate of concomitant fundoplication was significantly higher among children with a diagnosis of neurologic impairment as compared to those without (9.3% vs 6.4%, p < 0.001). While children with neurologic impairment had a significantly higher rate of fundoplication or GJ conversion at 5 years compared to children without (12.6% [95% confidence interval (CI): 11.4%-13.8%] vs 8.6% [95% CI 8.0%-9.2%], p < 0.001), the overall incidence remained low. CONCLUSION: Although children with neurologic impairment have a higher rate of requiring an antireflux procedure or GJ conversion than other children, the overall rate remains less than 15%. Fundoplication should not be utilized in children without clinical reflux on the basis of neurologic impairment alone.

A shortened course of Amoxicillin/Clavulanate is the preferred antibiotic treatment after surgery for perforated appendicitis in children.

BACKGROUND/PURPOSE: Despite evidence supporting short course outpatient antibiotic treatment following appendectomy for perforated appendicitis, evidence of real-world implementation and consensus for antibiotic choice is lacking. We therefore aimed to compare outpatient antibiotic treatment regimens in a national cohort. METHODS: We identified children who underwent surgery for perforated appendicitis between 2010 and 2018 using the PearlDiver database and compared 45-day disease-specific readmission between children who received shortened (5-8 days) versus prolonged (10-14 day) total antibiotic courses (inpatient intravenous and/or oral) completed with outpatient Amoxicillin/Clavulanate versus Ciprofloxacin/Metronidazole, and compared antibiotic type (5-14 days) to each other. RESULTS: 4916 children were identified, 2001 (90.0%) treated with Amoxicillin/Clavulanate (5-14 days), 381 (19.0%) with shortened (5-8 days), 1464 (73.2%) with prolonged (10-14 days) courses. 222 (10.0%) were treated with Ciprofloxacin/Metronidazole, 44 (19.8%) with shortened, 174 (78.4%) with prolonged courses. Freedom from readmission was not different between prolonged and shortened course whether they received Amoxicillin/Clavulanate (adjusted hazard ratio [AHR] 1.54, 95%CI 0.95-2.5) or Ciprofloxacin/Metronidazole (AHR 3.49, 95%CI 0.45-27.3). Antibiotic type did not affect readmission rate (Amoxicillin/Clavulanate versus Ciprofloxacin/Metronidazole, AHR 1.21, 95%CI 0.71-2.05). CONCLUSION: Prolonged antibiotic regimens are routinely prescribed despite evidence suggesting shorter courses and antibiotic choice are not associated with greater treatment failure. As it is better tolerated, we recommend a shortened course of Amoxicillin/Clavulanate for oral management of perforated appendicitis. STUDY DESIGN: Retrospective. LEVEL OF EVIDENCE: Level III.

Minimally Invasive Approaches and Use of a Patch Are Not Associated with Increased Recurrence Rates After Congenital Diaphragmatic Hernia Repair.

Background: Minimally invasive surgery (MIS) is increasingly used for repair of congenital diaphragmatic hernia (CDH). Reported recurrence after MIS repair varies and is limited by short follow-up and low volume. Our objective was to compare recurrence after MIS versus open repair of CDH. Materials and Methods: Infants who underwent CDH repair between 2010 and 2020 were identified using the PearlDiver Mariner database, a national patient claims data set allowing longitudinal follow-up of patients across systems. Kaplan-Meier analysis and Cox proportional hazards regression models were used to evaluate the association of surgical approach (MIS versus open) and use of a patch with time to recurrence while adjusting for comorbidities (congenital heart disease and pulmonary hypertension) and length of stay (LOS). Results: In a cohort of 629 infants, 25.6% (n = 161) underwent MIS repair with a median follow-up of 4.8 years and recurrence rate of 38.6% (n = 243). Rates of recurrence after MIS repair were lower than open (5 years: 38.6% versus 44.3%; P = .03) and higher with use of patch (5 years: 60.1% versus 40.1%; P = .02). After adjustment for comorbidities and LOS as a proxy for patient complexity, there was no significant difference in recurrence based on approach (adjusted hazard ratio [aHR]: 0.79; confidence interval [95% CI]: 0.57-1.10; P = .16) or use of patch (aHR: 1.22; 95% CI: 0.83-1.79; P = .32). Conclusions: Recurrence rates after repair of CDH were not different based on surgical approach or use of patch after adjustment. Previous data were likely biased by patient complexity, and surgeons should consider these factors in determining approach.

Microbial-Derived Toll-like Receptor Agonism in Cancer Treatment and Progression.

Toll-like receptors (TLRs) are typical transmembrane proteins, which are essential pattern recognition receptors in mediating the effects of innate immunity. TLRs recognize structurally conserved molecules derived from microbes and damage-associated molecular pattern molecules that play an important role in inflammation. Since the first discovery of the Toll receptor by the team of J. Hoffmann in 1996, in Drosophila melanogaster, numerous TLRs have been identified across a wide range of invertebrate and vertebrate species. TLR stimulation leads to NF-κB activation and the subsequent production of pro-inflammatory cytokines and chemokines, growth factors and anti-apoptotic proteins. The expression of TLRs has also been observed in many tumors, and their stimulation results in tumor progression or regression, depending on the TLR and tumor type. The anti-tumoral effects can result from the activation of anti-tumoral immune responses and/or the direct induction of tumor cell death. The pro-tumoral effects may be due to inducing tumor cell survival and proliferation or by acting on suppressive or inflammatory immune cells in the tumor microenvironment. The aim of this review is to draw attention to the effects of TLR stimulation in cancer, the activation of various TLRs by microbes in different types of tumors, and, finally, the role of TLRs in anti-cancer immunity and tumor rejection.

Long-Term Recurrence Risk Following Pleurectomy or Pleurodesis for Primary Spontaneous Pneumothorax.

INTRODUCTION: Recurrent primary spontaneous pneumothorax (PSP) is often managed with a wedge resection (or blebectomy) and either pleurectomy or pleurodesis. There is a conflicting data regarding which approach is superior to reduce recurrence. Our objective is to evaluate the long-term recurrence rates following pleurectomy versus mechanical pleurodesis for recurrent PSP. METHODS: The PearlDiver Mariner Patient Claims Database was queried for patients aged 10-25 who were presented with PSP and underwent either pleurectomy or mechanical pleurodesis between 2010 and 2020. The primary outcome was recurrence and secondary outcomes included 30-day opioid prescriptions, pain diagnoses, and reimbursement. Kaplan-Meier analysis and Cox proportional hazards regression models were used with adjustment for age and sex. RESULTS: Of 18,955 patients presenting with PSP, 5.1% (n = 968) were managed operatively with either pleurectomy (18.3%, n = 177) or mechanical pleurodesis (81.7%, n = 791). There was no difference in the rate of recurrence between pleurectomy and mechanical pleurodesis (5-year risk of recurrence: 25.8% versus 26.5%, adjusted hazard ratio (HR) = 1.12 [95% confidence interval (CI): 0.79, 1.58]). Furthermore, there was no difference in rate of outpatient opioid prescription (49.2% versus 52.8%, P = 0.58) or pain diagnoses (22.0% versus 22.8%, P = 0.46) between pleurectomy and mechanical pleurodesis, respectively. The median reimbursement was higher following pleurectomy as compared to mechanical pleurodesis ($14,040 versus $5,811, P = 0.02). CONCLUSIONS: There is no significant difference in recurrence based on type of procedure performed for recurrent primary spontaneous pneumothorax. However, reimbursement is higher following pleurectomy. Given the similar outcomes but higher cost, we recommend mechanical pleurodesis over pleurectomy for recurrent PSP.

Recurrence following laparoscopic repair of bilateral inguinal hernia in children under five.

BACKGROUND: Reported recurrence rates after laparoscopic versus open inguinal hernia repair have been limited to high volume centers with short follow-up. We sought to compare national rates of recurrence after laparoscopic versus open bilateral inguinal hernia repair. METHODS: Children under five who underwent bilateral inguinal hernia repair between 2010 and 2020 were identified using the PearlDiver Mariner database. Time to recurrence was compared using Kaplan Meier analysis and Cox proportional hazards regression models. RESULTS: Hernia recurrence requiring reoperation occurred in 182 (2.2%) of 8,367 children. Rate of recurrence was higher following laparoscopic repair compared to open (1-year: 2.8% vs. 1.5%; 3-year: 3.7% vs. 2.0%; p < 0.01). This difference remained after adjustment for demographic and operative characteristics (adjusted hazard ratio [aHR]: 2.00 [95% confidence interval [CI]: 1.31, 3.05]). CONCLUSIONS: Risk of recurrence was higher after laparoscopic compared to open repair of bilateral inguinal hernia repair in a national cohort of children under age five.

Expression of Immunomodulatory Checkpoint Molecules in Drug-Resistant Neuroblastoma: An Exploratory Study.

Neuroblastoma is a common childhood cancer with poor prognosis when at its advanced stage. Checkpoint molecule inhibition is successful in treating multiple advanced adult cancers. We investigated PD-L1 and other checkpoint molecule expression to determine their roles in drug resistance and usefulness as targets for drug therapy. We developed three doxorubicin-resistant (DoxR) cell lines from parental cell lines. Matrigel in vitro invasion assays were used to compare invasiveness. Western blot assays were used to compare PD-L1 expression. Immuno-oncology checkpoint protein panels were used to compare concentrations of 17 checkpoint molecules both cellular and soluble. PD-L1 and 12 other checkpoint molecules were present in all cell lysates of each cell line without significantly different levels. Three were solubilized in the media of each cell line. PD-L1 is expressed in all DoxR and parental neuroblastoma cells and may be a potential target for drug therapy although its role in drug resistance remains unclear. Benchmarking checkpoint molecules provides the basis for future studies identifying targets for directed therapy and biomarkers for cancer detection or prognosis.

The effect of standardized discharge instructions after gastrostomy tube placement on postoperative hospital utilization.

BACKGROUND/PURPOSE: Gastrostomy tube (GT) placement is a common pediatric procedure with high postoperative resource utilization. We aimed to determine if standardized discharge instructions (SDI) reduced healthcare utilization rates. METHODS: We performed a retrospective cohort study comparing postoperative hospital utilization of patients who underwent initial GT placement pre- and post-SDI protocol implementation from 2014-2019. Statistical analyses included Chi-square tests, multivariable adjusted logistic regression, adjusted Cox proportion hazard regression, and adjusted Poisson regression models when appropriate. RESULTS: 197 patients were included, 102 (51.8%) before and 95 (48.2%) after protocol implementation. On primary analysis, SDI patients did not have significantly different total postoperative hospital utilization events at 30-days (48.0% vs. 38.9%, p = 0.25). On secondary analysis, SDI patients had lower rates of ED (8.4% vs. 19.6%, p = 0.026) and office visits (11.6% vs. 25.5%, p = 0.017) at 30-days. Non-SDIs patients had greater odds of ED visits (OR2.7, 95%CI 1.3-5.9, p = 0.01), office visits (OR3.7, 95%CI 1.7-8.1, p = 0.001) and phone calls (OR2.6, 95%CI 1.2-5.7, p = 0.016) at 1-year. The adjusted hazard ratio was 2.0 (95%CI 1.4-3.0, p < 0.001). Incident rate ratio were 1.8 (95%CI 1.2-2.5, p = 0.002) at 30-days and 1.9 (95%CI 1.5-2.4, p < 0.001) at 1-year post-discharge. CONCLUSIONS: SDIs post-GT placement may reduce multiple aspects of postoperative hospital utilization.

Percutaneous peritoneal drain placement: A pilot study of pediatric surgery simulation-based training for general surgery residents.

INTRODUCTION: General surgery residents often feel unprepared to perform pediatric surgery procedures since case volume and experience may be low. Previously, we successfully implemented a simulation-based training (SBT) module for placement of a silastic silo for gastroschisis. Therefore, we designed a single institution pilot study to assess whether SBT for placement of a percutaneous peritoneal drain for perforated necrotizing enterocolitis (NEC) was feasible and lead to skill acquisition and increased confidence. METHODS: Our newly created NEC module within our pediatric surgery SBT curriculum for general surgery residents was used. Residents completed two simulation sessions three months apart with confidence testing before and after each session. Skill acquisition and performance were assessed using a standardized case scenario and procedure checklist. Changes in residents' confidence and performance were determined using Wilcoxon Signed-Rank Tests. RESULTS: Nine post-graduate-year three general surgery residents completed this curriculum. Following completion, residents reported improved confidence completing each step of the procedure initially (p = 0.005) and at 3 months (p = 0.008) with improved technical scores (p = 0.011). The number of residents deemed proficient significantly improved (p = 0.031). CONCLUSION: Implementation of SBT module for perforated NEC was feasible and improved residents' confidence and proficiency completing the procedure.

Expression of programmed death ligand 1 in drug-resistant osteosarcoma: An exploratory study.

BACKGROUND: Inhibition of the programmed death ligand 1, programmed death 1 pathway has been successfully used for treatment of multiple advanced adult cancers. However, its use in pediatric osteosarcoma is still in its infancy. In this study, we investigated programmed death ligand 1 and other checkpoint molecules' expression to determine the potential usefulness as targets for drug therapy. METHODS: We incubated human wild-type osteosarcoma cells with incremental concentrations of doxorubicin to create a doxorubicin-resistant cell line. Matrigel in vitro invasion assays were used to compare invasiveness. Comparative programmed death ligand 1 expression was evaluated by Western blot assays. An immuno-oncology checkpoint protein panel was used to compare concentrations of 16 other checkpoint molecules. Chi-square tests and Wilcoxon rank-sum tests were used to determine significant differences. RESULTS: A doxorubicin-resistant cell line was successfully created and was significantly more invasive than wild-type cells (0.47 vs 0.07, P < .001). On Western blot assay, doxorubicin-resistant but not wild-type cells expressed programmed death ligand 1. Doxorubicin-resistant cells had significantly higher levels of T-cell immunoglobulin-3 and cluster of differentiation 86 and higher cluster of differentiation 27, cluster of differentiation 40, lymphocyte-activation gene-3, cluster of differentiation 80, programmed death ligand 1, programmed death ligand 2, and inducible T-cell costimulatory expression than wild-type cells. Both lines expressed B- and T-lymphocyte attenuator, cluster of differentiation 28, herpesvirus entry mediator, and programmed death 1. Herpesvirus entry mediator, cluster of differentiation 40, and programmed death ligand 2 were also present in the culture media of both cell lines. CONCLUSION: Doxorubicin-resistant osteosarcoma seems to express higher programmed death ligand 1 than nonresistant wild-type cells. Benchmarking checkpoint molecules may provide the basis for future studies that elucidate pathways of drug resistance and tumor metastasis, biomarkers for cancer prognosis or recurrence, and future targets for directed drug therapy.

Outcomes of Laparoscopic Versus Open Ladd Procedures and Risk Factors for Conversion.

Background: Malrotation is a common congenital anomaly that can lead to bowel obstruction and ischemia if not corrected with a Ladd procedure. Controversy exists between open and laparoscopic approaches. We sought to compare postoperative outcomes and determine risk factors for conversion to an open procedure. Methods: The National Surgical Quality Improvement Program (NSQIP)-Pediatric was used to identify patients undergoing Ladd procedures from 2013 to 2018. Propensity score matching was used to account for differences in patient characteristics between open and laparoscopically treated cohorts. Chi-square tests and adjusted logistic regression analysis were used to determine patient outcomes differences between treatment groups and factors associated with conversion. Results: A total of 2437 patients were identified, 1889 (77.5%) open, 548 (22.5%) laparoscopic, and 193 (35.2%) laparoscopic converted to open. Patients undergoing laparoscopic compared with open procedures had shorter length of stay (5 versus 7 days, P < .001) and lower overall complication rates (13.1% versus 18.1%, P = .025), despite longer operative times (108.9 versus 93.7 minutes, P < .001). Patients requiring conversion were more likely to be younger, have an urgent/emergent case, sepsis/septic shock, and nutritional support requirement. Conclusions: After risk adjustment, laparoscopic Ladd procedure is associated with decreased complications and minimal operative time increases compared with an open approach. Risk factors associated with conversion should be considered during operative planning.

Pediatric Surgery Simulation-Based Training for the General Surgery Resident.

BACKGROUND: Surgical simulation-based training (SBT) can increase resident confidence and improve performance. SBT in pediatric surgery is in its infancy and often geared toward training pediatric surgery fellows. Since case volume for various pediatric surgery-specific procedures can be low based on the rarity of the pathology involved and the level of care provided by the institution, our aim was to create a pediatric surgery simulation-based curriculum for general surgery residents to address this need. MATERIALS AND METHODS: We performed an institutional needs assessment consisting of 4 pediatric surgeons' and 28 general surgery residents' confidence in resident ability to independently perform pediatric surgery-specific tasks and procedures using a Likert-scaled survey. These included the placement of a silastic silo for gastroschisis, a percutaneous drain for perforated necrotizing enterocolitis, and completion of a laparoscopic pyloromyotomy for pyloric stenosis. Models simulating these pathologies and curriculum for performing each procedure were generated. RESULTS: We successfully created a model and SBT curriculum to teach general surgery residents how to place a silastic silo for patients with gastroschisis, a percutaneous drain for patients with perforated necrotizing enterocolitis, and how to complete a laparoscopic pyloromyotomy for patients with pyloric stenosis. These were deemed high fidelity models based on a survey of our pediatric surgeons. CONCLUSIONS: We created a pediatric surgery SBT curriculum for general surgery residents, which can be used to supplement learning of various high-acuity, low-occurrence procedures. Assessment of residents and validation of scores is underway.

Silo placement in gastroschisis: A pilot study of simulation-based training for general surgery residents.

INTRODUCTION: General surgery residents often feel unprepared for rotations on pediatric surgical services as case volume and experience performing pediatric procedures may be inadequate for high acuity, low volume procedures. We designed a single institution pilot study to assess whether simulation-based training (SBT) for placement of a silastic silo for gastroschisis was feasible and lead to skill acquisition, retention and increased resident confidence. METHODS: We used our newly created gastroschisis module within our pediatric surgery SBT curriculum for general surgery residents. Residents completed two simulation sessions three months apart, completed confidence testing before and after each session, and were assessed using a standardized case scenario and procedure checklist. Wilcoxon Signed-Rank Tests evaluated changes in residents' confidence and performance. RESULTS: Ten post-graduate-year three general surgery residents completed this curriculum. Residents reported improved confidence completing each step of the procedure initially (p=0.008) and at 3 months (p=0.005). They had improved technical scores across all steps of the procedure (p=0.005). The number of residents deemed proficient significantly improved (p=0.008). CONCLUSION: We demonstrated the feasibility of assessing the technical skills of general surgery residents performing a simulated placement of a silastic silo for gastroschisis. Residents' confidence and proficiency improved over the three-month period. STUDY TYPE: Prospective LEVEL OF EVIDENCE: Level II.

Early Diagnosis and Treatment of Chylous Mesenteric Cysts.

Mesenteric cysts are benign congenital cysts typically discovered incidentally during abdominal explorations for other reasons. When feasible, they should be excised to prevent recurrence, bowel obstruction or volvulus, and resulting complications. We present a unique case of an infant, diagnosed prenatally by ultrasound with possible bowel obstruction, found to have micro and macro chylous mesenteric cysts. Although initially asymptomatic with normal abdominal x-ray and discharged on day of life 2, the parents were taught how to recognize symptoms of bowel obstruction. He presented at 1 month with obstructive symptoms, was confirmed to have large mesenteric cystic structures on ultrasound, and was immediately taken to the operating room. Due to the extensive number of cysts and intimate involvement of the largest cyst with the superior mesenteric artery, he was treated with partial excision and observation since resection may have resulted in short gut syndrome. Given a prenatal ultrasound suggestive of mesenteric cysts, we recommend abdominal imaging at birth with close follow-up until the appropriate time for elective resection. When disease is extensive precluding full enucleation and resection, we advocate for enucleation in combination with unroofing of as many cysts as possible followed by postoperative surveillance ultrasounds and family counseling.

Gonadal Tissue Cryopreservation for a Girl With Partial Androgen Insensitivity Syndrome.

Individuals with differences/disorders of sex development (DSD) have increased rates of infertility. For children and youth undergoing prophylactic gonadectomy for malignancy risk, our institution offers gonadal tissue cryopreservation, an experimental technique to preserve fertility cryopotential. An 11-year-old girl with partial androgen insensitivity syndrome presented for evaluation for fertility preservation in the setting of a planned bilateral gonadectomy at an outside institution. At presentation, the patient had begun puberty with an elevated serum androgen level and was experiencing undesired virilization. She expressed a strong female gender identity, an understanding of the various treatment options, and a preference for gonadectomy to prevent further virilization. After thorough counseling with the patient and family in our institution's multidisciplinary DSD clinic, she underwent bilateral gonadectomy with gonadal tissue cryopreservation. Her gonadal pathologic examination demonstrated well-developed peripubertal testes, with present, albeit decreased, numbers of spermatogonial germ cells, decreased Leydig cells, and nonspecific degenerative changes. The patient and her family chose to maintain the cryopreserved tissue for the patient's potential future use. To the best of our knowledge, the present case is the first reported case of gonadal tissue cryopreservation in a patient with partial androgen insensitivity syndrome. Storage of gonadal tissue is a feasible method of germ cell preservation in patients with DSD undergoing gonadectomy, although further research advances are required to facilitate development of this tissue into mature gametes capable of biological fertility.

Laparoscopic unilateral oophorectomy for ovarian tissue cryopreservation in children.

BACKGROUND/PURPOSE: Many survivors of childhood cancer will experience premature gonadal insufficiency or infertility as a consequence of their medical treatments. Ovarian tissue cryopreservation (OTC) remains an experimental means of fertility preservation with few reports focused on the surgical technique and postoperative outcomes for OTC in children. METHODS: This is a single institution, retrospective review of OTC cases from January 2011 to December 2017. Children were eligible for OTC if they had a greater than 80% risk of premature ovarian insufficiency or infertility owing to their anticipated gonadotoxic medical treatment. RESULTS: OTC was performed in 64 patients. Median age was 12 years old (range: 5 months-23 years). Nearly half (48%) of the patients were premenarchal. Laparoscopic unilateral oophorectomy was performed in 84% of patients. There were no surgical complications. In 76% of patients, OTC was performed in conjunction with an ancillary procedure. The majority (96%) of patients were discharged within 24 hours. Median time from operation to medical therapy was six days, with no unanticipated treatments delays attributable to OTC. CONCLUSIONS: Laparoscopic unilateral oophorectomy for OTC can be performed safely, in combination with other ancillary procedures, as an outpatient procedure without delaying medical therapy for children facing a fertility-threatening diagnosis or treatment. LEVEL OF EVIDENCE: IV.

Fertility and hormone preservation and restoration for female children and adolescents receiving gonadotoxic cancer treatments: A systematic review.

BACKGROUND/PURPOSE: The purpose of this systematic review by the American Pediatric Surgical Cancer Committee was to summarize evidence from the current medical literature regarding fertility restoration and hormone replacement for female children and adolescents treated with gonadotoxic treatments. METHODS: Using PRISMA guidelines, questions were addressed by searching Medline, Cochrane, Embase Central and National clearing house databases using relevant search terms. Eligible studies included those that addressed ovarian tissue cryopreservation (OTC), oocyte harvest, ovarian transposition, and ovarian tissue auto-transplantation for females under the age of 20. Four reviewers independently screened studies for eligibility, extracted data and assessed the risk of bias. Study outcomes were summarized in a narrative synthesis. RESULTS: Two thousand two hundred seventy-six studies were identified by database search and manual review and 2185 were eliminated based on defined exclusion criteria. Ninety-one studies served as the basis for the systematic review. There were 1019 patients who underwent OTC with ages ranging from 0.4 to 20.4 years old, with 298 under the age of 13. Twenty patients aged 13-20 years old underwent successful oocyte harvest. Thirty-seven children underwent ovarian transposition as a means of fertility preservation. Eighteen patients underwent auto-transplantation of thawed ovarian cortical tissue that was harvested before the age of 21 years resulting in 10 live births. CONCLUSIONS: Clinically accepted and experimental fertility preservation options such as OTC, oocyte cryopreservation, and ovarian transposition are available to females aged 20 years and younger who are at risk for premature ovarian insufficiency and infertility due to gonadotoxic treatments. There is a large cohort of pediatric-aged patients, with a wide variety of diagnoses and treatments, who have undergone fertility preservation. Currently, fertility and hormone restoration experience for patients who were 20- years of age or younger at the time of fertility preservation remains limited. LEVEL OF EVIDENCE: IV.