Evaluation of Postoperative Outcomes After Enterostomy Closure in Low Body Weight Infants: A Multi-Center Retrospective Analysis.

BACKGROUND: The minimum weight for enterostomy closure (EC) in infants remains debated with the current acceptable cut-off of >2 kg. As enterostomy-related complications or high enterostomy output (>30cc/kg/d) may prohibit a premature infant from reaching 2 kg, additional data is needed to evaluate the safety of EC in infants <2 kg. The objective of this study was to evaluate postoperative outcomes in low body weight (<2 kg) infants undergoing EC compared to larger infants. METHODS: We performed a multi-center retrospective analysis from 1/1/2012-12/31/2022 of all infants (age <1 year) who were <4 kg at time of EC. Primary outcomes included postoperative complications and 30-day mortality. Non-parametric analysis was performed using the Kruskal-Wallis one-way analysis of variance and chi-square tests. Univariable logistic regression was performed to identify factors associated with postoperative complications. RESULTS: Of 92 infants, 15 infants (16.3%) underwent EC at <2 kg, 16 (17.4%) at 2-2.49 kg, 31 (33.7%) at 2.5-2.99 kg, and 30 (32.6%) at ≥3 kg. Infants <2 kg at time of EC exhibited higher rates of hyperbilirubinemia (P = .030), neurologic comorbidities (P = .030), and high enterostomy output (P = .041). There was no difference in postoperative complications (P = .460) or 30-day mortality (P = .460) between the <2 kg group and larger weight groups. Low body weight was not associated with an increased risk for developing a postoperative complication (OR: 1.001, 95% CI: 1.001-1.001; P = .032). CONCLUSION: Our findings suggest that EC in infants <2 kg may be safe with comparable postoperative outcomes to larger weight infants. Thus, the timing of EC should be based on the infant's physiologic status, in contrast to a predetermined minimum weight cut-off.

Differential RNA Expression Between Metastatic and Primary Neuroblastoma Cells.

INTRODUCTION: Neuroblastoma (NB) is the most common extra-cranial malignancy in children. Poor survival in high-risk NB is attributed to recurrent metastatic disease. To better study metastatic disease, we used a novel mouse model to investigate differential gene expression between primary tumor cells and metastatic cells. We hypothesized that metastatic NB cells have a different gene expression profile from primary tumor cells and cultured cells. METHODS: Using three human NB cell lines (NGP, CHLA255, and SH-SY5Y), orthotopic xenografts were established in immunodeficient nod/scid gamma mice via subcapsular renal injection. Mice were sacrificed and NB cells were isolated from the primary tumor and from sites of metastasis (bone marrow, liver). RNA sequencing, gene set analysis, and pathway analysis were performed to identify differentially expressed genes and molecular pathways in the metastatic cells compared to primary tumor cells. RESULTS: There were 266 differentially expressed genes in metastatic tumor cells (bone marrow and liver combined) compared to primary tumor cells. The top upregulated gene was KCNK1 and the top downregulated genes were PDE7B and NEBL. Top upregulated pathways in the metastatic cells were involved in ion transport, cell signaling, and cell proliferation. Top downregulated pathways were involved in DNA synthesis, transcription, and cellular metabolism. CONCLUSIONS: In metastatic NB cells, our study identified the upregulation of biologic processes involved in cell cycle regulation, cell proliferation, migration, and invasion. Ongoing studies aim to validate downstream translation of these genomic alterations, as well as target these pathways to more effectively suppress and inhibit recurrent metastatic disease in NB.

Management of undifferentiated embryonal sarcoma of the liver: A Pediatric Surgical Oncology Research Collaborative study.

BACKGROUND: Undifferentiated embryonal sarcoma of the liver (UESL) is a rare tumor for which there are few evidence-based guidelines. The aim of this study was to define current management strategies and outcomes for these patients using a multi-institutional dataset curated by the Pediatric Surgical Oncology Research Collaborative. METHODS: Data were collected retrospectively for patients with UESL treated across 17 children's hospitals in North America from 1989 to 2019. Factors analyzed included patient and tumor characteristics, PRETEXT group, operative details, and neoadjuvant/adjuvant regimens. Event-free and overall survival (EFS, OS) were the primary and secondary outcomes, respectively. RESULTS: Seventy-eight patients were identified with a median age of 9.9 years [interquartile range [IQR): 7-12]. Twenty-seven patients underwent resection at diagnosis, and 47 patients underwent delayed resection, including eight liver transplants. Neoadjuvant chemotherapy led to a median change in maximum tumor diameter of 1.6 cm [IQR: 0.0-4.4] and greater than 90% tumor necrosis in 79% of the patients undergoing delayed resection. R0 resections were accomplished in 63 patients (81%). Univariate analysis found that metastatic disease impacted OS, and completeness of resection impacted both EFS and OS, while multivariate analysis revealed that R0 resection was associated with decreased expected hazards of experiencing an event [hazard ratio (HR): 0.14, 95% confidence interval (CI): 0.04-0.6]. At a median follow-up of 4 years [IQR: 2-8], the EFS was 70.0% [95% CI: 60%-82%] and OS was 83% [95% CI: 75%-93%]. CONCLUSION: Complete resection is associated with improved survival for patients with UESL. Neoadjuvant chemotherapy causes minimal radiographic response, but significant tumor necrosis.

A Multi-Institutional Study Comparing Stoma Location in Neonates With Intestinal Perforation.

INTRODUCTION: Neonates with intestinal perforation often require laparotomy and intestinal stoma creation, with the stoma placed in either the laparotomy incision or a separate site. We aimed to investigate if stoma location is associated with risk of postoperative wound complications. METHODS: A multi-institutional retrospective review was performed for neonates ≤3 mo who underwent emergent laparotomy and intestinal stoma creation for intestinal perforation between January 1, 2009 and April 1, 2021. Patients were stratified by stoma location (laparotomy incision versus separate site). Outcomes included wound infection/dehiscence, stoma irritation, retraction, stricture, and prolapse. Multivariable regression identified factors associated with postoperative wound complications, controlling for gestational age, age and weight at surgery, and diagnosis. RESULTS: Overall, 79 neonates of median gestational age 28.8 wk (interquartile range [IQR]: 26.0-34.2 wk), median age 5 d (IQR: 2-11 d) and median weight 1.4 kg (IQR: 0.9-2.42 kg) had perforated bowel from necrotizing enterocolitis (40.5%), focal intestinal perforation (31.6%), or other etiologies (27.8%). Stomas were placed in the laparotomy incision for 41 (51.9%) patients and separate sites in 38 (48.1%) patients. Wound infection/dehiscence occurred in 7 (17.1%) neonates with laparotomy stomas and 5 (13.2%) neonates with separate site stomas (P = 0.63). There were no significant differences in peristomal irritation, stoma retraction, or stoma stricture between the two groups. On multivariable regression, separate site stomas were associated with increased likelihood of prolapse (odds ratio 6.54; 95% confidence interval: 1.14-37.5). CONCLUSIONS: Stoma incorporation within the laparotomy incision is not associated with wound complications. Separate site stomas may be associated with prolapse. Patient factors should be considered when planning stoma location in neonates undergoing surgery for intestinal perforation.

The First Generation of Asian American Pediatric Surgical Trainees in North America.

INTRODUCTION: Pediatric surgical trainees come from diverse races and ethnicities. However, Asian-Americans (AAs) including West, South, and East Asians may represent a unique group of individuals. We sought to identify any unique challenges and experiences. METHODS: Pediatric surgical trainees were identified from, "The Genealogy of North American Pediatric Surgery: From Ladd to Now" and "Celebrating 50 Years: Canadian Association of Paediatric Surgeons/Association Canadienne de Chirurgie Pediatrique". A database was compiled, and AAs identified who completed their pediatric surgical training on or before 1980. Personal interviews and online sources provided further information. RESULTS: Of 635 pediatric surgical trainees in North America (NA) there were 49 AA trainees (7.7%). There was insufficient information for seven, thus leaving 42 (41 male, one female) for review. The region of Asia of origin included 16 East, 16 West, and 10 South. Thirty-seven (88.0%) had moved to NA for training. The most frequent training programs included seven from Toronto and four each at Buffalo, Detroit, Pittsburgh, and Chicago (Children's Memorial). Thirty-five (83%) trainees spent most of their careers in NA while 7 (17%) practiced in their home country. CONCLUSIONS: The first AA pediatric surgical trainees voiced few examples of discrimination but indicated needs to adjust to the NA culture and often confusion over non-Western names. Mentorship was valued and gratitude expressed over the opportunity offered to train in NA. While some had intended to return to their home countries, plans changed due to meeting spouses or political turmoil. Many of those reviewed sought each other out at national meetings.

Precision Oncology in Pediatric Cancer Surgery.

Pediatric precision oncology has provided a greater understanding of the wide range of molecular alterations in difficult-to-treat or rare tumors with the aims of increasing survival as well as decreasing toxicity and morbidity from current cytotoxic therapies. In this article, the authors discuss the current state of pediatric precision oncology which has increased access to novel targeted therapies while also providing a framework for clinical implementation in this unique population. The authors evaluate the targetable mutations currently under investigation-with a focus on pediatric solid tumors-and discuss the key surgical implications associated with novel targeted therapies.

Optimizing the Postoperative Management of Children Undergoing Resection of High-Risk Abdominal Neuroblastoma.

BACKGROUND: Surgical resection is a mainstay of treatment in high-risk neuroblastoma (HR-NB), but there exists wide variability in perioperative management practices. The aim of this study was to evaluate two standardized adult perioperative enhanced recovery practices (ERPs) in pediatric patients undergoing open resection of abdominal HR-NB. METHODS: All patients with abdominal HR-NB surgically resected at a free-standing children's hospital between 12/2010 and 7/2020 were retrospectively reviewed. Perioperative ERPs of interest included avoidance of routine nasogastric tube (NGT) use and the use of neuraxial anesthesia. Primary outcomes included time to enteral intake, urinary catheter use, opioid utilization, and length of stay (LOS). RESULTS: Overall, 37 children, median age 33 months (IQR: 20-48 months), were identified. Avoidance of an NGT allowed for earlier feeding after surgery (P = .03). Neuraxial anesthesia use more frequently required an indwelling urinary catheter (P < .01) for a longer duration (P = .02), with no difference in total opioid utilization (P = .77) compared to patients without neuraxial anesthesia. Postoperative LOS was unaffected by avoidance of routine NGT use (P = .68) or use of neuraxial anesthesia (P = .89). CONCLUSION: Children undergoing open resection of abdominal HR-NB initiated diet sooner when an NGT was not left postoperatively, and the need for a urinary catheter was significantly higher in patients who received neuraxial anesthesia. However, these two ERP components did not decrease postoperative LOS. To optimize the postoperative management of NB patients, postoperative NGTs should be avoided, while the benefit of neuraxial anesthesia is less clear as it necessitates the placement of a urinary catheter without decreasing opioid utilization.

Factors Associated with Postoperative Opioid Use in Adolescents.

BACKGROUND: We aimed to identify factors associated with postoperative prescription opioid use in adolescents. METHODS: Adolescents aged 13-20 years undergoing surgery were prospectively recruited from a children's hospital. Adolescent-parent dyads completed a preoperative survey, measuring clinical and sociodemographic factors, and two postoperative surveys evaluating self-reported opioid use at 30- and 90-days. Poisson regression analysis identified factors associated with the number of pills used within 90-days, adjusting for age, gender, race/ethnicity, surgery type, and pain at discharge. RESULTS: We enrolled 119 adolescents who reported postoperative opioid use following posterior spinal fusion (PSF) (50 %), arthroscopy (23 %), pectus excavatum repair (11 %), tonsillectomy (8 %), and hip reconstruction (7 %). Overall, 81 % of adolescents reported unused opioids. The median pain score at discharge was 7 (IQR:5-8). Adolescents reported using a median of 7 (IQR:2-15) opioid pills, with 20 (IQR:7-30) pills left unused. Compared to all other surgeries, adolescents undergoing PSF reported the highest median pill use (10, IQR:5-29; p = 0.004). Adolescents undergoing tonsillectomy reported the lowest median pill use (1, IQR:0-7; p = 0.03). On regression analysis, older patient age was associated with a 12 % increase in pill use (95 % CI:3%-23 %). Undergoing PSF was associated with a 63 % increase in pill use (95 % CI:15%-31 %). Each additional pain scale point reported at discharge was associated with a 13 % increase in pill use (95 % CI:5%-22 %). CONCLUSIONS: Older age, surgery type, and patient-reported pain at discharge are associated with postoperative prescription opioid use in adolescents. Understanding patient and surgery-specific factors associated with opioid use may guide surgeons to minimize excess opioid prescribing. LEVEL OF EVIDENCE: II.