Nissen Fundoplication in Infants With Severe Bronchopulmonary Dysplasia: A Propensity-Matched Analysis.

INTRODUCTION: Bronchopulmonary dysplasia (BPD) is a common respiratory morbidity among premature infants. Nissen fundoplication may be performed on infants with BPD to protect the lungs from gastroesophageal reflux-related aspiration, but the indications and benefits associated with fundoplication are not well-defined. This study evaluated associations of Nissen with clinical outcomes in infants with severe BPD (sBPD), using propensity score matching to minimize bias and confounding. METHODS: Infants ≤31 wk gestational age with sBPD (grade 2-3) admitted to a single neonatal intensive care unit (NICU) between January 2016 and October 2021 were included. Patients with sBPD who underwent Nissen fundoplication during initial NICU admission were propensity score-matched at a 1:2 ratio with control patients who did not undergo Nissen (no-Nissen). Outcomes were compared, including time to freedom from respiratory support (defined as ≤2 L nasal cannula), time to initial NICU discharge, and incidence of hospital readmission or death within 1 y postdischarge. RESULTS: After propensity score matching, 18 Nissen infants were compared with 30 no-Nissen infants. The Nissen group trended toward longer time to freedom from respiratory support (median 105 versus 70 d, P = 0.09), and had longer initial hospital stays (188 versus 111 d, P = 0.002), more 1-y hospital readmissions (83% versus 50%, P = 0.04), and more tracheostomies (28% versus 0%, P = 0.005). Mortality during first-year postdischarge was similar (6% versus 10%, P = 1.0). CONCLUSIONS: Despite adjustment for confounding variables, Nissen fundoplication was associated with prolonged support and greater resource utilization among infants with sBPD. Prospective studies are needed to clarify indications for fundoplication in this population.

Programmed cell death ligand 1 expression associated with subtypes of post-transplant lymphoproliferative disorder among pediatric kidney transplant recipients.

BACKGROUND: Programmed cell death ligand 1 (PD-L1) expression on tumor cells engages the PD-1 receptor on T cells, inhibiting anti-tumor responses. PD-L1 has been detected in cases of post-transplant lymphoproliferative disorder (PTLD) but reports are limited. Here we examine PD-L1 expression and evaluate for clinical correlations. METHODS: Twenty-one cases of PTLD were identified among pediatric kidney transplant recipients at our institution from February 1996 to April 2017. Using paraffin-embedded tissue biopsies, we examined 21 primary tumors for expression using PD-L1 monoclonal antibody performed with PAX5 as a double stain. We scored expression of PD-L1 on lesional B-cells as a percentage of positive cells. Clinical course and outcome were obtained from retrospective chart review. RESULTS: Applying revised 2017 WHO PTLD classification showed five non-destructive, nine polymorphic, and seven monomorphic cases. Average PD-L1 expression based upon PTLD subtype was: non-destructive 11%, polymorphic 43%, and monomorphic 73% (p = .01). Two patients transferred shortly after diagnosis, five received chemotherapy, and three died from PTLD. Among the fatalities, all showed monomorphic PTLD and 90% of lesional B-cells expressed PD-L1. CONCLUSION: In this case series, significant differences in PD-L1 expression were seen among different subtypes, and monomorphic PTLD demonstrated the highest expression. Study of a larger cohort is needed, and if the correlation of PD-L1 expression and PTLD subtype is confirmed, this may highlight the potential utility of checkpoint inhibitor therapy in cases of severe or refractory disease among kidney transplant recipient in whom the risk of allograft loss is acceptable given the option of chronic dialysis.

Language Differences by Race on Letters of Recommendation for the Pediatric Surgery Match.

OBJECTIVE: This study aims to evaluate if there is any significant linguistic difference in LoR based on applicant's race/ethnicity. DESIGN: Retrospective review of applications to pediatric surgery fellowship at a single institution (2016-2020). Race was self-reported by applicants. LoR were analyzed via the Linguistic Inquiry and Word Count (LIWC) software program. SETTING: Johns Hopkins All Children's Hospital, St. Petersburg, Florida USA. A free-standing tertiary pediatric hospital. PARTICIPANTS: Pediatric surgery fellowship applicants from 2016 to 2020. RESULTS: A total of 1086 LoR from 280 applicants (52% female) were analyzed. Racial distribution was Caucasians 62.1%, Asian 12.1%, Hispanics 7.1%, multiracial 6.4% African Americans 5%, and other/unknown 7.1%. Letter writers were largely male (84%), pediatric surgeons (63%) and professors (57%). There was no difference in LoR word count across races. LoR for female multiracial candidates contained higher use of affiliation and negative emotion terms compared to Hispanic females (p = 0.002 and 0.048, respectively), and past focus terms when compared to Caucasian and Asian female applicants (p < 0.001 and p = 0.003, respectively). Religion terms were more common in LoR for Asian females when compared to Caucasian females (p < 0.001). CONCLUSION: This study demonstrates linguistic differences in LoR for pediatric surgery training programs based on applicant race/ethnicity. While differences are present, these do not suggest overt bias based on applicants race or ethnicity.

Attitudes Toward Surgical Innovation Research in the Pediatric Surgery Fellowship Match.

INTRODUCTION: Pediatric surgery applicants are increasingly pursuing research in non-traditional fields including surgical innovation. This study aims to evaluate the relative value that pediatric surgeons involved in fellow selection place on innovation experience compared to traditional research. METHODS: A cross-sectional web-based survey of American Pediatric Surgical Association members involved in the selection of pediatric surgical fellows was conducted. Respondents reported their own innovation experience and were asked to identify valuable traits of applicants who completed an innovation fellowship. They rated the value of traditional research metrics including publications, presentations, and advanced degrees compared to patents and other innovation-related metrics. Comparisons were made between those with and without innovation experience with respect to gender, years in practice, and institutional role. RESULTS: One hundred thirty respondents were involved in pediatric surgery fellow selection. Innovation work was felt to be equal to or more valuable than basic science by 75% of respondents (84% vs. clinical/outcomes, 93% vs. other non-traditional, 72% vs. other clinical fellowships). Commonly cited concerns included "fewer publications" (21%) and "preoccupation with financial reward" (19%). The most valuable innovation-related metrics were "developing a novel surgical procedure" (67%) and "developing a novel device" (58%). When asked if the respondent would advise a junior resident to pursue an innovation fellowship, 49% would, 9% would not, and 43% were unsure. Seventeen percent expressed concern for match success. CONCLUSION: Innovation experience is generally viewed positively by pediatric surgeons involved in fellow selection. However, applicants and mentors would benefit from focusing on traditional academic outputs to ensure competitiveness. TYPE OF STUDY: Cross-sectional observational study. LEVEL OF EVIDENCE: III.

Presentation and outcomes of post-transplant lymphoproliferative disorder at a single institution pediatric transplant center.

BACKGROUND: This study aimed to characterize features present at the time of diagnosis and describe outcomes in patients with post-transplant lymphoproliferative disorder (PTLD) following pediatric solid organ transplantation. METHODS: We performed a retrospective review of solid organ transplant patients who developed pathologically confirmed PTLD at our center from 2006 to 2016. RESULTS: Of 594 patients included in this study, 41(6.9%) were diagnosed with PTLD. Median age at transplant was 5.6(IQR 1.7-16.1) years. Proportion of PTLD cases by organ transplanted and median time (IQR) to disease onset were: heart 11/144(7.6%) at 13.6(8.5-55.6) months, lung 7/52(13.5%) at 9.1(4.9-35) months, kidney 8/255(3.1%) at 39.5(13.9-57.1) months, liver 12/125(9.6%) at 7.7(5.5-22) months, intestine 0/4(0%), and multi-visceral 3/14(21.4%) at 5.4(5.4-5.6) months. No significant correlation was seen between recipient EBV status at transplant and timing of development of PTLD. There were six early lesions, 15 polymorphic, 19 monomorphic, and one uncharacterizable PTLD. Following immunosuppression reduction, 30 patients received rituximab, and 14 required chemotherapy. At median 25(IQR 12-53) months follow-up from the onset of PTLD, eight patients died secondary to transplant related complications, three are alive with active disease, and 30 have no evidence of disease. CONCLUSION: PTLD is a significant complication following pediatric solid organ transplantation. EBV levels in conjunction with symptomatic presentation following transplant may assist in detection of PTLD. Most patients can achieve long-term disease-free survival through immunosuppression reduction, anti-CD20 treatment, and chemotherapy in refractory cases.

Donor-to-recipient weight ratio is a risk factor for hepatic artery thrombosis after whole-liver transplantation in children under 25 kg.

Hepatic artery thrombosis (HAT) following pediatric liver transplantation increases morbidity and risk of graft failure. We performed a retrospective chart review of all patients who underwent deceased-donor liver transplantation from August 2002 to July 2016. Multi-organ transplant recipients were excluded. We examined the incidence of HAT at our institution and sought to identify associated donor or recipient risk factors. A total of 127 deceased-donor liver transplant patients with a median age of 1.7 years (IQR 0.67-6.7) were identified. Of those, 14 developed HAT, all weighing under 25 kg. Among 100 patients under 25 kg, whole-liver graft recipients had an odds ratio of 3.98 (95% confidence interval [CI]: 1.03, 15.34; P = .045) for developing HAT compared with split-liver graft recipients. Within the whole-liver recipient group under 25 kg, 11 patients developed HAT with a median donor-to-recipient ratio (DRWR) of 0.9 (IQR: 0.7-1.2) compared with a median DRWR of 1.4 (IQR: 1.1-1.9) for those who did not develop HAT. Multivariate analysis showed DRWR to be an independent risk factor for HAT in patients weighing under 25 kg who received whole organ grafts, with an odds ratio of 3.89 (95% CI: 1.43, 10.54; P = .008) for each 0.5 unit decrease in DRWR. Our results suggest that in recipients under 25 kg 1) split-liver grafts may have a lower rate of HAT and 2) selecting whole organ donors with a higher DRWR may decrease the incidence of HAT.

Perioperative renal transplantation management in small children using adult-sized living or deceased donor kidneys: A single-center experience.

Kidney transplantation remains the treatment of choice for children with ESRD. Optimal perioperative management is critical in small recipients of ASK to assure adequate graft perfusion. We present a single-center experience outlining management for patients weighing <20 kg who underwent primary renal transplantation with ASKs between 2007 and 2016. Sixty-three patients met study criteria and underwent 34 living-related, six living-unrelated, and 23 deceased donor kidney transplants. Median age and weight at transplant were 25 months (IQR 18-37 months; range 11 months-6 years) and 11.0 kg (IQR 9.2-14.5 kg; range 7.1-19.5 kg). Eighty-nine percent of patients required vasoactive agents intra-operatively, with twenty patients requiring prolonged vasoactive agents post-operatively. Intra-operatively, patients received 51.9 mL/kg of crystalloid, 27.3 mL/kg of 5% albumin, and 13.6 mL/kg of packed red blood cells. Most (93.7%) patients were extubated on POD#0. Weights peaked on post-operative days three through five. Over a median follow-up of 49 months (IQR 31-86 months; range 0-130 months), four grafts were lost, two due to thrombosis and two secondary to chronic rejection. There was one patient death six months post-transplant due to causes unrelated to transplantation. Graft survival at 1, 5, and 10 years was 98.4%, 96.6%, and 84.2%, respectively. Of surviving allografts, the median 1, 5, and 10 years post-transplant eGFR was 122.9, 90.0, and 59.2 mL/min/1.73 m2 as determined by the 2009 Schwartz formula. Renal transplantation in small children using ASKs requires meticulous perioperative management including adequate fluid resuscitation and judicious use of pressors to assure adequate graft perfusion. The use of ASKs from living or deceased donors results in satisfactory short and long-term outcomes.

Predictors of Need for Liver Transplantation in Children Undergoing Hepatoportoenterostomy for Biliary Atresia.

PURPOSE: The purpose of this study was to determine perioperative risk factors for need of liver transplantation following hepatoportoenterostomy. METHODS: A retrospective review of patients undergoing hepatoportoenterostomy for biliary atresia at our institution from 1990 to 2016 was completed. RESULTS: A total of 81 patients were identified with a median age of 51 days (IQR: 33-68) at hepatoportoenterostomy and a median follow-up time of 5.7 years (IQR: 1-11.6). Ten-year overall survival was 93% (95% CI: 84-97). Thirty-six patients (44%) ultimately required transplantation at a median time from hepatoportoenterostomy of 8.9 months (IQR: 5.2-19). The 10-year transplant-free survival was 36% (95%CI: 24-49). Steroid use (N=42) was not associated with improved 10-yr transplant-free survival (33% vs. 38%, p=0.690). Age at hepatoportoenterostomy was not significantly associated with the need for transplantation. Multivariable logistic regression analysis demonstrated that total bilirubin >2mg/dL (OR: 97, p<0.001) and albumin < 3.5g/dL (OR: 24, p=0.027) at 3 months after surgery were independent predictors of the need for transplantation, while adjusting for age, sex, prematurity, and steroid use. CONCLUSION: Overall survival for children with biliary atresia is excellent, although most patients will ultimately require liver transplantation. Total bilirubin and albumin level at 3 months following hepatoportoenterostomy are predictive of the need for transplantation. Steroid use is not associated with improved outcomes.

Autologous intestinal reconstruction surgery.

The management of short bowel syndrome has mainly been focused on intestinal rehabilitation as part of multidisciplinary team approach in specialized centers. While some patients go through a process of bowel adaptation that allows them to reach enteral autonomy, others reach a plateau before this and require prolonged parenteral nutrition and/or intestinal transplantation. Various autologous intestinal reconstruction procedures centered on bowel tapering have been described to increase functional intestinal area and help gain enteral autonomy. This review discusses the surgical techniques, advantages, limitations, and general outcomes of each procedure.

Long-term outcomes of liver transplantation for hepatoblastoma: A single-center 14-year experience.

HB is the most common primary liver tumor in children. Complete tumor excision, either by partial resection or by total hepatectomy and liver transplantation, in combination with chemotherapy provides the best chance for cure. We performed a retrospective analysis of patients who underwent liver transplantation for HB and herein present our 14-year single-institution experience. Twenty-five patients underwent liver transplantation for HB at a median age of 26 months (IQR: 15-44). Graft survival was 96%, 87%, and 80% at 1, 3, and 5 years, respectively. There were four patient deaths, three of them due to disease recurrence within the first year post-transplant. Ten-year overall survival was 84%. Three recipients initially presented with pulmonary metastases and underwent resection of metastatic disease, of which two are alive at 3.9 years. Of three patients who underwent salvage transplants, two are alive at 1.5 years after transplant. Non-survivors were associated with lower median alpha fetoprotein value at presentation compared to survivors (21 707 vs 343 214; P = .04). In conclusion, the overall long-term outcome of primary liver transplantation for HB is excellent. Tumor recurrence was the highest contributor to mortality. Even patients with completely treated pulmonary metastases prior to transplant demonstrated a favorable survival.

Tissue expander-stimulated lengthening of arteries for the treatment of midaortic syndrome in children.

BACKGROUND: Midaortic syndrome (MAS) is a rare condition characterized by stenosis of the abdominal aorta. Patients with disease refractory to medical management will usually require either endovascular therapy or surgery with use of prosthetic graft material for bypass or patch angioplasty. We report our early experience with a novel approach using a tissue expander (TE) to lengthen the normal native arteries in children with MAS, allowing primary aortic repair without the need for prosthetic graft material. METHODS: We conducted a retrospective review of patients with MAS undergoing the TE-stimulated lengthening of arteries (TESLA) procedure at our institution from 2010 to 2014. Data are presented as mean (range). RESULTS: Five patients aged 4.8 years (3-8 years) underwent the TESLA procedure. Stages of this procedure include the following: stage I, insertion of retroaortic TE; stage II, serial TE injections; and stage III, final repair with excision of aortic stenosis and primary end-to-end aortic anastomosis. Stage II was completed in 4 months (1-9 months) with 12 (7-20) TE injections. Goal lengthening was achieved in all patients. Stage III could not be completed in one patient because of extreme aortic inflammation, which precluded safe excision of the aortic stenosis and required use of a prosthetic bypass graft. The other four patients completed stage III with two (one to three) additional vessels also requiring reconstruction (renal or mesenteric arteries). At 3.2 years (1-6 years) of follow-up, all patients are doing well. CONCLUSIONS: The TESLA procedure allows surgical correction of MAS without the need for prosthetic grafts in young children who are still growing.

Bilateral native nephrectomy to reduce oxalate stores in children at the time of combined liver-kidney transplantation for primary hyperoxaluria type 1.

OBJECTIVE: Primary hyperoxaluria type-1 (PH-1) is a rare genetic disorder in which normal hepatic metabolism of glyoxylate is disrupted resulting in diffuse oxalate deposition and end-stage renal disease (ESRD). While most centers agree that combined liver-kidney transplant (CLKT) is the appropriate treatment for PH-1, perioperative strategies for minimizing recurrent oxalate-related injury to the transplanted kidney remain unclear. We present our management of children with PH-1 and ESRD on hemodialysis (HD) who underwent CLKT at our institution from 2005 to 2015. METHODS: On chart review, three patients (2 girls, 1 boy) met study criteria. Two patients received deceased-donor split-liver grafts, while one patient received a whole liver graft. All patients underwent bilateral native nephrectomy at transplant to minimize the total body oxalate load. Median preoperative serum oxalate was 72 µmol/L (range 17.8-100). All patients received HD postoperatively until predialysis serum oxalate levels fell <20 µmol/L. All patients, at a median of 7.5 years of follow-up (range 6.5-8.9), demonstrated stable liver and kidney function. CONCLUSIONS: While CLKT remains the definitive treatment for PH-1, bilateral native nephrectomy at the time of transplant reduces postoperative oxalate stores and may mitigate damage to the renal allograft.