Obstruction from Deflux leading to significant kidney function loss and chemotherapeutic challenges in pediatric Ewing sarcoma

Abstract

This report presents the case of an 8-year-old female with a history of vesicoureteral reflux (VUR) treated with Deflux injections, who developed Ewing sarcoma metastasized to the lungs. Despite the initial resolution of VUR following Deflux procedures, recurrent urinary tract infections prompted further evaluation revealing significant ureteral obstruction. Pre-chemotherapy workup included renal ultrasonography, nuclear medicine renal scan, and cystogram, identifying obstructive uropathy necessitating bilateral ureteral stent placement. This discussion encompasses the challenges of managing VUR, Deflux complications, and the importance of tailored follow-up protocols.

1 Introduction

Vesicoureteral reflux (VUR), the retrograde flow of urine from the bladder into the ureters and kidneys, poses significant challenges in pediatric urology. The management of VUR has evolved from conservative approaches to minimally invasive interventions such as endoscopic injection therapies. Among these, dextranomer/hyaluronic acid copolymer (Deflux®) has emerged as a popular choice for its efficacy and low-risk profile. However, despite its widespread use, concerns persist regarding potential complications, including ureteral obstruction, emphasizing the importance of comprehensive preoperative evaluation and meticulous postoperative monitoring. This report discusses the case of an 8-year-old female with a history of VUR treated with Deflux, who subsequently presented with Ewing Sarcoma, necessitating careful urologic evaluation before initiating chemotherapy.

2 Case presentation

The patient’s urologic history began with a febrile UTI at 6 months old caused by Klebsiella and Pseudomonas, which led to a renal ultrasound (US) and voiding cystourethrogram (VCUG), revealing bilateral SFU grade 2 hydronephrosis and bilateral grade 4 VUR. She was started on daily Bactrim prophylaxis. At one year old, she underwent bilateral Deflux injections, and a subsequent VCUG two years later was normal, allowing discontinuation of prophylaxis. At six years old, she experienced two UTIs (one was febrile). Repeat renal US showed SFU grade 3 hydronephrosis on the left, and VCUG indicated grade 2 VUR on the right. A second bilateral Deflux injection was performed without subsequent follow up. Her last UTI, E. coli positive, occurred at eight years old in October 2023. All treatments and care were at a separate institution.

In December 2023, this 8-year-old female presented with worsening right thigh pain and a limp. Initially attributed to growing pains, her symptoms were refractory to Tylenol and NSAIDs. Examination revealed tenderness in the superior thigh with elevated ESR (72 mm/hr) and CRP (12.194 mg/L). X-ray revealed an aggressive-appearing, expansile lytic lesion with periosteal reaction in the right femoral mid-diaphysis. Chest X-ray identified a 4 mm nodule at the medial right lung base. MRI and chest CT confirmed Ewing sarcoma with lung metastasis. Before initiating chemotherapy, a thorough review of her urological medical history was conducted.

Pre-chemotherapy evealuation included a renal ultrasound, revealing right grade 2 hydronephrosis and left grade 4 hydronephrosis. Nuclear medicine renal MAG3 scan demonstrated high-grade obstruction of the left kidney, partial to moderate obstruction of the right, and renal function of 4 % from the left kidney and 96 % from the right. The right side had a T ½ of 30–40 minutes, while the T ½ could not be calculated on the left side. VCUG was normal. A PIC cystogram revealed no reflux, but bilateral cystourethroscopy showed right ureter with proximal and distal Deflux blebs, and a left ureteral orifice (UO) displaced laterally by Deflux ( Fig. 1 ). Right retrograde pyelogram showed dilation of the right UO with intramural narrowing distal ureter while left RPG showed dilation of the entire ureter. Bilateral double J stents (4.7 × 16 cm) were placed to address the obstructions with a 5 week follow up ultrasound revealing reduction to right-sided grade 1 and left-sided grade 3 hydronephrosis. She was subsequently started on COG protocol AEWS1221 Regimen A on January 2024, which consists of cycles of vincristine/doxorubicin/cyclophosphamide (VDC) and ifosfamide/etoposide (IE) and is the standard treatment for localized and metastatic Ewing Sarcoma in pediatric populations.

This case highlights the complexity of managing pediatric Ewing sarcoma in the presence of Deflux-related ureteral obstruction and significant renal function impairment, emphasizing the need for careful pre-chemotherapy evaluation and intervention.

3 Discussion

The management of VUR involves various approaches, including spontaneous resolution with prophylactic antibiotics, surgical intervention, and endoscopic treatments like Deflux injections. Spontaneous resolution is more likely in lower grades of VUR (I–III) in younger children, with an annual resolution rate of 5 % for grades IV–V. The VUR Index (VURx) was a simple scoring tool designed to identify factors associated with VUR resolution in children under 2 years old and predict improvement and resolution ( Fig. 2 .). VURx 1 to 5–6 had improvement/resolution rates of 89 %, 69 %, 53 %, 16 % and 11 %, respectively. In our patient, initially diagnosed with grade 4 VUR before the first Deflux procedure, the condition persisted and later recurred. Early repair of higher-grade VUR (IV–V) should be considered after 18 months of age.