Pediatric Sedation Unit: A Safe, Effective, and Satisfactory Alternative to Outpatient Pediatric Urological Procedures Under Anesthesia.

INTRODUCTION: The operating room is an increasingly expensive and limited resource. The aim of this study was to evaluate the efficacy, safety, cost, and parental satisfaction of transitioning minor pediatric urology procedures from an operating room setting to a pediatric sedation unit. METHODS: Minor urological procedures were transitioned from the operating room to the pediatric sedation unit if they could be completed in 20 minutes using minimal instrumentation. Information regarding patient demographics, procedure characteristics, rates of success and complications, and cost were collected from urology procedures performed in the pediatric sedation unit between August 2019 and September 2021. Patient demographics and cost data from the most common urology procedures performed in the pediatric sedation unit were compared to data from historical controls of cases occurring in the operating room. Parent surveys were performed following the completion of procedures in the pediatric sedation unit. RESULTS: A total of 103 patients, ranging from 6-207 months old (mean 72 months), underwent procedures in the pediatric sedation unit. The most common procedures were lysis of adhesions and meatotomy. All procedures were successfully completed with procedural sedation, and no procedure was complicated by serious sedation adverse events. The cost reduction for lysis of adhesions in the pediatric sedation unit was 53.5% compared to the operating room, and meatotomy was 27.9%, leading to approximately $57,000 cost savings per year. Fifty families completed a follow-up satisfaction survey, and 83% of parents were satisfied with the care their family received. CONCLUSIONS: The pediatric sedation unit can provide a successful and cost-efficient alternative to the operating room while preserving safety and high rates of parental satisfaction.

Antibody-drug conjugate T-DM1 treatment for HER2+ breast cancer induces ROR1 and confers resistance through activation of Hippo transcriptional coactivator YAP1.

BACKGROUND: A newly developed drug trastuzumab emtansine (T-DM1) has improved the survival of breast cancer (BC) patients. Despite an impressive initial clinical response, a subgroup of patient develop resistance and present therapeutic challenges. The underlying resistance mechanisms are not fully investigated. We report that T-DM1 treatment modulates the expression of ROR1 (type 1 receptor tyrosine kinase-like orphan receptor) and induces self-renewal of cancer stem cells (CSCs) leading to therapeutic resistance. METHODS: Using BC patient tumor samples, and BC cell lines we gained insight into the T-DM1 treatment induced ROR1 overexpression and resistance. In vitro sphere forming assays and in vivo extreme dilution assays were employed to analyze the stemness and self-renewal capacity of the cells. A series of molecular expression and protein assays including qRT-PCR, FACS-sorting, ELISA, immunostaining, Western blotting were used to provide evidence. FINDINGS: Exposure of cells to T-DM1 shifted ROR1 expression from low to high, enriched within the CSC subpopulation, coincident with increased Bmi1 and stemness factors. T-DM1 induced ROR1 cells showed high spheroid and tumor forming efficiency in vitro and in an animal model exhibiting shorter tumor-free time. Mechanistically, the overexpression of ROR1 is partly induced by the activation of YAP1 and its target genes. Silencing of ROR1 and YAP1 by pharmacologic inhibitors and/or sh/siRNA inhibited spheroid formation, the initiation of tumors and the capacity for self-renewal and ROR1 overexpression. INTERPRETATIONS: The results presented here indicate that simultaneous targeting of ROR1 and YAP1 may suppress CSC self-renewal efficacy and inhibit tumor progression in BC. In this manner such treatments may overcome the T-DM1 mediated therapeutic resistance and improve clinical outcome. FUND: This study was supported by Neurogen Technologies for interdisciplinary research.

Outcomes of seromuscular bladder augmentation versus standard ileocystoplasty: A single institution experience over 14 years.

INTRODUCTION: Ileocystoplasty is the standard technique used for bladder augmentation, and has been used widely for decades. However, it is known to be associated with complications such as stone formation, mucus production, metabolic acidosis, urinary tract infections, intestinal obstruction, and a long-term risk of bladder cancer. Seromuscular bladder augmentation (SMBA) is an alternative to the standard ileocystoplasty, and has been associated with a lower incidence of bladder stones. Few reports have been published on intermediate outcomes of SMBA. Herein, we report long-term outcomes of SMBA from a single institution compared with standard ileocystoplasty. METHODS: After Institutional Review Board approval, a retrospective chart review of all patients who underwent bladder augmentation at our institution over a 14-year period was performed. The status of patients after SMBA (10 patients) was compared according to age, sex, and diagnosis with patients who underwent traditional ileocystoplasty (30 patients). Parameters such as demographic information, pre- and postoperative bladder capacity as assessed by urodynamic studies, urinary tract infections (UTIs), bladder calculi, incontinence, need for secondary surgical procedures, and spontaneous bladder perforation were compared in the two groups. All the patients were on a clean intermittent catheterization (CIC) regimen. RESULTS: Over the study period, 10 patients underwent SMBA and 30 patients (according to age, sex, and diagnosis) underwent standard ileocystoplasty; the average age at surgery was 10.3 and 10 years respectively, with a mean follow up of 6.7 years in the SMBA group and 6 years in the ileocystoplasty group. There were no statistically significant differences in the rate of UTIs, urinary incontinence, subsequent surgery, or spontaneous bladder perforation. The mean bladder capacity increased significantly for both groups as assessed by pre- and postoperative urodynamic studies, although the difference in the rate of bladder calculi between the two groups (0 [0%] vs. 8 [27%], p = 0.06) did not reach statistical significance (Table). CONCLUSIONS: SMBA is safe and efficacious and may result in a lower rate of stone formation than standard ileocystoscopy. SMBA should be considered as a viable alternative to standard ileocystoplasty.

Ureteroureterostomy: An Alternative to Ureteroneocystostomy in Select Cases of Pediatric Renal Transplantation.

PURPOSE: Ureteroneocystostomy is the standard mode of establishing urinary drainage in renal transplantation. However, donor-to-recipient ureteroureterostomy may be considered in the presence of a challenging bladder or an augmented bladder, or when the donor ureter might be compromised or is too short. This approach also preserves a nonrefluxing system with an orthotopic ureteral orifice. MATERIALS AND METHODS: We retrospectively reviewed the records of all pediatric renal transplantations in which ureteroureterostomy was performed at a single tertiary care pediatric center over the 12-year period from 2004 to 2015. Ureteroureterostomy was performed in end-to-side fashion from donor-to-recipient ureter. Patients with a history of symptomatic vesicoureteral reflux were excluded from ureteroureterostomy. Parameters were reviewed, including age, gender, source of renal transplantation (deceased or living donor), indications for ureteroureterostomy and complications. RESULTS: Primary ureteroureterostomy was performed at 23 of the 213 renal transplantations (10.8%). At transplantation mean ± SD age was 11.7 ± 4.9 years and mean weight was 33.5 ± 18.9 kg. Two secondary ureteroureterostomies were done to salvage the ureter due to complications after ureteroneocystostomy. Of the patients 60% and 40% underwent ureteroureterostomy during deceased and living donor renal transplantation, respectively. The most common indications included a challenging small bladder due to anuria, a valve bladder and a neurogenic augmented bladder. Two urinary leaks (8%) occurred and no allografts were lost. CONCLUSIONS: Ureteroureterostomy is a safe alternative to standard ureteroneocystostomy in renal transplantation. Ureteroureterostomy should be considered a primary option in certain complex situations and secondarily as a salvage procedure when ureteral problems develop after ureteroneocystostomy in patients who undergo renal transplantation.

Impact of bladder-derived acellular matrix, growth factors, and extracellular matrix constituents on the survival and multipotency of marrow-derived mesenchymal stem cells.

We investigate the effect of bladder-derived acellular matrix (ACM) on bone marrow mesenchymal stem cells (BM-MSC) growth, survival, and differentiation, and evaluate the effect of collagen I and IV on BM-MSC differentiation potential to SMC. BM-MSCs isolated from CD1(_) mice were characterized by surface markers and differentiation into different lineages. BM-MSC SMC potential was further evaluated in stem cell medium alone or supplemented with TGF-ß1 and recombinant human platelet-derived growth factor (PDGF-BB) on plastic, collagen I and IV using western blot. Furthermore, BM-MSCs were seeded on porcine derived ACM-fortified with hyaluronic acid and cultured in Mesencult+-growth factors, bone, or fat induction media for 3 weeks. Seeded constructs were evaluated by H&E, Ki67 assay, Oil red O, and Alizarin red stain. SMC differentiation was semiquantified via immunohistochemistry. BM-MSCs differentiated into fat and bone when induced. In Mesencult, BM-MSCs differentiated into SMC, expressing α-SMA, calponin, and MHC. BM-MSCs cultured on collagen I and IV reduced expression of SMC and MHC compared to plastic. On ACM-HA, BM-MSCs maintained multipotent state by differentiating to bone and fat when induced. In Mesencult, BM-MSC-seeded ACM-HA expressed α-SMA, calponin, and MHC. TGF-ß1 and PDGF-BB enhanced SMC differentiation on collagens and ACM-HA. SMC proteins expression by BM-MSC varies depending on culture substrate. SMC markers are expressed higher on plastic and lower on collagen I, IV, and ACM-HA, suggesting these substrates preferentially maintain undifferentiated state of BM-MSC, which could be advantageous for incorporation of cell-seeded grafts to permit host modulation of tissue regeneration.

Minimally invasive approach for treatment of urinary and fecal incontinence in selected patients with spina bifida.

OBJECTIVES: At our institution, the use of cecostomy tubes has provided a successful method for managing severe constipation in patients with spina bifida, with good patient and caretaker satisfaction and minimal morbidity. We have developed a modified technique to allow placement of the cecostomy tube under direct vision during laparoscopic appendicovesicostomy. We present our initial experience and technique. METHODS: Patients with a normal bladder capacity and compliance who were scheduled for creation of an appendicovesicostomy and who also had refractory constipation were offered concurrent cecostomy tube placement. At the laparoscopic procedure, we performed percutaneous placement of the cecostomy tube through the abdominal wall under direct visualization. Subsequently, dissection of the appendix with its mesentery was performed. The detrusor muscle was dissected and a trough for the appendix created. Laparoscopic anastomosis of the appendix to the bladder mucosa and approximation of the detrusor over the appendix created a nonrefluxing channel. RESULTS: Three patients have undergone concurrent cecostomy tube placement at appendicovesicostomy. No complications have been encountered thus far. On follow-up, the cecostomy tube scar has been well concealed and appears no different from the ones placed under radiologic guidance. The patients have been using the catheterizable channel to access the bladder and dry performing intermittent catheterization without difficulties. CONCLUSIONS: In patients with a neurogenic bladder who do not qualify for major bladder reconstructive procedures, such as augmentation cystoplasty or bladder neck repair, social continence and independence can be achieved with minimally invasive surgery. Concomitant laparoscopic appendicovesicostomy and cecostomy tube placement may be a suitable surgical option.